MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®
International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic
MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.
U.S. BRAND NAMES — Lotronex®
PHARMACOLOGIC CATEGORY
Selective 5-HT3 Receptor Antagonist
DOSING: ADULTS — IBS: Female: Oral: Initial: 0.5 mg twice daily for 4 weeks, with or without food; if tolerated, but response is inadequate, may be increased after 4 weeks to 1 mg twice daily. If response is inadequate after 4 weeks of 1 mg twice-daily dosing, discontinue treatment.
Note: Discontinue immediately if constipation or signs/symptoms of ischemic colitis occur. Do not reinitiate in patients who develop ischemic colitis.
DOSING: ELDERLY — Refer to adult dosing. Dosage adjustment is not required; however, postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.
DOSING: RENAL IMPAIRMENT — The need for dosage adjustment has not been defined (due to limited information on activity of metabolites).
DOSING: HEPATIC IMPAIRMENT — In mild-to-moderate dysfunction (Child-Pugh score ≤ 9), use caution. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lotronex®: 0.5 mg, 1 mg
DOSAGE FORMS: CONCISE
Tablet:
Lotronex®: 0.5 mg, 1 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food; however, when administered with food, absorption may be reduced by approximately 25%.
USE — Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional therapy
ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Constipation (dose related; 29%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, ulcerative colitis, urinary frequency, urticaria
CONTRAINDICATIONS — Do not start treatment in patients who are constipated. Hypersensitivity to alosetron or any component of the formulation; history of severe or chronic constipation or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; history of impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; patients unable to understand or comply with "Patient-Physician" agreement; concomitant administration with fluvoxamine
WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. Constipation: See "Concerns related to adverse effects" below. Ischemic colitis: See "Concerns related to adverse effects" below. Patient-Physician agreement: See "Other warnings/precautions" below.
Concerns related to adverse effects: Constipation: [U.S. Boxed Warning]: Discontinue immediately in patients who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation may be increased in elderly, debilitated patients, or with concurrent use of other medications which decrease GI motility. Nonsevere constipation may be managed by temporarily interrupting therapy. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate immediately in patients who experience rectal bleeding or a sudden worsening of abdominal pain, and do not restart therapy if ischemic colitis is diagnosed.
Disease-related concerns: Hepatic impairment: Use caution in mild-to-moderate hepatic impairment (Child-Pugh score ≤ 9); contraindicated in severe impairment (Child-Pugh score ≥ 10).
Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in Prometheus' Prescribing Program for Lotronex® may prescribe this medication. Program stickers must be affixed to all prescriptions; no phone, fax, or computerized prescriptions are permitted with this program.
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with food, absorption may be reduced by ~25%.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Alosetron should be used in pregnant women only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Animal studies indicate that alosetron and/or metabolites are excreted in breast milk. It is not known if alosetron in excreted in human milk. Caution should be used in administering alosetron to a nursing woman.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Tablets (Lotronex)
1 mg (30): $428.32
MECHANISM OF ACTION — Alosetron is a potent and selective antagonist of a subtype of the serotonin 5-HT3 receptor. 5-HT3 receptors are ligand-gated ion channels extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions. In patients with irritable bowel syndrome, blockade of these channels may reduce pain, abdominal discomfort, urgency, and diarrhea.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 65-95 L
Protein binding: 82%
Metabolism: Extensive hepatic metabolism. Alosetron is metabolized by CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.
Bioavailability: Mean: 50% to 60% (range: 30% to >90%); decreased with food (25%)
Half-life elimination: 1.5 hours for alosetron
Time to peak: 1 hour after oral administration
Excretion: Urine (73%) and feces (24%); 7% as unchanged drug (1% feces, 6% urine)
PATIENT INFORMATION — Take with or without food. Do not take if you are frequently constipated; constipation is a side effect associated with this medication and can lead to serious complications. Stop taking this medication and call your prescriber if you become constipated, or if you have sudden worsening of abdominal pain, severe constipation, or blood in your stool. Do not continue taking the medication until you have spoken with your prescriber; if after stopping the medication, constipation does not resolve, call your prescriber again. Notify your prescriber if you are pregnant, plan on becoming pregnant, or if you are breast-feeding.
Alosetron
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®
International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic
MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.
U.S. BRAND NAMES — Lotronex®
PHARMACOLOGIC CATEGORY
Selective 5-HT3 Receptor Antagonist
DOSING: ADULTS — IBS: Female: Oral: Initial: 0.5 mg twice daily for 4 weeks, with or without food; if tolerated, but response is inadequate, may be increased after 4 weeks to 1 mg twice daily. If response is inadequate after 4 weeks of 1 mg twice-daily dosing, discontinue treatment.
Note: Discontinue immediately if constipation or signs/symptoms of ischemic colitis occur. Do not reinitiate in patients who develop ischemic colitis.
DOSING: ELDERLY — Refer to adult dosing. Dosage adjustment is not required; however, postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.
DOSING: RENAL IMPAIRMENT — The need for dosage adjustment has not been defined (due to limited information on activity of metabolites).
DOSING: HEPATIC IMPAIRMENT — In mild-to-moderate dysfunction (Child-Pugh score ≤ 9), use caution. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lotronex®: 0.5 mg, 1 mg
DOSAGE FORMS: CONCISE
Tablet:
Lotronex®: 0.5 mg, 1 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food; however, when administered with food, absorption may be reduced by approximately 25%.
USE — Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional therapy
ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Constipation (dose related; 29%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, ulcerative colitis, urinary frequency, urticaria
CONTRAINDICATIONS — Do not start treatment in patients who are constipated. Hypersensitivity to alosetron or any component of the formulation; history of severe or chronic constipation or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; history of impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; patients unable to understand or comply with "Patient-Physician" agreement; concomitant administration with fluvoxamine
WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. Constipation: See "Concerns related to adverse effects" below. Ischemic colitis: See "Concerns related to adverse effects" below. Patient-Physician agreement: See "Other warnings/precautions" below.
Concerns related to adverse effects: Constipation: [U.S. Boxed Warning]: Discontinue immediately in patients who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation may be increased in elderly, debilitated patients, or with concurrent use of other medications which decrease GI motility. Nonsevere constipation may be managed by temporarily interrupting therapy. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate immediately in patients who experience rectal bleeding or a sudden worsening of abdominal pain, and do not restart therapy if ischemic colitis is diagnosed.
Disease-related concerns: Hepatic impairment: Use caution in mild-to-moderate hepatic impairment (Child-Pugh score ≤ 9); contraindicated in severe impairment (Child-Pugh score ≥ 10).
Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in Prometheus' Prescribing Program for Lotronex® may prescribe this medication. Program stickers must be affixed to all prescriptions; no phone, fax, or computerized prescriptions are permitted with this program.
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with food, absorption may be reduced by ~25%.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Alosetron should be used in pregnant women only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Animal studies indicate that alosetron and/or metabolites are excreted in breast milk. It is not known if alosetron in excreted in human milk. Caution should be used in administering alosetron to a nursing woman.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Tablets (Lotronex)
1 mg (30): $428.32
MECHANISM OF ACTION — Alosetron is a potent and selective antagonist of a subtype of the serotonin 5-HT3 receptor. 5-HT3 receptors are ligand-gated ion channels extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions. In patients with irritable bowel syndrome, blockade of these channels may reduce pain, abdominal discomfort, urgency, and diarrhea.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 65-95 L
Protein binding: 82%
Metabolism: Extensive hepatic metabolism. Alosetron is metabolized by CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.
Bioavailability: Mean: 50% to 60% (range: 30% to >90%); decreased with food (25%)
Half-life elimination: 1.5 hours for alosetron
Time to peak: 1 hour after oral administration
Excretion: Urine (73%) and feces (24%); 7% as unchanged drug (1% feces, 6% urine)
PATIENT INFORMATION — Take with or without food. Do not take if you are frequently constipated; constipation is a side effect associated with this medication and can lead to serious complications. Stop taking this medication and call your prescriber if you become constipated, or if you have sudden worsening of abdominal pain, severe constipation, or blood in your stool. Do not continue taking the medication until you have spoken with your prescriber; if after stopping the medication, constipation does not resolve, call your prescriber again. Notify your prescriber if you are pregnant, plan on becoming pregnant, or if you are breast-feeding.
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®
International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic
MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.
U.S. BRAND NAMES — Lotronex®
PHARMACOLOGIC CATEGORY
Selective 5-HT3 Receptor Antagonist
DOSING: ADULTS — IBS: Female: Oral: Initial: 0.5 mg twice daily for 4 weeks, with or without food; if tolerated, but response is inadequate, may be increased after 4 weeks to 1 mg twice daily. If response is inadequate after 4 weeks of 1 mg twice-daily dosing, discontinue treatment.
Note: Discontinue immediately if constipation or signs/symptoms of ischemic colitis occur. Do not reinitiate in patients who develop ischemic colitis.
DOSING: ELDERLY — Refer to adult dosing. Dosage adjustment is not required; however, postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.
DOSING: RENAL IMPAIRMENT — The need for dosage adjustment has not been defined (due to limited information on activity of metabolites).
DOSING: HEPATIC IMPAIRMENT — In mild-to-moderate dysfunction (Child-Pugh score ≤ 9), use caution. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lotronex®: 0.5 mg, 1 mg
DOSAGE FORMS: CONCISE
Tablet:
Lotronex®: 0.5 mg, 1 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food; however, when administered with food, absorption may be reduced by approximately 25%.
USE — Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional therapy
ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Constipation (dose related; 29%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, ulcerative colitis, urinary frequency, urticaria
CONTRAINDICATIONS — Do not start treatment in patients who are constipated. Hypersensitivity to alosetron or any component of the formulation; history of severe or chronic constipation or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; history of impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; patients unable to understand or comply with "Patient-Physician" agreement; concomitant administration with fluvoxamine
WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. Constipation: See "Concerns related to adverse effects" below. Ischemic colitis: See "Concerns related to adverse effects" below. Patient-Physician agreement: See "Other warnings/precautions" below.
Concerns related to adverse effects: Constipation: [U.S. Boxed Warning]: Discontinue immediately in patients who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation may be increased in elderly, debilitated patients, or with concurrent use of other medications which decrease GI motility. Nonsevere constipation may be managed by temporarily interrupting therapy. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate immediately in patients who experience rectal bleeding or a sudden worsening of abdominal pain, and do not restart therapy if ischemic colitis is diagnosed.
Disease-related concerns: Hepatic impairment: Use caution in mild-to-moderate hepatic impairment (Child-Pugh score ≤ 9); contraindicated in severe impairment (Child-Pugh score ≥ 10).
Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in Prometheus' Prescribing Program for Lotronex® may prescribe this medication. Program stickers must be affixed to all prescriptions; no phone, fax, or computerized prescriptions are permitted with this program.
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with food, absorption may be reduced by ~25%.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Alosetron should be used in pregnant women only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Animal studies indicate that alosetron and/or metabolites are excreted in breast milk. It is not known if alosetron in excreted in human milk. Caution should be used in administering alosetron to a nursing woman.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Tablets (Lotronex)
1 mg (30): $428.32
MECHANISM OF ACTION — Alosetron is a potent and selective antagonist of a subtype of the serotonin 5-HT3 receptor. 5-HT3 receptors are ligand-gated ion channels extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions. In patients with irritable bowel syndrome, blockade of these channels may reduce pain, abdominal discomfort, urgency, and diarrhea.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 65-95 L
Protein binding: 82%
Metabolism: Extensive hepatic metabolism. Alosetron is metabolized by CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.
Bioavailability: Mean: 50% to 60% (range: 30% to >90%); decreased with food (25%)
Half-life elimination: 1.5 hours for alosetron
Time to peak: 1 hour after oral administration
Excretion: Urine (73%) and feces (24%); 7% as unchanged drug (1% feces, 6% urine)
PATIENT INFORMATION — Take with or without food. Do not take if you are frequently constipated; constipation is a side effect associated with this medication and can lead to serious complications. Stop taking this medication and call your prescriber if you become constipated, or if you have sudden worsening of abdominal pain, severe constipation, or blood in your stool. Do not continue taking the medication until you have spoken with your prescriber; if after stopping the medication, constipation does not resolve, call your prescriber again. Notify your prescriber if you are pregnant, plan on becoming pregnant, or if you are breast-feeding.
Almotriptan
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 5-HT1B, 1D Receptor Agonist
DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as malate:
Axert®: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE
Tablet:
Axert®: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Acute treatment of migraine with or without aura in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended. Renal impairment: Use with caution in patients with moderate-to-severe renal failure. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
Concurrent drug therapy issues: Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — May be taken without regard to meals
PRICING — (data from drugstore.com)
Tablets (Axert)
6.25 mg (6): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed
Distribution: Vd: ~180-200 L
Protein binding: ~35%
Metabolism: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 5-HT1B, 1D Receptor Agonist
DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as malate:
Axert®: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE
Tablet:
Axert®: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Acute treatment of migraine with or without aura in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended. Renal impairment: Use with caution in patients with moderate-to-severe renal failure. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
Concurrent drug therapy issues: Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — May be taken without regard to meals
PRICING — (data from drugstore.com)
Tablets (Axert)
6.25 mg (6): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed
Distribution: Vd: ~180-200 L
Protein binding: ~35%
Metabolism: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.
Almotriptan
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 5-HT1B, 1D Receptor Agonist
DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as malate:
Axert®: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE
Tablet:
Axert®: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Acute treatment of migraine with or without aura in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended. Renal impairment: Use with caution in patients with moderate-to-severe renal failure. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
Concurrent drug therapy issues: Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — May be taken without regard to meals
PRICING — (data from drugstore.com)
Tablets (Axert)
6.25 mg (6): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed
Distribution: Vd: ~180-200 L
Protein binding: ~35%
Metabolism: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 5-HT1B, 1D Receptor Agonist
DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as malate:
Axert®: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE
Tablet:
Axert®: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Acute treatment of migraine with or without aura in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended. Renal impairment: Use with caution in patients with moderate-to-severe renal failure. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
Concurrent drug therapy issues: Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — May be taken without regard to meals
PRICING — (data from drugstore.com)
Tablets (Axert)
6.25 mg (6): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed
Distribution: Vd: ~180-200 L
Protein binding: ~35%
Metabolism: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.
Allopurinol MEDICATION SAFETY ISSUES Sound-alike/look-alike issues: Allopurinol may be confused with Apresoline Zyloprim® may be confused with X
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®, Zovirax®
U.S. BRAND NAMES — Aloprim™ ; Zyloprim®
PHARMACOLOGIC CATEGORY
Xanthine Oxidase Inhibitor
DOSING: ADULTS — Doses >300 mg should be given in divided doses.
Gout: Oral: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage. Maximum daily dose: 800 mg/day.
Secondary hyperuricemia associated with chemotherapy:
Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy
I.V.: 200-400 mg/m2/day (maximum: 600 mg/day)
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses
DOSING: PEDIATRIC
(For additional information see "Allopurinol: Pediatric drug information")
Gout: Children >10 years: Refer to adult dosing.
Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.
Secondary hyperuricemia associated with chemotherapy:
Oral: Children ≤ 10 years: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m2/day in 2-4 divided doses, maximum: 800 mg/24 hours, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy)
Alternative (manufacturer labeling):
<6 years: 150 mg/day in 3 divided doses
6-10 years: 300 mg/day in 2-3 divided doses
>10 years: Refer to adult dosing.
I.V.:
Children ≤ 10 years: Starting dose: 200 mg/m2/day
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Children >10 years: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Oral: Must be adjusted due to accumulation of allopurinol and metabolites;
Adult Maintenance Doses of Allopurinol
Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute. Clcr 140 mL/minute: 400 mg daily Clcr 120 mL/minute: 350 mg daily Clcr 100 mL/minute: 300 mg daily Clcr 80 mL/minute: 250 mg daily Clcr 60 mL/minute: 200 mg daily Clcr 40 mL/minute: 150 mg daily Clcr 20 mL/minute: 100 mg daily Clcr 10 mL/minute: 100 mg every 2 days Clcr 0 mL/minute: 100 mg every 3 days
I.V.:
Clcr 10-20 mL/minute: Administer 200 mg/day.
Clcr 3-10 mL/minute: Administer 100 mg/day.
Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION
Oral: Should administer oral forms after meals with plenty of fluid.
I.V.: Infuse over 15-60 minutes. The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.
COMPATIBILITY — Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.
USE
Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi
I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy
ADVERSE REACTIONS SIGNIFICANT
Dermatologic: Rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Alkaline phosphatase increased, liver enzymes increased
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression. Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. Dosage adjustments needed.
Concurrent drug therapy issues: ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors. Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine; dosage adjustment necessary. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification
Pivampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Pivampicillin. Risk C: Monitor therapy
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: May decrease effectiveness.
Iron supplements: Hepatic iron uptake may be increased.
Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.
LACTATION — Enters breast milk/use caution (AAP rates "compatible")
DIETARY CONSIDERATIONS — Should administer oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
PRICING — (data from drugstore.com)
Tablets (Zyloprim)
100 mg (30): $23.99
300 mg (30): $56.04
MONITORING PARAMETERS — CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy
REFERENCE RANGE — Uric acid, serum: An increase occurs during childhood
Adults:
Male: 3.4-7 mg/dL or slightly more
Female: 2.4-6 mg/dL or slightly more
Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); AL (PH); Alinol (TH); Allo (CO); Allo 300 (DE); Allo-Puren (DE); Allobeta (AU); Allohexal (AU); Allopin (TH); Allopur (CH, NO); Allopurinol (PL); Allopurinol-ratiopharm (LU); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allpargin (LU); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpuric (LU); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (PL); Aprinol (JP); Apurin (FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Etindrax (MX); Foligan (DE); Genozyl (MX); Gichtex (AT); Hamarin (GB); Hexanurat (DK); Huma-Purol (HU); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (PH); Masaton (JP); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Milurit (BG, HK, HN, HU, PL); Miniplanor (JP); Neufan (JP); Nilapur (ID); Nipurol (VE); No-Uric (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Pritanol (ID); Progout (AU, HK, SG); Proxuric (ID); Puribel 300 (MX); Puricemia (ID); Puricos (ZA); Purinol (MY); Puristen (PH); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Trianol (PH); Unizuric 300 (MX); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM, ZW); Urosin (AT, DE, EC, LU); Xandase (TH); Xanturic (FR); Xanurace (PH); Zylapour (GR); Zyloprim (AU, BB, BM, BS, BZ, CR, DO, GY, JM, MX, NI, NL, PA, PH, PY, SR, SV, TT); Zyloric (AE, AT, BE, BF, BG, BH, BJ, BR, CH, CI, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HN, ID, IE, IL, IN, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Zyroric (KP)
MECHANISM OF ACTION — Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
PHARMACODYNAMICS / KINETICS
Onset of action: Peak effect: 1-2 weeks
Absorption: Oral: ~80%; Rectal: Poor and erratic
Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk
Protein binding: <1%
Metabolism: ~75% to active metabolites, chiefly oxypurinol
Bioavailability: 49% to 53%
Half-life elimination:
Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours
End-stage renal disease: Prolonged
Time to peak, plasma: Oral: 30-120 minutes
Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)
Allopurinol and oxypurinol are dialyzable
PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®, Zovirax®
U.S. BRAND NAMES — Aloprim™ ; Zyloprim®
PHARMACOLOGIC CATEGORY
Xanthine Oxidase Inhibitor
DOSING: ADULTS — Doses >300 mg should be given in divided doses.
Gout: Oral: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage. Maximum daily dose: 800 mg/day.
Secondary hyperuricemia associated with chemotherapy:
Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy
I.V.: 200-400 mg/m2/day (maximum: 600 mg/day)
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses
DOSING: PEDIATRIC
(For additional information see "Allopurinol: Pediatric drug information")
Gout: Children >10 years: Refer to adult dosing.
Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.
Secondary hyperuricemia associated with chemotherapy:
Oral: Children ≤ 10 years: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m2/day in 2-4 divided doses, maximum: 800 mg/24 hours, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy)
Alternative (manufacturer labeling):
<6 years: 150 mg/day in 3 divided doses
6-10 years: 300 mg/day in 2-3 divided doses
>10 years: Refer to adult dosing.
I.V.:
Children ≤ 10 years: Starting dose: 200 mg/m2/day
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Children >10 years: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Oral: Must be adjusted due to accumulation of allopurinol and metabolites;
Adult Maintenance Doses of Allopurinol
Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute. Clcr 140 mL/minute: 400 mg daily Clcr 120 mL/minute: 350 mg daily Clcr 100 mL/minute: 300 mg daily Clcr 80 mL/minute: 250 mg daily Clcr 60 mL/minute: 200 mg daily Clcr 40 mL/minute: 150 mg daily Clcr 20 mL/minute: 100 mg daily Clcr 10 mL/minute: 100 mg every 2 days Clcr 0 mL/minute: 100 mg every 3 days
I.V.:
Clcr 10-20 mL/minute: Administer 200 mg/day.
Clcr 3-10 mL/minute: Administer 100 mg/day.
Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION
Oral: Should administer oral forms after meals with plenty of fluid.
I.V.: Infuse over 15-60 minutes. The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.
COMPATIBILITY — Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.
USE
Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi
I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy
ADVERSE REACTIONS SIGNIFICANT
Dermatologic: Rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Alkaline phosphatase increased, liver enzymes increased
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression. Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. Dosage adjustments needed.
Concurrent drug therapy issues: ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors. Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine; dosage adjustment necessary. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification
Pivampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Pivampicillin. Risk C: Monitor therapy
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: May decrease effectiveness.
Iron supplements: Hepatic iron uptake may be increased.
Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.
LACTATION — Enters breast milk/use caution (AAP rates "compatible")
DIETARY CONSIDERATIONS — Should administer oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
PRICING — (data from drugstore.com)
Tablets (Zyloprim)
100 mg (30): $23.99
300 mg (30): $56.04
MONITORING PARAMETERS — CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy
REFERENCE RANGE — Uric acid, serum: An increase occurs during childhood
Adults:
Male: 3.4-7 mg/dL or slightly more
Female: 2.4-6 mg/dL or slightly more
Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); AL (PH); Alinol (TH); Allo (CO); Allo 300 (DE); Allo-Puren (DE); Allobeta (AU); Allohexal (AU); Allopin (TH); Allopur (CH, NO); Allopurinol (PL); Allopurinol-ratiopharm (LU); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allpargin (LU); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpuric (LU); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (PL); Aprinol (JP); Apurin (FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Etindrax (MX); Foligan (DE); Genozyl (MX); Gichtex (AT); Hamarin (GB); Hexanurat (DK); Huma-Purol (HU); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (PH); Masaton (JP); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Milurit (BG, HK, HN, HU, PL); Miniplanor (JP); Neufan (JP); Nilapur (ID); Nipurol (VE); No-Uric (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Pritanol (ID); Progout (AU, HK, SG); Proxuric (ID); Puribel 300 (MX); Puricemia (ID); Puricos (ZA); Purinol (MY); Puristen (PH); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Trianol (PH); Unizuric 300 (MX); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM, ZW); Urosin (AT, DE, EC, LU); Xandase (TH); Xanturic (FR); Xanurace (PH); Zylapour (GR); Zyloprim (AU, BB, BM, BS, BZ, CR, DO, GY, JM, MX, NI, NL, PA, PH, PY, SR, SV, TT); Zyloric (AE, AT, BE, BF, BG, BH, BJ, BR, CH, CI, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HN, ID, IE, IL, IN, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Zyroric (KP)
MECHANISM OF ACTION — Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
PHARMACODYNAMICS / KINETICS
Onset of action: Peak effect: 1-2 weeks
Absorption: Oral: ~80%; Rectal: Poor and erratic
Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk
Protein binding: <1%
Metabolism: ~75% to active metabolites, chiefly oxypurinol
Bioavailability: 49% to 53%
Half-life elimination:
Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours
End-stage renal disease: Prolonged
Time to peak, plasma: Oral: 30-120 minutes
Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)
Allopurinol and oxypurinol are dialyzable
PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness
Allopurinol MEDICATION SAFETY ISSUES Sound-alike/look-alike issues: Allopurinol may be confused with Apresoline Zyloprim® may be confused with X
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®, Zovirax®
U.S. BRAND NAMES — Aloprim™ ; Zyloprim®
PHARMACOLOGIC CATEGORY
Xanthine Oxidase Inhibitor
DOSING: ADULTS — Doses >300 mg should be given in divided doses.
Gout: Oral: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage. Maximum daily dose: 800 mg/day.
Secondary hyperuricemia associated with chemotherapy:
Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy
I.V.: 200-400 mg/m2/day (maximum: 600 mg/day)
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses
DOSING: PEDIATRIC
(For additional information see "Allopurinol: Pediatric drug information")
Gout: Children >10 years: Refer to adult dosing.
Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.
Secondary hyperuricemia associated with chemotherapy:
Oral: Children ≤ 10 years: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m2/day in 2-4 divided doses, maximum: 800 mg/24 hours, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy)
Alternative (manufacturer labeling):
<6 years: 150 mg/day in 3 divided doses
6-10 years: 300 mg/day in 2-3 divided doses
>10 years: Refer to adult dosing.
I.V.:
Children ≤ 10 years: Starting dose: 200 mg/m2/day
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Children >10 years: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Oral: Must be adjusted due to accumulation of allopurinol and metabolites;
Adult Maintenance Doses of Allopurinol
Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute. Clcr 140 mL/minute: 400 mg daily Clcr 120 mL/minute: 350 mg daily Clcr 100 mL/minute: 300 mg daily Clcr 80 mL/minute: 250 mg daily Clcr 60 mL/minute: 200 mg daily Clcr 40 mL/minute: 150 mg daily Clcr 20 mL/minute: 100 mg daily Clcr 10 mL/minute: 100 mg every 2 days Clcr 0 mL/minute: 100 mg every 3 days
I.V.:
Clcr 10-20 mL/minute: Administer 200 mg/day.
Clcr 3-10 mL/minute: Administer 100 mg/day.
Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION
Oral: Should administer oral forms after meals with plenty of fluid.
I.V.: Infuse over 15-60 minutes. The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.
COMPATIBILITY — Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.
USE
Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi
I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy
ADVERSE REACTIONS SIGNIFICANT
Dermatologic: Rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Alkaline phosphatase increased, liver enzymes increased
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression. Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. Dosage adjustments needed.
Concurrent drug therapy issues: ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors. Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine; dosage adjustment necessary. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification
Pivampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Pivampicillin. Risk C: Monitor therapy
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: May decrease effectiveness.
Iron supplements: Hepatic iron uptake may be increased.
Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.
LACTATION — Enters breast milk/use caution (AAP rates "compatible")
DIETARY CONSIDERATIONS — Should administer oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
PRICING — (data from drugstore.com)
Tablets (Zyloprim)
100 mg (30): $23.99
300 mg (30): $56.04
MONITORING PARAMETERS — CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy
REFERENCE RANGE — Uric acid, serum: An increase occurs during childhood
Adults:
Male: 3.4-7 mg/dL or slightly more
Female: 2.4-6 mg/dL or slightly more
Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); AL (PH); Alinol (TH); Allo (CO); Allo 300 (DE); Allo-Puren (DE); Allobeta (AU); Allohexal (AU); Allopin (TH); Allopur (CH, NO); Allopurinol (PL); Allopurinol-ratiopharm (LU); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allpargin (LU); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpuric (LU); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (PL); Aprinol (JP); Apurin (FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Etindrax (MX); Foligan (DE); Genozyl (MX); Gichtex (AT); Hamarin (GB); Hexanurat (DK); Huma-Purol (HU); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (PH); Masaton (JP); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Milurit (BG, HK, HN, HU, PL); Miniplanor (JP); Neufan (JP); Nilapur (ID); Nipurol (VE); No-Uric (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Pritanol (ID); Progout (AU, HK, SG); Proxuric (ID); Puribel 300 (MX); Puricemia (ID); Puricos (ZA); Purinol (MY); Puristen (PH); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Trianol (PH); Unizuric 300 (MX); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM, ZW); Urosin (AT, DE, EC, LU); Xandase (TH); Xanturic (FR); Xanurace (PH); Zylapour (GR); Zyloprim (AU, BB, BM, BS, BZ, CR, DO, GY, JM, MX, NI, NL, PA, PH, PY, SR, SV, TT); Zyloric (AE, AT, BE, BF, BG, BH, BJ, BR, CH, CI, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HN, ID, IE, IL, IN, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Zyroric (KP)
MECHANISM OF ACTION — Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
PHARMACODYNAMICS / KINETICS
Onset of action: Peak effect: 1-2 weeks
Absorption: Oral: ~80%; Rectal: Poor and erratic
Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk
Protein binding: <1%
Metabolism: ~75% to active metabolites, chiefly oxypurinol
Bioavailability: 49% to 53%
Half-life elimination:
Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours
End-stage renal disease: Prolonged
Time to peak, plasma: Oral: 30-120 minutes
Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)
Allopurinol and oxypurinol are dialyzable
PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®, Zovirax®
U.S. BRAND NAMES — Aloprim™ ; Zyloprim®
PHARMACOLOGIC CATEGORY
Xanthine Oxidase Inhibitor
DOSING: ADULTS — Doses >300 mg should be given in divided doses.
Gout: Oral: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage. Maximum daily dose: 800 mg/day.
Secondary hyperuricemia associated with chemotherapy:
Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy
I.V.: 200-400 mg/m2/day (maximum: 600 mg/day)
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses
DOSING: PEDIATRIC
(For additional information see "Allopurinol: Pediatric drug information")
Gout: Children >10 years: Refer to adult dosing.
Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.
Secondary hyperuricemia associated with chemotherapy:
Oral: Children ≤ 10 years: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m2/day in 2-4 divided doses, maximum: 800 mg/24 hours, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy)
Alternative (manufacturer labeling):
<6 years: 150 mg/day in 3 divided doses
6-10 years: 300 mg/day in 2-3 divided doses
>10 years: Refer to adult dosing.
I.V.:
Children ≤ 10 years: Starting dose: 200 mg/m2/day
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Children >10 years: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Oral: Must be adjusted due to accumulation of allopurinol and metabolites;
Adult Maintenance Doses of Allopurinol
Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute. Clcr 140 mL/minute: 400 mg daily Clcr 120 mL/minute: 350 mg daily Clcr 100 mL/minute: 300 mg daily Clcr 80 mL/minute: 250 mg daily Clcr 60 mL/minute: 200 mg daily Clcr 40 mL/minute: 150 mg daily Clcr 20 mL/minute: 100 mg daily Clcr 10 mL/minute: 100 mg every 2 days Clcr 0 mL/minute: 100 mg every 3 days
I.V.:
Clcr 10-20 mL/minute: Administer 200 mg/day.
Clcr 3-10 mL/minute: Administer 100 mg/day.
Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION
Oral: Should administer oral forms after meals with plenty of fluid.
I.V.: Infuse over 15-60 minutes. The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.
COMPATIBILITY — Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.
USE
Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi
I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy
ADVERSE REACTIONS SIGNIFICANT
Dermatologic: Rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Alkaline phosphatase increased, liver enzymes increased
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression. Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. Dosage adjustments needed.
Concurrent drug therapy issues: ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors. Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine; dosage adjustment necessary. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification
Pivampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Pivampicillin. Risk C: Monitor therapy
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: May decrease effectiveness.
Iron supplements: Hepatic iron uptake may be increased.
Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.
LACTATION — Enters breast milk/use caution (AAP rates "compatible")
DIETARY CONSIDERATIONS — Should administer oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
PRICING — (data from drugstore.com)
Tablets (Zyloprim)
100 mg (30): $23.99
300 mg (30): $56.04
MONITORING PARAMETERS — CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy
REFERENCE RANGE — Uric acid, serum: An increase occurs during childhood
Adults:
Male: 3.4-7 mg/dL or slightly more
Female: 2.4-6 mg/dL or slightly more
Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); AL (PH); Alinol (TH); Allo (CO); Allo 300 (DE); Allo-Puren (DE); Allobeta (AU); Allohexal (AU); Allopin (TH); Allopur (CH, NO); Allopurinol (PL); Allopurinol-ratiopharm (LU); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allpargin (LU); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpuric (LU); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (PL); Aprinol (JP); Apurin (FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Etindrax (MX); Foligan (DE); Genozyl (MX); Gichtex (AT); Hamarin (GB); Hexanurat (DK); Huma-Purol (HU); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (PH); Masaton (JP); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Milurit (BG, HK, HN, HU, PL); Miniplanor (JP); Neufan (JP); Nilapur (ID); Nipurol (VE); No-Uric (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Pritanol (ID); Progout (AU, HK, SG); Proxuric (ID); Puribel 300 (MX); Puricemia (ID); Puricos (ZA); Purinol (MY); Puristen (PH); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Trianol (PH); Unizuric 300 (MX); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM, ZW); Urosin (AT, DE, EC, LU); Xandase (TH); Xanturic (FR); Xanurace (PH); Zylapour (GR); Zyloprim (AU, BB, BM, BS, BZ, CR, DO, GY, JM, MX, NI, NL, PA, PH, PY, SR, SV, TT); Zyloric (AE, AT, BE, BF, BG, BH, BJ, BR, CH, CI, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HN, ID, IE, IL, IN, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Zyroric (KP)
MECHANISM OF ACTION — Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
PHARMACODYNAMICS / KINETICS
Onset of action: Peak effect: 1-2 weeks
Absorption: Oral: ~80%; Rectal: Poor and erratic
Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk
Protein binding: <1%
Metabolism: ~75% to active metabolites, chiefly oxypurinol
Bioavailability: 49% to 53%
Half-life elimination:
Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours
End-stage renal disease: Prolonged
Time to peak, plasma: Oral: 30-120 minutes
Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)
Allopurinol and oxypurinol are dialyzable
PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness
Alitretinoin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Panretin® may be confused with pancreatin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Panretin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Retinoic Acid Derivative
DOSING: ADULTS
Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.
T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel:
Panretin®: 0.1% (60 g)
DOSAGE FORMS: CONCISE
Gel:
Panretin®: 0.1% (60 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Do not use occlusive dressings.
USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma
USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Pain (0% to 34%)
Dermatologic: Rash (25% to 77%), pruritus (8% to 11%)
Neuromuscular & skeletal: Paresthesia (3% to 22%)
5% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)
CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.
Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.
Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.
CANADIAN BRAND NAMES — Panretin®
INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma
PHARMACODYNAMICS / KINETICS — Absorption: Not extensive
PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products
Sound-alike/look-alike issues:
Panretin® may be confused with pancreatin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Panretin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Retinoic Acid Derivative
DOSING: ADULTS
Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.
T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel:
Panretin®: 0.1% (60 g)
DOSAGE FORMS: CONCISE
Gel:
Panretin®: 0.1% (60 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Do not use occlusive dressings.
USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma
USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Pain (0% to 34%)
Dermatologic: Rash (25% to 77%), pruritus (8% to 11%)
Neuromuscular & skeletal: Paresthesia (3% to 22%)
5% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)
CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.
Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.
Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.
CANADIAN BRAND NAMES — Panretin®
INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma
PHARMACODYNAMICS / KINETICS — Absorption: Not extensive
PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products
Alitretinoin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Panretin® may be confused with pancreatin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Panretin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Retinoic Acid Derivative
DOSING: ADULTS
Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.
T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel:
Panretin®: 0.1% (60 g)
DOSAGE FORMS: CONCISE
Gel:
Panretin®: 0.1% (60 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Do not use occlusive dressings.
USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma
USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Pain (0% to 34%)
Dermatologic: Rash (25% to 77%), pruritus (8% to 11%)
Neuromuscular & skeletal: Paresthesia (3% to 22%)
5% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)
CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.
Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.
Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.
CANADIAN BRAND NAMES — Panretin®
INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma
PHARMACODYNAMICS / KINETICS — Absorption: Not extensive
PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products
Sound-alike/look-alike issues:
Panretin® may be confused with pancreatin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Panretin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Retinoic Acid Derivative
DOSING: ADULTS
Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.
T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel:
Panretin®: 0.1% (60 g)
DOSAGE FORMS: CONCISE
Gel:
Panretin®: 0.1% (60 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Do not use occlusive dressings.
USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma
USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Pain (0% to 34%)
Dermatologic: Rash (25% to 77%), pruritus (8% to 11%)
Neuromuscular & skeletal: Paresthesia (3% to 22%)
5% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)
CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.
Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.
Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.
CANADIAN BRAND NAMES — Panretin®
INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma
PHARMACODYNAMICS / KINETICS — Absorption: Not extensive
PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products
Aliskiren and hydrochlorothiazide
U.S. BRAND NAMES — Tekturna HCT®
PHARMACOLOGIC CATEGORY
Diuretic, Thiazide
Renin Inhibitor
DOSING: ADULTS — Hypertension: Oral: One tablet daily; dosage must be individualized (see below). May be substituted for previously titrated dosages of the individual components. Titrate at 2- to 4-week intervals as necessary.
Patients not controlled with single-agent therapy: Initiate by adding the lowest available dose of the alternative component (aliskiren 150 mg or hydrochlorothiazide 12.5 mg); titrate to effect (maximum daily aliskiren dose: 300 mg; maximum daily hydrochlorothiazide dose: 25 mg)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Not recommended in patients with Clcr <30 mL/minute
DOSING: HEPATIC IMPAIRMENT — Dosage adjustment not required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Tekturna HCT®:
150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg
150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg
300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg
300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
DOSAGE FORMS: CONCISE
Tablet:
Tekturna HCT®: 150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg; 150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg; 300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg; 300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer with or without meals.
USE — Treatment of hypertension (not recommended for initial treatment)
ADVERSE REACTIONS SIGNIFICANT — Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent.
>10%: Renal: BUN increased (12%)
1% to 10%:
Central nervous system: Dizziness (2%), vertigo (1%)
Endocrine & metabolic: Hypokalemia (2%), uric acid level increased (2%)
Gastrointestinal: Diarrhea (2%)
Hepatic: ALT increased (1%)
Neuromuscular & skeletal: Arthralgia (1%), weakness (1%)
Respiratory: Cough (1%)
Miscellaneous: Flu-like syndrome (2%)
<1% (Limited to important or life-threatening): Hematocrit decreased, hemoglobin decreased, hyperkalemia
Note: Angioedema and periorbital edema have been reported with aliskiren. Severe dermatologic reactions and pancreatitis have been reported with hydrochlorothiazide.
CONTRAINDICATIONS — Hypersensitivity to hydrochlorothiazide, thiazides, or sulfonamide-derived drugs; anuria
WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Angioedema: Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use caution in any patient with a history of angioedema (of any etiology) as angioedema has been observed (rarely) with aliskiren use. Discontinue immediately following any signs and symptoms of angioedema. Electrolyte disturbances: Hyperkalemia may occur with renin inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia. Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma. Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume- or salt-depleted patients. Photosensitivity: Due to the hydrochlorothiazide component photosensitization may occur. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure); deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. Hepatic impairment: Use caution in patients with hepatic impairment. Avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Renal artery stenosis: There has been no experience in treating patients with renal artery stenosis; use aliskiren with caution in patients with unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in patients with renal impairment; not recommended in patients with severe renal impairment (Clcr <30 mL/minute). Avoid hydrochlorothiazide in severe renal disease (ineffective); may precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
Concurrent drug therapy: High potential for interactions: use caution in patients taking strong inhibitors of P-glycoprotein (eg, cyclosporine); concomitant therapy with cyclosporine is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.
METABOLISM / TRANSPORT EFFECTS — See individual agents.
DRUG INTERACTIONS
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Atorvastatin: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
CycloSPORINE: May increase the serum concentration of Aliskiren. Risk X: Avoid combination
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ketoconazole: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — Take with or without meals; a high-fat meal reduces aliskiren absorption substantially.
PRICING — (data from drugstore.com)
Tablets (Tekturna HCT)
300-25 mg (30): $102.72
MONITORING PARAMETERS — Blood pressure; serum electrolytes, BUN, serum creatinine; fluid status
MECHANISM OF ACTION — Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.
PHARMACODYNAMICS / KINETICS — See individual agents.
PHARMACOLOGIC CATEGORY
Diuretic, Thiazide
Renin Inhibitor
DOSING: ADULTS — Hypertension: Oral: One tablet daily; dosage must be individualized (see below). May be substituted for previously titrated dosages of the individual components. Titrate at 2- to 4-week intervals as necessary.
Patients not controlled with single-agent therapy: Initiate by adding the lowest available dose of the alternative component (aliskiren 150 mg or hydrochlorothiazide 12.5 mg); titrate to effect (maximum daily aliskiren dose: 300 mg; maximum daily hydrochlorothiazide dose: 25 mg)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Not recommended in patients with Clcr <30 mL/minute
DOSING: HEPATIC IMPAIRMENT — Dosage adjustment not required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Tekturna HCT®:
150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg
150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg
300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg
300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
DOSAGE FORMS: CONCISE
Tablet:
Tekturna HCT®: 150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg; 150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg; 300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg; 300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer with or without meals.
USE — Treatment of hypertension (not recommended for initial treatment)
ADVERSE REACTIONS SIGNIFICANT — Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent.
>10%: Renal: BUN increased (12%)
1% to 10%:
Central nervous system: Dizziness (2%), vertigo (1%)
Endocrine & metabolic: Hypokalemia (2%), uric acid level increased (2%)
Gastrointestinal: Diarrhea (2%)
Hepatic: ALT increased (1%)
Neuromuscular & skeletal: Arthralgia (1%), weakness (1%)
Respiratory: Cough (1%)
Miscellaneous: Flu-like syndrome (2%)
<1% (Limited to important or life-threatening): Hematocrit decreased, hemoglobin decreased, hyperkalemia
Note: Angioedema and periorbital edema have been reported with aliskiren. Severe dermatologic reactions and pancreatitis have been reported with hydrochlorothiazide.
CONTRAINDICATIONS — Hypersensitivity to hydrochlorothiazide, thiazides, or sulfonamide-derived drugs; anuria
WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Angioedema: Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use caution in any patient with a history of angioedema (of any etiology) as angioedema has been observed (rarely) with aliskiren use. Discontinue immediately following any signs and symptoms of angioedema. Electrolyte disturbances: Hyperkalemia may occur with renin inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia. Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma. Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume- or salt-depleted patients. Photosensitivity: Due to the hydrochlorothiazide component photosensitization may occur. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure); deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. Hepatic impairment: Use caution in patients with hepatic impairment. Avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Renal artery stenosis: There has been no experience in treating patients with renal artery stenosis; use aliskiren with caution in patients with unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in patients with renal impairment; not recommended in patients with severe renal impairment (Clcr <30 mL/minute). Avoid hydrochlorothiazide in severe renal disease (ineffective); may precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
Concurrent drug therapy: High potential for interactions: use caution in patients taking strong inhibitors of P-glycoprotein (eg, cyclosporine); concomitant therapy with cyclosporine is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.
METABOLISM / TRANSPORT EFFECTS — See individual agents.
DRUG INTERACTIONS
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Atorvastatin: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
CycloSPORINE: May increase the serum concentration of Aliskiren. Risk X: Avoid combination
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ketoconazole: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — Take with or without meals; a high-fat meal reduces aliskiren absorption substantially.
PRICING — (data from drugstore.com)
Tablets (Tekturna HCT)
300-25 mg (30): $102.72
MONITORING PARAMETERS — Blood pressure; serum electrolytes, BUN, serum creatinine; fluid status
MECHANISM OF ACTION — Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.
PHARMACODYNAMICS / KINETICS — See individual agents.
Aliskiren and hydrochlorothiazide
U.S. BRAND NAMES — Tekturna HCT®
PHARMACOLOGIC CATEGORY
Diuretic, Thiazide
Renin Inhibitor
DOSING: ADULTS — Hypertension: Oral: One tablet daily; dosage must be individualized (see below). May be substituted for previously titrated dosages of the individual components. Titrate at 2- to 4-week intervals as necessary.
Patients not controlled with single-agent therapy: Initiate by adding the lowest available dose of the alternative component (aliskiren 150 mg or hydrochlorothiazide 12.5 mg); titrate to effect (maximum daily aliskiren dose: 300 mg; maximum daily hydrochlorothiazide dose: 25 mg)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Not recommended in patients with Clcr <30 mL/minute
DOSING: HEPATIC IMPAIRMENT — Dosage adjustment not required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Tekturna HCT®:
150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg
150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg
300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg
300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
DOSAGE FORMS: CONCISE
Tablet:
Tekturna HCT®: 150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg; 150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg; 300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg; 300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer with or without meals.
USE — Treatment of hypertension (not recommended for initial treatment)
ADVERSE REACTIONS SIGNIFICANT — Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent.
>10%: Renal: BUN increased (12%)
1% to 10%:
Central nervous system: Dizziness (2%), vertigo (1%)
Endocrine & metabolic: Hypokalemia (2%), uric acid level increased (2%)
Gastrointestinal: Diarrhea (2%)
Hepatic: ALT increased (1%)
Neuromuscular & skeletal: Arthralgia (1%), weakness (1%)
Respiratory: Cough (1%)
Miscellaneous: Flu-like syndrome (2%)
<1% (Limited to important or life-threatening): Hematocrit decreased, hemoglobin decreased, hyperkalemia
Note: Angioedema and periorbital edema have been reported with aliskiren. Severe dermatologic reactions and pancreatitis have been reported with hydrochlorothiazide.
CONTRAINDICATIONS — Hypersensitivity to hydrochlorothiazide, thiazides, or sulfonamide-derived drugs; anuria
WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Angioedema: Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use caution in any patient with a history of angioedema (of any etiology) as angioedema has been observed (rarely) with aliskiren use. Discontinue immediately following any signs and symptoms of angioedema. Electrolyte disturbances: Hyperkalemia may occur with renin inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia. Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma. Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume- or salt-depleted patients. Photosensitivity: Due to the hydrochlorothiazide component photosensitization may occur. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure); deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. Hepatic impairment: Use caution in patients with hepatic impairment. Avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Renal artery stenosis: There has been no experience in treating patients with renal artery stenosis; use aliskiren with caution in patients with unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in patients with renal impairment; not recommended in patients with severe renal impairment (Clcr <30 mL/minute). Avoid hydrochlorothiazide in severe renal disease (ineffective); may precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
Concurrent drug therapy: High potential for interactions: use caution in patients taking strong inhibitors of P-glycoprotein (eg, cyclosporine); concomitant therapy with cyclosporine is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.
METABOLISM / TRANSPORT EFFECTS — See individual agents.
DRUG INTERACTIONS
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Atorvastatin: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
CycloSPORINE: May increase the serum concentration of Aliskiren. Risk X: Avoid combination
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ketoconazole: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — Take with or without meals; a high-fat meal reduces aliskiren absorption substantially.
PRICING — (data from drugstore.com)
Tablets (Tekturna HCT)
300-25 mg (30): $102.72
MONITORING PARAMETERS — Blood pressure; serum electrolytes, BUN, serum creatinine; fluid status
MECHANISM OF ACTION — Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.
PHARMACODYNAMICS / KINETICS — See individual agents.
PHARMACOLOGIC CATEGORY
Diuretic, Thiazide
Renin Inhibitor
DOSING: ADULTS — Hypertension: Oral: One tablet daily; dosage must be individualized (see below). May be substituted for previously titrated dosages of the individual components. Titrate at 2- to 4-week intervals as necessary.
Patients not controlled with single-agent therapy: Initiate by adding the lowest available dose of the alternative component (aliskiren 150 mg or hydrochlorothiazide 12.5 mg); titrate to effect (maximum daily aliskiren dose: 300 mg; maximum daily hydrochlorothiazide dose: 25 mg)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Not recommended in patients with Clcr <30 mL/minute
DOSING: HEPATIC IMPAIRMENT — Dosage adjustment not required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Tekturna HCT®:
150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg
150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg
300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg
300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
DOSAGE FORMS: CONCISE
Tablet:
Tekturna HCT®: 150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg; 150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg; 300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg; 300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer with or without meals.
USE — Treatment of hypertension (not recommended for initial treatment)
ADVERSE REACTIONS SIGNIFICANT — Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent.
>10%: Renal: BUN increased (12%)
1% to 10%:
Central nervous system: Dizziness (2%), vertigo (1%)
Endocrine & metabolic: Hypokalemia (2%), uric acid level increased (2%)
Gastrointestinal: Diarrhea (2%)
Hepatic: ALT increased (1%)
Neuromuscular & skeletal: Arthralgia (1%), weakness (1%)
Respiratory: Cough (1%)
Miscellaneous: Flu-like syndrome (2%)
<1% (Limited to important or life-threatening): Hematocrit decreased, hemoglobin decreased, hyperkalemia
Note: Angioedema and periorbital edema have been reported with aliskiren. Severe dermatologic reactions and pancreatitis have been reported with hydrochlorothiazide.
CONTRAINDICATIONS — Hypersensitivity to hydrochlorothiazide, thiazides, or sulfonamide-derived drugs; anuria
WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Angioedema: Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use caution in any patient with a history of angioedema (of any etiology) as angioedema has been observed (rarely) with aliskiren use. Discontinue immediately following any signs and symptoms of angioedema. Electrolyte disturbances: Hyperkalemia may occur with renin inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia. Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma. Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume- or salt-depleted patients. Photosensitivity: Due to the hydrochlorothiazide component photosensitization may occur. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure); deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. Hepatic impairment: Use caution in patients with hepatic impairment. Avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Renal artery stenosis: There has been no experience in treating patients with renal artery stenosis; use aliskiren with caution in patients with unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in patients with renal impairment; not recommended in patients with severe renal impairment (Clcr <30 mL/minute). Avoid hydrochlorothiazide in severe renal disease (ineffective); may precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
Concurrent drug therapy: High potential for interactions: use caution in patients taking strong inhibitors of P-glycoprotein (eg, cyclosporine); concomitant therapy with cyclosporine is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.
METABOLISM / TRANSPORT EFFECTS — See individual agents.
DRUG INTERACTIONS
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Atorvastatin: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
CycloSPORINE: May increase the serum concentration of Aliskiren. Risk X: Avoid combination
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ketoconazole: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — Take with or without meals; a high-fat meal reduces aliskiren absorption substantially.
PRICING — (data from drugstore.com)
Tablets (Tekturna HCT)
300-25 mg (30): $102.72
MONITORING PARAMETERS — Blood pressure; serum electrolytes, BUN, serum creatinine; fluid status
MECHANISM OF ACTION — Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.
PHARMACODYNAMICS / KINETICS — See individual agents.
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