Alendronate

U.S. BRAND NAMES — Fosamax®
PHARMACOLOGIC CATEGORY Bisphosphonate Derivative
DOSING: ADULTS — Note: Patients treated with glucocorticoids and those with Paget's disease should receive adequate amounts of calcium and vitamin D.
Osteoporosis in postmenopausal females: Oral: Prophylaxis: 5 mg once daily or 35 mg once weekly Treatment: 10 mg once daily or 70 mg once weekly
Osteoporosis in males: Oral: 10 mg once daily or 70 mg once weekly
Osteoporosis secondary to glucocorticoids in males and females: Oral: Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.
Paget's disease of bone in males and females: Oral: 40 mg once daily for 6 months Retreatment: Relapses during the 12 months following therapy occurred in 9% of patients who responded to treatment. Specific retreatment data are not available. Following a 6-month post-treatment evaluation period, treatment with alendronate may be considered in patients who have relapsed based on increases in serum alkaline phosphatase, which should be measured periodically. Retreatment may also be considered in those who failed to normalize their serum alkaline phosphatase.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 35-60 mL/minute: None necessary.
Clcr <35 mL/minute: Alendronate is not recommended due to lack of experience.
DOSING: HEPATIC IMPAIRMENT — No adjustment necessary.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Note: Strength expressed as free acid
Solution, oral, as monosodium trihydrate: Fosamax™: 70 mg/75 mL [contains parabens; raspberry flavor]
Tablet, as sodium: Fosamax™: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
DOSAGE FORMS: CONCISE — Note: Strength expressed as free acid
Solution, oral: Fosamax®: 70 mg/75 mL
Tablet: Fosamax®: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (tablets 6-8 oz; oral solution follow with 2 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Do not take with mineral water or with other beverages. Patients should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation). Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
USE — Treatment and prevention of osteoporosis in postmenopausal females; treatment of osteoporosis in males; Paget's disease of the bone in patients who are symptomatic, at risk for future complications, or with alkaline phosphatase 2 times the upper limit of normal; treatment of glucocorticoid-induced osteoporosis in males and females with low bone mineral density who are receiving a daily dosage 7.5 mg of prednisone (or equivalent)
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence of adverse effects (mostly GI) increases significantly in patients treated for Paget's disease at 40 mg/day.
>10%: Endocrine & metabolic: Hypocalcemia (transient, mild, 18%); hypophosphatemia (transient, mild, 10%)
1% to 10%: Central nervous system: Headache (up to 3%) Gastrointestinal: Abdominal pain (1% to 7%), acid reflux (1% to 4%), dyspepsia (1% to 4%), nausea (1% to 4%), flatulence (up to 4%), diarrhea (1% to 3%), gastroesophageal reflux disease (1% to 3%), constipation (up to 3%), esophageal ulcer (up to 2%), abdominal distension (up to 1%), gastritis (up to 1%), vomiting (up to 1%), dysphagia (up to 1%), gastric ulcer (1%), melena (1%) Neuromuscular & skeletal: Musculoskeletal pain (up to 6%), muscle cramps (up to 1%)
<1% (Limited to important or life-threatening): Anastomotic ulcer, angioedema; bone, muscle, or joint pain (occasionally severe, considered incapacitating in rare cases); dizziness, duodenal ulcer, episcleritis, erythema, esophageal erosions, esophageal perforation, esophageal stricture, esophagitis, fever, flu-like syndrome, hypersensitivity reactions, hypocalcemia (symptomatic), joint swelling, lymphocytopenia, malaise, myalgia, oropharyngeal ulceration, osteonecrosis (jaw), peripheral edema, photosensitivity (rare), pruritus, rash, scleritis (rare), Stevens-Johnson syndrome, taste perversion, toxic epidermal necrolysis, urticaria, uveitis (rare), vertigo, weakness
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; oral solution should not be used in patients at risk of aspiration
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection, or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis; however, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia: Before therapy initiation hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS Aminoglycosides: May lower serum calcium levels with prolonged administration. Concomitant use may have an additive hypocalcemic effect.
Antacids: May decrease the absorption of bisphosphonate derivatives; should be administered at a different time of the day. Antacids containing aluminum, calcium, or magnesium are of specific concern.
Aspirin: May enhance the adverse/toxic effect of alendronate; specifically gastrointestinal adverse events.
Calcium salts: May decrease the absorption of bisphosphonate derivatives. Separate oral dosing in order to minimize risk of interaction.
Iron salts: May decrease the absorption of bisphosphonate derivatives. Only oral iron salts and oral bisphosphonates are of concern.
Magnesium salts: May decrease the absorption of bisphosphonate derivatives. Only oral magnesium salts and oral bisphosphonates are of concern.
Nonsteroidal anti-inflammatory drugs (NSAIDs): May enhance the gastrointestinal adverse/toxic effects (increased incidence of GI ulcers) of bisphosphonate derivatives.
Phosphate supplements: Bisphosphonate derivatives may enhance the hypocalcemic effect of phosphate supplements.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase risk of osteoporosis and gastric irritation).
Food: All food and beverages interfere with absorption. Coadministration with caffeine may reduce alendronate efficacy. Coadministration with dairy products may decrease alendronate absorption. Beverages (especially orange juice and coffee) and food may reduce the absorption of alendronate as much as 60%.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Safety and efficacy have not been established in pregnant women. Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake; however, wait at least 30 minutes after taking alendronate before taking any supplement. Alendronate must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Solution (Fosamax) 70 mg/75mL (75): $27.99
Tablets (Fosamax) 5 mg (30): $79.31 10 mg (30): $85.99 35 mg (4): $72.99 70 mg (4): $77.61
MONITORING PARAMETERS — Alkaline phosphatase should be periodically measured; serum calcium and phosphorus; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE — Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging; phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypocalcemia, hypophosphatemia, and upper GI adverse events (upset stomach, heartburn, esophagitis, gastritis or ulcer). Treat with milk or antacids to bind alendronate. Dialysis would not be beneficial. Do not induce vomiting (due to the risk of esophageal irritation); keep fully upright.
CANADIAN BRAND NAMES — Apo-Alendronate®; CO Alendronate; Fosamax®; Gen-Alendronate; Novo-Alendronate; PMS-Alendronate; ratio-Alendronate; Riva-Alendronate
INTERNATIONAL BRAND NAMES — Aldrox (CL); Alenato (AR); Alend (KR); Alenmax (KR); Alexonal (ID); Alnax (PY); Apo-Alendronate (CA); Arendal (PE); Armol (CO); Bifemelan (CO); Bifosa (IN); Bolend (KR); Bonapex (EG); CO Alendronate (CA); Endronax (BR); Eucalen (CO); Fixopan (EC); Fosalan (IL); Fosamax (AN, AR, AT, AU, BB, BE, BG, BM, BR, BS, BZ, CA, CH, CL, CR, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GT, GY, HK, HN, HU, ID, IE, IT, JM, KR, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, SE, SG, SR, SV, TH, TT, TW, VE, ZA); Fosaqueen (KR); Fosmin (PE); Fosval (PY); Gen-Alendronate (CA); Marvil (PE, UY); MaxiBone (IL); MaxiBone 70 (IL); Neobon (CO); Novo-Alendronate (CA); Osdron (BR); Osdronat (CO); Oseotenk (AR); Osficar (CO); Osteofar (ID); Osteofos (HK); Osteopor (UY); Osteosan (CL); Osteovan (CR); Osticalcin (CO); PMS-Alendronate (CA); Porosal (VE); ratio-Alendronate (CA); Riva-Alendronate (CA); Tibolene (CO); Voroste (ID)
MECHANISM OF ACTION — A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.
PHARMACODYNAMICS / KINETICS Distribution: 28 L (exclusive of bone)
Protein binding: ~78%
Metabolism: None
Bioavailability: Fasting: 0.6%; reduced 60% with food or drink
Half-life elimination: Exceeds 10 years
Excretion: Urine; feces (as unabsorbed drug)
PATIENT INFORMATION — Take as directed, with a full glass of water first thing in the morning and at least 30 minutes before the first food or beverage of the day. Wait at least 30 minutes after taking alendronate before taking anything else. Stay in sitting or standing position for 30 minutes following administration and until after the first food of the day to reduce potential for esophageal irritation. Consult prescriber to determine necessity of lifestyle changes (eg, decreased smoking, decreased alcohol intake, dietary supplements of calcium, or increased dietary vitamin D).