Alvimopan

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Alvimopan may be confused with almotriptan

U.S. BRAND NAMES — Entereg®

PHARMACOLOGIC CATEGORY
Gastrointestinal Agent, Miscellaneous
Opioid Antagonist, Peripherally-Acting

DOSING: ADULTS — Note: For hospital use only.

Management of postoperative ileus: Oral:
Initial: 12 mg administered 30 minutes to 5 hours prior to surgery
Maintenance: 12 mg twice daily beginning the day after surgery for a maximum of 7 days or until discharged from hospital (maximum total treatment doses: 15 doses)

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Mild-to-severe impairment: No adjustment needed; use caution.

ESRD: Use not recommended.

DOSING: HEPATIC IMPAIRMENT
Mild-to-moderate impairment (Child-Pugh class A and B): No adjustment needed; use caution.

Severe impairment (Child-Pugh class C): Use not recommended.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics ); consult specific product labeling.

Capsule:
Entereg®: 12 mg

DOSAGE FORMS: CONCISE
Capsule:
Entereg®: 12 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Patient must be hospitalized. Initial dose should be administered 30 minutes to 5 hours prior to surgery.

USE — Accelerate the time to upper and lower GI recovery following partial large or small bowel resection surgery with primary anastomosis

ADVERSE REACTIONS SIGNIFICANT — Note: Incidence reported limited to bowel resection patients only. 1% to 10%:

Endocrine & metabolic: Hypokalemia (10%)

Gastrointestinal: Dyspepsia (7%)

Genitourinary: Urinary retention (3%)

Hematologic: Anemia (5%)

Neuromuscular & skeletal: Back pain (3%)

CONTRAINDICATIONS — Patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan

WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below.

Concerns related to adverse effects: Cardiovascular effects: A trend towards an increased incidence of MI was observed in alvimopan (low dose) treated patients compared to placebo in a 12-month study in patients treated with opioids for chronic pain. MI was generally observed more frequently in the initial 1-4 months of treatment. Other studies have not observed this trend and a causal relationship has not been found.

Disease-related concerns: Complete bowel obstruction: Use not recommended in patients undergoing surgery for complete bowel obstruction. Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment (Child-Pugh classes A and B); use not recommended with severe impairment (Child-Pugh class C). Renal impairment: Use with caution in patients with renal impairment; use not recommended in patients with ESRD.

Concurrent drug therapy issues: Opioids: Use with caution in patients recently exposed to opioids; may be more sensitive to gastrointestinal adverse effects (eg, abdominal pain, diarrhea, nausea and vomiting). Contraindicated in patients who have received therapeutic opioids for >7 consecutive days immediately prior to use.

Special populations: Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: For short-term (≤ 15 doses) hospital use only. Only hospitals that have registered through the ENTEREG Access Support and Education (E.A.S.E.™ ) Program and met all requirements may use. It will not be dispensed to patients who have been discharged from the hospital.

RESTRICTIONS — Only hospitals enrolled in the ENTEREG Access Support and Education (E.A.S.E.™ ) Program may administer this medication. Hospital staff must be educated on need to limit to short-term (no more than 15 doses) and inpatient use. Hospitals may contact the E.A.S.E.™ program at 1-866-423-6567 (1-866-4ADOLOR).

METABOLISM / TRANSPORT EFFECTS — Substrate of P-glycoprotein

DRUG INTERACTIONS
Analgesics (Opioid): May enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification

ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with a high-fat meal, extent and rate of absorption may be reduced (Cmax and AUC decreased by ~38% and 21%, respectively).

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Animal studies have not shown teratogenic effects to the fetus. However, there are no adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.

LACTATION — Excretion in breast milk unknown/use caution

DIETARY CONSIDERATIONS — Take with or without food; high-fat meals may decrease the rate and extent of absorption

MECHANISM OF ACTION — An opioid receptor antagonist which blocks opioid binding at the mu receptor; alvimopan has restricted ability to cross the blood-brain barrier at therapeutic doses. It selectively and competitively binds to the GI tract mu opioid receptors and antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms.

PHARMACODYNAMICS / KINETICS
Distribution: Vd: 20-40 L

Protein binding: Parent drug: 80%; metabolite: 94% (both primarily to albumin)

Metabolism: Hydrolyzed to an amide hydrolysis compound (active metabolite) by gut microflora; further metabolism of active metabolite to glucuronide conjugates and other minor metabolites.

Bioavailability: ~6% (range: 1% to 19%)

Half-life elimination: 10-18 hours

Time to peak, plasma: ~2 hours

Excretion: Urine (35% as unchanged drug and metabolites); feces (via biliary excretion)