Alvimopan
FDA Drug Information • Also known as: Alvimopan
- Brand Names
- Alvimopan
- Dosage Form
- CAPSULE
- Product Type
- DRUG FOR FURTHER PROCESSING
⚠ Boxed Warning (Black Box)
WARNING: POTENTIAL RISK OF MYOCARDIAL INFARCTION WITH LONG-TERM USE: FOR SHORT-TERM HOSPITAL USE ONLY There was a greater incidence of myocardial infarction in alvimopan-treated patients compared to placebo-treated patients in a 12-month clinical trial, although a causal relationship has not been established. In short-term trials with alvimopan, no increased risk of myocardial infarction was observed [see Warnings and Precautions ( 5.1 )] . Because of the potential risk of myocardial infarction with long-term use, alvimopan is available only through a restricted program for short-term use (15 doses) under a Risk Evaluation and Mitigation Strategy (REMS) called the Alvimopan REMS Program [see Warnings and Precautions ( 5.1 , 5.2 )] . WARNING: POTENTIAL RISK OF MYOCARDIAL INFARCTION WITH LONG-TERM USE: FOR SHORT-TERM HOSPITAL USE ONLY See full prescribing information for complete boxed warning. Increased incidence of myocardial infarction was seen in a clinical trial of patients taking alvimopan for long-term use. ( 5.1 ) Alvimopan capsules are available only through a restricted program for short-term use (15 doses) called the Alvimopan REMS Program. ( 5.1 , 5.2 )
Description
11 DESCRIPTION Alvimopan capsules contain alvimopan, an opioid antagonist. Chemically, alvimopan is the single stereoisomer [[2(S)-[[4( R )-(3-hydroxyphenyl)-3( R ),4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-phenylpropyl]amino]acetic acid dihydrate. It has the following structural formula: Alvimopan is a white to light beige powder with a molecular weight of 460.6, and the empirical formula is C 25 H 32 N 2 O 4
What Is Alvimopan Used For?
1 INDICATIONS AND USAGE Alvimopan capsules are indicated to accelerate the time to upper and lower gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis. Alvimopan capsules are an opioid antagonist indicated to accelerate the time to upper and lower gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For hospital use only. The recommended adult dosage of alvimopan capsules is 12 mg administered 30 minutes to 5 hours prior to surgery followed by 12 mg twice daily beginning the day after surgery until discharge for a maximum of 7 days. Patients should not receive more than 15 doses of alvimopan capsules. Alvimopan capsules can be taken with or without food [see Clinical Pharmacology ( 12.3 )] . For hospital use only. ( 2 ) The recommended dosage is 12 mg administered 30 minutes to 5 hours prior to surgery followed by 12 mg twice daily beginning the day after surgery until discharge for a maximum of 7 days. Patients should not receive more than 15 doses of alvimopan capsules. ( 2 )
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Potential Risk of Myocardial Infarction with Long-Term Use [see Warnings and Precautions ( 5.1 )] Gastrointestinal-Related Adverse Reactions in Opioid-Tolerant Patients [see Warnings and Precautions ( 5.3 )] Risk of Serious Adverse Reactions in Patients with Severe Hepatic Impairment [see Warnings and Precautions ( 5.4 )] Risk of Serious Adverse Reactions in Patients with Complete Gastrointestinal Obstruction [see Warnings and Precautions ( 5.6 )] Risk of Serious Adverse Reactions in Pancreatic and Gastric Anastomoses [see Warnings and Precautions ( 5.7 )] Most common adverse reaction (≥1.5%): dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared directly with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The adverse event information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. The data described below reflect exposure to alvimopan 12 mg in 1,793 patients in 10 placebo-controlled studies. The population was 19 to 97 years old, 64% were female, and 84% were Caucasian; 64% were undergoing a surgery that included bowel resection. The first dose of alvimopan was administered 30 minutes to 5 hours before the scheduled start of surgery and then twice daily until hospital discharge (or for a maximum of 7 days of postoperative treatment). Among alvimopan-treated patients undergoing surgeries that included a bowel resection, the most common adverse reaction (incidence ≥1.5%) occurring with a higher frequency than placebo was dyspepsia (alvimopan, 1.5%; placebo, 0.8%). Adverse reactions are events that occurred after the first dose of study medication treatment and within 7 days of the last dose of study medication or events present at baseline that increased in severity after the start of study medication treatment.
Drug Interactions
7 DRUG INTERACTIONS 7.1 Effects of Alvimopan on Intravenous Morphine Coadministration of alvimopan does not appear to alter the pharmacokinetics of morphine and its metabolite, morphine-6-glucuronide, to a clinically significant degree when morphine is administered intravenously. Dosage adjustment for intravenously administered morphine is not necessary when it is coadministered with alvimopan. 7.2 Effects of Concomitant Acid Blockers or Antibiotics A population pharmacokinetic analysis suggests that the pharmacokinetics of alvimopan were not affected by concomitant administration of acid blockers (proton pump inhibitors (PPIs), histamine-2 (H 2 ) receptor antagonists) or antibiotics. No dosage adjustments are necessary in patients taking acid blockers or antibiotics with alvimopan.
Contraindications
4 CONTRAINDICATIONS Alvimopan capsules are contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan capsules [see Warnings and Precautions ( 5.3 )] . Patients who have taken therapeutic doses of opioids for more than 7 consecutive days prior to taking alvimopan capsules. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary: Available data regarding use of alvimopan in pregnant women are limited, and are insufficient to inform a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. No fetal harm was observed in animal reproduction studies with oral administration of alvimopan during organogenesis to pregnant rats at doses 68 to 136 times the recommended human oral dose, or with intravenous administration during organogenesis to pregnant rats and pregnant rabbits at doses 3.4 to 6.8 times, and 5 to 10 times, respectively, the recommended human oral dose (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Embryo-fetal studies were performed in pregnant rats during organogenesis (gestation days 7 through 19, or 20) at oral doses up to 200 mg/kg/day (about 68 to 136 times the recommended human oral dose based on body surface area) and at intravenous doses up to 10 mg/kg/day (about 3.4 to 6.8 times the recommended human oral dose based on body surface area). A study in pregnant rabbits during organogenesis (gestation days 6 through 18) at intravenous doses up to 15 mg/kg/day (about 5 to 10 times the recommended human oral dose based on body surface area) revealed no evidence of harm to the fetus due to alvimopan. In an intravenous pre- and postnatal development study (gestation day 7 through lactation day 20) in rats, alvimopan did not cause any adverse effect on pre- and postnatal development at doses up to 10 mg/kg/day (about 6.8 times the recommended human oral dose based on body surface area).
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Alvimopan capsules, 12 mg, are blue, opaque hard gelatin capsules with “54 88” imprinted in black on both the body and the cap of the capsule. Alvimopan capsules are available in unit-dose packs of 30 capsules (30 doses) (NDC 51407-870-33) for hospital use only. Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.