ALVIMOPAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALVIMOPAN (ALVIMOPAN).
Alvimopan is a peripherally acting mu-opioid receptor antagonist (PAMORA). It selectively blocks mu-opioid receptors in the gastrointestinal tract without crossing the blood-brain barrier, thereby reversing opioid-induced constipation without affecting central analgesia.
| Metabolism | Alvimopan is primarily metabolized by gut microflora and hepatic CYP3A4 to a minimally active metabolite. The drug undergoes extensive conjugation and enterohepatic recirculation. |
| Excretion | Primarily fecal (approximately 96%) as unchanged drug; renal excretion accounts for <1%. |
| Half-life | Terminal elimination half-life is approximately 10-17 hours in patients with normal renal function; prolonged in severe renal impairment. |
| Protein binding | Approximately 94% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.2-0.3 L/kg, suggesting limited extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 2% due to extensive first-pass metabolism and P-glycoprotein efflux; intravenous administration results in 100% bioavailability. |
| Onset of Action | Oral: Onset of action occurs within 30 minutes to 1 hour post-dose. |
| Duration of Action | Duration of action persists for approximately 4 to 6 hours, but may extend up to 12 hours due to prolonged binding to mu-opioid receptors. |
12 mg orally twice daily, administered with or without food, starting at least 30 minutes before the first dose of opioid analgesic, then twice daily at approximately 12-hour intervals for up to 15 days; or 12 mg once daily for patients receiving a once-daily opioid regimen.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >=30 mL/min). For severe renal impairment (CrCl <30 mL/min) or end-stage renal disease, reduce dose to 12 mg once daily. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate hepatic impairment (Child-Pugh B): reduce dose to 12 mg once daily. Severe hepatic impairment (Child-Pugh C): not recommended (no studies). |
| Pediatric use | Safety and efficacy not established in pediatric patients <18 years; no recommended dose. |
| Geriatric use | No specific dose adjustment recommended; but monitor renal function as elderly may have reduced creatinine clearance; consider dose reduction if severe renal impairment present. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALVIMOPAN (ALVIMOPAN).
| Breastfeeding | It is unknown if alvimopan is excreted in human milk. In animal studies, drug-related material was detected in milk. M/P ratio not available. Caution is recommended, and breastfeeding should be avoided during therapy due to potential for adverse effects in the infant. |
| Teratogenic Risk | Alvimopan is classified as pregnancy category B. Animal studies have not revealed evidence of teratogenicity or fetal harm at doses up to 20 times the human exposure. No adequate and well-controlled studies in pregnant women exist. Risk cannot be ruled out; use only if clearly needed. |
■ FDA Black Box Warning
Alvimopan has a black box warning for increased risk of myocardial infarction in patients treated for opioid-induced constipation with long-term opioid use. It should be used only in hospitalized patients and administration should be limited to 15 doses for the FDA-approved surgical indication.
| Serious Effects |
["Patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan administration","Patients with severe hepatic impairment (Child-Pugh class C)","Patients with end-stage renal disease requiring dialysis","Patients with a history of hypersensitivity to alvimopan or any of its components"]
| Precautions | ["Risk of myocardial infarction (black box warning) in long-term opioid users","Potential for gastrointestinal adverse effects including diarrhea, abdominal pain, and nausea","Should not be used in patients with severe hepatic impairment or end-stage renal disease","Use only in hospitalized patients for the approved surgical indication due to cardiovascular risk"] |
| Food/Dietary |
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| Fetal Monitoring |
| No specific fetal monitoring required. Monitor for gastrointestinal adverse effects (e.g., diarrhea, abdominal pain) in the mother. Use with caution in patients with renal impairment. |
| Fertility Effects | In animal fertility studies, alvimopan had no effect on male or female fertility at doses up to 20 times the human exposure. No human data available. |
| No specific food interactions reported. Administer without regard to meals. For oral solution, do not mix with other liquids or foods. |
| Clinical Pearls | Alvimopan is a peripherally acting mu-opioid receptor antagonist indicated for the prevention of postoperative ileus following bowel resection. It is restricted to short-term use (≤15 doses) and only in hospitalized patients. Contraindicated in patients who have taken therapeutic doses of opioids for >7 days prior to surgery due to risk of opioid withdrawal. Monitor for GI adverse effects like abdominal pain, nausea, and diarrhea. Do not administer to patients with chronic opioid use or complete GI obstruction. |
| Patient Advice | Alvimopan is given only while you are in the hospital after your bowel surgery to help your bowel function return to normal. · It works by blocking the effect of pain medicines on your intestines without affecting pain relief. · Do not take other medications for constipation or diarrhea without asking your doctor. · Report any severe abdominal pain, vomiting, or inability to pass gas or have a bowel movement. · This medication is only for short-term use and will be stopped before you leave the hospital. |