MOVANTIK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MOVANTIK (MOVANTIK).
Selective antagonist of peripheral mu-opioid receptors; inhibits opioid binding without affecting central analgesic effects.
| Metabolism | Hepatic via CYP3A4, CYP2D6, and CYP2C9; minor role of CYP2D6 and CYP2C9. |
| Excretion | Primarily fecal (up to 76% of absorbed dose) and renal (up to 23% of absorbed dose as unchanged drug and metabolites). |
| Half-life | Terminal elimination half-life is approximately 7–11 hours in healthy subjects; prolonged in severe renal impairment (up to ~15 hours). |
| Protein binding | 93–95% bound, primarily to alpha-1-acid glycoprotein (AAG). |
| Volume of Distribution | Approximately 1.0 L/kg (range 0.8–1.3 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral: ~50% (absolute); subcutaneous: ~80%. |
| Onset of Action | Oral: within 30–60 minutes; subcutaneous: 15–30 minutes. |
| Duration of Action | Oral: ~4–8 hours; subcutaneous: ~4–6 hours; effect may persist longer in renal impairment. |
12.5 mg orally once daily; may increase to 25 mg once daily if tolerated, not to exceed 25 mg daily.
| Dosage form | TABLET |
| Renal impairment | CrCl < 30 mL/min: reduce dose to 12.5 mg once daily; CrCl < 15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class C: contraindicated; Child-Pugh Class A or B: no adjustment required. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MOVANTIK (MOVANTIK).
| Breastfeeding | No data available on presence in human milk, effects on breastfed infant, or milk production. Naloxegol is a P-glycoprotein substrate with low oral bioavailability; transfer into milk is possible but likely minimal. M/P ratio not determined. Caution advised; consider risk versus benefit. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate studies in pregnant women. In animal studies, naloxegol showed no teratogenicity at doses up to 208 times the human AUC at the maximum recommended dose (MRD). However, decreased fetal body weight and delayed ossification were observed at maternally toxic doses. Risk cannot be ruled out; use only if potential benefit justifies risk. |
■ FDA Black Box Warning
Not for use in patients with known or suspected gastrointestinal obstruction. Cases of gastrointestinal perforation have been reported.
| Serious Effects |
Known or suspected gastrointestinal obstruction; hypersensitivity to methylnaltrexone; concurrent use with opioids for OIC management contraindicated if history of bowel obstruction.
| Precautions | Risk of gastrointestinal perforation, especially in patients with underlying GI tract pathology; opioid withdrawal symptoms; avoid use in patients with compromised GI wall integrity; monitor for severe or persistent diarrhea. |
Loading safety data…
| Fetal Monitoring | Monitor for opioid withdrawal symptoms in mother (e.g., diaphoresis, mydriasis, abdominal pain) due to potential pharmacodynamic interaction with opioid agonists. Assess bowel function and pain control. No specific fetal monitoring recommended beyond standard prenatal care. |
| Fertility Effects | No human data on fertility effects. In animal studies, naloxegol had no adverse effects on male or female fertility in rats at doses up to 125 mg/kg/day (approximately 190 times the human AUC at MRD). Potential for reversible effects on ovulation or spermatogenesis is unknown. |