VIVITROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIVITROL (VIVITROL).
Naltrexone, as the active moiety of VIVITROL, is a competitive antagonist at opioid receptors (mu, kappa, and delta), blocking the euphoric effects of alcohol and opioids. It also modulates the hypothalamic-pituitary-adrenal axis and dopamine pathways implicated in alcohol craving.
| Metabolism | Naltrexone undergoes first-pass hepatic metabolism primarily by dihydrodiol dehydrogenase (AKR1C2/AKR1C3) to 6β-naltrexol, the major active metabolite. Minor pathways include conjugation to glucuronides. CYP450 enzymes are minimally involved. |
| Excretion | Naltrexol (6-β-naltrexol) and naltrexone: primarily renal (60-70% as metabolites, <5% as unchanged drug); biliary/fecal (minor route, <10%). |
| Half-life | Naltrexone terminal half-life: 4-13 hours (mean 9.7 h). Active metabolite 6-β-naltrexol: 10-15 hours. Clinically, naltrexone concentrations are sustained for ~30 days after IM injection. |
| Protein binding | Naltrexone: 21% bound to plasma proteins. 6-β-naltrexol: 23-27% bound. |
| Volume of Distribution | Naltrexone: 1350-1970 L (approx 16-24 L/kg for 70 kg patient), indicating extensive tissue distribution. |
| Bioavailability | IM injection: 100% (administered as a long-acting microsphere formulation). Oral: 5-40% (extensive first-pass metabolism). |
| Onset of Action | IM injection: peak plasma concentration at 1-2 hours; clinical effect (reduction of opioid craving) typically within 1-2 hours. |
| Duration of Action | IM injection: therapeutic effects persist for approximately 4 weeks (standard dosing 380 mg every 4 weeks). |
| Molecular Weight | 377.44 |
380 mg intramuscularly every 4 weeks, alternating gluteal injections.
| Dosage form | FOR SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl 30-90 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Contraindicated in acute hepatitis or hepatic failure. Use with caution in Child-Pugh Class B or C; no specific dose adjustment studies. |
| Pediatric use | Safety and effectiveness not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment; use with caution due to potential for hepatic impairment and comorbidities. |
| 1st trimester | Naltrexone crosses the placenta. Animal studies show increased risk of early fetal loss and developmental toxicity at high doses. Limited human data; use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for fetal harm based on animal studies. Use with caution. |
| 3rd trimester | May cause withdrawal in neonate if used near term. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for VIVITROL (VIVITROL).
| Placental transfer | Naltrexone crosses the placenta readily in animal models; human data limited but suggests transfer occurs. |
| Breastfeeding | Naltrexone and its active metabolite 6β-naltrexol are excreted into breast milk in low concentrations. Relative infant dose is estimated <2% of maternal weight-adjusted dose. No adverse effects reported in nursing infants, but caution is advised, especially in preterm or ill infants. Monitor for sedation or poor feeding. |
■ FDA Black Box Warning
VIVITROL has a boxed warning regarding the risk of hepatotoxicity. It can cause dose-related hepatocellular injury and acute hepatitis. Patients should be warned of the risk and monitored for signs of liver injury.
| Serious Effects |
Hypersensitivity to naltrexone or any componentPatients receiving opioid analgesicsPatients in acute opioid withdrawalHistory of opioid dependence without detoxificationAcute hepatitis or liver failure
| Precautions | Hepatotoxicity risk (dose-related; contraindicated in acute hepatitis or liver failure), Precipitated opioid withdrawal in opioid-dependent patients (must be opioid-free for 7-10 days), Risk of respiratory depression if opioids are taken concurrently or after noncompliance (reversal of opioid blockade may lead to overdose), Eosinophilic pneumonia (rare, discontinue if symptoms develop), Suicidality (monitor for depression/suicidal thoughts), Intramuscular injection site reactions (including necrosis, abscess) |
| Food/Dietary | No specific food interactions. Avoid alcohol during treatment for alcohol dependence. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Naltrexone is not associated with major congenital malformations in humans. First trimester: limited data, no clear increased risk. Second and third trimesters: no known specific risks. However, opioid withdrawal in neonates may occur if mother is opioid-dependent and naltrexone is used, due to precipitated withdrawal. |
| Fetal Monitoring | Monitor liver function tests periodically due to hepatotoxicity risk. Assess for signs of opioid withdrawal, especially in opioid-dependent patients. Consider fetal ultrasound if opioid withdrawal occurs during pregnancy. Ensure adherence to comprehensive treatment program. |
| Fertility Effects | Naltrexone may improve fertility in women with opioid use disorders by restoring normal menstrual cycling. No known direct adverse effects on spermatogenesis or ovarian function. In animal studies, no impairment of fertility at clinically relevant doses. |
| Clinical Pearls | VIVITROL (naltrexone extended-release) is an opioid receptor antagonist used for alcohol dependence and opioid use disorder. Administer via intramuscular injection in the gluteal muscle, alternating sides monthly. Do not use in patients currently dependent on opioids or in acute opioid withdrawal; ensure a 7-14 day opioid-free period before initiation. Avoid in acute hepatitis or liver failure. Monitor liver function tests. May precipitate withdrawal in opioid-dependent patients. For alcohol dependence, initiate after detoxification. Has no abuse potential. |
| Patient Advice | VIVITROL is a once-monthly injection to help reduce alcohol cravings or prevent relapse to opioid use. · Do not use opioids while on VIVITROL; it blocks opioid effects and can precipitate severe withdrawal. · You must be opioid-free for at least 7-14 days before starting VIVITROL; your doctor will confirm this. · Common side effects include injection site reactions, nausea, headache, and dizziness; contact your doctor if severe. · Avoid alcohol completely during treatment for alcohol dependence; VIVITROL is not a cure. · Carry a medical alert card or wear a bracelet stating you are on naltrexone in case of emergency. · Do not stop or delay your injection; adherence is critical for effectiveness. |