VIVITROL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIVITROL (VIVITROL).

How it works

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.

What the body does with it

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).

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIVITROL (VIVITROL).

Breastfeeding	Naltrexone and its active metabolite 6β-naltrexol are excreted into breast milk. The relative infant dose is estimated to be 0.04-0.06% of the maternal weight-adjusted dose. M/P ratio is approximately 0.6-0.8. No adverse effects reported in breastfed infants, but caution advised. Monitor infant for sedation or poor feeding.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Acute hepatitis or liver failure","Current opioid use or expected need for opioids (e.g., pain management)","Opioid withdrawal or recent opioid use (must be opioid-free for 7-10 days)","Known hypersensitivity to naltrexone or any component of the formulation"]

Clinical Precautions

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)"]

Clinical Tips & Counseling

Drug interactions

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VIVITROL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIVITROL (VIVITROL).

How it works

What the body does with it

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).

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIVITROL (VIVITROL).

Breastfeeding	Naltrexone and its active metabolite 6β-naltrexol are excreted into breast milk. The relative infant dose is estimated to be 0.04-0.06% of the maternal weight-adjusted dose. M/P ratio is approximately 0.6-0.8. No adverse effects reported in breastfed infants, but caution advised. Monitor infant for sedation or poor feeding.
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.