NALTREXONE HYDROCHLORIDE
Clinical safety rating: safe
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
Competitive antagonist at mu, kappa, and delta opioid receptors, with highest affinity for mu receptors. Also acts as an antagonist at the toll-like receptor 4 (TLR4).
| Metabolism | Primarily hepatic metabolism via dihydrodiol dehydrogenase (DD), with minor involvement of CYP450 enzymes (CYP2B6, CYP3A4). Major metabolites: 6-beta-naltrexol (active), 2-hydroxy-3-methoxy-6-beta-naltrexol. |
| Excretion | Renal: primarily as unchanged drug (<2%) and metabolites (mainly 6-β-naltrexol, glucuronide conjugates); approximately 60% of dose excreted in urine (including metabolites) and about 30% in feces via biliary excretion. |
| Half-life | Terminal elimination half-life: ~4 hours for naltrexone; its major active metabolite, 6-β-naltrexol, has a half-life of ~13 hours. The longer half-life of the metabolite contributes to sustained receptor blockade. |
| Protein binding | Approximately 20–21% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Apparent Vd: ~1.9 L/kg (oral); this relatively large volume indicates extensive tissue distribution. |
| Bioavailability | Oral: 5–40% (mean ~20%) due to extensive first-pass metabolism to 6-β-naltrexol. Intramuscular extended-release: ~100% (systemic availability). |
| Onset of Action | Oral: peak blockade of opioid receptors occurs within 1–2 hours; parenteral (extended-release IM): detectable levels within 1–2 hours, therapeutic levels by 2–3 hours. |
| Duration of Action | Oral: effective blockade of exogenous opioids lasts 24–72 hours after a single 50 mg dose, sufficient to block effects of up to 25 mg IV heroin. Extended-release IM (380 mg): sustained therapeutic levels for 4–6 weeks. |
50 mg orally once daily for opioid dependence; 25 mg orally once daily for alcohol dependence, may increase to 50 mg after one week.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (eGFR <30 mL/min/1.73m2), use is not recommended due to lack of data. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution, reduce dose to 25 mg daily. Child-Pugh Class C: Contraindicated due to increased risk of hepatotoxicity. |
| Pediatric use | Not FDA-approved for patients <18 years. Limited data: For opioid dependence in adolescents, 50 mg orally once daily after induction; consider weight-based dosing (1-2 mg/kg/day) in research settings. |
| Geriatric use | Start at 25 mg orally once daily, titrate to 50 mg daily based on tolerability and renal function. Monitor for increased sensitivity and hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| FDA category | Animal |
| Breastfeeding | Naltrexone and its major metabolite 6β-naltrexol are excreted into breast milk. The milk-to-plasma ratio is approximately 0.5. An exclusively breastfed infant would receive about 0.05% of the maternal weight-adjusted dose. Limited data suggest no adverse effects; however, monitor infant for irritability, sedation, or poor feeding. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | opioid use disorder |
| Serious Effects |
["Acute opioid withdrawal","Current opioid use (positive urine screen for opioids)","History of opioid agonist/partial agonist therapy (methadone, buprenorphine) within past 7-14 days","Severe hepatic impairment (Child-Pugh Class C)","Acute hepatitis or liver failure","Hypersensitivity to naltrexone or any component"]
| Precautions | ["Hepatotoxicity: Dose-related, risk increased with alcohol abuse, active liver disease, or concomitant hepatotoxic drugs; monitor liver function","Opioid withdrawal: Precipitates acute withdrawal in opioid-dependent patients; must be opioid-free for at least 7-10 days","Suicidality: Monitor for depression/suicidal ideation","Eosinophilic pneumonia: Discontinue if dyspnea/hypoxia occur","Renal impairment: Use with caution","Unintended opioid reversal: May block analgesic effects of opioids; manage pain with non-opioid agents"] |
Loading safety data…
| In animal studies, naltrexone (up to 100 mg/kg/day) did not demonstrate teratogenicity, but embryo/fetal toxicity occurred at high doses. Human data are insufficient; the drug should be used during pregnancy only if potential benefit outweighs risk. No specific trimester risks have been established. |
| Fetal Monitoring | Monitor maternal hepatic function (LFTs) at baseline and periodically. Monitor for opioid withdrawal symptoms in the mother, as naltrexone can precipitate withdrawal. In neonates, no specific monitoring is required unless maternal opioid use was present prior to naltrexone initiation. |
| Fertility Effects | Naltrexone has been shown to reverse opioid-induced hypogonadism and may improve fertility in opioid-dependent individuals. However, in women with amenorrhea due to hyperprolactinemia, naltrexone may normalize menstrual cycles. No adverse effects on fertility are known. |