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. |
| Molecular Weight | 341.41 |
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 | Avoid; limited human data; animal studies show fetal harm at high doses. |
| 2nd trimester | Avoid; potential risk of opioid withdrawal in fetus if mother is opioid-dependent. |
| 3rd trimester | Avoid; may precipitate withdrawal in opioid-dependent mother and fetus, leading to preterm labor or fetal distress. |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| FDA category | Animal |
| Placental transfer | Naltrexone crosses the placenta in animals; human data limited but likely crosses due to molecular weight. |
| Breastfeeding | Naltrexone is excreted into breast milk in low amounts; theoretical risk of withdrawal in opioid-dependent infants; caution advised; consider risk-benefit. |
■ FDA Black Box Warning
None
| Common Effects | opioid use disorder |
| Serious Effects |
Use of opioid analgesicsCurrent opioid dependenceAcute opioid withdrawalPositive urine screen for opioidsHepatitis or hepatic failureHypersensitivity to naltrexone
| 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 |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | 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. |
| Naltrexone may be taken with or without food, but taking with food can reduce gastrointestinal side effects. No specific dietary restrictions. Avoid alcohol; while naltrexone reduces alcohol craving, it does not prevent intoxication if alcohol is consumed. Grapefruit juice has no known interaction. High-fat meals may increase absorption slightly but this is not clinically significant. |
| Clinical Pearls | Naltrexone is an opioid receptor antagonist used for alcohol dependence and opioid use disorder. It can precipitate severe withdrawal in opioid-dependent patients; ensure a 7-10 day opioid-free period before initiation. Administer with food to reduce gastrointestinal upset. Monitor liver function tests due to dose-dependent hepatotoxicity. For alcohol use disorder, the typical dose is 50 mg once daily; for opioid use disorder, consider extended-release injectable formulation. Do not use in patients with acute hepatitis or hepatic failure. |
| Patient Advice | Do not use naltrexone if you are currently dependent on opioids or in opioid withdrawal; you must be opioid-free for at least 7-10 days. · Avoid taking opioid-containing medications (e.g., pain relievers, cough syrups) while on naltrexone; they will be ineffective and may cause serious reactions. · Take naltrexone with food to minimize stomach upset. · Report any signs of liver problems (yellowing of skin/eyes, dark urine, abdominal pain) to your healthcare provider immediately. · Naltrexone does not treat alcohol withdrawal symptoms; you must be fully detoxified before starting treatment. · If you miss a dose, take it as soon as you remember unless it is close to the next dose; do not double the dose. · Carry identification indicating you are taking naltrexone in case of emergency. |