NALTREXONE
Clinical safety rating: safe
Animal studies have demonstrated safety
Naltrexone is a pure opioid antagonist that competitively binds to μ-opioid receptors, blocking the effects of endogenous and exogenous opioids. It also antagonizes κ- and δ-opioid receptors to a lesser extent.
| Metabolism | Primarily metabolized in the liver via dihydrodiol dehydrogenase to 6β-naltrexol (active metabolite). Minor pathways include conjugation with glucuronic acid. CYP450 enzymes are not significantly involved. |
| Excretion | Primarily renal (60% as metabolites, including 6β-naltrexol; <2% unchanged) and biliary/fecal (30%). |
| Half-life | Naltrexone: 3.9–10.3 hours; active metabolite 6β-naltrexol: 12.9 hours. Context: Trough levels of 6β-naltrexol sustain receptor blockade for 24–48 h. |
| Protein binding | 21–28% bound to albumin. |
| Volume of Distribution | 2.1 L/kg (0.5–3.1 L/kg), indicating extensive extravasation. |
| Bioavailability | Oral: 5–40% (first-pass metabolism); IM: 100% (depot formulation). |
| Onset of Action | Oral: 30–60 min; IM depot: 1–2 h; IV: immediate (<5 min). |
| Duration of Action | Oral: opioid blockade 48–72 h after single 50 mg dose; IM depot: 28–30 days after 380 mg injection. |
| Molecular Weight | 341.4 |
Oral: 50 mg once daily for opioid dependence; 25 mg initially for first dose to minimize adverse effects. Intramuscular: 380 mg every 4 weeks for alcohol dependence.
| Dosage form | FOR SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥ 30 mL/min). Avoid use in severe renal impairment (CrCl < 30 mL/min) due to potential accumulation of metabolites. |
| Liver impairment | Contraindicated in acute hepatitis or hepatic failure. Child-Pugh Class A: use with caution; Class B or C: avoid use. |
| Pediatric use | Not FDA-approved for pediatric patients <18 years. Limited data: 0.5-1 mg/kg/day orally for opioid dependence off-label, not standard. |
| Geriatric use | Start at lower end of dosing range (25 mg orally daily) and titrate slowly due to potential decreased renal function and increased sensitivity. |
| 1st trimester | Limited human data; animal studies show fetal toxicity at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for opioid withdrawal in fetus if mother is opioid-dependent. Use with caution. |
| 3rd trimester | Risk of neonatal opioid withdrawal syndrome if used near term. Avoid unless essential. |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| Placental transfer | Crosses placenta; evidence in animal studies and human case reports. |
| Breastfeeding | Naltrexone and its active metabolite 6β-naltrexol are excreted into breast milk in low concentrations. The American Academy of Pediatrics considers it usually compatible with breastfeeding, but monitor infant for sedation, weight gain, and feeding problems. |
■ FDA Black Box Warning
Hepatotoxicity: Naltrexone has the potential to cause dose-related hepatocellular injury. Patients with acute hepatitis or hepatic failure should not receive naltrexone. Risk is increased with higher doses (>300 mg/day) and pre-existing liver disease.
| Common Effects | opioid use disorder |
| Serious Effects |
Current opioid use or opioid dependenceAcute opioid withdrawalSevere hepatic impairmentHypersensitivity to naltrexone
| Precautions | Hepatotoxicity risk; opioid withdrawal precautions (precipitates withdrawal in opioid-dependent patients); must be opioid-free for 7-10 days; depression/suicidality; eosinophilic pneumonia (rare); use with caution in renal impairment (dose adjustment may be needed). |
| Food/Dietary | No significant food interactions. Avoid excessive alcohol consumption due to hepatotoxicity risk. Grapefruit juice does not interact. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Limited human data; animal studies show no teratogenicity at clinically relevant doses. First trimester: low risk; second and third trimesters: no known adverse fetal effects. Use only if clearly needed. |
| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal liver function tests periodically due to potential hepatotoxicity. Observe infant for sedation, poor feeding, or withdrawal if maternal use continues. |
| Fertility Effects | Naltrexone may restore ovulation in some women with opioid-induced hyperprolactinemia. No known direct impairment of fertility. Animal studies show no adverse effects on fertility at therapeutic doses. |
| Clinical Pearls | Naltrexone is a mu-opioid receptor antagonist used for alcohol and opioid use disorders. Avoid in patients receiving opioid analgesics or with acute opioid withdrawal. Assess liver function before and during therapy due to hepatotoxicity risk. For opioid dependence, ensure patient is opioid-free for 7-10 days before initiation to prevent precipitated withdrawal. The extended-release injectable formulation improves adherence. May be used off-label for pruritus or impulse control disorders. |
| Patient Advice | Do not use any opioid medications (prescription or illicit) while taking naltrexone, as it can cause severe withdrawal or block pain relief. · Carry a medical alert card or ID stating you are taking naltrexone. · Report any signs of liver problems: yellow skin/eyes, dark urine, abdominal pain, persistent nausea. · If you miss a dose of oral naltrexone, take it as soon as remembered, unless it is almost time for the next dose; do not double doses. · Avoid alcohol or limit to less than 4 drinks per day (per FDA label) to reduce hepatotoxicity risk. · Naltrexone may cause dizziness or drowsiness; avoid driving until you know how it affects you. |