NALTREXONE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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.

Breastfeeding	Naltrexone and its major metabolite 6β-naltrexol are excreted in human milk; M/P ratio ~0.6-2.5. Limited data suggest no adverse effects in breastfed infants. American Academy of Pediatrics classifies as compatible with breastfeeding.
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

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	opioid use disorder
Serious Effects

Absolute Contraindications

Patients receiving opioid analgesics; current opioid dependence or acute opioid withdrawal; failed naloxone challenge test or positive opioid urine screen; acute hepatitis or hepatic failure; history of naloxone sensitivity.

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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