REVIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REVIA (REVIA).
Naltrexone is a mu-opioid receptor antagonist that competitively binds to opioid receptors, blocking the effects of endogenous and exogenous opioids. It also exhibits some antagonistic activity at kappa and delta opioid receptors.
| Metabolism | Primarily metabolized by dihydrodiol dehydrogenase (DD) to the major metabolite 6-beta-naltrexol, with minor contribution from cytochrome P450 enzymes. |
| Excretion | Renal: primarily as unchanged drug and glucuronide conjugates; fecal: minor; approximately 60% of a dose is excreted in urine within 48 hours (with about 20% as unchanged naltrexone and the rest as metabolites, mainly 6β-naltrexol). |
| Half-life | Terminal half-life of naltrexone is approximately 4 hours; its active metabolite, 6β-naltrexol, has a half-life of about 13 hours. Clinically, the prolonged blockade of opioid receptors (up to 72 hours after a single oral dose) is attributed to the metabolite's accumulation and high receptor affinity. |
| Protein binding | Approximately 21% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 19 L/kg (range 14–24 L/kg), indicating extensive tissue distribution and high penetration into the central nervous system. |
| Bioavailability | Oral: approximately 5–40% due to extensive first-pass metabolism (mean about 20%); IM sustained-release formulation (Vivitrol) has a bioavailability of 100%. |
| Onset of Action | Oral: onset of opioid receptor blockade occurs within 1 hour, with maximal blockade achieved within 2–3 hours. |
| Duration of Action | Oral: significant opioid receptor blockade persists for 24–72 hours; the duration is dose-dependent, with higher doses providing longer blockade. Clinically, standard 50 mg daily dosing ensures complete blockade over 24 hours, while a 100 mg dose may extend blockade to 48–72 hours. |
| Molecular Weight | 341.4 |
50 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (GFR < 30 mL/min); use with caution. |
| Liver impairment | Contraindicated in acute hepatitis or hepatic failure. In Child-Pugh Class A or B, use with caution; no specific dose adjustment established. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not approved for use in pediatric patients under 18 years of age. |
| Geriatric use | No specific dose adjustment recommended; use standard adult dosing with monitoring for adverse effects. |
| 1st trimester | Risk not ruled out. May cause fetal harm. Use only if benefit outweighs risk. |
| 2nd trimester | Risk not ruled out. May cause fetal harm. Use only if benefit outweighs risk. |
| 3rd trimester | Risk not ruled out. May cause fetal harm. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for REVIA (REVIA).
| Placental transfer | Naltrexone and its active metabolite 6-β-naltrexol cross the placenta. Animal studies have shown fetal toxicity at high doses; human data are limited. |
| Breastfeeding | Naltrexone is excreted into breast milk in low amounts. No adverse effects have been reported in breastfed infants, but data are limited. The American Academy of Pediatrics considers naltrexone compatible with breastfeeding. |
■ FDA Black Box Warning
HEPATOTOXICITY: Naltrexone has the capacity to cause dose-related hepatocellular injury. Patients should be warned of the risk of hepatic injury and advised to discontinue therapy if symptoms of acute hepatitis develop.
| Serious Effects |
Current use of opioid analgesicsCurrent opioid dependence or acute opioid withdrawalPositive urine screen for opioidsHistory of hypersensitivity to naltrexone
| Precautions | Hepatotoxicity risk; monitor liver function, Precipitated opioid withdrawal in opioid-dependent patients, Eosinophilic pneumonia, Hypersensitivity reactions, Suicidality, Should not be used in patients receiving opioid analgesics or with current physiologic opioid dependence |
| Food/Dietary | No specific food interactions. Grapefruit and grapefruit juice may increase naltrexone levels; avoid excessive consumption. Alcohol should be avoided as it can reduce the efficacy of treatment and increase risk of hepatotoxicity. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. Naltrexone is not recommended for use during pregnancy unless potential benefits outweigh risks. Animal studies have shown decreased fetal survival and growth retardation at high doses. There are no adequate and well-controlled studies in pregnant women. First trimester: unknown risk; animal data suggest possible harm. Second and third trimesters: limited data; use only if clearly needed. |
| Fetal Monitoring | Monitor liver function tests (LFTs) at baseline and periodically during therapy, as naltrexone can cause dose-related hepatocellular injury. Assess for signs of hepatic toxicity, including elevated transaminases. Monitor for opioid withdrawal symptoms if patient is opioid-dependent, especially during initiation. In pregnant patients, monitor fetal growth and development via ultrasound and other standard prenatal monitoring as clinically indicated. Also monitor for maternal depressed mood and suicidal ideation. |
| Fertility Effects | Naltrexone has been reported to restore ovulation in some women with hypothalamic amenorrhea, possibly due to opioid receptor antagonism affecting GnRH secretion. In males, naltrexone may increase serum testosterone and LH levels. However, no definitive studies on fertility impairment exist; use during pregnancy should be evaluated on a case-by-case basis. |
| Clinical Pearls | Revia (naltrexone) is used for alcohol dependence and opioid dependence. Monitor for hepatotoxicity; contraindicated in acute hepatitis or liver failure. Do not administer to patients currently physically dependent on opioids, as it can precipitate severe withdrawal. Liver function tests should be assessed before and during therapy. Naltrexone may reduce the euphoric effects of alcohol and opioids. It is not a controlled substance. |
| Patient Advice | Do not take Revia if you are currently using opioids or if you are in opioid withdrawal; it can cause severe sudden opioid withdrawal. · Inform your doctor if you have liver disease, kidney disease, or a history of substance abuse. · Avoid alcohol or other substances while taking this medication. · Carry a medical ID card or wear a bracelet that identifies you as taking Revia in case of emergency. · Report any signs of liver problems: yellowing skin/eyes, dark urine, abdominal pain, or unusual fatigue. · Do not stop taking Revia abruptly without consulting your doctor. |