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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REVIA (REVIA).
| Breastfeeding | Naltrexone and its major metabolite 6-beta-naltrexol are excreted in human milk. The milk-to-plasma ratio (M/P) is not well established, but studies indicate naltrexone concentrations in milk are low to moderate. Caution should be exercised in nursing mothers due to potential adverse reactions in infants. Consider the importance of the drug to the mother and the potential risk to the infant. Breastfeeding is generally not recommended during naltrexone therapy unless the mother is closely monitored. |
| 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. |
■ 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 physiologic opioid dependence or acute opioid withdrawal","Positive urine screen for opioids","Currently receiving opioid analgesics","Acute hepatitis or liver failure","Known 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"] |
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| 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. |