Dosing and uses of ReVia, Vivitrol, Depade (naltrexone)
Adult dosage forms and strengths
tablet
- 50mg
microspheres for IM injection
- 380mg
Opioid Dependence
Prevention of relapse after opioid detoxification; to be used only after patient has been opioid-free for 7-10 days and after negative naloxone challenge (no symptom withdrawal after naloxone administration)
PO: 25 mg initially, then observation for 1 hr, then 50 mg once daily starting on day 2; flexible dosing regimens can be employed to accommodate patient convenience or ensure compliance
IM: 380 mg in gluteal muscle every 4 weeks for maintenance of abstinence
Alcohol Dependence
Treatment in patients who have been able to abstain from alcohol in outpatient settings before treatment initiation
PO: 50 mg once daily for ≤12 weeks
IM: 380 mg in gluteal muscle every 4 weeks for maintenance of abstinence
Hepatitis (Orphan)
Orphan designation for treatment of autoimmune hepatitis
Sponsor
- TaiwanJ Pharmaceuticals Co., Ltd, Room 204 A, Bldg 53; 195 Chung Hsing Rd., Sec 4; Chutung, Hsinchu, Taiwan
Postherpetic Neuralgia (Orphan)
Orphan designation for treatment of postherpetic neuralgia
Sponsor
- Allodynic Therapeutics, LLC; 1785 NE 123rd Street; North Miami, FL 33181-2537
Pediatric dosage forms and strengths
Safety and efficacy not established
Crohn Disease (Orphan)
Treatment in pediatric patients
Orphan indication sponsor
- Jill P Smith, MD, Pennsylvania State University, 500 University Drive, Hershey, PA 17033
ReVia, Vivitrol, Depade (naltrexone) adverse (side) effects
>10%
Injection site reaction (69%; includes bruising, induration, nodules, pain, pruritus, swelling, tenderness)
Nausea (33%)
Headache (25%)
Decreased appetite (14%)
Insomnia (14%)
Vomiting (14%)
Diarrhea (13%)
Dizziness (13%)
Upper respiratory tract infection (URTI) (13%)
Anxiety (12%)
Arthralgia (12%)
Increased creatine phosphokinase (11%)
Pharyngitis (11%)
1-10%
Depression (8%)
Muscle cramps (8%)
Back pain (6%)
Rash (6%)
Dry mouth (5%)
Somnolence (4%)
Increased aspartate aminotransferase (AST) (2%)
<1%
Alopecia
Dyspnea
Edema
Hepatocellular injury
Increased systolic and diastolic blood pressures
Liver function abnormalities
Labored breathing
Nonspecific electrocardiographic (ECG) changes
Opiate withdrawal (mild to severe signs and symptoms, including drug craving, confusion, drowsiness, visual hallucinations, abdominal pain, vomiting, diarrhea)
Palpitation
Phlebitis
Tachycardia
Warnings
Contraindications
Patients who are on opioid analgesics, are opioid-dependent (eg, opioid agonists [methadone], opioid partial agonists [buprenorphine]), are in acute opioid withdrawal, have positive urine test for opioids, or fail to pass naloxone challenge
Hypersensitivity
Cautions
Depression, suicide, and suicidality cited in postmarketing reports; causal relation not demonstrated
Vulnerability to opioid overdose: Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after discontinuance of naltrexone
Opioid withdrawal precipitated abruptly by administration of opioid antagonist to opioid-dependent patient may result in withdrawal syndrome severe enough to necessitate hospitalization (see Contraindications)
Risk of hepatotoxicity with increasing doses; dose related hepatocellular injury; discontinue therapy if signs/symptoms of acute hepatitis develop
Injection may cause severe injection-site reactions (eg, cellulitis, necrosis, hematoma)
Injectable microspheres are for IM use only; inadvertent SC/IV administration may increase risk of severe injection-site reactions
Cases of eosinophilic pneumonia reported; consider in patients with symptoms of progressive hypoxia and dyspnea
Use caution in patients with hepatic failure or with bleeding disorder including thrombocytopenia and hemophilia, or patients taking anticoagulant therapy; beeding hematoma may occur from IM administration
Use caution in renal impairment or hepatic impairment
Patients should be opioid free for a minimum of 7-10 days before initiating therapy; a naltrexone challenge test recommended to confirm opioid-free status
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug is excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of ReVia, Vivitrol, Depade (naltrexone)
Mechanism of action
Opioid competitive receptor antagonist; shows highest affinity for mu receptors; congener of oxymorphone
Absorption
96% absorbed from gastrointestinal tract, but because of first-pass metabolism, only 5-40% reaches systemic circulation
Bioavailability: 5-40%
Onset: 15-30 min
Duration: 24 hr
Peak plasma time: PO tablet, 1 hr; PO solution, 0.6 hr
Peak plasma concentration (50-mg dose): Naltrexone, 10.6-13.7 ng/mL; 6-β-naltrexol, 109-139 ng/mL
Distribution
Protein bound: 21-28%
Vd: 1350 L
Metabolism
Metabolized in liver
Metabolites: 6-β-naltrexol (major), 2-hydroxy-3-methoxy-6-β-naltrexol (HMN), 2-hydroxy-3-metho-xynaltrexone, noroxymorphone, 3-methoxy-6-β-naltrexoL
Elimination
Half-life: PO, 4 hr; 6-β-naltrexol, 13 hr; IM and 6-β-naltrexol and IM: 5-10 days
Excretion: Urine (mainly)
Administration
IM Administration
Administer IM as gluteal injection, alternating buttocks for each subsequent injection
