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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(nal TREKS one)
Generic Available (U.S.)
Yes: Tablet
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Vivitrol®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM206669.pdf
REMS Components
Vivitrol®: Medication Guide
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of ethanol dependence; prevention of relapse in opioid dependent patients, following opioid detoxification
Pregnancy Risk Factor
C
Pregnancy Considerations
Evidence of early fetal loss has been observed in animal studies with oral naltrexone. Reproduction studies have not been conduced using the sustained release I.M formulation. There are no adequate and well-controlled studies of naltrexone in pregnant women.
Lactation
Enters breast milk/not recommended
Contraindications
Hypersensitivity to naltrexone or any component of the formulation; narcotic dependence or current use of opioid analgesics; acute opioid withdrawal; failure to pass naloxone challenge or positive urine screen for opioids; acute hepatitis; liver failure
Warnings/Precautions
Boxed warnings:
• Hepatocellular injury: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Accidental opioid overdose: Patients who had been treated with naltrexone may respond to lower opioid doses than previously used. This could result in potentially life-threatening opioid intoxication. Patients should be aware that they may be more sensitive to lower doses of opioids after naltrexone treatment is discontinued, after a missed dose, or near the end of the dosing interval. Warn patients that any attempt to overcome opioid blockade during naltrexone therapy, could potentially lead to fatal opioid overdose; the opioid competitive receptor blockade produced by naltrexone is potentially surmountable in the presence of large amounts of opioids.
• Acute opioid withdrawal: May precipitate symptoms of acute withdrawal in opioid-dependent patients, including pain, hypertension, sweating, agitation, and irritability; in neonates: shrill cry, failure to feed.
• Eosinophilic pneumonia: Cases of eosinophilic pneumonia have been reported and should be considered in patients presenting with progressive hypoxia and dyspnea.
• Hepatocellular injury: [U.S. Boxed Warning]: Dose-related hepatocellular injury is possible; the margin of separation between the apparent safe and hepatotoxic doses appears to be ≤ fivefold. Discontinue therapy if signs/symptoms of acute hepatitis develop.
• Hypersensitivity reactions: Hypersensitivity, including anaphylaxis, has been reported.
• Injection site reactions: Serious injection site reactions (eg, cellulitis, induration, hematoma, abscess, necrosis) have been reported with use, including severe cases requiring surgical debridement. Females appear to be at a higher risk. Patients should any injection site pain, swelling, bruising, pruritus, or redness that does not improve (or worsens). For I.M. use only in the gluteal muscle, do not administer I.V., SubQ, or into fatty tissue; incorrect administration may increase the risk of injection site reactions.
• Suicidal thoughts/depression: Suicidal thoughts and depression have been reported in both alcohol- and opioid-dependent patients; monitor closely.
Disease-related concerns:
• Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia) and/or patients on anticoagulant therapy; bleeding/hematoma may occur from I.M. administration.
• Hepatic impairment: Use with caution in patients with hepatic impairment; not studied in severe impairment. Use is contraindicated in patients with acute hepatitis or hepatic failure.
• Renal impairment: Use with caution in patients with renal impairment; not studied in moderate-to-severe impairment.
Dosage form specific issues:
• Injection: Vehicle used in the injectable naltrexone formulation (polylactide-co-glycolide microspheres) has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis following injection of other drug products that also use the polylactide-co-glycolide microspheres vehicle.
Other warnings/precautions:
• Detoxified opioid addiction: Patients should be opioid-free for a minimum of 7-10 days; use naloxone challenge test to confirm patient is opioid-free prior to therapy if there is any suspicion since urinary opioid screen may not be sufficient proof. Use of naltrexone does not eliminate or diminish withdrawal symptoms.
• Emergency pain management: In naltrexone-treated patients requiring emergency pain management, consider alternatives to opioid therapy (eg, regional analgesia, nonopioid analgesics, general anesthesia). If opioid therapy is required for pain therapy, patients should be under the direct care of a trained anesthesia provider.
Adverse Reactions
Combined reporting of adverse events from oral and injectable formulations:
>10%:
Cardiovascular: Syncope (13%)
Central nervous system: Headache (3% to 25%), insomnia (3% to 14%), dizziness (4% to 13%), anxiety (2% to 12%), nervousness (4% to >10%)
Gastrointestinal: Nausea (10% to 33%), vomiting (3% to 14%), appetite decreased (14%), diarrhea (13%), abdominal pain (11%), abdominal cramping
Hepatic: ALT increased (13%)
Local: Injection site reaction (≤69%; includes bruising, induration, nodules, pain, pruritus, swelling, tenderness)
Neuromuscular & skeletal: Arthralgia (12%), CPK increased (11% to 39%)
Respiratory: Pharyngitis (7% to 11%)
1% to 10%:
Cardiovascular: Hypertension (5%)
Central nervous system: Suicidal thoughts (≤10%), depression (8%), somnolence (2% to 4%), fatigue (4%), chills, energy increased, feeling down, irritability
Dermatologic: Rash (6%)
Endocrine & metabolic: Polydipsia
Gastrointestinal: Dry mouth (5%), toothache (4%)
Genitourinary: Delayed ejaculation, impotency
Hepatic: AST increased (2% to 10%), GGT increased (7%)
Neuromuscular & skeletal: Muscle cramps (8%), back pain (6%)
Miscellaneous: Influenza (5%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Angina, atrial fibrillation, blood pressure increased, blurred vision, cerebral aneurysm, chest pain, chest tightness, cholecystitis, cholelithiasis, colitis, COPD, dehydration, delirium, diaphoresis, DVT, dyspnea, ECG changes, eosinophilia (transient), eosinophilic pneumonia, euphoria, fever, GI hemorrhage, HF, hallucinations, hypercholesterolemia, hypersensitivity reaction (includes anaphylaxis, angioedema, and urticaria), ischemic stroke, leukocytosis, lymphadenopathy, MI, narcotic withdrawal, palpitation, pancreatitis, paralytic ileus, paranoia, PE, perirectal abscess, pneumonia, rigors, seizure, shortness of breath, suicide, tachycardia, thrombocytopenia, UTI
Drug Interactions
There are no known significant interactions.
Storage
Injection: Store unopened kit at 2°C to 8°C (36°F to 46°F). Kit may be kept at room temperature of ≤25°C (77°F) for ≤7 days prior to use; do not freeze. Following reconstitution of the suspension, administer immediately.
Tablet: Store at room temperature. Protect from light.
Reconstitution
Injection: Prior to reconstitution, allow drug vial and provided diluent to reach room temperature (~45 minutes). Using the provided 1-inch preparation needle, reconstitute with 3.4 mL of the diluent and allow to dissolve by vigorously shaking the vial for ~1 minute. Mixed suspension will be milky white, free of clumps, and will move freely down the walls of the vial. Immediately after suspension, withdraw 4.2 mL of the suspension using the same preparation needle.
Prior to administration, replace the preparation needle with the appropriate size provided administration needle (1.5-inch Terumo® needle or 2-inch Needle-Pro® needle). Prior to injection, remove any air bubbles and push on the plunger until 4 mL of the suspension remains in the syringe. Following reconstitution of the suspension, administer immediately.
Mechanism of Action
Naltrexone (a pure opioid antagonist) is a cyclopropyl derivative of oxymorphone similar in structure to naloxone and nalorphine (a morphine derivative); it acts as a competitive antagonist at opioid receptor sites, showing the highest affinity for mu receptors.
Pharmacodynamics/Kinetics
Duration: Oral: 50 mg: 24 hours; 100 mg: 48 hours; 150 mg: 72 hours; I.M.: 4 weeks
Absorption: Oral: Almost complete
Distribution: Vd: ~1350 L; widely throughout the body but considerable interindividual variation exists
Metabolism: Extensively metabolized via noncytochrome-mediated dehydrogenase conversion to 6-beta-naltrexol (primary metabolite) and related minor metabolites; glucuronide conjugates are also formed from naltrexone and its metabolites
Oral: Extensive first-pass effect
Protein binding: 21%
Bioavailability: Oral: Variable range (5% to 40%)
Half-life elimination: Oral: 4 hours; 6-beta-naltrexol: 13 hours; I.M.: naltrexone and 6-beta-naltrexol: 5-10 days
Time to peak, serum: Oral: ~60 minutes; I.M.: Biphasic: ~2 hours (first peak), ~2-3 days (second peak)
Excretion: Primarily urine (as metabolites and small amounts of unchanged drug)
Dosage
Adults: Note: Do not initiate therapy until patient is opioid-free for at least 7-10 days as determined by urinalysis; consider naloxone challenge test to confirm patient is opioid-free if there is any suspicion since urinary opioid screen may not be sufficient proof.
Oral: Alcohol dependence, opioid dependence: Initial: 25 mg; if no withdrawal signs occur, administer 50 mg on day 2; maintenance regimen: 50 mg/day; alternative maintenance regimens may be used and include: 50 mg on weekdays with a 100 mg dose on Saturday; 100 mg every other day; or 150 mg every 3 days (degree of blockade may be reduced with extended dosing interval regimens and doses >50 mg may increase risk of hepatocellular injury)
I.M.: Alcohol dependence, opioid dependence: 380 mg once every 4 weeks
Dosage adjustment in renal impairment: Use caution. No adjustment needed in mild impairment. Not adequately studied in moderate-to-severe renal impairment.
Dosage adjustment in hepatic impairment: Use caution. An increase in naltrexone AUC of approximately five- and 10-fold in patients with compensated or decompensated liver cirrhosis respectively, compared with normal liver function has been reported No adjustment required with mild-to-moderate hepatic impairment. Not adequately studied in severe hepatic impairment. Use is contraindicated in patients with acute hepatitis or hepatic failure.
Administration: Oral
May be administered with or without food. Administration with food or after meals may minimize adverse gastrointestinal effects. Advise patient not to self-administer opiates while receiving naltrexone therapy.
Administration: I.M.
Vivitrol®: Administer I.M. into the upper outer quadrant of the gluteal area; must inject dose using one of the provided needles for administration. Use either the 1.5-inch 20-gauge needle or the 2-inch 20-gauge needle (for patients with a larger amount of subcutaneous tissue overlying the gluteal muscle). Avoid inadvertent injection into a blood vessel; do not administer I.V., SubQ, or into fatty tissue (the risk of serious injection site reaction is increased if given incorrectly as a SubQ injection or into fatty tissue instead of the gluteal muscle). Injection should alternate between the 2 buttocks. Do not substitute any components of the dose-pack.
Monitoring Parameters
For narcotic withdrawal; liver function tests; injection site reactions
Test Interactions
May cause cross-reactivity with some opioid immunoassay methods.
Patient Education
This medication will help you achieve abstinence from opiates if taken as directed. Do not use opiates. Carry documentation to alert medical personnel you are taking medication in the event of an emergency. You may experience drowsiness, dizziness, or blurred vision; trouble sleeping; decreased appetite; abdominal cramping, nausea or vomiting; low energy; or decreased sexual function (reversible when drug is discontinued). Report yellowing of skin or eyes; change in color of stool or urine; suicide ideation; increased perspiration or chills; acute headache; palpitations; unusual joint pain; signs and symptoms of pneumonia (trouble breathing, coughing, or wheezing); or injection site pain, swelling, or unresolved redness.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Dry mouth.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Do not use until patient has been opioid-free for 7-10 days. Assess carefully for several days following start of therapy for narcotic withdrawal symptoms or severe adverse reactions. Monitor injection site for reaction. Use non-narcotic analgesics for pain. Monitor for suicide ideation.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, microspheres for suspension, extended release:
Vivitrol®: 380 mg [contains polylactide-co-glycolide; supplied with diluent]
Tablet, oral, as hydrochloride: 50 mg
ReVia®: 50 mg [scored]
Pricing: U.S. (www.drugstore.com)
Suspension (reconstituted) (Vivitrol)
380 mg (1): $1099.96
Tablets (Naltrexone HCl)
50 mg (30): $103.99
Tablets (ReVia)
50 mg (30): $275.32
References
Kleber HD, “Naltrexone,” J Subst Abuse Treat, 1985, 2(2):117-22.
Mitchell JE, “Naltrexone and Hepatotoxicity,” Lancet, 1986, 1(8491):1215.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
O'Connor PG and Kosten TR, “Rapid and Ultrarapid Opioid Detoxification Techniques,” JAMA, 1998, 279(3):229-34.
Tang J, and Weiter JJ, “Branch Retinal Artery Occlusion After Injection of a Long-Acting Risperidone Preparation,” Annals Intern Med, 2007, 147(4): 283-3.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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