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Trade Names:
ReVia
- Tablets 50 mg

Trade Names:
Vivitrol
- Suspension, extended-release injection 380 mg per vial

Mechanism of Action

Pharmacology

Opioid receptor antagonist markedly attenuating or completely blocking, reversibly, the subjective effects of IV administered opioids.

Pharmacokinetics

Absorption

Rapidly and nearly completely absorbed (96%) from the GI tract.

Transient initial peak within 2 hr, followed by a second peak approximately 2 to 3 days later. About 14 days after dosing, concentrations decline slowly, with measurable levels for more than 1 mo. Exposure is 3- to 4-fold higher following IM administration compared with oral naltrexone.

Distribution

Vd is estimated to be 1,350 L. Plasma protein binding is 21%.

Metabolism

Over 98% metabolized and extrahepatic sites may exist. The major metabolite is 6-β-naltrexol, which accounts for 43% of an oral dose. There are 2 minor metabolites. Less 6-β-naltrexone is generated after IM administration compared with oral.

Elimination

Renal Cl of naltrexone ranges from 30 to 127 mL/min, suggesting that renal elimination is primarily glomerular filtration. Urinary excretion of unchanged naltrexone is less than 2%, while urinary excretion of unchanged and conjugated 6-β-naltrexol accounts for 43%. Naltrexone and its metabolites may undergo enterohepatic recirculation.

Following administration of the extended-release injectable suspension, the elimination t _½ is 5 to 10 days.

Indications and Usage

Alcohol dependence; blockade of exogenously administered opioids (oral); treatment of alcohol dependence in patients able to abstain from alcohol in an outpatient setting (IM injection).

Unlabeled Uses

Eating disorders; postconcussional syndrome unresponsive to other treatments.

Contraindications

Receiving opioid analgesics; currently dependent on opioids, including those maintained on opiate agonists (eg, methadone); in acute opioid withdrawal; patients who have failed the naloxone challenge test or have positive urine screen for opioids; a history or sensitivity to naloxone or the phenanthrene-containing opioids; acute hepatitis or liver failure (oral).

Dosage and Administration

PO 50 mg once daily for up to 12 wk is sufficient for most patients. IM 380 mg q 4 wk or once a month.

PO Start with 25 mg; if no withdrawal signs occur, patient may be started on 50 mg daily thereafter. Do not attempt treatment if patient has not remained opioid-free for at least 7 to 10 days or if signs of opioid withdrawal are observed following naloxone challenge.

General Advice

• Oral
• Administer tablets without regard to meals but administer with food if GI upset occurs.

• Injection
• IM injection must be administered by a health care provider.
• Administer IM injection as a gluteal injection, alternating buttocks, and use the carton components provided (eg, microspheres diluent, preparation needle, administration needle).
• If an IM dose is missed, give the next dose as soon as possible.
• Properly mixed suspension will be milky white, will not contain clumps, and will move freely down the wall of the vial. Visually inspect for particulate matter and discoloration prior to administration.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F). Store entire dose pack of the injectable suspension in the refrigerator (36° to 46°F). Store unrefrigerated at temperatures not exceeding 77°F for no more than 7 days. Do not freeze.

Drug Interactions

May increase the risk of hepatotoxicity.

Because of antagonistic effects of naltrexone, patients may not benefit from opioid medication.

Lethargy and somnolence have been reported with coadministration of naltrexone.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (36%); dizziness/syncope (16%); depression (0% to 15%); insomnia, sleep disorder (14%); low energy, nervousness (more than 10%); feeling down, increased energy, irritability, loss of appetite (less than 10%); fatigue (4%); anxiety, sedation/somnolence (2%); suicidal attempt/ideation (1% or less).

Dermatologic

Skin rash (12%).

EENT

Pharyngitis (17%).

GI

Nausea (33%); dry mouth (24%); abdominal pain (16%); vomiting (14%); diarrhea (13%); abdominal cramps (more than 10%); increased thirst (less than 10%); constipation (3%).

Genitourinary

Decreased potency, delayed ejaculation (less than 10%).

Hepatic

Hepatocellular injury.

Lab Tests

Increased AST (2%); decreased platelet count, increased CPK, increased eosinophil count.

Local

Tenderness (72%); induration (35%); other injection site reactions, including nodules and swelling (32%); asthenic conditions (23%); pain (17%); pruritus (10%); ecchymosis (7%).

Metabolic

Anorexia/appetite decreased/appetite disorder (20%).

Musculoskeletal

Arthralgia/arthritis/joint stiffness (12%); joint and muscle pain (more than 10%); muscle cramps (8%); back pain/stiffness (7%).

Respiratory

Upper respiratory tract infection (13%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Because naltrexone and its primary metabolite are excreted mainly in the urine, use with caution in patients with moderate to severe renal function impairment.

Abstinence syndrome

To prevent occurrence of an acute abstinence syndrome, patient must be opioid-free for a minimum of 7 to 10 days.

Accidental precipitation of withdrawal

Severe opioid withdrawal syndromes precipitated by accidental ingestion of naltrexone may occur in opioid-dependent individuals. Withdrawal symptoms may appear within 5 min and last 48 hr.

Naloxone challenge

Do not perform in patients showing clinical signs or symptoms of opioid withdrawal or in patients whose urine contains opioids.

Overcoming blockade

Overcoming the antagonism by taking opioids is dangerous and may lead to fatal overdose.

Rapid opioid withdrawal

Safe use has not been established.

Special risk patients

Use with caution in patients with renal or hepatic function impairment.

Suicide

Risk is not abated by naltrexone treatment.

Overdosage

Symptoms

Abdominal pain, dizziness, nausea, somnolence.

Patient Information

• Explain name, dose, action, and potential adverse reactions of drug.
• Obtain patient history, including drug history and any known allergies.
• Advise patient that medication will be most effective when taken exactly as prescribed and combined with participation in a community-based support group.
• Advise patient that dose may be adjusted periodically in order to achieve max benefit.
• Advise patient to take without regard to meals but to take with food if stomach upset occurs.
• Advise patient to carry or wear medical identification (eg, MedicAlert ) indicating naltrexone use.
• Advise patient that self-administration of small doses of heroin or any other opiate will not produce noticeable effects. Caution patient that self-administration of large doses of heroin or any other opiate may overcome the naltrexone blockade and can cause coma or death.
• Advise patient that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness and coordination until tolerance is determined.
• Advise patient to stop taking and notify health care provider of any of the following: allergic reaction, stomach pain lasting more that a few days, white bowel movements, dark urine, yellowing of the eyes.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Caution patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise patient who have previously used opioids that they may be more sensitive to lower doses of opioids after naltrexone treatment.
• Advise patient that treatment of alcohol dependence is part of a program that includes counseling and support.
• Advise patient that follow-up visits and lab tests may be necessary to monitor therapy and to keep appointments.

• IM injection
• Advise patient that Vivitrol may cause allergic pneumonia and to immediately notify health care provider if signs and symptoms of pneumonia (eg, shortness of breath, coughing, wheezing) develop.
• Advise patient to seek medical attention for worsening skin reactions, particularly if reaction does not improve 1 month after injection.
• Advise patient that nausea may be experienced following initial injection and that these episodes of nausea tend to be mild and subside within a few days.