Vivitrol (naltrexone microspheres)

Dosage of oral naltrexone is expressed in terms of the hydrochloride salt; dosage of the extended-release IM injection is expressed in terms of naltrexone. The following dosage recommendations are usual dosages recommended by the manufacturer; alternative flexible dosing schedules in which the dose and/or frequency of administration of the drug are altered in an attempt to improve compliance have also been suggested.

Administer naltrexone orally or by IM injection. Do not administer the parenteral preparation by IV or subcutaneous injection.

Therapy may be initiated with the parenteral preparation; it is not necessary to initiate therapy with oral naltrexone and then switch to parenteral preparation.

No dosing information is available for this tab.

The manufacturer states that concomitant administration of naltrexone with drugs other than opioid agonists has not been studied; therefore, naltrexone should be used with caution in patients receiving other drugs.

Naltrexone is not metabolized by the cytochrome P-450 (CYP) isoenzyme system.

Naltrexone does not inhibit or induce major CYP enzymes.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Opioid Antagonists/Opioid Analgesics

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Naltrexone, nalmefene, and samidorphan are opioid antagonists and thus inhibit the effects of opioid analgesics.(1-3)

CLINICAL EFFECTS: Concurrent administration or the administration of naltrexone within 7-10 days of opioids may induce acute abstinence syndrome or exacerbate a pre-existing subclinical abstinence syndrome.(1,4) Patients taking naltrexone may not experience beneficial effects of opioid-containing medications.(4) Samidorphan can precipitate opioid withdrawal in patients who are dependent on opioids. In patients who use opioids, delay initiation of samidorphan for a minimum of 7 days after last use of short-acting opioids and 14 days after last use of long-acting opioids.(3) Concurrent use of nalmefene tablets with opioid agonists may prevent the beneficial effects of the opioid.(2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of naltrexone states that the administration of naltrexone concurrently with opioids or to patients dependent on opioids is contraindicated.(1,4) Patients previously dependent on short-acting opioids should be opioid-free for a minimum of seven to ten days before beginning naltrexone therapy. Patients previously on buprenorphine or methadone may be vulnerable to withdrawal symptoms for as long as 2 weeks.(1,4) The manufacturer of naltrexone states that the naloxone challenge test, described in the naltrexone prescribing information, can be administered to determine if patients are opioid free.(1) The manufacturer of samidorphan states the concurrent use of samidorphan in patients using opioids or undergoing acute opioid withdrawal is contraindicated. Prior to initiating samidorphan, there should be at least a 7-day opioid free interval from the last use of short-acting opioids, and at least a 14-day opioid free interval from the last use of long-acting opioids.(3) The UK manufacturer of nalmefene tablets (for reduction of alcohol consumption) states the concurrent use of opioid analgesics is contraindicated.(2) Suspend the use of nalmefene tablets for 7 days prior to the anticipated use of opioids (e.g., elective surgery).(2)

DISCUSSION: A double-blind, randomized, placebo-control study evaluated pain relief and side effects of 35 opioid-naive patients undergoing cesarean section. All patients received spinal anesthesia (bupivacaine and morphine) and were randomized to also receive placebo, naltrexone 3 mg, or naltrexone 6 mg. Patients treated with naltrexone experienced shorter duration of pain relief (not statistically significant), however incidence of opioid-induced side effects was reduced. Patients in the naltrexone 6 mg group had lower rates of pruritus, vomiting, and somnolence (all statistically significant) compared to the placebo group.(5) In a double-blind, randomized, placebo-control trial ten recreational opioid users were studied to determine the effects of hydromorphone (4 mg and 16 mg), tramadol (87.5 mg, 175 mg, and 350 mg), and placebo after pretreatment with naltrexone (50 mg) or placebo. Results show that lower doses of hydromorphone and tramadol acted similar to placebo. Hydromorphone 16 mg alone caused euphoria and miosis which were blocked by naltrexone. Tramadol 350 mg produced a lower magnitude of euphoria and miosis compared to hydromorphone. Naltrexone partially diminished the euphoria caused by tramadol, while it enhanced some of the unpleasant monoaminergic effects (flushing, malaise, vomiting).(6) A case report describes a 28 year-old ex-heroin addict who was stable on methadone 100 mg daily and simultaneously stopped using heroin and began drinking alcohol. He was admitted to the hospital for alcohol detoxification and, by mistake, was given naltrexone 100 mg instead of methadone 100 mg. The patient experienced withdrawal symptoms including chills, agitation, muscle and abdominal pain, generalized piloerection, and dilated pupils. Treatment of withdrawal was titrated to treat symptoms and required administration 78 mg of parenteral hydromorphone, after which the patient experienced relief for the following six hours.(8) Intentional administration of an opioid antagonist, naloxone, with opioid analgesics has been performed with close monitoring to lower required opioid dose by inducing withdrawal. Three case reports describe patients who had improved pain relief on significantly reduced doses of opioid analgesics.(8) In a double-blind controlled trial, 267 trauma patients were randomized to receive 0.05 mg/kg intravenous morphine either alone or in combination with 5 mg naltrexone oral suspension. Evaluated endpoints include reduction of pain and incidence of side effects. Results indicate that ultra-low dose naltrexone does not alter opioid requirements for pain control, but does lower incidence of nausea [2 (1.16%) vs 16 (11.6%), p<0.001].(9)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Patients receiving opioid analgesics.

*Patients with current physiologic opioid dependence, including those currently maintained on opiate agonists (e.g., methadone) or partial agonists (e.g., buprenorphine).

*Patients in acute opioid withdrawal.

*Patients who have failed the naloxone challenge test or who have a positive urine screen for opioids.

*Patients with known hypersensitivity to naltrexone or any components of the products. I

• Acute hepatic failure
• Opioid use last 4 hours in narcotic-dependent patient
• Opioid withdrawal symptoms

• Acute hepatitis
• Depression
• Eosinophilic pneumonia
• Suicidal ideation

There are no moderate contraindications for this drug.

The most common adverse effects in patients with opioid use disorder receiving naltrexone extended-release injectable suspension (incidence >=2% and at least twice as frequent as with placebo) include hepatic enzyme abnormalities, injection site pain, nasopharyngitis, insomnia, and toothache.

The most common adverse effects in patients with opioid use disorder receiving naltrexone oral tablets (incidence >=10%) include difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache.

The most common adverse effects in patients with alcohol use disorder receiving naltrexone extended-release injectable suspension (incidence >=5% and at least twice as frequent as with placebo) include nausea, vomiting, injection site reactions (including induration, pruritus, nodules and swelling), muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, and decreased appetite or other appetite disorders.

The most common adverse effects in patients with alcohol use disorder receiving naltrexone oral tablets (incidence >=2%) include depression, nausea, headache, dizziness, nervousness, fatigue, insomnia, vomiting, anxiety, and somnolence.

More Frequent

• Injection site sequelae
• Pharyngitis

Less Frequent

• Arthralgia
• Increased aspartate transaminase

Rare or Very Rare

• Abnormal hepatic function tests
• Acute myocardial infarction
• Acute pancreatitis
• Anaphylaxis
• Angina
• Angioedema
• Atrial fibrillation
• Biliary calculus
• Cellulitis
• Cerebrovascular accident
• Cholecystitis
• Chronic heart failure
• Colitis
• Deep venous thrombosis
• Dehydration
• Depression
• Dermal necrosis
• Eosinophilia
• Eosinophilic pneumonia
• Gastroenteritis
• Gastrointestinal hemorrhage
• Hepatitis
• Hypersensitivity drug reaction
• Increased creatine kinase level
• Leukocytosis
• Lymphadenopathy
• Paralytic ileus
• Pneumonia
• Pulmonary thromboembolism
• Seizure disorder
• Skin rash
• Sleep apnea
• Suicidal ideation
• Thrombocytopenic disorder
• Urticaria

More Frequent

• Anorexia
• Cramps
• Dizziness
• Drowsy
• General weakness
• Induration of skin
• Insomnia
• Nausea
• Pruritus of skin
• Toothache
• Vomiting

Less Frequent

• Acute abdominal pain
• Appetite changes
• Diarrhea
• Headache disorder
• Symptoms of anxiety
• Xerostomia

Rare or Very Rare

• Agitation
• Blurred vision
• Bronchitis
• Bruising
• Chest pain
• Chest tightness
• Chills
• Conjunctivitis
• Constipation
• Dental abscess
• Disturbance of attention
• Dream disorder
• Dysgeusia
• Dyspnea
• Erythema
• Euphoria
• Facial edema
• Fever
• Flatulence
• Flushing
• Gastroesophageal reflux disease
• Hematoma
• Hemorrhoids
• Hypercholesterolemia
• Hyperhidrosis
• Injection site abscess
• Irritability
• Joint stiffness
• Laryngitis
• Lethargy
• Libido changes
• Migraine
• Muscle spasm
• Myalgia
• Night sweats
• Pain
• Palpitations
• Paresthesia
• Sinusitis
• Skin swelling
• Upper respiratory infection
• Urinary tract infection
• Weight gain
• Weight loss

No enhanced messaging available.

The safety and efficacy of naltrexone have not been established in pediatric patients younger than 18 years of age.

In reproduction studies in rats and rabbits, oral naltrexone increased the incidence of early fetal loss. There are no adequate and well-controlled studies of oral naltrexone use in pregnant women. Available data from published case series of naltrexone extended-release injectable suspension are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Naltrexone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes, such as low birth weight, preterm birth, and fetal death, and often results in continued or relapsing illicit opioid use. Published studies have demonstrated that alcohol is associated with fetal harm, including growth restriction, facial abnormalities, CNS abnormalities, behavioral disorders, and impaired intellectual development.

Naltrexone and its major metabolite, 6beta-naltrexol, are present in human milk. There are no data on the effects of the drug on the breastfed infant or on milk production. Consider the developmental health benefits of breastfeeding along with the mother's clinical need for naltrexone and any potential adverse effects on the breastfed infant from naltrexone or the underlying maternal condition.

Clinical studies of naltrexone extended-release injectable suspension did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients. In trials of alcohol-dependent patients, 2.6% of patients were over 65 years of age, and one patient was over 75 years of age. No individuals older than 65 years of age were included in studies of opioid dependency.

The pharmacokinetics of naltrexone have not been evaluated in the geriatric population. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function in this population.