During two randomized, double-blind placebo-controlled 12 week trials to evaluate the efficacy of REVIA (naltrexone) as an adjunctive treatment of alcohol dependence, most patients tolerated REVIA (naltrexone) well. In these studies, a total of 93 patients received REVIA (naltrexone) at a dose of 50 mg once daily. Five of these patients discontinued REVIA (naltrexone) because of nausea. No serious adverse events were reported during these two trials.

While extensive clinical studies evaluating the use of REVIA (naltrexone) in detoxified, formerly opioid-dependent individuals failed to identify any single, serious untoward risk of REVIA (naltrexone) use, placebo-controlled studies employing up to five-fold higher doses of REVIA (naltrexone) (up to 300 mg per day) than that recommended for use in opiate receptor blockade have shown that REVIA (naltrexone) causes hepatocellular injury in a substantial proportion of patients exposed at higher doses (see WARNINGS and PRECAUTIONS: Laboratory Tests ).

Aside from this finding, and the risk of precipitated opioid withdrawal, available evidence does not incriminate REVIA (naltrexone) , used at any dose, as a cause of any other serious adverse reaction for the patient who is "opioid free." It is critical to recognize that REVIA (naltrexone) can precipitate or exacerbate abstinence signs and symptoms in any individual who is not completely free of exogenous opioids.

Patients with addictive disorders, especially opioid addiction, are at risk for multiple numerous adverse events and abnormal laboratory findings, including liver function abnormalities. Data from both controlled and observational studies suggest that these abnormalities, other than the dose-related hepatotoxicity described above, are not related to the use of REVIA (naltrexone) .

Among opioid free individuals, REVIA (naltrexone) administration at the recommended dose has not been associated with a predictable profile of serious adverse or untoward events. However, as mentioned above, among individuals using opioids, REVIA (naltrexone) may cause serious withdrawal reactions (see CONTRAINDICATIONS, WARNINGS, DOSAGE AND ADMINISTRATION ).

Reported Adverse Events

REVIA (naltrexone) has not been shown to cause significant increases in complaints in placebo-controlled trials in patients known to be free of opioids for more than 7-10 days. Studies in alcoholic populations and in volunteers in clinical pharmacology studies have suggested that a small fraction of patients may experience an opioid withdrawal-like symptom complex consisting of tearfulness, mild nausea, abdominal cramps, restlessness, bone or joint pain, myalgia, and nasal symptoms. This may represent the unmasking of occult opioid use, or it may represent symptoms attributable to naltrexone. A number of alternative dosing patterns have been recommended to try to reduce the frequency of these complaints (see Individualization of Dosage ).

Alcoholism:

In an open label safety study with approximately 570 individuals with alcoholism receiving REVIA (naltrexone) , the following new-onset adverse reactions occurred in 2% or more of the patients: nausea (10%), headache (7%), dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), vomiting (3%), anxiety (2%) and somnolence (2%).

Depression, suicidal ideation, and suicidal attempts have been reported in all groups when comparing naltrexone, placebo, or controls undergoing treatment for alcoholism.

Although no causal relationship with REVIA (naltrexone) is suspected, physicians should be aware that treatment with REVIA (naltrexone) does not reduce the risk of suicide in these patients (see PRECAUTIONS ).

Opioid Addiction:

The following adverse reactions have been reported both at baseline and during the REVIA (naltrexone) clinical trials in opioid addiction at an incidence rate of more than 10%:

Difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache.

The incidence was less than 10% for:

Loss of appetite, diarrhea, constipation, increased thirst, increased energy, feeling down, irritability, dizziness, skin rash, delayed ejaculation, decreased potency, and chills.

The following events occurred in less than 1% of subjects:

Respiratory:   nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath.

Cardiovascular:   nose bleeds, phlebitis, edema, increased blood pressure, non-specific ECG changes, palpitations, tachycardia.

Gastrointestinal:    excessive gas, hemorrhoids, diarrhea, ulcer.

Musculoskeletal:   painful shoulders, legs or knees; tremors, twitching.

Genitourinary:    increased frequency of, or discomfort during, urination; increased or decreased sexual interest.

Dermatologic:    oily skin, pruritus, acne, athlete's foot, cold sores, alopecia.

Psychiatric:    depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams.

Special senses:   eyes blurred, burning, light sensitive, swollen, aching, strained; ears "clogged", aching, tinnitus.

General:   increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head "pounding", inguinal pain, swollen glands, "side" pains, cold feet, "hot spells."

Post-Marketing Experience:    Data collected from post-marketing use of REVIA (naltrexone) show that most events usually occur early in the course of drug therapy and are transient. It is not always possible to distinguish these occurences from those signs and symptoms that may result from a withdrawal syndrome. Events that have been reported include anorexia, asthenia, chest pain, fatigue, headache, hot flushes, malaise, changes in blood pressure, agitation, dizziness, hyperkinesia, nausea, vomiting, tremor, abdominal pain, diarrhea, elevations in liver enzymes or bilirubin, hepatic function abnormalities or hepatitis, palpitations, myalgia, anxiety, confusion, emphoria, hallucinations, insomnia, nervousness, somnolence, abnormal thinking, dyspnea, rash, increased sweating, and vision abnormalities.

Depression, suicide, attempted suicide and suicidal ideation have been reported in the post-marketing experience with REVIA (naltrexone) used in the treatment of opioid dependence. No causal relationship has been demonstrated. In the literature, endogenous opioids have been theorized to contribute to a variety of conditions. In some individuals the use of opioid antagonists has been associated with a change in baseline levels of some hypothalamic, pituitary, adrenal, or gonadal hormones. The clinical significance of such changes is not fully understood.

Adverse events, including withdrawal symptoms and death, have been reported with the use of REVIA (naltrexone hydrochloride) in ultra rapid opiate detoxification programs. The cause of death in these cases is not known (see WARNINGS).

Laboratory Tests:   With the exception of liver test abnormalities (see WARNINGSand PRECAUTIONS ), results of laboratory tests, like adverse reaction reports, have not shown consistent patterns of abnormalities that can be attributed to treatment with REVIA (naltrexone) .

Idiopathic thrombocytopenic purpura was reported in one patient who may have been sensitized to REVIA (naltrexone) in a previous course of treatment with REVIA (naltrexone) . The condition cleared without sequelae after discontinuation of REVIA (naltrexone) and corticosteroid treatment.

DRUG ABUSE AND DEPENDENCE:

REVIA (naltrexone) is a pure opioid antagonist. It does not lead to physical or psychological dependence. Tolerance to the opioid antagonist effect is not known to occur.

Read the Revia (naltrexone) Side Effects Center for a complete guide to possible side effects »

Studies to evaluate possible interactions between REVIA (naltrexone) and drugs other than opiates have not been performed. Consequently, caution is advised if the concomitant administration of REVIA (naltrexone) and other drugs is required.

The safety and efficacy of concomitant use of REVIA (naltrexone) and disulfiram is unknown, and the concomitant use of two potentially hepatotoxic medications is not ordinarily recommended unless the probable benefits outweigh the known risks.

Lethargy and somnolence have been reported following doses of REVIA (naltrexone) and thioridazine.

Patients taking REVIA (naltrexone) may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrheal preparations, and opioid analgesics. In an emergency situation when opioid analgesia must be administered to a patient receiving REVIA (naltrexone) , the amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged (see PRECAUTIONS ).

Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.