Revia Side Effects Center

SIDE EFFECTS

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

While extensive clinical studies evaluating the use of REVIA in detoxified, formerly opioid-dependent individuals failed to identify any single, serious untoward risk of REVIA use, placebo-controlled studies employing up to fivefold higher doses of REVIA (up to 300 mg per day) than that recommended for use in opiate receptor blockade have shown that REVIA 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, 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 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.

Among opioid-free individuals, REVIA 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 may cause serious withdrawal reactions (see CONTRAINDICATIONS, WARNINGS, DOSAGE AND ADMINISTRATION).

Reported Adverse Events

REVIA 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 to 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.

Alcoholism

In an open label safety study with approximately 570 individuals with alcoholism receiving REVIA, 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.

RATE RANGES OF NEW ONSET EVENTS

Although no causal relationship with REVIA is suspected, physicians should be aware that treatment with REVIA 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 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.”

Postmarketing Experience

Data collected from postmarketing use of REVIA show that most events usually occur early in the course of drug therapy and are transient. It is not always possible to distinguish these occurrences 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, palpitations, myalgia, anxiety, confusion, euphoria, hallucinations, insomnia, nervousness, somnolence, abnormal thinking, dyspnea, rash, increased sweating, vision abnormalities, and idiopathic thrombocytopenic purpura.

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 in ultra rapid opiate detoxification programs. The cause of death in these cases is not known (see WARNINGS).

Laboratory Tests

In a placebo controlled study in which REVIA was administered to obese subjects at a dose approximately five-fold that recommended for the blockade of opiate receptors (300 mg per day), 19% (5/26) of REVIA recipients and 0% (0/24) of placebo-treated patients developed elevations of serum transaminases (i.e., peak ALT values ranging from 121 to 532; or 3 to 19 times their baseline values) after three to eight weeks of treatment. The patients involved were generally clinically asymptomatic, and the transaminase levels of all patients on whom follow-up was obtained returned to (or toward) baseline values in a matter of weeks.

Transaminase elevations were also observed in other placebo controlled studies in which exposure to REVIA at doses above the amount recommended for the treatment of alcoholism or opioid blockade consistently produced more numerous and more significant elevations of serum transaminases than did placebo. Transaminase elevations occurred in 3 of 9 patients with Alzheimer's Disease who received REVIA (at doses up to 300 mg/day) for 5 to 8 weeks in an open clinical trial.

Drug Abuse And Dependence

REVIA 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 entire FDA prescribing information for Revia (Naltrexone)