Treatment of ethanol dependence; blockade of the effects of exogenously administered opioids
Pharmacodynamic Actions: REVIA is a pure opioid antagonist. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids.
When co-administered with morphine, on a chronic basis, REVIA blocks the physical dependence to morphine, heroin and other opioids.
REVIA has few, if any, intrinsic actions besides its opioid blocking properties. However, it does produce some pupillary constriction, by an unknown mechanism.
The administration of REVIA is not associated with the development of tolerance or dependence. In subjects physically dependent on opioids, REVIA will precipitate withdrawal symptomatology.
Do not give until patient is opioid-free for 7-10 days as determined by urine analysis
Adults: Oral: 25 mg; if no withdrawal signs within 1 hour give another 25 mg; maintenance regimen is flexible, variable and individualized (50 mg/day to 100-150 mg 3 times/week for 12 weeks); up to 800 mg/day has been tolerated in adults without an adverse effect
Dosing cautions in renal/hepatic impairment: Caution in patients with renal and hepatic impairment. 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.
If there is any question of occult opioid dependence, perform a naloxone challenge test; do not attempt treatment until naloxone challenge is negative.
Naltrexone is administered orally; to minimize adverse gastrointestinal effects, administer with food or antacids or after meals; advise patient not to self-administer opiates while receiving naltrexone therapy
Tablet, as hydrochloride: 50 mg
DOSAGE AND ADMINISTRATION
IF THERE IS ANY QUESTION OF OCCULT OPIOID DEPENDENCE, PERFORM A NALOXONE CHALLENGE TEST AND DO NOT INITIATE REVIA THERAPY UNTIL THE NALOXONE CHALLENGE IS NEGATIVE.
Treatment of Alcoholism:
A dose of 50 mg once daily is recommended for most patients (see Individualization of Dosage ). The placebo-controlled studies that demonstrated the efficacy of REVIA as an adjunctive treatment of alcoholism used a dose regimen of REVIA 50 mg once daily for up to 12 weeks. Other dose regimens or durations of therapy were not evaluated in these trials.
A patient is a candidate for treatment with REVIA if:
The patient is willing to take a medicine to help with alcohol dependence.
The patient is opioid free for 7-10 days.
The patient does not have severe or active liver or kidney problems (Typical guidelines suggest liver function tests no greater than 3 times the upper limits of normal, and bilirubin normal.)
The patient is not allergic to REVIA , and no other contraindications are present.
REVIA should be considered as only one of many factors determining the success of treatment of alcoholism. Factors associated with a good outcome in the clinical trials with REVIA were the type, intensity, and duration of treatment; appropriate management of comorbid conditions; use of community-based support groups; and good medication compliance. To achieve the best possible treatment outcome, appropriate compliance-enhancing techniques should be implemented for all components of the treatment program, especially medication compliance.
Treatment of Opioid Dependence:
Initiate treatment with REVIA using the following guidelines:
1.) Treatment should not be attempted unless the patient has remained opioid-free for at least 7-10 days. Self-reporting of abstinence from opioids in opioid addicts should be verified by analysis of the patient's urine for absence of opioids. The patient should not be manifesting withdrawal signs or reporting withdrawal symptoms.
2.) If there is any question of occult opioid dependence, perform a naloxone challenge test. If signs of opioid withdrawal are still observed following naloxone challenge, treatment with REVIA should not be attempted. The naloxone challenge can be repeated in 24 hours.
3.) Treatment should be initiated carefully, with an initial dose of 25 mg of REVIA. If no withdrawal signs occur, the patient may be started on 50 mg a day thereafter.
Naloxone Challenge Test: The naloxone challenge test should not be performed in a patient showing clinical signs or symptoms of opioid withdrawal, or in a patient whose urine contains opioids. The naloxone challenge test may be administered by either the intravenous or subcutaneous routes.
Inject 0.2 mg naloxone.
Observe for 30 seconds for signs or symptoms of withdrawal.
If no evidence of withdrawal, inject 0.6 mg of naloxone.
Observe for an additional 20 minutes.
Administer 0.8 mg naloxone.
Observe for 20 minutes for signs or symptoms of withdrawal.
Note: Individual patients, especially those with opioid dependence, may respond to lower doses of naloxone. In some cases, 0.1 mg IV naloxone has produced a diagnostic response.
Interpretation of the Challenge: Monitor vital signs and observe the patient for signs and symptoms of opioid withdrawal. These may include, but are not limited to: nausea, vomiting, dysphoria, yawning, sweating, tearing, rhinorrhea, stuffy nose, craving for opioids, poor appetite, abdominal cramps, sense of fear, skin erythema, disrupted sleep patterns, fidgeting, uneasiness, poor ability to focus, mental lapses, muscle aches or cramps, pupillary dilation, piloerection, fever, changes in blood pressure, pulse or temperature, anxiety, depression, irritability, back ache, bone or joint pains, tremors, sensations of skin crawling or fasciculations. If signs or symptoms of withdrawal appear, the test is positive and no additional naloxone should be administered.
Warning: If the test is positive, do NOT initiate REVIA therapy. Repeat the challenge in 24 hours. If the test is negative, REVIA therapy may be started if no other contraindictions are present. If there is any doubt about the result of the test, hold REVIA and repeat the challenge in 24 hours.
Alternative Dosing Schedules:
Once the patient has been started on REVIA, 50 mg every 24 hours will produce adequate clinical blockade of the actions of parenterally administered opioids (i.e., this dose will block the effects of a 25 mg intravenous heroin challenge). A flexible approach to a dosing regimen may need to be employed in cases of supervised administration. Thus, patients may receive 50 mg of REVIA every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. The degree of blockade produced by REVIA may be reduced by these extended dosing intervals.
There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits.