NALTREXONE HYDROCHLORIDE- naltrexone hydrochloride tablet, film coated
Mallinckrodt, Inc.
DESCRIPTION
Naltrexone hydrochloride, an opioid antagonist, is a synthetic congener of oxymorphone with no opioid agonist properties. Naltrexone differs in structure from oxymorphone in that the methyl group on the nitrogen atom is replaced by a cyclopropylmethyl group. Naltrexone hydrochloride is also related to the potent opioid antagonist, naloxone, or n-allylnoroxymorphone.
Naltrexone hydrochloride has the chemical name of 17-(cyclopropylmethyl)-4,5?-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride. Naltrexone hydrochloride is a white, crystalline compound. The hydrochloride salt is soluble in water to the extent of about 100 mg/mL. Naltrexone Hydrochloride Tablets USP for oral administration are available as film coated tablets, containing 50 mg of naltrexone hydrochloride.
In addition, each tablet contains the following inactive ingredients: crospovidone, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, silicon dioxide, titanium dioxide, yellow iron oxide and red iron oxide. INDICATIONS AND USAGE
Naltrexone hydrochloride tablets are indicated:
In the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids.
Naltrexone hydrochloride tablets have not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for the addictions. DOSAGE AND ADMINISTRATION
IF THERE IS ANY QUESTION OF OCCULT OPIOID DEPENDENCE, PERFORM A NALOXONE CHALLENGE TEST AND DO NOT INITIATE NALTREXONE THERAPY UNTIL THE NALOXONE CHALLENGE IS NEGATIVE.
Treatment of Alcoholism
A dose of 50 mg once daily is recommended for most patients (see CLINICAL PHARMACOLOGY, Individualization of Dosage). The placebo-controlled studies that demonstrated the efficacy of naltrexone hydrochloride as an adjunctive treatment of alcoholism used a dose regimen of naltrexone hydrochloride 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 naltrexone if:
the patient is willing to take a medicine to help with alcohol dependence
the patient is opioid free for 7 to 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 naltrexone, and no other contraindications are present
Refer to CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections for additional information.
Naltrexone 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 naltrexone 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 naltrexone using the following guidelines �
Treatment should not be attempted unless the patient has remained opioid-free for at least 7 to 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.
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 naltrexone should not be attempted. The naloxone challenge can be repeated in 24 hours.
Treatment should be initiated carefully, with an initial dose of 25 mg of naltrexone hydrochloride. 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.
Intravenous:
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.
Subcutaneous:
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, backache, 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 naltrexone therapy. Repeat the challenge in 24 hours. If the test is negative, naltrexone therapy may be started if no other contraindications are present. If there is any doubt about the result of the test, hold naltrexone and repeat the challenge in 24 hours.
Alternative Dosing Schedules
Once the patient has been started on naltrexone hydrochloride, 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 naltrexone hydrochloride 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 naltrexone 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 (see WARNINGS and CLINICAL PHARMACOLOGY, Individualization of Dosage).
Patient Compliance
Naltrexone should be considered as only one of many factors determining the success of treatment. To achieve the best possible treatment outcome, appropriate compliance-enhancing techniques should be implemented for all components of the treatment program, including medication compliance.
