In a placebo controlled study in which naltrexone hydrochloride 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 naltrexone hydrochloride recipients and 0% (0/24) of placebo-treated patients developed elevations in 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 naltrexone hydrochloride 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 naltrexone hydrochloride (at doses up to 300 mg/day) for 5 to 8 weeks in an open clinical trial.
To report SUSPECTED ADVERSE REACTIONS, contact AvKARE, Inc. at 1-855-361-3993; email email@example.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Naltrexone hydrochloride 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.
There is limited clinical experience with naltrexone hydrochloride overdosage in humans. In one study, subjects who received 800 mg daily of naltrexone hydrochloride for up to one week showed no evidence of toxicity.
In the mouse, rat and guinea pig, the oral LD50s were 1,100 to 1,550 mg/kg; 1,450 mg/kg; and 1,490 mg/kg; respectively. High doses of naltrexone hydrochloride (generally ÿ1,000 mg/kg) produced salivation, depression/reduced activity, tremors, and convulsions. Mortalities in animals due to high-dose naltrexone hydrochloride administration usually were due to clonic-tonic convulsions and/or respiratory failure.
In view of the lack of actual experience in the treatment of naltrexone hydrochloride overdose, patients should be treated symptomatically in a closely supervised environment. Physicians should contact a poison control center for the most up-to-date information.
To reduce the risk of precipitated withdrawal in patients dependent on opioids, or exacerbation of a preexisting subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride tablets treatment. An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids.
There are no systematically collected data that specifically address the switch from buprenorphine or methadone to naltrexone hydrochloride tablets; however, review of postmarketing case reports have indicated that some patients may experience severe manifestations of precipitated withdrawal when being switched from opioid agonist therapy to opioid antagonist therapy (see WARNINGS). Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Healthcare providers should be prepared to manage withdrawal symptomatically with non-opioid medications.
A dose of 50 mg once daily is recommended for most patients. 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.
Naltrexone hydrochloride tablets 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 hydrochloride tablets 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 should be initiated with an initial dose of 25 mg of naltrexone hydrochloride tablets. If no withdrawal signs occur, the patient may be started on 50 mg a day thereafter.
A dose of 50 mg once a day will produce adequate clinical blockade of the actions of parenterally administered opioids. As with many non-agonist treatments for addiction, naltrexone hydrochloride tablets are of proven value only when given as part of a comprehensive plan of management that includes some measure to ensure the patient takes the medication.
Clinicians are reminded that there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. A naloxone challenge test may be helpful if there is any question of occult opioid dependence. If signs of opioid withdrawal are still observed following naloxone challenge, treatment with naltrexone hydrochloride tablets should not be attempted. The naloxone challenge can be repeated in 24 hours.
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 20 minutes 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.
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 hydrochloride tablets and repeat the challenge in 24 hours.
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 hydrochloride 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).
Naltrexone hydrochloride tablets 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.
Naltrexone Hydrochloride Tablets, USP are available as:
50 mg; yellow, round film-coated tablets, bisected on one side, debossed with “EL” on one side of the bisect and “15” on the other side of the bisect. They are available in bottles of:
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Protect from light.
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
These are not all the possible side effects of Naltrexone Hydrochloride Tablets, USP. Call your doctor for medical advice about side effects. You may report side effects to AvKARE, Inc. at 1-855-361-3993 or to FDA at 1-800-FDA-1088. For more information go to www.avkare.com.
For inquiries call AvKARE, Inc. at 1-855-361-3993 or e-mail
Pulaski, TN 38478
Mfg. Rev. 08/17
AV Rev. 10/18 (P)
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