Complete SPL Sections#
DESCRIPTION
DESCRIPTION SECTION
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 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 are available as film coated tablets, containing 50 mg of naltrexone hydrochloride. Naltrexone hydrochloride tablets also contain: crospovidone, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, silicon dioxide, titanium dioxide, yellow iron oxide and red iron oxide.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
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.
CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
Naltrexone is contraindicated in: 1. Patients receiving opioid analgesics. 2. Patients currently dependent on opioids, including those currently maintained on opiate agonists (e.g., methadone) or partial agonists (e.g., buprenorphine). 3. Patients in acute opioid withdrawal ( see WARNINGS ). 4. Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids. 5. Any individual with a history of sensitivity to naltrexone or any other components of this product. It is not known if there is any cross-sensitivity with naloxone or the phenanthrene containing opioids.
WARNINGS
WARNINGS SECTION
PRECAUTIONS
PRECAUTIONS SECTION
ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
During two randomized, double-blind placebo-controlled 12-week trials to evaluate the efficacy of naltrexone as an adjunctive treatment of alcohol dependence, most patients tolerated naltrexone well. In these studies, a total of 93 patients received naltrexone hydrochloride at a dose of 50 mg once daily. Five of these patients discontinued naltrexone because of nausea. No serious adverse events were reported during these two trials. While extensive clinical studies evaluating the use of naltrexone in detoxified, formerly opioid-dependent individuals failed to identify any single, serious untoward risk of naltrexone use, placebo-controlled studies employing up to five-fold higher doses of naltrexone hydrochloride (up to 300 mg per day) than that recommended for use in opiate receptor blockade have shown that 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 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 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 naltrexone. Among opioid-free individuals, 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, naltrexone may cause serious withdrawal reactions ( see CONTRAINDICATIONS , WARNINGS and DOSAGE AND ADMINISTRATION ).
DRUG ABUSE AND DEPENDENCE
DRUG ABUSE AND DEPENDENCE SECTION
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.
OVERDOSAGE
OVERDOSAGE SECTION
There is limited clinical experience with naltrexone overdosage in humans. In one study, subjects who received 800 mg daily 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 ≥ 1,000 mg/kg) produced salivation, depression/reduced activity, tremors, and convulsions. Mortalities in animals due to high-dose naltrexone administration usually were due to clonic-tonic convulsions and/or respiratory failure.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
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 treatment. An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids. Switching from Buprenorphine, Buprenorphine/Naloxone, or Methadone There are no systematically collected data that specifically address the switch from buprenorphine or methadone to naltrexone; 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.
HOW SUPPLIED
HOW SUPPLIED SECTION
Naltrexone Hydrochloride Tablets USP 50 mg are available as a yellow film coated capsule-shaped tablet with a convex surface, debossed with a number “50” and a full bisect in between the 5 and 0 on one side and “1170” on the other side. Bottles of 30……………NDC 0406-1170-03 Bottles of 100…………..NDC 0406-1170-01 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight container. Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. © 2022 Mallinckrodt. SpecGx LLC Webster Groves, MO 63119 USA Rev 07/2022 Mallinckrodt™ Pharmaceuticals
PACKAGE LABEL - PRINCIPAL DISPLAY PANEL - 50 mg
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 0406-1170-01 100 TABLETS Naltrexone Hydrochloride Tablets USP 50 mg Rx only Each tablet contains: Naltrexone Hydrochloride USP . . . . . . 50 mg Mallinckrodt™ L00N02 Rev 07/2017
