NALTREXONE HCL

Chemistry - A synthetic opiate antagonist, naltrexone HCl occurs as white crystals having a bittertaste. 100 mg are soluble in one ml of water.

Storage, Stability, Compatibility

Naltrexone tablets should be stored at room temperature inwell-closed containers.

Pharmacology - NALTREXONE HCL

Naltrexone is an orally available narcotic antagonist. It competitively binds toopiate receptors in the CNS, thereby preventing both endogenous opiates (e.g., endorphins) andexogenously administered opiate agonists or agonist/antagonists from occupying the site.
Naltrexone may be more effective in blocking the euphoric aspects of the opiates and less effectiveat blocking the respiratory depressive or miotic effects.
Naltrexone may also increase plasma concentrations of luteinizing hormone (LH), cortisol and ACTH. In dogs with experimentally-induced hypovolemic shock, naltrexone (like naloxone) given IV in high dosages increased mean arterial pressure, cardiac output, stroke volume, and leftventricular contractility.

Uses, Indications

Naltrexone may be useful in the treatment of self-mutilating or tail-chasingbehaviors in dogs or cats.

Pharmacokinetics - NALTREXONE HCL

In humans, naltrexone is rapidly and nearly completed absorbed, but undergoes a significant first-pass effect as only 5-12% of a dose reaches the systemic circulation.
Naltrexone circulates throughout the body and CSF levels are approximately 30% of those found inthe plasma. Only about 20-30% is bound to plasma proteins. It is unknown whether naltrexonecrosses the placenta or enters milk. Naltrexone is metabolized in the liver primarily to 6-beta-naltrexol, which has some opiate blocking activity. In humans, serum half life of naltrexone is about4 hours; 6-beta-naltrexol, about 13 hours. Naltrexone, as metabolites are then eliminated primarilyvia the kidney.

Contraindications, Precautions, Reproductive Safety

Naltrexone is generally considered to becontraindicated in patients physically dependent on opiate drugs, in hepatic failure or with acutehepatitis. The benefits of the drug versus its risks should be weighed in patients with hepatic dysfunction or who have had a history of allergic reaction to naltrexone or naloxone.
Very high doses have caused increased embryotoxicity in some laboratory animals. It should beused during pregnancy only when the benefits outweigh any potential risks. It is unknown whethernaltrexone enters maternal milk.

Adverse Effects, Warnings

At usual doses, naltrexone is relatively free of adverse effects in nonopioid dependent patients. Some human patients have developed abdominal cramping, nausea andvomiting, nervousness, insomnia, joint or muscle pain, skin rashes. Dose-dependent hepatotoxicityhas been described in humans on occasion.
Naltrexone will block the analgesic, antidiarrheal and antitussive effects of opiate agonist or agonist/antagonist agents. Withdrawal symptoms may be precipitated in physically dependent patients.

Overdosage, Acute Toxicity

Naltrexone appears to be relatively safe even after very large doses.
The LD50 in dogs after subcutaneous injection has been reported to be 200 mg/kg. Oral LD50's inspecies tested range from 1.1 g/kg in mice to 3 g/kg in monkeys (dogs or cats not tested). Death atthese doses were a result of respiratory depression and/or tonic-clonic seizures. Massive overdosesshould be treated using gut emptying protocols when warranted and giving supportive treatment.

Drug Interactions

In addition to blocking the effects of pure opiate agonists (e.g., morphine, meperidine, codeine, oxymorphone, etc.) naltrexone also reverses the effects of opioid agonist/antagonists such as butorphanol, pentazocine or nalbuphine.
Laboratory Considerations - Naltrexone reportedly does not interfere with TLC, GLC, or HPLCmethods of determining urinary morphine, methadone or quinine. Naltrexone may causeincreases in hepatic function tests (e.g., AST, ALT) (see adverse effects above).