Review of naltrexone, a long-acting opiate antagonist

Abstract

The basis for using narcotic antagonists for the treatment of opiate addiction is discussed briefly, and the chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of naltrexone hydrochloride, an opiate antagonist drug, are reviewed. Naltrexone is rapidly and completely absorbed after oral administration but undergoes substantial first-pass extraction and metabolism by the liver. Naltrexone has a half-life of 3.9-10.3 hours and a slow terminal elimination-phase half-life of 96 hours. The major metabolite of naltrexone is 6-beta-naltrexol, which is present in plasma in greater concentrations than the parent drug. Problems in study design and patient adherence to treatment have made assessment of naltrexone's clinical efficacy difficult; however, studies have consistently demonstrated that patients who remained off opiates longer were those who took naltrexone longer. Factors associated with successful treatment outcomes include sustained therapy with naltrexone, participation in multidisciplinary programs of behavioral therapy and psychotherapy, and good family and social support systems. Gastrointestinal irritation and, in some studies, clinically insignificant increases in blood pressure, have been the most common adverse effects. Currently available data suggest that naltrexone is a very safe drug. The usual dosage of naltrexone hydrochloride is 50 mg orally once daily or 350 mg orally per week in three divided doses. Patients should be detoxified and opiate free for two to five days before initiation of naltrexone therapy. Naltrexone appears to be a useful adjunct to therapy in opiate addicts who are well motivated and who have strong psychological support systems.