Non-nucleoside RT-inhibitors

on 19.10.09 with 0 comments

These substances bind to reverse transcriptase and inhibit the enzyme.

  • Nevirapine (Viramune®). The recommended dose is one 200 mg tablet/day for 2 weeks, followed by one 200 mg tablet twice daily. This initial regimen is necessary as the compound induces its own breakdown. If initially 400 mg per day is given this would result in overdosing. Hypersensitivity reactions with skin rash occur. The blood level falls by 35% if St John’s wort is taken at the same time (interaction via CYP3A4). The drug is destined to play an important role in the prevention of neonatal transmission in developing countries. In July 2000 Boehringer Ingelheim Company decided to offer Viramune® free for a period of five years for the prevention of transmission of HIV-1 from mother to child in certain developing areas. In some countries, like Thailand, certain generic fixed drug-combinations, such as d4T, 3TC and nevirapine (GPO-Vir) are supplied in one pill. Taking a pill twice per day costs half a Euro (i.e. half a US dollar).

  • Efavirenz (Stocrin®, Sustiva®). The drug is administered in the evening as a single 600 mg dose (200 mg tablets). A single-tablet formulation is being developed. Skin rash (in 20%) may improve with antihistamines. Alterations in the patients' psychological condition have been reported (restlessness, nightmares, etc.). These side-effects usually disappear within the first four weeks. It lowers the blood level of indinavir, so that the latter has to be given in higher doses (1 g TDS). Efavirenz has a long half-life (48 hours), and hence is more “forgiving” when a dose is missed. Efavirenz is not used in the early stages of pregnancy, as it is teratogenic in monkeys and apes in the first three months of gestation.

  • Experimental. Diarylpyrimidines (DAPYs) compounds are a new class of NNRTIs which are highly active on both wild type HIV and mutant HIV. Examples are TMC120 (dapivirine) and TMC125 (etravirine). At present these products are still in the test phase and have therefore not yet obtained a therapeutic place in clinical practice.

Category: Medical Subject Notes , Medicine Notes



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