Non-nucleoside reverse transcriptase inhibitors

Non-nucleoside reverse transcriptase inhibitors

NNRTIs are used in combination with other antiretrovirals to treat

HIV infection. The three agents in this class include:

·                 delavirdine

·                 efavirenz

·                 nevirapine. (See Combining antiretroviral drugs.)

Pharmacokinetics

Efavirenz and delavirdine are highly protein-bound after absorp-tion and distribution, and nevirapine is widely distributed through-out the body. All three drugs are metabolized by the cytochrome P-450 liver enzyme system and excreted in urine and stool.

Pharmacodynamics

Nevirapine and delavirdine bind to the reverse transcriptase en-zyme, preventing it from exerting its effect, and thus preventing HIV replication. Efavirenz competes for the enzyme through non-competitive inhibition.

Pharmacotherapeutics

NNRTIs are used in combination with other antiretrovirals in HIV treatment; nevirapine is specifically indicated for the patient whose clinical condition and immune status have deteriorated.

Drug interactions

NNRTIs may be responsible for many drug interactions.

·                 Nevirapine may decrease the activity of protease inhibitors and hormonal contraceptives; these drugs shouldn’t be used together.

·                 Delavirdine may increase levels of benzodiazepines, clar-ithromycin, rifabutin, saquinavir, and warfarin; it may also signifi-cantly increase concentrations of indinavir, requiring a decrease in the indinavir dosage.

·                 The indinavir dosage will need to be increased when given with efavirenz.

·                  Nevirapine has been associated with a severe rash that may be life-threatening. If a rash occurs, discontinue the drug. (See Ad-verse reactions to NNRTIs.)