Coadministration with other CYP3A enzymatic pathway drugs Clarithromycin cisapride terfenadine

astemizole, warfarin, PIs, certain benzodiazepines, and certain calcium channel blockers share the same enzymatic pathway (146). Coadministration of delavir-dine with these drugs and others may result in significant and potentially life-threatening adverse effects.

Coadministration with anticonvulsants and anti-mycobacterial agents. Certain anticonvulsants and antimycobacterial agents are not recommended due to the decrease in plasma delavirdine levels. Certain H2 receptor antagonists reduce the gastrointestinal absorption of delavirdine.

Coadministration of statins and protease inhibitors. HIV-positive patients with hypercholesterolemia must be careful as to which statins are used when taking PIs such as delavirdine. For example, pravastatin and atorvastatin are recommended while lovastatin and simvastatin should be avoided. Although atorvas-tatin and delavirdine were coadministered as recommended, a case of rhabdomyolysis with acute renal failure has been reported (147).

Rash. The most frequent and significant adverse effect with delavirdine is a rash, which occurred in 18% of clinical trial participants (138,140). The rash is typically a diffuse, erythematous, maculopapular exanthem on the upper body and proximal arms, with or without pruritus. It usually arises within one to three weeks of treatment initiation, and resolves between 3 to 14 days after onset and usually does not require dose reduction or discontinuation (after interrupted treatment). A severe rash (requiring discontinuation of drug) was reported in 3.6% of subjects in the clinical trials (146). Delavirdine should be promptly discontinued if the rash is associated with fever, mucous membrane involvement, swelling, or arthralgias.

Erythema multiforme. Erythema multiforme occurs in approximately one of 1000 patients taking delavirdine.

Stevens-Johnson syndrome. Stevens-Johnson syndrome has been reported in one of 1000 patients taking delavirdine (148).

Special Considerations

Coadministration with antacids. Patients should wait at least one hour between taking an antacid and delavirdine for maximum efficacy. Pregnancy and breast-feeding. Delavirdine has not been studied in pregnant women although it has been shown to cause birth defects in animal studies. It is not known if delavirdine passes into the breast milk.

Efavirenz [EFV] (Sustiva®)

Efavirenz (EFV) is the most recently FDA-approved NNRTI. The structure, brand names, and approved uses are shown in Fig. 2.12. It is a potent drug that is well-tolerated and can be given once daily (138). As in the case of all NNRTIs, resistant viruses emerge rapidly when efavirenz is used as monother-apy. Thus, it cannot be used as a single agent to treat HIV-1 or added on as a sole agent to a failing regimen. It must be administered with a PI and/or an NRTI. The guidelines for the treatment of pediatric HIV infection have been altered to allow efavirenz to be substituted for the PI in the preferred regimen of two nucleoside analogues and a PI.

Efavirenz appears to have some unique characteristics. For example, in vitro studies indicate that high-level resistance will develop more slowly as it requires two mutations to occur before viral resistance is effective. Efavirenz, used in combination with zidovudine and lamivudine, resulted in complete remission of Kaposi's sarcoma in an AIDS patient

Generic Name

Structure

Viral Diseases Treated

Efavirenz

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