Delavirdine adverse effects

Delavirdine (Rescriptor) is approved for the treatment of HIV-1 infection in adults and adolescents over age 16 as part of a combination therapy. Rash accompanied by pruritus is the most frequent adverse effect of this agent however, it usually resolves within several weeks of treatment. Severe skin reactions are rare. Headache, nausea, vomiting, diarrhea, fatigue, and elevated hepatic enzymes also may be associated with delavirdine administration. 

The most frequent adverse effect of delavirdine is a rash, which usually occurs during the first 3 months of therapy in up to 50% of individuals. It is usually mild and resolves spontaneously in most patients or can be treated successfully with a short course of antihistamines. Interruption of treatment is required in less than 4% of patients (1,2). 

Food has no clinically relevant effect on the levels of delavirdine or nevirapine. Food modestly increases efavirenz levels, and the manufacturer su ests that this might increase the frequency of adverse effects. 

In general, efavirenz and nevirapine decrease the levels of protease inhibitors, whereas delavirdine increases them. Ritonavir is sometimes used to elevate the levels of other protease inhibitors when efavirenz or nevirapine are required. Amprenavir and nelflnavir decrease the levels of delavirdine. Most protease inhibitors do not appear to affect the levels of efavirenz or nevirapine. There is some evidence of increased adverse effects with antiviral doses of ritonavir and efavirenz, or saquinavir and delavirdine, including raised liver enzymes. Note that NNRTIs are not given with protease inhibitors in current first-line regimens for HIV infection either an NNRTI or protease inhibitors are combined with dual NRTIs. 

Rifabutin and rifampicin (rifampin) cause a very marked fall in delavirdine plasma levels rifabutin levels are raised when the delavirdine dose is increased to compensate for this. Rifabutin does not affect efavirenz levels, whereas efavirenz decreases rifabutin levels. There is usually no important interaction between rifabutin and nevirapine, although some patients may have a higher risk of rifabutin adverse effects. 

Cytochrome P450 inhibition Coadministration of delavirdine tablets with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, calcium channel blockers, ergot alkaloid preparations, amphetamines, and cisapride may result in potentially serious or life-threatening adverse events caused by possible effects of delavirdine on the hepatic metabolism of certain drugs metabolized by CYP3A and... 

This group includes nevirapine, efavirenz and delavirdine. Nevirapine was the first agent of this new class of drugs. It has convincingly been shown that combinations of AZT and ddl with nevirapine were more effective than AZT and ddl alone. It was also shown that the use of nevirapine alone rapidly induced resistance. The most frequently occurring adverse reaction to nevirapine is rash and it is advised to discontinue nevirapine in patients who develop a severe rash. 

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