Nelfinavir CYP3A4/5/7 substrate

Saquinavir is subject to extensive first-pass metabolism by CYP3A4 and functions as a CYP3A4 inhibitor as well as a substrate thus, there are many potential drug-drug interactions (Table 49-4). A decreased dose of saquinavir is recommended when -administered with nelfinavir. Increased saquinavir levels when -administered with omeprazole necessitate close monitoring for toxicities. Digoxin levels may increase if co administered with saquinavir and should therefore be monitored. Liver function tests should be monitored if saquinavir is -administered with delavirdine or rifampin. There is no evidence of human teratogenicity from saquinavir there is short-term safety data for both mother and infant. 

Drug-drug transport interactions are important in combinationtherapy with HIV protease inhibitors (117). Many protease inhibitors are substrates for and inhibitors of CYP3A4 and P-gp. Different combination effects (e.g./ intrinsic clearance of amprenavir is reduced by nelfinavir and indinavir but not saquinavir) depend on the extent to which one or both of these enzymes are affected. 

An interaction of nelfinavir with the macrolide immunosuppressant tacrolimus has been reported in a patient co-infected with HIV and hepatitis C virus who had undergone orthotopic liver transplantation (18). The dose of tacrolimus had to be reduced to a 70th of the normal dose to avoid adverse effects. Nelfinavir serum concentrations were not affected by tacrolimus. The authors suggested that this effect had resulted from inhibition of the metabolism of tacrolimus, because both compounds are substrates of CYP3A4. 

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