Fosamprenavir adverse effects

CYP3A4 Amprenavir is metabolized by CYP3A4 and is an inhibitor (and possibly an inducer) of CYP3A4. Coadministration of fosamprenavir and drugs that induce CYP3A4, such as rifampin, may decrease amprenavir concentrations and reduce its therapeutic effect. Coadministration of fosamprenavir and drugs that inhibit CYP3A4 may increase amprenavir concentrations and increase the incidence of adverse effects. 

The most common adverse effects of fosamprenavir are headache, nausea, diarrhea, perioral paresthesias, depression, and rash. Up to 3% of patients may experience rashes (including Stevens-Johnson syndrome) severe enough to warrant drug discontinuation. 

The data on the effect of protease inhibitors on ketoconazole are more limited. Amprenavir caused a modest increase in ketoconazole levels, and the UK manufacturer of amprenavir suggests that no ketoeonazole dose adjustment is necessary with amprenavir alone, although the US manufacturer recommends increased monitoring for adverse effeets and states that a dose reduction may be needed in patients receiving ketoconazole in doses of more than 400 mg daily. However, a marked effect was seen for ritonavir alone and for ritonavir combined with darunavir, fosamprenavir, lopinavir, saquinavir and theoretically tipranavir. This may increase the adverse effects of ketoconazole. Most protease inhibitor manufacturers say that doses greater than 200 mg a day of ketoconazole are not recommended. Similarly, the UK manufacturers of ketoconazole and ritonavir say that a dose reduction of ketoconazole should be considered when it is given with ritonavir. ... 

Preliminary data suggest that the combination of amprenavir 600 mg twice daily with lopinavir/ritonavir 400/100 mg twice daily resulted in amprenavir trough plasma levels that were lower than with the combination of amprenavir/ritonavir at the same doses. Similarly the lopinavir levels were lower than those without amprenavir. Others have reported similar findings, and increasing the dose of ritonavir did not prevent a decrease in amprenavir levels with lopinavir. Similar findings were also reported for fosamprenavir with lopinavir/ritonavir, and further study showed that separation of doses reduced the effect of amprenavir on lopinavir/ritonavir levels, but increased the effect on amprenavir levels. " However, the manufacturer notes that combining lopinavir/ritonavir 400/100 mg with fosamprenavir/ritonavir 700/100 mg, both twice daily, increased the AUC and minimum level of lopinavir by 37% and 52%, respectively, whereas the AUC and minimum level of amprenavir were decreased by 63% and 65%, respectively. " In addition, the US manufacturer says that the rate of adverse effects was higher with this combination. ... 

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