In a letter to US doctors, Glaxo-Wellcome has revealed that adding a 200mg (two tablets) dose of ritonavir to the normal amprenavir dosage (1200mg) cancels out the negative effects of efavirenz on amprenavir blood levels. 1250mg of nelfinavir twice daily (five tablets twice daily) had a similar effect.
Researchers at the US National Institutes of Health looked at a sub-group of 17 individuals participating in a salvage study of amprenavir, efavirenz and abacavir who added either ritonavir or nelfinavir. Efavirenz has been observed to reduce the minimum concentration of amprenavir by 49%, increasing the risk that resistance to amprenavir could emerge when the two drugs are used together. This interaction has led to the suggestion that amprenavir should be dosed three times daily with efavirenz to avoid reduced drug levels, an unattractive prospect for a drug which is selling in the US on its reputation of twice daily dosing, without or without food.
However, adding ritonavir increased the minimum amprenavir concentration six-fold compared with others in the salvage study who did not add ritonavir, removing the need for three-times daily dosing. Adding nelfinavir increased the minimum concentration of amprenavir three fold.
This means that NNRTI-naïve individuals may be able to assemble a viable salvage regimen composed of amprenavir, efavirenz and another drug if they use a booster dose of ritonavir. The nelfinavir dose used in this study is the standard therapeutic dose, but may not be effective for people with previous protease inhibitor experience because of cross-resistance. Amprenavir is the only protease inhibitor currently available which appears to be active against virus already resistant to indinavir, ritonavir and saquinavir in the majority of individuals.
Amprenavir is currently available through an expanded access scheme in the UK. The drug is already licensed for twice daily use in the United States.