Effect of food
For a number of drugs the absorption is greatly influenced by food. Food interactions are depicted in Table 1. For some drugs (zidovudine, ritonavir, indinavir + ritonavir) the tolerability improves when it can be taken with food. All boosted PIs should be taken with food to ensure adequate absorption of both the PI and of Ritonavir.
Table 1:
Food interactions with various ARV
|
Drug
|
Food interaction
|
Recommendation
|
|
Didanosine
|
Fasting increases absorption
|
Should be given fasting or 2 hours after a meal
|
|
Saquinavir
|
High fat meal increases absorption
|
Should be given with a high fat meal
|
|
Ritonavir, Atazanavir, Tipranavir, Lopinavir, Darunavir
|
Meals increases absorption
|
Should be given with meals .Capsules and syrups of lopinavir should be given with meals
|
|
Indinavir
|
Fasting increases absorption
|
Should be given in fasting state
|
|
Etavirine
|
Meals increase absorption
|
Should be given after a meal
|
Drug – Drug interaction
CYP3A is the most important enzyme for metabolism of Drugs in general, and for anti-HIV drugs in particular. It metabolizes all currently available PIs and NNRTIs. PIs are substrates of CYP3A are often also inhibitors of these enzymes. The NNRTIs are not only substrates of CYP3A but they are also able to induce this enzyme. As a result plasma levels of the drug itself will decrease before reaching steady-state. (7-14 days). Both nevirapine and efavirenz are inducers of CYP3A; when combined with PIs, the plasma levels of most PIs (i.e. indinavir, saquinavir, amprenavir, atazanavir, Lopinavir) will decrease.
Some anticonvulsant's are strong enzyme inducers: phenytoin, phenobarbital, and carbamazepine. Plasma levels of PIs or NNRTIs will decrease when combined with these anticonvulsant's. On the other hand, PI increase plasma levels of carbamazepine which enhances the risk for toxicity.