NRTIs are prodrugs, which need to be activated by phosphorylation within cells. Drugs may therefore interact with
NRTIs by increasing or decreasing intracellular activation.
NRTIs are water soluble, and are mainly eliminated by the kidneys (didanosine,
lamivudine, stavudine, and zalcitabine) or undergo
hepatic glucuronidation (abacavir, zidovudine). The few important interactions with these drugs primarily involve altered
renal clearance. For zidovudine (and possibly abacavir) some interactions occur via altered glucuronidation, but the
clinical relevance of these are less clear. Cytochrome P450-mediated interactions are not important for this class of drugs. Didanosine chewable tablets are formulated with antacid buffers that are intended to facilitate didanosine absorption by minimising acid-induced hydrolysis in the stomach. These preparations can therefore alter the absorption of other drugs that are affected by antacids (e.g. azole antifungals, quinolone antibacterials, tetracyclines). This interaction may be minimised by separating
administration by at least 2 hours. Alternatively, the enteric-coated preparation of didanosine (gastro-resistant capsules) may be used.