Zidovudine drugs clinical interactions with

Stavudine possesses several clinically significant interactions with other drugs. Although hydroxyurea enhances the antiviral activity of stavudine and didanosine, combination therapy that includes stavudine and didanosine, with or without hydroxyurea, increases the risk of pancreatitis. Combinations of stavudine and didanosine should not be given to pregnant women because of the increased risk of metabolic acidosis. Zidovudine inhibits the phosphorylation of stavudine thus, this combination should be avoided. 

NRTIs are water soluble, and are mainly eliminated by the kidneys (di-danosine, lamivudine, stavudine, and zalcitabine) or undergo hepatie glu-curonidation (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 (e.g. rifampicin , (p.792)). Cytochrome P450-mediated interactions are not important for this class of drugs. 

Established interactions. With the NRTTs that are actively excreted via the kidneys (e.g. lamivudine, stavudine, and zaicitabine), it is unlikely that dosage alterations are necessary unless the patient has renal impairment. However, when both drugs are needed, patients should be closely monitored for signs of toxicity. Moreover, the UK manufacturer of lamivudine recommends that the use of lamivudine with high-dose co-trimoxazole for the treatment of Pneumocystis pneumonia and toxoplasmosis should be avoided. Since renal clearance represents only 20 to 30% of the total clearance of zidovudine, the authors of two of these reports " suggest that this interaction is unlikely to be clinically important for zidovudine unless the glucuronidation by the liver is impaired by liver disease or other drugs. Didanosine also does not appear to interact to a clinically relevant extent. 

Buffered didanosine decreases the AUC of indinavir, and the drugs shouid be given one hour apart. Buffered didanosine interacts simiiarly with atazanavir. Tipranavir with low-dose ritonavir modestly reduced the AUC of abacavir and zidovudine, and such combinations are not recommended in the UK. The changes in pharmacokinetics seen when giving other combinations of protease inhibitors with NRTIs do not appear to be clinically significant. Protease inhibitors do not affect the intracellular activation of NRTIs. 

Studies in animals have shown that the AUC of zidovudine is increased and its volume of distribution and clearance rate decreased when it is given with nimodipine. The clinical relevance of the interaction is not known, but as the adverse effects of zidovudine are dose related, the manufacturer of nimodipine suggests that the possibility of this interaction should be borne in mind in patients given both drugs. ... 

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