Retrovir Drug Interactions

Limited data suggests that co-administration of zidovudine with rifampicin decreases the AUC (area under the plasma concentration curve) of zidovudine by 48% ± 34%. This may result in a partial loss or total loss of efficacy of zidovudine. The concomitant use of rifampicin with zidovudine should be avoided (see Precautions).
Zidovudine in combination with stavudine is antagonistic in vitro. The concomitant use of stavudine with zidovudine should be avoided (see Precautions).
Probenecid increases the AUC of zidovudine by 106% (range 100 to 170%). Patients receiving both drugs should be closely monitored for haematological toxicity.
A modest increase in Cmax (28%) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) was not significantly altered. Zidovudine has no effect on the pharmacokinetics of lamivudine.
Phenytoin blood levels have been reported to be low in some patients receiving Retrovir, while in one patient a high level was noted. These observations suggest that phenytoin levels should be carefully monitored in patients receiving both drugs.
Zidovudine does not appear to affect the pharmacokinetics of atovaquone. However, pharmacokinetic data have shown that atovaquone appears to decrease the rate of metabolism of zidovudine to its glucuronide metabolite (steady state AUC of zidovudine was increased by 33% and peak plasma concentration of the glucuronide was decreased by 19%). At zidovudine dosages of 500 or 600 mg/day it would seem unlikely that a three week, concomitant course of atovaquone for the treatment of acute PCP would result in an increased incidence of adverse reactions attributable to higher plasma concentrations of zidovudine. Extra care should be taken in monitoring patients receiving prolonged atovaquone therapy.
Valproic acid, fluconazole or methadone when co-administered with zidovudine have been shown to increase the AUC with a corresponding decrease in its clearance. As only limited data are available the clinical significance of these findings is unclear but if zidovudine is used concurrently with either valproic acid, fluconazole or methadone, patients should be monitored closely for potential toxicity of zidovudine.
Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated. The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see Precautions). Consideration should be given to replacing zidovudine in a combination ART regimen if this is already established. This would be particularly important in patients with a known history of zidovudine induced anaemia.
Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive drugs (eg. systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine and doxorubicin) may also increase the risk of adverse reactions to zidovudine. If concomitant therapy with any of these drugs is necessary then extra care should be taken in monitoring renal function and haematological parameters and, if required, the dosage of one or more agents should be reduced.
Limited data from clinical trials do not indicate a significantly increased risk of adverse reactions to zidovudine with cotrimoxazole, aerosolised pentamidine, pyrimethamine and aciclovir at doses used in prophylaxis.
Oral solution: Clarithromycin tablets reduce the absorption of zidovudine. This can be avoided by separating the administration of zidovudine and clarithromycin by at least two hours.