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Drug Interactions between abacavir / lamivudine / zidovudine and Zerit XR

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

zidovudine stavudine

Applies to: abacavir / lamivudine / zidovudine and Zerit XR (stavudine)

GENERALLY AVOID: In vitro data have demonstrated an antagonistic relationship between zidovudine and stavudine. The proposed mechanism is competition for phosphorylating enzymes required for nucleoside activation. A 41% reduction in active stavudine metabolites was reported when zidovudine was administered with stavudine. No effect on zidovudine activity was noted. Reduced stavudine activation and loss of antiviral activity due to prior zidovudine modification of intracellular phosphorylation has been suggested, but this was not confirmed by other studies. Further clarification is needed.

MANAGEMENT: The manufacturer recommends against concurrent use.

References

  1. (2001) "Product Information. Retrovir (zidovudine)." Glaxo Wellcome
  2. Hoggard PG, Veal GJ, Wild MJ, Barry MG, Back DJ (1995) "Drug interactions with zidovudine phosphorylation in vitro." Antimicrob Agents Chemother, 39, p. 1376-8
  3. Merrill DP, Moonis M, Chou TC, Hirsch MS (1996) "Lamivudine or stavudine in two- and three-drug combinations against human immunodeficiency virus type 1 replication in vitro." J Infect Dis, 173, p. 355-64
  4. Barry M, Mulcahy F, Merry C, Gibbons S, Back D (1999) "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet, 36, p. 289-304
  5. Havlir DV, Tierney C, Friedland GH, Pollard RB, Smeaton L, Sommadossi JP, Fox L, Kessler H, Fife KH, Richman DD (2000) "In vivo antagonism with zidovudine plus stavudine combination therapy." J Infec Dis, 182, p. 321-5
  6. Hoggard PG, Kewn S, Barry MG, Khoo SH, Back DJ (1997) "Effects of drugs on 2',3'-didehydrothymidine phosphorylation in vitro." Antimicrob Agents Chemother, 41, p. 1231-6
  7. Hoggard PG, Barry MG, Khoo SH, Back DJ (1996) "Drug interactions with d4T phosphorylation in vitro." Br J Clin Pharmacol, 42, 278P
View all 7 references

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Drug and food interactions

Minor

zidovudine food

Applies to: abacavir / lamivudine / zidovudine

Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration. In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast. In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state. In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting. Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected. The clinical significance of these alterations, if any, is unknown. The product labeling states that zidovudine may be taken with or without food.

References

  1. Lotterer E, Ruhnke M, Trautman M, et al. (1991) "Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal." Eur J Clin Pharmacol, 40, p. 305-8
  2. Unadkat JD, Collier AC, Crosby SS, et al. (1990) "Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal." AIDS, 4, p. 229-32
  3. (2001) "Product Information. Retrovir (zidovudine)." Glaxo Wellcome
  4. Sahai J, Gallicano K, Garber G, et al. (1992) "The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients." Br J Clin Pharmacol, 33, p. 657-60
View all 4 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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