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Drug Interactions between ribavirin and zidovudine

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

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Interactions between your drugs

Moderate

zidovudine ribavirin

Applies to: zidovudine and ribavirin

GENERALLY AVOID: Ribavirin, a nucleoside analog, has been shown to antagonize the in vitro antiviral activity of zidovudine against HIV. The mechanism is feedback inhibition of thymidine kinase induced by ribavirin, resulting in decreased intracellular phosphorylation of zidovudine to its active triphosphate metabolite. The clinical relevance of this finding is unknown. Preliminary data from a small number of HCV-HIV coinfected patients receiving interferon-ribavirin therapy and different antiretroviral regimens containing zidovudine do not support a major clinical impact related to the in vitro effect. However, the potential for diminished antiretroviral activity should be considered, as three patients in one study had an increase in HIV viral load of more than 0.5 log after 3 to 6 months of interferon-ribavirin therapy which led to discontinuation of ribavirin in one. In addition, the risk of myelosuppression and mitochondrial toxicities such as lipodystrophy, peripheral neuropathy, pancreatitis, and lactic acidosis associated with nucleoside reverse transcriptase inhibitors may be increased during coadministration with ribavirin. Nucleoside analogs alone and in combination have been associated with these and other toxicities.

MANAGEMENT: Coadministration of ribavirin with zidovudine should generally be avoided. Patients should be advised to promptly seek medical attention if they experience symptoms of toxicity such as nausea, vomiting, abdominal pain/distention, fatigue, infection, unexplained weight loss, tachypnea, dyspnea, motor weakness, numbness, tingling, and pain in hands and feet. Dosage reduction or discontinuation of ribavirin should be considered if worsening toxicities are observed.

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. Taburet AM, Singlas E (1996) "Drug interactions with antiviral drugs." Clin Pharmacokinet, 30, p. 385-401
  4. Vogt MW, Hartshorn KL, Furman PA, et al. (1987) "Ribavirin antagonizes the effect of azidothymidine on HIV replication." Science, 235, p. 1376-9
  5. Lafeuillade A, Hittinger G, Chadapaud S (2001) "Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection." Lancet, 357, p. 280-1
  6. Landau A, Batisse D, Piketty C, Jian R, Kazatchkine MD (2000) "Lack of interference between ribavirin and nucleosidic analogues in HIV/HCV co-infected individuals undergoing concomitant antiretroviral and anti-HCV combination therapy." AIDS, 14, p. 1857-8
  7. 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
  8. Guyader D, Poinsignon Y, Cano Y, Saout L (2002) "Fatal lactic acidosis in a HIV-positive patient treated with interferon and ribavirin for chronic hepatitis C." J Hepatol, 37, p. 289-91
  9. Zylberberg H, Benhamou Y, Lagneaux JL, et al. (2000) "Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report." Gut, 47, p. 694-7
  10. (2003) "Product Information. Copegus (ribavirin)." Roche Laboratories
  11. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  12. Cerner Multum, Inc. "Australian Product Information."
View all 12 references

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Drug and food interactions

Moderate

ribavirin food

Applies to: ribavirin

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of ribavirin. Administration of a single oral dose of ribavirin following a high-fat meal delayed absorption (Tmax was doubled) but increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by up to 70% compared to administration in the fasting state.

MANAGEMENT: To ensure maximal oral absorption, ribavirin should be administered with or immediately after a meal.

References

  1. (2003) "Product Information. Copegus (ribavirin)." Roche Laboratories
  2. (2004) "Product Information. Rebetol (ribavirin)." Schering-Plough Corporation

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Minor

zidovudine food

Applies to: 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.

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