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Drug Interactions between stavudine and Virazole

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

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Interactions between your drugs

Moderate

ribavirin stavudine

Applies to: Virazole (ribavirin) and stavudine

MONITOR: Ribavirin, a nucleoside analog, has been shown to antagonize the in vitro antiviral activity of stavudine against HIV. The mechanism is feedback inhibition of thymidine kinase induced by ribavirin, resulting in decreased intracellular phosphorylation of stavudine 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 stavudine 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 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 stavudine should be undertaken with caution and only if the benefit is anticipated to outweigh the potential risks. 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
View all 10 references

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Drug and food interactions

Moderate

ribavirin food

Applies to: Virazole (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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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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