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Drug Interactions between darunavir and rifabutin

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

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Interactions between your drugs

Moderate

rifabutin darunavir

Applies to: rifabutin and darunavir

ADJUST DOSE: Coadministration of rifabutin and darunavir/ritonavir is expected to increase the plasma concentrations of rifabutin and decrease the plasma concentrations of darunavir. The proposed mechanism involves ritonavir inhibition of rifabutin metabolism via CYP450 3A4 and, conversely, rifabutin induction of darunavir metabolism via the same isoenzyme. Although the interaction has not been studied specifically with darunavir/ritonavir, it has been observed with other protease inhibitors, resulting in increased systemic exposure (AUC) of rifabutin by 110% to 300% and that of its 25-O-desacetyl metabolite by 13- to 35-fold. Uveitis secondary to rifabutin toxicity has been reported in some cases. The effect of rifabutin on protease inhibitors may vary. Rifabutin had negligible effects on some protease inhibitors but reduced the AUC of others such as indinavir, nelfinavir, and saquinavir by 30% to nearly 50%.

MANAGEMENT: To minimize the risk of rifabutin toxicity including leukopenia, uveitis, arthralgias and skin discoloration, darunavir labeling recommends that rifabutin dosage be reduced to 150 mg every other day in patients treated with darunavir/ritonavir. A complete blood count should be performed at least weekly and as clinically indicated to monitor for development of neutropenia.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  2. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  3. Gariano RF, Gooney EL (1997) "Uveitis following administration of the protease inhibitor indinavir to a patient with AIDS." Clin Infect Dis, 24, p. 529
  4. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  5. Cato A, Cavanaugh J, Shi H, Hsu A, Leonard J, Granneman R (1998) "The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin." Clin Pharmacol Ther, 63, p. 414-21
  6. Fournier S, Deplus S, Janier M, Poinsignon Y, Decazes JM, Modai J (1998) "Anterior uveitis in 3 HIV-infected patients treated with antiprotease." Presse Med, 27, p. 844-8
  7. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  8. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  9. Polk RE, Brophy DF, Israel DS, Patron R, Sadler BM, Chittick GE, Symonds WT, Lou Y, Kristoff D, Stein DS (2001) "Pharmacokinetic interaction between amprenavir and rifabutin or rifampin in healthy males." Antimicrob Agents Chemother, 45, p. 502-8
  10. Burman WJ, Jones BE (2001) "Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy." Am J Respir Crit Care Med, 164, p. 7-12
  11. (2000) "Notice to readers: updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibiotrs." MMWR Morb Mortal Wkly Rep, 49, p. 185-9
  12. Moyle GJ, Buss NE, Goggin T, Snell P, Higgs C, Hawkins DA (2002) "Interaction between saquinavir soft-gel and rifabutin in patients infected with HIV." Br J Clin Pharmacol, 54, p. 178-82
  13. Hamzeh FM, Benson C, Gerber J, et al. (2003) "Steady-state pharmacokinetic interaction of modified-dose indinavir and rifabutin." Clin Pharmacol Ther, 73, p. 159-69
  14. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  15. American Thoracic Society, CDC, Infectious Diseases Society of America (2003) "Treatment of tuberculosis." MMWR Morb Mortal Wkly Rep, 52(RR-11), p. 1-77
  16. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  17. (2005) "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim
  18. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
View all 18 references

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Drug and food interactions

Moderate

darunavir food

Applies to: darunavir

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References

  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc

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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.

See also

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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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