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Drug Interactions between darunavir and rifapentine

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

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Interactions between your drugs

Major

rifapentine darunavir

Applies to: rifapentine and darunavir

GENERALLY AVOID: Coadministration with rifapentine may decrease the plasma concentrations and antiretroviral effects of protease inhibitors. The mechanism is rifapentine induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of protease inhibitors. In one study, rifapentine (600 mg) was given twice weekly for 14 days followed by rifapentine (600 mg) twice weekly with indinavir (800 mg) 3 times daily for 14 days. Indinavir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 55% and 70%, respectively, while rifapentine pharmacokinetics were unaffected. No data are available concerning the use of rifapentine with other protease inhibitors.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, the use of rifapentine should be avoided in patients receiving protease inhibitors.

References

  1. (2001) "Product Information. Invirase (saquinavir)." Roche Laboratories
  2. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  3. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  4. Barry M, Gibbons S, Back D, Mulcahy F (1997) "Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations." Clin Pharmacokinet, 32, p. 194-209
  5. (2001) "Product Information. Priftin (rifapentine)." Hoechst Marion Roussel
  6. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  7. Acosta EP, Henry K, Baken L, Page LM, Fletcher CV (1999) "Indinavir concentrations and antiviral effect." Pharmacotherapy, 19, p. 708-12
  8. Temple ME, Nahata MC (1999) "Rifapentine: its role in the treatment of tuberculosis." Ann Pharmacother, 33, p. 1203-10
  9. Sommadossi JP (1999) "HIV protease inhibitors: pharmacologic and metabolic distinctions." AIDS, 13, s29-40
  10. Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, DelGiudice P, Montagne N, Schapiro JM, Dellamonica P (2000) "Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study." Aids, 14, p. 1333-9
  11. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  12. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  13. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  14. (2005) "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim
  15. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  16. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  17. (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
  18. (2021) "Product Information. Priftin (rifapentine)." sanofi-aventis
  19. Macleods Pharmaceuticals Limited (2024) Rifapentine 300 mg tablets (Macleods Pharmaceuticals Ltd), TB398. WHO-PQ recommended summary of product characteristics. https://extranet.who.int/prequal/sites/default/files/whopar_files/TB398part4v1.pdf
  20. Dooley KE, Bliven-Sizemore EE, Weiner M, et al. (2012) "Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers." Clin Pharmacol Ther, 91, p. 881-8
View all 20 references

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Drug and food interactions

Moderate

rifapentine food

Applies to: rifapentine

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.

References

  1. (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
  2. (2021) "Product Information. Priftin (rifapentine)." sanofi-aventis

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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.

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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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