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Drug Interactions between bosentan and Crixivan

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

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Interactions between your drugs

Moderate

indinavir bosentan

Applies to: Crixivan (indinavir) and bosentan

ADJUST DOSE: Coadministration of a protease inhibitor (PI) in combination with bosentan may increase the plasma concentration of bosentan and decrease that of the PI, unless ritonavir is included as a pharmacokinetic booster. Both PIs and bosentan are primarily metabolized by CYP450 3A4. Because PIs are also inhibitors of CYP450 3A4, they can inhibit the metabolic clearance of bosentan. Conversely, bosentan may induce the metabolism of PIs, although the effects are probably not significant in the presence of ritonavir, which is a potent CYP450 3A4 inhibitor.

MANAGEMENT: Protease inhibitors should generally not be used in combination with bosentan unless ritonavir is also added as a pharmacokinetic booster. Dose adjustment of bosentan has been recommended. In patients who are starting bosentan and have been receiving PI therapy for at least 10 days, it has been recommended to start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. When starting PI therapy in patients already on bosentan, it has been recommended to discontinue bosentan for at least 36 hours prior to initiation of PI therapy. After at least 10 days following the initiation of PI therapy, bosentan may be resumed at 62.5 mg once daily or every other day based upon individual tolerability. According to some authorities, use of the fixed combination atazanavir-cobicistat with bosentan is not recommended.

References (11)
  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. (2001) "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical
  5. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  6. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  7. (2005) "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim
  8. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  9. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  10. Cerner Multum, Inc. "Australian Product Information."
  11. (2015) "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb

Drug and food interactions

Moderate

indinavir food

Applies to: Crixivan (indinavir)

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References (3)
  1. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S (1998) "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother, 42, p. 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R (2001) "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol, 41, p. 435-42

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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