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Drug Interactions between Crixivan and simeprevir

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

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Interactions between your drugs

Major

indinavir simeprevir

Applies to: Crixivan (indinavir) and simeprevir

GENERALLY AVOID: Coadministration with potent and some moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simeprevir, which is primarily metabolized by the isoenzyme. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions including rash and photosensitivity. In 24 healthy study subjects administered simeprevir (150 mg once daily) in combination with the moderate CYP450 3A4 and P-glycoprotein substrate/inhibitor erythromycin (500 mg three times a day) for 7 days, mean simeprevir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) increased by approximately 4.5-, 7.5 and 12.7-fold, respectively. Erythromycin Cmax, AUC and Cmin also increased by about 1.6-, 1.9- and 3.1-fold, respectively, presumably due to inhibition of CYP450 3A4 and P-glycoprotein by simeprevir. In another study, simeprevir (200 mg once daily for 7 days) given with the potent CYP450 3A4 inhibitor ritonavir (100 mg twice daily for 15 days) to 12 healthy subjects resulted in approximately 4.7-, 7.2 and 14.4-fold increases in simeprevir Cmax, AUC and Cmin, respectively. Likewise, when simeprevir (50 mg and 150 mg once daily) was given with darunavir/ritonavir (800 mg/100 mg once daily) to 25 healthy subjects for 7 days, simeprevir Cmax, AUC and Cmin increased by about 1.8-, 2.6 and 4.6-fold, respectively, while ritonavir Cmax, AUC and Cmin increased by 1.2-, 1.3 and 1.4-fold, respectively. Darunavir Cmin increased by 1.3-fold.

MANAGEMENT: The use of simeprevir in combination with potent and some moderate CYP450 3A4 inhibitors such as azole antifungal agents, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics should generally be avoided. Some authorities recommend avoiding concomitant use of simeprevir during and for 2 weeks after treatment with itraconazole.

References (3)
  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2013) "Product Information. Olysio (simeprevir)." Janssen Pharmaceuticals

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
Moderate

simeprevir food

Applies to: simeprevir

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of simeprevir, although the type of food does not seem to matter. In healthy study subjects, administration of simeprevir after a high-fat, high-caloric (928 kcal) breakfast increased systemic exposure (AUC) by 61% and delayed absorption by 1 hour, while administration after a normal caloric (533 kcal) breakfast increased AUC by 69% and delayed absorption by 1.5 hours.

MANAGEMENT: To ensure maximal oral absorption, simeprevir should be administered with food.

References (1)
  1. (2013) "Product Information. Olysio (simeprevir)." Janssen Pharmaceuticals

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Protease inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'protease inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'protease inhibitors' category:

  • Crixivan (indinavir)
  • simeprevir

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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