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Drug Interactions between Aponvie and indinavir

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

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Interactions between your drugs

Moderate

indinavir aprepitant

Applies to: indinavir and Aponvie (aprepitant)

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of aprepitant, which is primarily metabolized by the isoenzyme. According to the manufacturer, administration of a single 125 mg dose of aprepitant on day 5 of treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 10 days) resulted in a 5-fold increase in mean aprepitant systemic exposure (AUC) and a 3-fold increase in mean terminal half-life. In patients with mild to moderate hypertension, coadministration of aprepitant (approximately 230 mg once a day) and the moderate inhibitor diltiazem (120 mg three times a day for 5 days) resulted in a 2-fold increase in the AUC of aprepitant and a 1.7-fold increase in that of diltiazem. No clinically significant changes in ECG, heart rate, or blood pressure were observed beyond those induced by diltiazem alone.

MANAGEMENT: Caution is advised if aprepitant is prescribed in combination with CYP450 3A4 inhibitors, particularly potent ones like itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, conivaptan, idelalisib, nefazodone, telithromycin, cobicistat, delavirdine, and protease inhibitors. Pharmacologic response to aprepitant should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. In addition, many CYP450 3A4 inhibitors are also substrates of the isoenzyme, thus pharmacologic response to these agents should also be monitored during coadministration with aprepitant.

References

  1. (2003) "Product Information. Emend (aprepitant)." Merck & Co., Inc
  2. (2008) "Product Information. Emend for Injection (fosaprepitant)." Merck & Co., Inc

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Drug and food interactions

Moderate

indinavir food

Applies to: 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

  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

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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

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

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