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Drug Interactions between midazolam and Olysio

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

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Interactions between your drugs

Moderate

midazolam simeprevir

Applies to: midazolam and Olysio (simeprevir)

MONITOR: Coadministration with simeprevir may increase the plasma concentrations of oral midazolam and triazolam, which are primarily metabolized by CYP450 3A4. In vivo, simeprevir mildly inhibits intestinal CYP450 3A4, but does not affect hepatic CYP450 3A4 activity. In 16 healthy study subjects, administration of a single 0.075 mg/kg oral dose of midazolam in combination with simeprevir 150 mg once daily for 10 days increased mean midazolam peak plasma concentration (Cmax) by 31% and systemic exposure (AUC) by 45% compared to midazolam administered alone. In contrast, when a single 0.025 mg/kg dose of midazolam was given intravenously with simeprevir 150 mg once daily for 11 days, mean midazolam Cmax decreased by 22% and AUC increased by 10%. No data are available for triazolam, although it is a known sensitive substrate of CYP450 3A4.

MANAGEMENT: No empiric dosage adjustment is required for oral midazolam or triazolam when prescribed with simeprevir. However, because these agents have a narrow therapeutic index, it may be appropriate to monitor pharmacologic response and drug levels more closely following initiation or discontinuation of simeprevir, and the dosage adjusted if necessary.

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

Drug and food interactions

Moderate

midazolam food

Applies to: midazolam

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References (7)
  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther, 58, p. 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
Moderate

simeprevir food

Applies to: Olysio (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

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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