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Drug Interactions between doravirine and ivosidenib

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

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Interactions between your drugs

Moderate

ivosidenib doravirine

Applies to: ivosidenib and doravirine

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. In 10 study subjects, administration of a single 100 mg dose of doravirine with the potent CYP450 3A4 inducer rifampin (600 mg once daily) decreased doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) by an average of 57%, 88% and 97%, respectively, compared to administration of doravirine alone. When doravirine was administered with rifabutin 300 mg once daily in 12 study subjects, doravirine Cmax did not change, but AUC and C24hr decreased by an average of 50% and 68%, respectively. When doravirine 100 mg once daily was initiated following cessation of treatment with efavirenz 600 mg once daily in 17 study subjects, doravirine Cmax, AUC and C24hr decreased by an average of 35%, 62% and 85%, respectively, on the first day and 14%, 32% and 50%, respectively, 14 days later. The extent to which other, less potent CYP450 3A4 inducers may affect doravirine is unknown.

MANAGEMENT: The potential for diminished pharmacologic effects of doravirine should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

References

  1. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
  2. (2018) "Product Information. Pifeltro (doravirine)." Merck & Co., Inc

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Drug and food interactions

Major

ivosidenib food

Applies to: ivosidenib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivosidenib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. Pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, itraconazole, and the moderate inhibitor, fluconazole. When a single 250 mg dose of ivosidenib was administered with itraconazole 200 mg once daily for 18 days, ivosidenib systemic exposure (AUC) increased to 269% of control, with no change in peak plasma concentration (Cmax). Based on physiologically-based pharmacokinetic modeling, coadministration of a 500 mg dose of ivosidenib with fluconazole (dosed to steady-state) is predicted to increase ivosidenib single-dose AUC to 173% of control, while multiple-dosing of both is predicted to increase ivosidenib steady-state Cmax and AUC to 152% and 190% of control, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to ivosidenib may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

GENERALLY AVOID: Coadministration with a high-fat meal may increase the plasma concentrations of ivosidenib. According to the product labeling, administration of a single dose with a high-fat meal (approximately 900 to 1000 calories; 500 to 600 calories in fat, 250 calories in carbohydrate, 150 calories in protein) increased ivosidenib Cmax and AUC by 98% and 25%, respectively, in healthy study subjects.

MANAGEMENT: Ivosidenib may be administered with or without food, but should not be administered with a high-fat meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with ivosidenib.

References

  1. (2018) "Product Information. Tibsovo (ivosidenib)." Agios Pharmaceuticals, 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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