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Drug Interactions between ivosidenib and voriconazole

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

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Interactions between your drugs

Major

voriconazole ivosidenib

Applies to: voriconazole and ivosidenib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ivosidenib, which is primarily metabolized by the isoenzyme. When a single 250 mg dose of ivosidenib was administered with the potent CYP450 3A4 inhibitor 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). 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 ivosidenib may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4, including many of the known potent inhibitors of the isoenzyme such as clarithromycin, conivaptan, delavirdine, idelalisib, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and all protease inhibitors. Ivosidenib is an inducer of CYP450 3A4 and induces its own metabolism following multiple dosing.

MANAGEMENT: Concomitant use of ivosidenib with potent CYP450 3A4 inhibitors, particularly those that are also substrates of CYP450 3A4, should generally be avoided. If coadministration is required, a reduction of the ivosidenib dosage to 250 mg once daily is recommended. Following discontinuation of the potent inhibitor for at least 5 half-lives, ivosidenib therapy should be returned to the recommended dosage of 500 mg once daily. Monitoring of electrocardiograms and electrolytes should be conducted regularly.

References

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

voriconazole food

Applies to: voriconazole

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

References

  1. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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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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