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Drug Interactions between caspofungin and ivosidenib

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

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Interactions between your drugs

Moderate

caspofungin ivosidenib

Applies to: caspofungin and ivosidenib

MONITOR: Coadministration with inducers or mixed inducer/inhibitors of certain metabolic pathways may produce clinically meaningful reductions in the plasma concentrations of caspofungin. This assumption is based on results from regression analyses of patient pharmacokinetic data derived from a small number of patients who were administered the drugs efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone, or carbamazepine prior to and/or concurrently with caspofungin. There are no data from formal drug interaction studies to evaluate these regression analyses, and it is not known which metabolic pathway involved in caspofungin clearance may be inducible.

MANAGEMENT: Caspofungin product labeling recommends that during coadministration with efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone or carbamazepine, an increase in the daily dosage to 70 mg (following the usual 70 mg loading dose) should be considered in patients who are not clinically responding. While data are lacking for other drugs that are known to induce hepatic enzymes, the possibility of a similar interaction should be considered.

References (1)
  1. (2001) "Product Information. Cancidas (caspofungin)." Merck & Co., Inc

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

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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