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Drug Interactions between cladribine and glasdegib

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

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Interactions between your drugs

Moderate

cladribine glasdegib

Applies to: cladribine and glasdegib

MONITOR: Coadministration with glasdegib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) efflux transporters. In vitro data suggest that glasdegib may have the potential to inhibit P-gp (in the gastrointestinal (GI) tract) and BCRP (systemically and in the GI tract) at clinically relevant concentrations, which may result in decreased clearance of concomitantly administered P-gp and BCRP substrates. The clinical relevance is unknown.

MANAGEMENT: Caution is advised if glasdegib is coadministered with drugs that are substrates of P-gp and/or BCRP, particularly those with a narrow therapeutic range. Clinical and laboratory monitoring should be considered whenever glasdegib is added to or withdrawn from therapy with these drugs, and dosages adjusted as necessary. Patients should be monitored for the development of adverse effects.

References

  1. (2023) "Product Information. Daurismo (glasdegib)." Pfizer U.S. Pharmaceuticals Group
  2. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Ltd
  3. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Canada ULC

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Drug and food interactions

Moderate

cladribine food

Applies to: cladribine

ADJUST DOSING INTERVAL: Oral cladribine may increase the bioavailability of other drugs, which may increase the risk or severity of adverse reactions. Cladribine tablets may contain hydroxypropyl betadex, which could form a complex with the active ingredients of other drugs, especially agents with low solubility. The clinical relevance of this interaction remains unknown.

MANAGEMENT: Administration of oral cladribine should be separated from any other oral drug by at least 3 hours.

References

  1. (2001) "Product Information. Leustatin (cladribine)." Ortho Biotech Inc
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."

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Moderate

glasdegib food

Applies to: glasdegib

GENERALLY AVOID: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of glasdegib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. When glasdegib was coadministered with ketoconazole, a potent CYP450 3A4 inhibitor, glasdegib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.4- and 2.4-fold, respectively, compared to administration of glasdegib alone. The interaction has not been studied with other, less potent CYP450 3A4 inhibitors. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

When administered with a high-fat, high-calorie meal (800 to 1000 total calories, 500 to 600 fat calories, 250 carbohydrate calories, and 150 protein calories), glasdegib Cmax and AUC decreased by 31% and 16%, respectively.

MANAGEMENT: Glasdegib may be administered with or without food. Coadministration of grapefruit or grapefruit juice with glasdegib should preferably be avoided.

References

  1. (2023) "Product Information. Daurismo (glasdegib)." Pfizer U.S. Pharmaceuticals Group
  2. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Ltd
  3. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Canada ULC

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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.

See also

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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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