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Drug Interactions between glasdegib and Tikosyn

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

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Interactions between your drugs

Major

dofetilide glasdegib

Applies to: Tikosyn (dofetilide) and glasdegib

GENERALLY AVOID: Like other class III antiarrhythmic agents, dofetilide can cause dose-related QT interval prolongation. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of dofetilide with other drugs that can prolong the QT interval has not been studied and is not recommended.

References

  1. (2001) "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  4. Cerner Multum, Inc. "Australian Product Information."
View all 4 references

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Drug and food interactions

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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Minor

dofetilide food

Applies to: Tikosyn (dofetilide)

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.

References

  1. (2001) "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals

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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.