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Drug Interactions between avapritinib and valganciclovir

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

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Interactions between your drugs

Moderate

valGANciclovir avapritinib

Applies to: valganciclovir and avapritinib

GENERALLY AVOID: The use of ganciclovir or its prodrug, valganciclovir, with other drugs associated with myelosuppression and/or nephrotoxicity may increase the risk and severity of these adverse reactions due to additive effects on the kidney and bone marrow. Valganciclovir is rapidly and extensively converted to ganciclovir, which has had the following adverse reactions observed with its treatment when used alone: severe leucopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow depression, aplastic anemia, increased serum creatinine levels, and acute renal failure. Additionally, ganciclovir is primarily renally excreted; therefore, patients with impaired renal function will have increased concentrations of ganciclovir and may be at an even greater risk of experiencing adverse reactions from treatment. Theoretically when two or more medications with similar side effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased.

MANAGEMENT: Ganciclovir or its prodrug, valganciclovir, should generally not be combined with other drugs associated with myelosuppression and/or nephrotoxicity unless the benefits are anticipated to outweigh the potential risks. Extreme caution is advised if they are used in patients who have recently received or are receiving treatment with myelotoxic and/or nephrotoxic drugs, and vice versa. If coadministration is required, reduced dosages of one or more of the drugs may be required, and the patient should be monitored for the development of hematologic and/or renal adverse effects both during and after discontinuation of therapy.

References

  1. (2002) "Product Information. Cytovene (ganciclovir)." Genentech
  2. (2001) "Product Information. Valcyte (valganciclovir)." Roche Laboratories
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
View all 4 references

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Drug and food interactions

Major

avapritinib food

Applies to: avapritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avapritinib. 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. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. Based on pharmacokinetic modeling, administration of avapritinib (300 mg once daily) in combination with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 600% at steady state, while administration with the moderate CYP450 3A4 inhibitor fluconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 210% at steady state. 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 avapritinib may increase the risk and/or severity of serious adverse effects such as intracranial hemorrhage, cognitive impairment, mood disorders, hallucinations, edema, and decreases in hemoglobin, leukocytes, neutrophils, and platelets.

ADJUST DOSING INTERVAL: Food may increase the oral absorption of avapritinib. When avapritinib was administered with a high-calorie, high-fat meal (approximately 909 calories; 58 g carbohydrate, 56 g fat, 43 g protein), avapritinib Cmax and AUC increased by 59% and 29%, respectively, compared to administration in the fasted state.

MANAGEMENT: Avapritinib should be administered on an empty stomach at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with avapritinib.

References

  1. (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation

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Moderate

valGANciclovir food

Applies to: valganciclovir

ADJUST DOSING INTERVAL: Food increases the bioavailability of ganciclovir from the prodrug, valganciclovir. In 16 HIV-positive subjects, the administration of valganciclovir 875 mg once daily with a high-fat meal containing approximately 600 calories resulted in a 30% increase in the steady-state area under the plasma concentration-time curve (AUC) and a 14% increase in the peak plasma concentration (Cmax) of ganciclovir, with no delay in the time to reach peak plasma concentration (Tmax). The mechanism is unknown.

MANAGEMENT: The manufacturer recommends that valganciclovir be taken with meals.

References

  1. (2001) "Product Information. Valcyte (valganciclovir)." Roche Laboratories
  2. Brown F, Banken L, Saywell K, Arum I (1999) "Pharmacokinetics of valganciclovir and ganciclovir following multiple oral dosages of valganciclovir in HIV- and CMV-seropositiv volunteers." Clin Pharmacokinet, 37, p. 167-76

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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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