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Drug Interactions between ibrutinib and valganciclovir

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

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Interactions between your drugs

Moderate

valGANciclovir ibrutinib

Applies to: valganciclovir and ibrutinib

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 (4)
  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."

Drug and food interactions

Major

ibrutinib food

Applies to: ibrutinib

GENERALLY AVOID: Coadministration with grapefruit, grapefruit juice, or Seville oranges may significantly increase the plasma concentrations of ibrutinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Pharmacokinetic modeling suggests that other moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase ibrutinib systemic exposure (AUC) by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ibrutinib. The mechanism of interaction is unknown. According to the product labeling, administration with food increases ibrutinib exposure approximately 2-fold compared to administration after overnight fasting.

MANAGEMENT: Patients treated with ibrutinib should avoid consumption of Seville oranges, grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ibrutinib should be taken once daily at approximately the same time each day.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Imbruvica (ibrutinib)." Pharmacyclics Inc
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 (2)
  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

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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