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Drug Interactions between Envarsus XR and Victrelis

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

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Interactions between your drugs

Major

tacrolimus boceprevir

Applies to: Envarsus XR (tacrolimus) and Victrelis (boceprevir)

ADJUST DOSE: Coadministration with the hepatitis C virus (HCV) NS3/4A protease inhibitors, boceprevir and telaprevir, may significantly increase the plasma concentrations of tacrolimus. The proposed mechanism is inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme responsible for the metabolic clearance of tacrolimus. Enhanced tacrolimus oral bioavailability due to inhibition of intestinal P-glycoprotein efflux transporter may also contribute. In 9 study subjects, administration of a single 0.5 mg dose of tacrolimus during treatment with telaprevir 750 mg every 8 hours for 11 days increased the tacrolimus peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 2.3- and 17.6-fold, respectively, compared to administration of a single 2 mg dose of tacrolimus alone. Adjusted for dose, tacrolimus Cmax and AUC increased by 9.4- and 70.3-fold, respectively, during coadministration with telaprevir. When a single 0.5 mg dose of tacrolimus was coadministered with boceprevir 800 mg three times a day for 7 days, tacrolimus Cmax increased by 9.9-fold and AUC increased by 17.1-fold. Clinically, these changes may result in an increased risk of nephro- and neurotoxicity, as well as other adverse effects associated with tacrolimus such as malignancies, infections, diabetes, hyperkalemia, hypertension, and QT prolongation. Tacrolimus had no effect on the pharmacokinetics of boceprevir.

MANAGEMENT: Caution is advised when tacrolimus is used with boceprevir or telaprevir. Dosage reduction and/or prolongation of the dosing interval for tacrolimus will likely be required. Tacrolimus blood levels and renal function should be checked frequently and the dosage adjusted accordingly, particularly following initiation or discontinuation of the HCV NS3/4A protease inhibitor. Patients should be advised to seek medical attention if they experience adverse effects such as fever, infection, diarrhea, tremor, decreased urination, headache, paraesthesia, seizures, and changes in motor function, mental status, or sensory function. Some authorities recommend against the use of telaprevir in organ transplant candidates or patients.

References

  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2011) "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation
  3. (2011) "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals

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Drug and food interactions

Moderate

tacrolimus food

Applies to: Envarsus XR (tacrolimus)

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

References

  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11

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Moderate

boceprevir food

Applies to: Victrelis (boceprevir)

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.

References

  1. (2011) "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation

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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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