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Drug Interactions between Evotaz and venetoclax

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

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Interactions between your drugs

Major

atazanavir venetoclax

Applies to: Evotaz (atazanavir / cobicistat) and venetoclax

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of venetoclax, which is a substrate of the isoenzyme. In 11 previously treated non-Hodgkin's lymphoma patients, venetoclax peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.3- and 6.4-fold, respectively, when coadministered with 400 mg once daily for 7 days of ketoconazole, a potent CYP450 3A4 inhibitor that also inhibits P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Concomitant use of venetoclax with moderate CYP450 3A4 inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends that venetoclax dosage be reduced by at least 50%. The dosage used prior to initiating the CYP450 3A4 inhibitor may be resumed 2 to 3 days after discontinuation of the inhibitor.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Venclexta (venetoclax)." AbbVie US LLC (2016):

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Major

cobicistat venetoclax

Applies to: Evotaz (atazanavir / cobicistat) and venetoclax

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of venetoclax, which is primarily metabolized by the isoenzyme. In 11 previously treated non-Hodgkin's lymphoma patients, venetoclax peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.3- and 6.4-fold, respectively, when coadministered with 400 mg once daily for 7 days of ketoconazole, a potent CYP450 3A4 inhibitor. Additionally, inhibition of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporters by ketoconazole may contribute. Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Concomitant use of potent CYP450 3A4 inhibitors at initiation and during the dosage ramp-up phase of venetoclax is considered contraindicated. If a potent CYP450 3A4 inhibitor is required after the ramp-up phase, the manufacturer recommends that venetoclax dosage be reduced by at least 75%. The dosage used prior to initiating the CYP450 3A4 inhibitor may be resumed 2 to 3 days after discontinuation of the inhibitor.

References

  1. "Product Information. Venclexta (venetoclax)." AbbVie US LLC (2016):

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Drug and food interactions

Major

venetoclax food

Applies to: venetoclax

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of venetoclax. Relative to fasting conditions, venetoclax systemic exposure (AUC) increased by approximately 3.4-fold when administered with a low-fat meal and by 5.1- to 5.3-fold when administered with a high-fat meal.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of venetoclax. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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 venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Venetoclax should be administered with a meal and water at approximately the same time each day. Patients should avoid consumption of grapefruit products, Seville oranges, and starfruit during treatment with venetoclax.

References

  1. "Product Information. Venclexta (venetoclax)." AbbVie US LLC (2016):

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Moderate

atazanavir food

Applies to: Evotaz (atazanavir / cobicistat)

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):

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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

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