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Drug Interactions between atazanavir / cobicistat and Cotellic

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

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Interactions between your drugs

Major

atazanavir cobimetinib

Applies to: atazanavir / cobicistat and Cotellic (cobimetinib)

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of cobimetinib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers given a single 10 mg dose of cobimetinib with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily for 14 days), mean cobimetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.2- and 6.7-fold, respectively, compared to cobimetinib administered alone. The risk and/or severity of adverse effects such as diarrhea, nausea, vomiting, stomatitis, hemorrhage, cardiomyopathy, rash, photosensitivity, retinopathy, retinal vein occlusion, liver enzyme abnormalities, and rhabdomyolysis may be increased.

MANAGEMENT: Concomitant use of cobimetinib with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of cobimetinib during and for 2 weeks after treatment with itraconazole.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Cotellic (cobimetinib)." Genentech (2015):

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Major

cobicistat cobimetinib

Applies to: atazanavir / cobicistat and Cotellic (cobimetinib)

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of cobimetinib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers given a single 10 mg dose of cobimetinib with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily for 14 days), mean cobimetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.2- and 6.7-fold, respectively, compared to cobimetinib administered alone. The risk and/or severity of adverse effects such as diarrhea, nausea, vomiting, stomatitis, hemorrhage, cardiomyopathy, rash, photosensitivity, retinopathy, retinal vein occlusion, liver enzyme abnormalities, and rhabdomyolysis may be increased.

MANAGEMENT: Concomitant use of cobimetinib with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of cobimetinib during and for 2 weeks after treatment with itraconazole.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Cotellic (cobimetinib)." Genentech (2015):

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Drug and food interactions

Moderate

atazanavir food

Applies to: 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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Moderate

cobimetinib food

Applies to: Cotellic (cobimetinib)

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme, such as cobimetinib. However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of cobimetinib. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Cotellic (cobimetinib)." Genentech (2015):

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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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