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Drug Interactions between cobimetinib and zidovudine

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

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Interactions between your drugs

Moderate

zidovudine cobimetinib

Applies to: zidovudine and cobimetinib

MONITOR: Coadministration of zidovudine with other bone marrow depressive or cytotoxic agents may increase the risk and/or severity of zidovudine hematologic toxicity. Zidovudine has been associated with hematologic toxicities such as: neutropenia, granulocytopenia and severe anemia that required blood transfusions particularly in patients with advanced HIV disease.

MANAGEMENT: Hematological parameters should be closely monitored. Some authorities recommend dosages of one or both agents may be adjusted if necessary.

References

  1. (2001) "Product Information. Retrovir (zidovudine)." Glaxo Wellcome
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
View all 4 references

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Drug and food interactions

Moderate

cobimetinib food

Applies to: 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."
  2. (2015) "Product Information. Cotellic (cobimetinib)." Genentech

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Minor

zidovudine food

Applies to: zidovudine

Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration. In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast. In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state. In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting. Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected. The clinical significance of these alterations, if any, is unknown. The product labeling states that zidovudine may be taken with or without food.

References

  1. Lotterer E, Ruhnke M, Trautman M, et al. (1991) "Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal." Eur J Clin Pharmacol, 40, p. 305-8
  2. Unadkat JD, Collier AC, Crosby SS, et al. (1990) "Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal." AIDS, 4, p. 229-32
  3. (2001) "Product Information. Retrovir (zidovudine)." Glaxo Wellcome
  4. Sahai J, Gallicano K, Garber G, et al. (1992) "The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients." Br J Clin Pharmacol, 33, p. 657-60
View all 4 references

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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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