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Drug Interactions between axitinib and Robimycin

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

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Interactions between your drugs

Major

erythromycin axitinib

Applies to: Robimycin (erythromycin) and axitinib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of axitinib, which is primarily metabolized by the isoenzyme. In 32 healthy volunteers, administration of a single 5 mg dose of axitinib on day 4 of treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 7 days) resulted in a 1.5-fold increase in mean axitinib peak plasma concentration (Cmax) and 2-fold increase in mean systemic exposure (AUC) compared to administration of axitinib alone. The mean plasma half-life of axitinib also increased from 9.4 hours when given alone to 13.1 hours in the presence of ketoconazole. The combination was well tolerated by study subjects. Most treatment-related adverse events were mild in severity, with headache and nausea reported most frequently. No clinically significant effects on blood pressure were observed for single-dose axitinib plus ketoconazole relative to axitinib alone.

MANAGEMENT: Concomitant use of axitinib with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of axitinib during and for 2 weeks after treatment with itraconazole. Alternative agents with no or minimal CYP450 3A4 inhibition potential are recommended whenever possible. Should concomitant treatment with a potent inhibitor be required, the manufacturer recommends that axitinib dosage be reduced by approximately one-half, as this is predicted to adjust the axitinib systemic exposure (AUC) to the range observed without inhibitors; however, clinical data are lacking. Subsequent dosage adjustments can be made according to individual therapeutic response and tolerability. Following discontinuation of the potent CYP450 3A4 inhibitor, the axitinib dosage should be returned (after 3 to 5 half-lives of the inhibitor) to that used prior to initiation of the inhibitor.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Inlyta (axitinib)." Pfizer U.S. Pharmaceuticals Group (2012):
View all 4 references

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Drug and food interactions

Moderate

erythromycin food

Applies to: Robimycin (erythromycin)

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

References

  1. Welling PG, Huang H, Hewitt PF, Lyons LL "Bioavailability of erythromycin stearate: influence of food and fluid volume." J Pharm Sci 67 (1978): 764-6
  2. Welling PG, Elliott RL, Pitterle ME, et al. "Plasma levels following single and repeated doses of erythromycin estolate and erythromycin stearate." J Pharm Sci 68 (1979): 150-5
  3. Welling PG "Influence of food and diet on gastrointestinal drug absorption: a review." J Pharmacokinet Biopharm 5 (1977): 291-334
  4. Coyne TC, Shum S, Chun AH, Jeansonne L, Shirkey HC "Bioavailability of erythromycin ethylsuccinate in pediatric patients." J Clin Pharmacol 18 (1978): 194-202
  5. Malmborg AS "Effect of food on absorption of erythromycin. A study of two derivatives, the stearate and the base." J Antimicrob Chemother 5 (1979): 591-9
  6. Randinitis EJ, Sedman AJ, Welling PG, Kinkel AW "Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation." J Clin Pharmacol 29 (1989): 79-84
  7. Kanazawa S, Ohkubo T, Sugawara K "The effects of grapefruit juice on the pharmacokinetics of erythromycin." Eur J Clin Pharmacol 56 (2001): 799-803
View all 7 references

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Moderate

axitinib food

Applies to: axitinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Axitinib may be administered with or without food.

References

  1. "Product Information. Inlyta (axitinib)." Pfizer U.S. Pharmaceuticals Group (2012):

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Minor

erythromycin food

Applies to: Robimycin (erythromycin)

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.

References

  1. Morasso MI, Chavez J, Gai MN, Arancibia A "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol 28 (1990): 426-9

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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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