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Drug Interactions between Delidose and fostamatinib

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

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Interactions between your drugs

Moderate

estradiol fostamatinib

Applies to: Delidose (estradiol) and fostamatinib

MONITOR: Coadministration with fostamatinib may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme and/or P-glycoprotein (P-gp) transporter. The proposed mechanism is decreased clearance in the intestine and/or liver due to inhibition of CYP450 3A4-mediated metabolism and P-gp-mediated efflux by fostamatinib. According to the product labeling, administration of a single 40 mg dose of the CYP450 3A4 substrate simvastatin with fostamatinib 100 mg twice daily increased simvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by 113% and 64%, respectively. In addition, simvastatin acid Cmax increased by 83% and AUC increased by 64%. When the P-gp substrate digoxin (0.25 mg once daily) was administered with fostamatinib (100 mg twice daily), digoxin Cmax and AUC increased by 70% and 37%, respectively.

MANAGEMENT: Caution is advised when fostamatinib is used concurrently with drugs that are known substrates of CYP450 3A4 and/or P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever fostamatinib is added to or withdrawn from therapy.

References

  1. "Product Information. Tavalisse (fostamatinib)." Rigel Pharmaceuticals (2018):

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Drug and food interactions

Minor

estradiol food

Applies to: Delidose (estradiol)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

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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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