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Drug Interactions between fostamatinib and Zytiga

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

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Interactions between your drugs

Moderate

abiraterone fostamatinib

Applies to: Zytiga (abiraterone) and fostamatinib

MONITOR: Coadministration of fostamatinib with inhibitors of CYP450 3A4 may increase exposure to the active metabolite known as R406, the predominant moiety in the systemic circulation following fostamatinib administration. Fostamatinib is metabolized in the gut by alkaline phosphatase to R406, which then undergoes oxidation via CYP450 3A4 and glucuronidation via UGT1A9. In vitro, R406 is also a substrate of the P-glycoprotein (P-gp) efflux transporter. When a single 80 mg dose of fostamatinib (0.53 times the 150 mg dosage) was administered with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 3.5 days), R406 peak plasma concentration (Cmax) and systemic exposure (AUC) increased on average by 37% and 102%, respectively, compared to fostamatinib administered alone. When a single 150 mg dose of fostamatinib was administered with the moderate CYP450 3A4 inhibitor verapamil (80 mg three times daily for 4 days), R406 Cmax and AUC increased on average by 6% and 39%, respectively. Increased exposure to R406 may result in increased risk of adverse effects such as diarrhea, hepatotoxicity, hypertension, and neutropenia. Both ketoconazole and verapamil are also significant inhibitors of P-gp, although the extent to which P-gp inhibition may contribute to the interaction is unknown.

MANAGEMENT: Patients should be monitored for toxicities of fostamatinib during concomitant use of potent or moderate CYP450 3A4 inhibitors or dual CYP450 3A4/P-gp inhibitors, and the fostamatinib dosage adjusted as necessary in accordance with the product labeling.

References

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

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Drug and food interactions

Moderate

abiraterone food

Applies to: Zytiga (abiraterone)

ADJUST DOSING INTERVAL: Food may significantly increase the oral bioavailability of some formulations of abiraterone acetate. Compared to administration in the fasted state, abiraterone peak plasma concentration (Cmax) and systemic exposure (AUC) were approximately 7- and 5-fold higher, respectively, when a single dose of abiraterone acetate was administered with a low-fat meal (7% fat; 300 calories) and approximately 17- and 10-fold higher, respectively, when it was administered with a high-fat meal (57% fat; 825 calories). Given the normal variation in the content and composition of meals, taking abiraterone acetate with meals has the potential to result in increased and highly variable exposures. The safety of these increased exposures during multiple dosing has not been assessed. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, was found to have an approximately 6.5-fold higher Cmax and 4.4-fold higher AUC when a single dose of 500 mg (4 tablets) was administered with a high-fat meal (56% - 60% fat, 900 - 1000 calories) compared to overnight fasting in healthy volunteers. These differences were not considered clinically significant for this formulation.

MANAGEMENT: Some formulations of abiraterone acetate must be taken on an empty stomach. No food should be consumed for at least two hours before and one hour after the abiraterone acetate dose. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, can be taken with or without food. The manufacturer's product labeling should be consulted for specific guidance.

References

  1. (2011) "Product Information. Zytiga (abiraterone)." Centocor Inc
  2. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Biotech, Inc.
  3. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Inc
  4. (2021) "Product Information. Zytiga (abiraterone)." Janssen Biotech, Inc.
  5. (2022) "Product Information. Yonsa (abiraterone)." Sun Pharmaceutical Industries
  6. (2023) "Product Information. Apo-Abiraterone (abiraterone)." Apotex Inc
  7. (2021) "Product Information. Zytiga (abiraterone)." Janssen-Cilag Pty Ltd
  8. (2023) "Product Information. Abiraterone (abiraterone)." Wockhardt UK Ltd
  9. (2023) "Product Information. Yonsa Mpred (abiraterone-methylprednisolone)." Sun Pharma ANZ Pty Ltd
View all 9 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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