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Drug Interactions between abiraterone and Xermelo

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

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Interactions between your drugs

Moderate

abiraterone telotristat ethyl

Applies to: abiraterone and Xermelo (telotristat)

MONITOR: Coadministration with telotristat ethyl may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4 and/or 2B6 isoenzymes. The proposed mechanism is accelerated clearance due to induction of CYP450 3A4 and/or 2B6 (in vitro) isoenzymes by telotristat ethyl. When the probe CYP450 3A4 substrate midazolam (3 mg) was administered orally after 5 days of treatment with telotristat ethyl 500 mg three times daily (twice the recommended dosage), mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 25% and 48%, respectively, compared to administration of midazolam alone. The mean Cmax and AUC of the active metabolite, 1'-hydroxymidazolam, also decreased by 34% and 48%, respectively. This suggests induction by telotristat ethyl of the glucuronidation of 1'-hydroxymidazolam.

MANAGEMENT: When drugs that are known substrates of CYP450 3A4 and/or 2B6 are coadministered with telotristat ethyl, the possibility of a diminished therapeutic response to those drugs should be considered. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs, particularly those with a narrow therapeutic range, whenever telotristat ethyl is added to or withdrawn from therapy.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Xermelo (telotristat ethyl)." Lexicon Pharmaceuticals, Inc. (2017):

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Drug and food interactions

Moderate

abiraterone food

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

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Moderate

telotristat ethyl food

Applies to: Xermelo (telotristat)

ADJUST DOSING INTERVAL: Food increases the systemic exposure to both telotristat ethyl and its active metabolite, telotristat. Following administration of a single 500 mg dose of telotristat ethyl (twice the recommended dose) with a high-fat meal, telotristat ethyl peak plasma concentration (Cmax) and systemic exposure (AUC) were 112% and 264% higher, respectively, compared to administration under fasted conditions. The Cmax and AUC values for telotristat were also increased by 47% and 33%, respectively. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase has been shown to be approximately 29 times higher than that of the parent drug.

MANAGEMENT: Telotristat ethyl should be administered with food.

References

  1. "Product Information. Xermelo (telotristat ethyl)." Lexicon Pharmaceuticals, Inc. (2017):

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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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