A clinically relevant decrease in abiraterone exposure associated with carbamazepine use in a patient with castration-resistant metastatic prostate cancer.

Abstract

ADVERSE EVENT:

Decreased abiraterone exposure after introducing carbamazepine.

DRUGS IMPLICATED:

Abiraterone acetate and carbamazepine.

THE PATIENT:

A 65-year-old man with metastatic castration resistant prostate cancer, was treated with abiraterone acetate and prednisolone, and received concomitant carbamazepine for treatment of facial neuropathy.

EVIDENCE THAT LINKS THE DRUG TO THE EVENT:

The interaction was confirmed by a decrease in abiraterone exposure >2-fold (area-under-the-curve and trough levels). After discontinuation of carbamazepine therapy, the abiraterone exposure normalized. No alternative causes were found that explain the decrease in abiraterone exposure.

MECHANISM:

Induction of CYP3A and potentially phase I metabolism (SULT2A1) by carbamazepine.

IMPLICATIONS FOR THERAPY:

Clinicians and pharmacists should be aware of this clinically relevant interaction. The national drug-drug interaction checker does not warn for this interaction, whereas both the Lexicomp® and Micromedex® advice to avoid if possible or to increase the abiraterone dose frequency to twice daily. Carbamazepine should not be combined with abiraterone to avoid underexposure and suboptimal therapy. Therapeutic drug monitoring of abiraterone is useful to guide therapy when drug-drug interactions cannot be avoided.

• Authors: Guillemette E Benoist, Maarten J van der Doelen, Rob Ter Heine, Nielka P van Erp, Niven Mehra
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 84 Issue 5 Pg. 1064-1067 (05 2018) ISSN: 1365-2125 [Electronic] England
• PMID: 29384591 (Publication Type: Case Reports)
• Copyright: © 2018 The British Pharmacological Society.

Chemical References

• Analgesics, Non-Narcotic
• Antineoplastic Agents
• Cytochrome P-450 CYP3A Inducers
• Carbamazepine
• Prednisolone
• Abiraterone Acetate

Topics

• Abiraterone Acetate (blood, pharmacokinetics)
• Aged
• Analgesics, Non-Narcotic (pharmacology, therapeutic use)
• Antineoplastic Agents (blood, pharmacokinetics)
• Carbamazepine (pharmacology, therapeutic use)
• Cytochrome P-450 CYP3A Inducers (pharmacology)
• Drug Interactions
• Facial Nerve Diseases (drug therapy)
• Humans
• Male
• Prednisolone (therapeutic use)
• Prostatic Neoplasms, Castration-Resistant (drug therapy)