Overview

Abiraterone is an androgen hormone antagonist that helps to reduce the level of testosterone and other androgen hormone in the blood.¹ It is indicated with prednisone or prednisolone for treatment of prostate cancer.

From in vitro studies, abiraterone demonstrated a strong inhibition of CYP1A2, CYP2C8 and CYP2D6 character.² For enzyme CYP2C9, CYP2C19 and CYP3A4/5, the inhibition ability is moderate. For example, antidiabetic drugs like pioglitazone and repaglinide are metabolized in the liver through enzyme CYP2C8. Due to the strong inhibition character of abiraterone, when pioglitazone/repaglinide administered together with abiraterone, interaction can happen and resulted in hypoglycaemia.

Due to lack of evidence like rechallenge/dechallenge positive cases, disproportionate reporting and in vivo or clinical data, at this moment, the interaction is inconclusive for other antidiabetic drugs or other class of drugs.

Currently, there are four (4) products containing abiraterone registered in Malaysia.

Background of Safety Issue

Based on the cases of hypoglycaemia (interaction with pioglitazone/repaglinide) received and evidence from literature, the Pharmacovigilance Risk Assessment Committee (PRAC), European Medicines Agency (EMA) has requested the product registration holders of abiraterone to update package insert with this risk.³

Adverse Drug Reaction Reports

The NPRA has received a total of 202 reports with 291 adverse events suspected to be related to abiraterone containing products.⁴ To date, no ADR related to hypoglycaemia due to drug interaction following the use of abiraterone has been reported to the NPRA.

Advice for Healthcare Professionals

• Be alert on the risk of hypoglycaemia due to drug interaction following the concurrent use of abiraterone and pioglitazone/repaglinide products.
• Drugs with low risk of drug interaction or antidiabetic drugs with low risk of hypoglycaemia should be preferred in patients taking abiraterone.
• Report all suspected adverse events associated with abiraterone containing products to the NPRA.

In Malaysia, NPRA has completed a review of this safety issue and a directive [Ruj. Kami: NPRA.600-1/9/13 (12)] has been issued for registration holders of abiraterone products to update the local package inserts to reflect this safety information.

References:

1. National Pharmaceutical Regulatory Agency. Malaysian Product Registration Database (Quest 3+). Abiraterone acetate 250 mg tablet local package insert [Internet]. Last revision date: 2019 July [Cited 2020 September 10]. Available from https://npra.gov.my
2. Tucci M, Roca E, Ferrari L, Pia A, Dalla Volta A, Bedussi F, Buttigliero C, Scagliotti GV, Sigala S, Berruti A. Abiraterone and prednisone therapy may cause severe hypoglycemia when administered to prostate cancer patients with type 2 diabetes receiving glucose-lowering agents [Internet]. Endocrine. 2019 June [Cited 2020 September 10];64(3):724-6.
3. PRAC Recommendations on Signals. Recommendations for update of the product information. 2020 February 10 [Cited 2020 Septermber 10]. EMA/PRAC/8637/2020
4. National Pharmaceutical Regulatory Agency. The Malaysian National ADR Database [Internet]. 2021 [Cited 2020 September 10]. Available from: https://npra.gov.my

DISCLAIMER

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.