Using Package Inserts to Disseminate Information Regarding Drug Interactions Mediated by CYP3A Inhibition: Status and Issues
- VernacularTitle:CYP3A 阻害作用に基づく薬物相互作用の添付文書における注意喚起の現状と課題
- Author:
Yoshiyuki OHNO
1
;
Naomi NAGAI
2
;
Akihiro HISAKA
3
;
Tappei TAKADA
1
Author Information
- Keywords: drug interaction; package inserts; regulatory guideline; CYP3A
- From:Japanese Journal of Drug Informatics 2023;25(1):38-46
- CountryJapan
- Language:Japanese
- Abstract: Objective: In Japan, the Guideline on Drug Interaction for Drug Development and Appropriate Provision of Information (GL) was notified in 2018. In the GL and the associated document, it was determined that package inserts of drugs which need to be categorized as precaution due to the significant degree of drug interactions by CYP3A inhibition should describe possible perpetrator drugs using designated expressions, such as “strong CYP3A inhibitor.” For contraindication, it was decided that all drugs should be described individually. In 2021, as supplementary information to the GL, a list of CYP substrates, inhibitors and inducers, classified based on interaction strength and CYP isoenzymes (i.e., the drug list), was published. In this study, we aimed to survey the information on drug interactions by CYP3A inhibition described in the package inserts based on information in the drug list, and to clarify the status and issues.Methods: The package inserts of 24 substrate drugs of CYP3A with contraindications for itraconazole, a strong CYP3A inhibitor, were examined, and the descriptions of strong, moderate, and other CYP3A inhibitors were studied.Results: The frequencies of contraindication for strong CYP3A inhibitors were cobicistat (75%), grapefruit juice (0%), ritonavir (92%), voriconazole (67%), clarithromycin (50%), ceritinib (0%), and posaconazole (33%). On the other hand, some CYP3A substrate drugs was contraindicated with moderate CYP3A inhibitors but not with these strong CYP3A inhibitors. Furthermore, 19 CYP3A inhibitors, which were not on the drug list published in 2021, were identified as contraindications for co-administration. Majority of these were protease inhibitors, and some have been discontinued or not available in Japan.Conclusion: The findings of this study imply the necessity of organizing scientific description based on the GL strength classification. Moreover, it is important to disseminate the information and precautions for drug interactions provided in the package inserts to medical practice.
