Evaluation of the Effectiveness of Additional Risk Minimization Measures for Voriconazole in the EU: Findings and Lessons Learned from a Healthcare Professional Survey

• Published in: Pharmaceutical medicine Vol. 33; no. 2; pp. 121 - 133
• Main Authors: Lem, Joanna, Younus, Muhammad, Aram, Jalal A., Moosavi, Shahrzad, Freivogel, Klaus, Lewis, Anne, Sobel, Rachel E.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2019; Springer Nature B.V
• Subjects: Antifungal agents; Antifungal Agents - adverse effects; Antifungal Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Blood diseases; Brochures; Carcinoma, Squamous Cell - chemically induced; Checklist; Chemical and Drug Induced Liver Injury; Cross-Sectional Studies; Dermatitis, Phototoxic - complications; Drug-Related Side Effects and Adverse Reactions; European Union - organization & administration; Fungal infections; Health Care Surveys - methods; Health Personnel - statistics & numerical data; Humans; International organizations; Invasive Pulmonary Aspergillosis - drug therapy; Knowledge; Mycoses - drug therapy; Original Research Article; Patients; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacotherapy; Pharmacovigilance; Physicians; Polls & surveys; Response rates; Risk Reduction Behavior; Self Report; Skin cancer; Skin Neoplasms - pathology; Squamous cell carcinoma; Transplants & implants; Voriconazole - adverse effects; Voriconazole - therapeutic use
• ISSN: 1178-2595; 1179-1993
• DOI: 10.1007/s40290-019-00273-4

Background Voriconazole is an extended-spectrum antifungal agent approved for the treatment and prophylaxis of invasive aspergillosis and other serious fungal infections. In 2014, additional risk minimization measures (aRMM) consisting of a Healthcare Professional (HCP) Question and Answer (Q&A) Brochure, HCP Checklist, and Patient Alert Card were implemented on a rolling basis across the European Union (EU) to mitigate three key risks with voriconazole: phototoxicity, squamous cell carcinoma (SCC) of the skin, and hepatotoxicity. The risks of phototoxicity and hepatotoxicity have been documented in the Summary of Product Characteristics (SmPC) since voriconazole was first approved in the EU in 2002. However, the risk of SCC of the skin was a more recent addition to the SmPC (added in 2010). Objectives We evaluated the effectiveness of the aRMM, as per EU Good Pharmacovigilance Practices Module XVI, via a survey of HCPs. Methods An online survey was conducted among specialty care HCPs in 10 EU countries who had received by mail aRMM tools 12 months previously. Survey questions evaluated HCPs’ receipt and utilization of aRMM tools, and knowledge of the three risks. Results Of 27,396 HCPs invited to participate, 332 eligible respondents completed the survey (response rate: 447/26,735; 1.7%). In total, 19.6% of respondents recalled receiving the HCP Q&A Brochure, 22.6% the HCP Checklist, and 25.9% the Patient Alert Card. HCPs had a high level of knowledge of phototoxicity and hepatotoxicity; however, knowledge of SCC was lower. Knowledge of the three risks and self-reported risk minimization behavior was slightly improved in those who had read the HCP Q&A Brochure compared with those who had not. Conclusion The effectiveness of the voriconazole aRMM cannot be meaningfully inferred from the results due to the low survey response rate. The assessment indirectly points to the SmPC or other resources being the main source of risk information for HCPs. Engaging HCPs before designing and implementing an aRMM program is crucial to ensure an effective and focused program. (EU PAS registration number: EUPAS12624).