Shashi Bhushan1, R S Ray2, Jai Prakash3, G N Singh4. 1. National Coordination Centre-Pharmacovigilance Programme of India, Indian Pharmacopoeia Commission, Ministry of Health and Family Welfare, Government of India, Ghaziabad, India. Electronic address: shashg8u@gmail.com. 2. National Coordination Centre-Pharmacovigilance Programme of India, Indian Pharmacopoeia Commission, Ministry of Health and Family Welfare, Government of India, Ghaziabad, India. Electronic address: pharma.ray@gmail.com. 3. National Coordination Centre-Pharmacovigilance Programme of India, Indian Pharmacopoeia Commission, Ministry of Health and Family Welfare, Government of India, Ghaziabad, India. Electronic address: jaiprakash.ipc@gov.in. 4. National Coordination Centre-Pharmacovigilance Programme of India, Indian Pharmacopoeia Commission, Ministry of Health and Family Welfare, Government of India, Ghaziabad, India. Electronic address: drgnsinghipc@gmail.com.
Abstract
PURPOSE: In 2011, France and Germany banned pioglitazone due to a concomitant risk for bladder cancer. There has been continued debate about this topic. Therefore, we present a detailed analysis of data from individual case safety reports of pioglitazone use (PG-ICSRs) associated with bladder cancer reported worldwide and in India. METHODS: Data from PG-ICSRs reported by the National Coordination Centre's Pharmacovigilance Programme of India, as well as over 131 World Health Organization member countries in the Uppsala Monitoring Centre's VigiLyze pharmacovigilance database system, from January 1, 1967, to March 4, 2018, were collected. Comparisons between data from global and Indian PG-ICSRs were made by applying filters such as country, bladder cancer, age group, gender, time period, information component, and data mining. FINDINGS: Among the adverse drug reactions (ADRs) reported with pioglitazone use worldwide, bladder cancer and related terms were the most highly reported (43%). The most frequently co-reported concurrently used drug was metformin, which was included in 25% and 40% of overall and bladder cancer-specific PG-ICSRs, respectively. Suspected bladder cancer-specific pioglitazone-related reactions were reported in 27 countries, with 8548 serious and 1858 fatal cases and an information components value of 9.15. The Americas had the highest relative percentage of suspected bladder cancer in PG-ICSRs (53%), while the prevalence was much lower in India (2%). In both cohorts, men over the age of 45 years constituted the most highly reported population. IMPLICATIONS: India has a very low prevalence of reported overall and bladder cancer-specific pioglitazone-related ADRs compared to Europe and the Americas. Possible explanations for the difference in reporting rates include variance in genetic makeup, low BC risk factor, pioglitazone prescription at a lower therapeutic dose, greater use of chemopreventive spices in the diet, higher frequency of metformin as a concurrent drug, and under-reporting of ADRs.
PURPOSE: In 2011, France and Germany banned pioglitazone due to a concomitant risk for bladder cancer. There has been continued debate about this topic. Therefore, we present a detailed analysis of data from individual case safety reports of pioglitazone use (PG-ICSRs) associated with bladder cancer reported worldwide and in India. METHODS: Data from PG-ICSRs reported by the National Coordination Centre's Pharmacovigilance Programme of India, as well as over 131 World Health Organization member countries in the Uppsala Monitoring Centre's VigiLyze pharmacovigilance database system, from January 1, 1967, to March 4, 2018, were collected. Comparisons between data from global and Indian PG-ICSRs were made by applying filters such as country, bladder cancer, age group, gender, time period, information component, and data mining. FINDINGS: Among the adverse drug reactions (ADRs) reported with pioglitazone use worldwide, bladder cancer and related terms were the most highly reported (43%). The most frequently co-reported concurrently used drug was metformin, which was included in 25% and 40% of overall and bladder cancer-specific PG-ICSRs, respectively. Suspected bladder cancer-specific pioglitazone-related reactions were reported in 27 countries, with 8548 serious and 1858 fatal cases and an information components value of 9.15. The Americas had the highest relative percentage of suspected bladder cancer in PG-ICSRs (53%), while the prevalence was much lower in India (2%). In both cohorts, men over the age of 45 years constituted the most highly reported population. IMPLICATIONS: India has a very low prevalence of reported overall and bladder cancer-specific pioglitazone-related ADRs compared to Europe and the Americas. Possible explanations for the difference in reporting rates include variance in genetic makeup, low BC risk factor, pioglitazone prescription at a lower therapeutic dose, greater use of chemopreventive spices in the diet, higher frequency of metformin as a concurrent drug, and under-reporting of ADRs.