Monitoring and analysis of adverse reactions associated with medicines recently approved for treatment of cardiovascular disease collected through the spontaneous reporting system

Abstract

Several medicines for treatment of cardiovascular disease and other risk factors such as diabetes, dyslipidemia, and hypertension are available in the market. However, at the moment of drug approval, the safety profile should be considered provisional due to the limitations of the pre-marketing clinical trials. Also, relevant safety information about newly launched medicines usually arises in the first post-marketing years. The aim of this thesis is to contribute to the knowledge regarding safety profile of new marketed cardiovascular drugs using reports collected in the Spanish spontaneous reporting system. A group of cardiovascular drugs launched in Spain between 2007 and 2011 was selected. All the spontaneous reports involving the study drugs until the end of 2014 were retrieved and carefully analysed. Also, a review of case reports published and other scientific information was done. Statistical methods were applied to strengthen the potential ADR-drug associations. The main results were described in two original studies. In study I, an association between gliptins use and musculoskeletal reactions was found in the Spanish database. Gliptins are a new antidiabetic class that inhibits the action of dypeptidil peptidase-4 enzyme for controlling the glucose blood level in type 2 diabetic patients. In May 2012, thirty-four reports describing musculoskeletal complaints with gliptins were found in the database; twenty-seven for sitagliptin, six for vildagliptin and one for saxagliptin. These cases represented the 10% of all gliptins reports. Moreover, in two of them positive re-exposure was described. These adverse reactions were hardly described with gliptins use. Despite not being serious, these symptoms may impair the treatment adherence in patients with type 2 diabetes. In study II, the potential association between the use of dronedarone and renal impairment was analysed. The effect of dronedarone on renal function was supported by limited information. Dronedarone, a new antiarrhythmic drug, is a noniodinated amiodarone derivative indicated for the treatment of atrial fibrillation. In the Spanish database ten cases were found and, in addition, eight cases were identified in medical literature. These eighteen cases described renal impairment during dronedarone treatment. All cases showed a plausible temporal association, although the baseline conditions could be considered as potential confounder. Renal impairment associated with this drug could seriously aggravate the clinical condition of patients with atrial fibrillation, especially in those who also suffer from heart failure. Despite the fact that, either in musculoskeletal reactions associated with gliptins or renal impairment with dronedarone, further observational studies are needed in order to verify these potential safety signals, in the meantime clinicians should be aware of these potential reactions in clinical practice. The knowledge of safety information of marketed medicines is a constant process that is built-up over time. Pharmacovigilance was the first method for post-marketing surveillance and despite its inherent limitations such as lack of information or underreporting, it still contribute to the main objectives of post-marketing surveillance: to increase patients’ safety and to decrease the prescribers’ euphoria in front of new medicines.

Date of Award	27 Nov 2015
Original language	Undefined/Unknown
Supervisor	Albert Jesús Figueras Suñé (Director)