Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug-drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition. We reviewed all available cases plus the case of an 87-year-old female Croatian/Caucasian patient who developed rhabdomyolysis following concomitant treatment with rosuvastatin and ticagrelor. The results of the pharmacogenetic analysis indicated that the patient was a carrier of inactivating alleles CYP2C9*1/*3, CYP3A4*1/*22, CYP3A5*3/*3, CYP2D6*1/*4, UGT1A1*28/*28, UGT2B7 -161C/T, ABCB1 3435C/T and ABCB1 1237C/T which could have added to the interactions not only between ticagrelor and rosuvastatin but also other concomitantly prescribed medicines, such as amiodarone and proton pump inhibitors. In this case report, the possible multifactorial causes for rhabdomyolysis following concomitant use of rosuvastatin and ticagrelor such as old age, polypharmacy, renal impairment, along with pharmacogenetics will be discussed.

The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years have passed since the legislation was introduced and the key question is: does pharmacovigilance yet make optimal use of patient-reported safety information? Independent research has shown beyond doubt that patients make an important contribution to pharmacovigilance signal detection. Patient reports provide first-hand information about the suspected ADR and the circumstances under which it occurred, including medication errors, quality failures, and 'near misses'. Patient-reported safety information leads to a better understanding of the patient's experiences of the ADR. Patients are better at explaining the nature, personal significance and consequences of ADRs than healthcare professionals' reports on similar associations and they give more detailed information regarding quality of life including psychological effects and effects on everyday tasks. Current methods used in pharmacovigilance need to optimise use of the information reported from patients. To make the most of information from patients, the systems we use for collecting, coding and recording patient-reported information and the methodologies applied for signal detection and assessment need to be further developed, such as a patient-specific form, development of a severity grading and evolution of the database structure and the signal detection methods applied. It is time for a renaissance of pharmacovigilance.

AimTo analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence.MethodsIn this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them.ResultsHALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n = 4) was significantly higher (P < 0.001) than among the remaining reports (580 out of 1982; n = 2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter.ConclusionThe study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education.

Our preliminary data demonstrate an association between fluvastatin-induced ADRs in RTRs and genetic variants in the CYP2C9 and ABCG2 genes.

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