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Rosuvastatin‐Induced Rhabdomyolysis – Possible Role of Ticagrelor and Patients’ Pharmacogenetic Profile
Author(s) -
Vrkić Kirhmajer Majda,
Macolić Šarinić Viola,
Šimičević Livija,
Ladić Iva,
Putarek Krešimir,
Banfić Ljiljana,
Božida
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13035
Subject(s) - rosuvastatin , rhabdomyolysis , medicine , pharmacogenetics , ticagrelor , atorvastatin , pharmacology , statin , cyp2c19 , rosuvastatin calcium , concomitant , clopidogrel , aspirin , cytochrome p450 , genotype , biology , biochemistry , metabolism , gene
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 ( CYP s and UGT s) and drug transporter levels ( ABCB 1, ABCG 2, OATP 1B1) 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 CYP 2C9*1/*3, CYP 3A4*1/*22, CYP 3A5*3/*3, CYP 2D6 *1/*4, UGT 1A1*28/*28, UGT 2B7 ‐161C/T, ABCB 1 3435C/T and ABCB 1 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.