The Interaction Between Rosuvastatin and Ticagrelor Leading to Rhabdomyolysis: A Case Report and Narrative Review

Abstract

Objective: Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature. Method: We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status. Results: The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein. Conclusion: Future pharmacokinetic studies are warranted to better understand the interaction.

Rosuvastatin Induces Renal HO-1 Activity and Expression Levels as a Main Protective Mechanism against STZ-Induced Diabetic Nephropathy

“…Administration of RSV was reported to cause proximal tubule damage and renal toxicity in rats [ 35 ] and acute interstitial nephritis in humans [ 36 ]. In addition, RSV caused renal damage associated with severe rhabdomyolysis, whether RSV was given alone [ 37 , 38 , 39 ], or in combination with colchicine [ 40 ], ticagrelor [ 41 ], or cocaine and heroin [ 42 ]. Despite that the results of the current study suggested that RSV had protective effects against DN, long-term follow-up studies are needed to confirm whether RSV improves DN or just delays its progress.…”

The Problem of Drug Interactions Between Rosuvastatin and Ticagrelor in the Aspect of the Risk of Rhabdomyolysis: Discussion of the Problem and Description of the Clinical Case

“…Несмотря на очевидные преимущества комбинированной антиагрегантной и гиполипидемической терапии, возможное взаимодействие между статинами и тикагрелором может привести к миопатии и рабдомиолизу [8][9][10][11][12][13][14][15][16][17]. В обзорной статье P.T.…”

“…В настоящее время имеется ряд публикаций о клинических случаях рабдомиолиза у пациентов, одновременно принимающих после ЧКВ широко используемые статины (розувастатин, аторвастатин, симвастатин) и антитромбоцитарный препарат тикагрелор [8][9][10][11][12][13][14][15][16][17].…”

“…Rational Pharmacotherapy in Cardiology 2022;18(5) / Рациональная Фармакотерапия в Кардиологии 2022;18(5) Кроме того, существуют и другие факторы, которые могут привести к повышению концентрации статинов: фармакокинетические взаимодействия на уровне метаболизирующих ферментов (таких как CYP и UGT) [15,17,21] и белков-транспортеров (таких как OATP1B1 и P-гликопротеин) [26][27][28]. Межлекарственные взаимодействия возможны не только между розувастатином и тикагрелором, но и с другими одновременно назначаемыми лекарствами, конкурирующими на уровне белков-транспортеров, что может приводить к снижению желчной и почечной экскреции розувастатина [15].…”

Ticagrelor Increases Exposure to the Breast Cancer Resistance Protein Substrate Rosuvastatin

“…Although usually well‐tolerated, rosuvastatin can cause muscle symptoms of varying severity, especially at higher doses 1 . Previously published case reports have suggested that concomitant use of rosuvastatin and the platelet‐inhibitor ticagrelor may have led to severe, even fatal, cases of rosuvastatin‐induced rhabdomyolysis 2–13 . Because the risk of rosuvastatin‐induced myotoxicity is concentration‐dependent, the rhabdomyolysis cases suggest a potential pharmacokinetic drug–drug interaction between ticagrelor and rosuvastatin.…”