Severe Rhabdomyolysis due to Presumed Drug Interactions between Atorvastatin with Amlodipine and Ticagrelor

Abstract

Atorvastatin and ticagrelor combination is a widely accepted therapy for secondary prevention of ischaemic heart disease. However, rhabdomyolysis is a well-known rare side effect of statins which should be considered when treatments are combined with cytochrome P450 3A4 enzyme inhibitors. We report a case of atorvastatin and ticagrelor associated severe rhabdomyolysis that progressed to multiorgan failure requiring renal replacement therapy, inotropes, intubation, and mechanical ventilation. Despite withdrawal of the precipitating cause and the supportive measures including renal replacement therapy, creatinine kinase increased due to ongoing rhabdomyolysis rapidly progressing to upper and lower limbs weakness. A muscle biopsy was performed to exclude myositis which confirmed extensive myonecrosis, consistent with statin associated rhabdomyolysis. After a prolonged ventilatory course in the intensive care unit, patient's condition improved with recovery from renal and liver dysfunction. The patient slowly regained her upper and lower limb function; she was successfully weaned off the ventilator and was discharged for rehabilitation. To our knowledge, this is a second case of statin associated rhabdomyolysis due to interaction between atorvastatin and ticagrelor. However, our case differed in that the patient was also on amlodipine, which is considered to be a weak cytochrome P450 3A4 inhibitor and may have further potentiated myotoxicity.

Ticagrelor and Statin Interaction Induces Rhabdomyolysis and Acute Renal Failure: Case reports and Scoping Review

“…A review of literature revealed eleven [14][15][16][17][18][19][20][21][22][23][24] reported cases of ticagrelor induced ARF and rhabdomyolysis (Table 1). 10 cases were found in patients who were also on prescription of high intensity statins with rosuvastatin being the most commonly used statin.…”

Assessment of the Risk of Rhabdomyolysis and Myopathy During Concomitant Treatment with Ticagrelor and Statins

“…Concomitant administration of other drugs might also elevate the risk of rhabdomyolysis. In a case of a 74-year-old female, severe rhabdomyolysis was diagnosed [ 61 ]. The patient was treated with amlodipine (5 mg) and atorvastatin (20 mg) for several years before hospital admission.…”

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

“…3,21 Other factors increasing the risk of statininduced rhabdomyolysis include statin dose, age, female gender, low body mass index, and untreated or uncontrolled hypothyroidism. 1,3,4,22 On the contrary, ticagrelor, a direct-acting oral antiplatelet drug approved in 2011, 1,3 is not known to cause myotoxicity. Compared to clopidogrel, ticagrelor does not require metabolic activation, so its effects are more predictable and consistent across patients.…”