A Unique Case of Drug Interaction between Ticagrelor and Statin Leading to Acute Renal Failure

Samuel, Gbeminiyi; Atanda, Adebayo; Onyemeh, Alex; Awan, Ahmad

doi:10.7759/cureus.1633

Cited by 9 publications

(18 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A possible rosuvastatin-ticagrelor interaction was also reported for a 49-year-old female patient [ 65 ]. Beside 90 mg ticagrelor twice daily and rosuvastatin 20 mg, the patient was treated with lisinopril 20 mg, metformin 500 mg, metoprolol 50 mg twice daily, and pantoprazole 40 mg.…”

Section: Review Of Reported Case Studies With a Possible Ticagrelor-smentioning

confidence: 85%

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

Danielak

Karaźniewicz−Łada

Główka

2018

Drugs

View full text Add to dashboard Cite

The introduction of ticagrelor, one of the first directly-acting oral antiplatelet drugs, provided new possibilities in the prevention of thrombotic events in patients with acute coronary syndromes (ACS). Current guidelines recommend ticagrelor in dual antiplatelet therapy with aspirin over clopidogrel for prevention of stent thrombosis in patients with ACS. Moreover, in the management of ACS, lipid-lowering treatment with high-intensity statin therapy is advised for secondary prevention of cardiovascular events over the long term. Despite the apparent advantages of combined antiplatelet and lipid-lowering treatments, a possible interaction between statins and ticagrelor may lead to myopathy and rhabdomyolysis. In this review, relevant information was gathered on the ticagrelor-statin interaction that might lead to this life-threatening condition. This review focuses on the most widely used statins—simvastatin, atorvastatin, and rosuvastatin. Possible mechanisms of this interaction are discussed, including CYP3A4 isoenzymes, organic anion transporter polypeptide (OATPs), P-glycoprotein and glucuronidation. PubMed database was searched for relevant case reports and all data gathered from the introduction of ticagrelor to March 2018 are presented and discussed. In summary, co-administration of statins and ticagrelor was found to be relatively safe in routinely prescribed doses. However, caution should be exercised, especially in elder populations.

show abstract

Section: Review Of Reported Case Studies With a Possible Ticagrelor-smentioning

confidence: 85%

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

Danielak

Karaźniewicz−Łada

Główka

2018

Drugs

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Kariyanna

Haseeb

Chowdhury

et al. 2019

AJMCR

View full text Add to dashboard Cite

Ever since evidence about the increased risk of stent thrombosis with drug eluting stents (DES) surfaced in 2005, the Food and Drug Administration (FDA) has recommended the use of dual antiplatelet therapy (aspirin with P2Y12 inhibitor) following DES placement. The PLATO trial demonstrated lower mortality rates with the use of Ticagrelor when compared to clopidogrel (9.8% vs. 11.7%, p<0.001) when treating patients with acute coronary syndrome. Given their pleiotropic benefits, statins are today the second most prescribed drug in the United States and often co-prescribed with Ticagrelor. FDA's post market surveillance of Ticagrelor use along with statins in post-myocardial infarction care is now revealing novel and serious adverse events. We present two cases of rhabdomyolysis and acute renal failure (ARF) which develop while the patients were on statins and Ticagrelor. Case 1: A 66-year-old female presented with bilateral thigh pain for 3 days. One month prior to presentation, she was managed for non-ST segment elevation myocardial infarction (NSTEMI) and had been started on aspirin, ticagrelor and simvastatin. Laboratory values revealed creatinine kinase (CK) level at 40,000 U/L and creatinine 3.2 mg/dL suggesting rhabdomyolysis and ARF. Case 2: A 63-year-old male presented with generalized body aches and fatigue for 4 days. He had sustained STEMI two months before and received two drug eluting stents (DES) and aspirin, ticagrelor and rosuvastatin had been initiated. CK was 380,000 U/L and creatinine 7.94 mg/dL suggesting rhabdomyolysis and ARF. Both patients presented with rhabdomyolysis and acute renal failure within weeks after ticagrelor and statin were commenced. A review of the literature indicated that 11 similar cases of ticagrelor-induced ARF and rhabdomyolysis had been reported. Ticagrelor competes with statins when metabolized by cytochrome P450 (CYP) 3A4 leading to statin retention, leading to major adverse effects like rhabdomyolysis and acute renal failure. Our review is intended to alert clinicians about this important drug interaction.

show abstract

“…In 2017, two more case reports were published. Samuel and collaborators described a case of drug interaction between rosuvastatin and ticagrelor, resulting in rhabdomyolysis and acute renal failure necessitating dialysis in a 49‐year‐old African‐American female . The patient was also taking lisinopril and prior to hospitalization, she attended a rigorous exercise routine at a cardiac rehabilitation centre 3 days per week which resulted in significant weight loss for a couple of months.…”

Section: Discussionmentioning

confidence: 99%

“…The exact mechanism leading to the worsening of renal function by ticagrelor is unknown, but the PLATO trial showed that serum creatinine concentration was increased by more than 30% in 25.5% of the patients receiving ticagrelor. Worsening of the renal function was more pronounced in patients over 75 years of age, in patients receiving angiotensin receptor inhibitors and patients with pre‐existing renal dysfunction . It is speculated that inhibition of adenosine reuptake by ticagrelor reduces glomerular filtration rate through vasoconstriction of the afferent renal arteriole .…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin‐Induced Rhabdomyolysis – Possible Role of Ticagrelor and Patients’ Pharmacogenetic Profile

Kirhmajer

Šarinić

Šimičević

et al. 2018

Basic Clin Pharma Tox

View full text Add to dashboard Cite

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.

show abstract

A Unique Case of Drug Interaction between Ticagrelor and Statin Leading to Acute Renal Failure

Cited by 9 publications

References 6 publications

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

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

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

Rosuvastatin‐Induced Rhabdomyolysis – Possible Role of Ticagrelor and Patients’ Pharmacogenetic Profile

Contact Info

Product

Resources

About