A Rare Case of Delayed Onset Multi-Drug Interaction Resulting in Rhabdomyolysis in a 66-Year-Old Male

Osborn, Harmony; Grossman, Daniel; Kochhar, Smriti; Kanukuntla, Anish Kumar; Kata, Priyaranjan; Cheriyath, Pramil

doi:10.7759/cureus.20035

Cited by 3 publications

(5 citation statements)

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“…In the literature, we found a total of 11 reported cases of rhabdomyolysis during concomitant treatment with ticagrelor and rosuvastatin (Table S4). 2–12 The patients (7 female, 4 male) were aged 49–87 years. The daily dose of rosuvastatin was 20–40 mg, and daily dose of ticagrelor 90–180 mg. Time to rhabdomyolysis onset from the start of concomitant medication was 2 weeks to 8 months (median 1.75 months).…”

Section: Resultsmentioning

confidence: 99%

“…In the literature, we found a total of 11 reported cases of rhabdomyolysis during concomitant treatment with ticagrelor and rosuvastatin (Table S4). [2][3][4][5][6][7][8][9][10][11][12] The patients (7 female, 4 male) were aged 49-87 years.…”

Section: Literature Reviewmentioning

confidence: 99%

“…The treatment is usually well tolerated. However, clinicians have reported multiple cases of rhabdomyolysis during concomitant use of rosuvastatin and ticagrelor, [2][3][4][5][6][7][8][9][10][11][12] leading to a growing suspicion of an underlying drug-drug interaction. Three cases were recently identified and are described in this article for the first time.…”

Section: Introductionmentioning

confidence: 99%

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Rhabdomyolysis during concomitant ticagrelor and rosuvastatin: A breast cancer resistance protein‐mediated drug interaction?

Lehtisalo

Kiander

Filppula

et al. 2023

Brit J Clinical Pharma

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We present 3 patients diagnosed with rhabdomyolysis 1–6 months after the initiation of concomitant rosuvastatin and ticagrelor medication. A literature review and Food and Drug Administration adverse event reporting system revealed >40 reports of rhabdomyolysis during concomitant ticagrelor and rosuvastatin, including 3 with a fatal outcome. We show that ticagrelor inhibits breast cancer resistance protein‐, organic anion transporting polypeptide (OATP) 1B1‐, 1B3‐ and 2B1‐mediated transport of rosuvastatin in vitro with half‐maximal unbound inhibitory concentrations of 0.36, 4.13, 7.5 and 3.26 μM, respectively. A static drug interaction model predicted that ticagrelor may inhibit intestinal breast cancer resistance protein and thus increase rosuvastatin plasma exposure 2.1‐fold, whereas the OATP‐mediated hepatic uptake of rosuvastatin should not be inhibited due to relatively low portal ticagrelor concentrations. Taken together, concomitant use of ticagrelor with rosuvastatin may increase the systemic exposure to rosuvastatin and the risk of rosuvastatin‐induced rhabdomyolysis. Further studies are warranted to investigate the potential pharmacokinetic interaction between ticagrelor and rosuvastatin in humans.

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Section: Resultsmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rhabdomyolysis during concomitant ticagrelor and rosuvastatin: A breast cancer resistance protein‐mediated drug interaction?

Lehtisalo

Kiander

Filppula

et al. 2023

Brit J Clinical Pharma

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“…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.…”

mentioning

confidence: 99%

“…led to severe, even fatal, cases of rosuvastatin-induced rhabdomyolysis. [2][3][4][5][6][7][8][9][10][11][12][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.…”

mentioning

confidence: 99%

Ticagrelor Increases Exposure to the Breast Cancer Resistance Protein Substrate Rosuvastatin

Lehtisalo,

Tarkiainen,

Neuvonen

et al. 2023

Clin Pharma and Therapeutics

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Ticagrelor and rosuvastatin are often used concomitantly after atherothrombotic events. Several cases of rhabdomyolysis during concomitant ticagrelor and rosuvastatin have been reported, suggesting a drug‐drug interaction. We showed recently that ticagrelor inhibits breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1 ‐mediated rosuvastatin transport in vitro. The aim of this study was to investigate the effects of ticagrelor on rosuvastatin pharmacokinetics in humans. In a randomized, cross‐over study, nine healthy volunteers ingested a single dose of 90 mg ticagrelor or placebo, followed by a single 10 mg dose of rosuvastatin 1 hour later. Ticagrelor 90 mg or placebo were additionally administered 12, 24, and 36 hours after their first dose. Ticagrelor increased rosuvastatin area under the plasma concentration‐time curve (AUC) and peak plasma concentration 2.6‐fold (90% confidence intervals 1.8‐3.8 and 1.7‐4.0, P=0.001 and P=0.003), and prolonged its half‐life from 3.1 to 6.6 hours (P=0.009). Ticagrelor also decreased the renal clearance of rosuvastatin by 11% (3‐19%, P=0.032). The N‐desmethylrosuvastatin:rosuvastatin AUC0‐10 h ratio remained unaffected by ticagrelor. Ticagrelor had no effect on the plasma concentrations of the endogenous OATP1B substrates glycodeoxycholate 3‐O‐glucuronide, glycochenodeoxycholate 3‐O‐glucuronide, glycodeoxycholate 3‐O‐sulfate, and glycochenodeoxycholate 3‐O‐sulfate, or the sodium‐taurocholate cotransporting polypeptide substrate taurocholic acid. These data indicate that ticagrelor increases rosuvastatin concentrations more than two‐fold in humans, probably mainly by inhibiting intestinal BCRP. Since the risk for rosuvastatin‐induced myotoxicity increases along with rosuvastatin plasma concentrations, using ticagrelor concomitantly with high doses of rosuvastatin should be avoided.

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Current View on the Use of Extracorporeal Detoxification Methods for the Treatment of Rhabdomyolysis (Review)

Masolitin

Проценко

Tyurin

et al. 2023

Obŝaâ reanimatologiâ

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Rhabdomyolysis is a syndrome caused by destruction and necrosis of muscle tissue, which is accompanied by the release of intracellular contents into the systemic circulation. The etiology of rhabdomyolysis is multifaceted, however, regardless of the etiological factor, the central element of its pathophysiology is systemic endotoxemia with multiple organ failure syndrome. Acute renal failure is one of the most common manifestations of organ dysfunction. Considering the pathogenetic model of the development of systemic endotoxemia, the timely use of extracorporeal therapy, which reduces mortality in organ failure, seems promising. All the current types of extracorporeal therapy can be divided into convection (hemoﬁltration), diﬀusion (hemodialysis), convection/diﬀusion (hemodiaﬁltration), sorption (hemoperfusion) and plasma exchange (plasmapheresis, plasma exchange, plasma sorption, etc.) methods based on physical principle.The aim of the review was to summarize the available clinical data on extracorporeal treatments for rhabdomyolysis and to assess the feasibility and best indications for these methods based on the current pathogenetic model of rhabdomyolysis.Material and methods. The search for information was carried out in the Web of Science, Scopus, Medline, PubMed, RSCI, E-library and other databases. Eighty-one sources were identiﬁed containing current therapeutic approaches and relevant data of clinical and scientiﬁc research on the subject of this review.Results. In this review, the main etiological, epidemiological and pathogenetic models of acute renal injury in rhabdomyolysis have been discussed. The main methods of extracorporeal therapy have been reviewed and evaluated based on current understanding, and latest clinical data on their eﬀectiveness have been summarized.Conclusion. The choice of the optimal extracorporeal treatment method, the time of initiation and duration of the procedure still remain controversial. The solution to this issue can potentially help to better correct the electrolyte disturbances and could protect against organ dysfunction, which would improve the outcome in patients with rhabdomyolysis.

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A Rare Case of Delayed Onset Multi-Drug Interaction Resulting in Rhabdomyolysis in a 66-Year-Old Male

Cited by 3 publications

References 10 publications

Rhabdomyolysis during concomitant ticagrelor and rosuvastatin: A breast cancer resistance protein‐mediated drug interaction?

Rhabdomyolysis during concomitant ticagrelor and rosuvastatin: A breast cancer resistance protein‐mediated drug interaction?

Ticagrelor Increases Exposure to the Breast Cancer Resistance Protein Substrate Rosuvastatin

Current View on the Use of Extracorporeal Detoxification Methods for the Treatment of Rhabdomyolysis (Review)

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