Levofloxacin‐induced rhabdomyolysis in a patient on concurrent atorvastatin: Case report and literature review

Abstract

Rhabdomyolysis is a clinical syndrome associated with electrolyte abnormalities and myoglobinuria. Signs and symptoms of rhabdomyolysis include elevated creatinine phosphokinase (CPK) and aspartate transaminase (AST), muscle pain, urine discoloration, fatigue, nausea, vomiting and fever. 1 If untreated, rhabdomyolysis can lead to renal failure and death. 2 Rhabdomyolysis can occur as a result of traumatic injury or chemical causes. 1-3 Prior case reports describing fluoroquinolone-induced rhabdomyolysis occurred within the first week of fluoroquinolone initiation. 4-10 Most of these involved the co-administration of simvastatin and either ciprofloxacin or levofloxacin. 4,5,7-10 We report a rare case of delayed-onset acute rhabdomyolysis that coincided with initiation of levofloxacin in a patient on long-term atorvastatin. A literature search of articles published in English through August 2018 was conducted using PubMed to identify other publications on fluoroquinolone-induced rhabdomyolysis with and without concomitant statin therapy. The following search terms were used alone and in combination: rhabdomyolysis, fluoroquinolone, statin, levofloxacin, atorvastatin. Citations of included articles were also reviewed to identify additional publications. | C A S E DE SCRIP TI ONA 65-year-old white male presented to an outside hospital with complaints of right knee pain, swelling, subjective fevers, chills, and inability to bear weight in the setting of prior right total knee arthroplasty. He was started on vancomycin and aztreonam for empiric treatment of a right knee prosthetic joint infection and was subsequently transferred to our facility for surgical intervention. The

Rhabdomyolysis associated with newer-generation anti-seizure medications (ASMs): a real-world retrospective and pharmacovigilance study

“…A previous postmarketing analysis from the FAERS data raised a safety signal detecting 48 reports of LEV-induced rhabdomyolysis from 2004 to 2015, which had a median time to onset of a few Frontiers in Pharmacology frontiersin.org days (Carnovale et al, 2017). This interval is comparable to that of rhabdomyolysis induced by other drugs, such as antibiotics, particularly quinolone (Bouchard et al, 2019), but shorter than in paradoxical cases reported with statins (Vinci et al, 2021), with which it occurs within a few weeks to months. There was one report of a 36-year-old male who took levetiracetam for 2 years before rhabdomyolysis onset, whom we did not include in the calculation of the median onset time to avoid negative skewing of the results (Alshehabi et al, 2022).…”

A systematic review of the drug-drug interaction between Statins and Quinolones

“…Only one patient was readmitted for myopathy 3 months after the combination, but the exact timing of the ADR was not clear [12]. High-intensity statins were implicated in 5 case reports [7,[13][14]17,19], with four patients taking 80mg per day of atorvastatin and one patient using 80mg per day of simvastatin, while moderate-intensity statins in 9 case reports [9,11,13,[16][17][18][19][20][21][22]. It was unclear from two case reports about the statin dosage, one involving atorvastatin and one involving simvastatin [8] [11].…”

“…ADRs in the included literature were rhabdomyolysis (n = 12) [7][8][9]11,13,[16][17][18][19][20][21][22], acute hepatitis(n = 1) [15], muscle weakness(n = 1) [14], tendinopathy of hip(n = 1) [10], and myopathy(n = 1) [12] (Table 2). CK was reported in 81%(n = 13) of the case reports with a range between 183 to 816,000 units/L, which all above the normal value for CK [7][8][9][12][13][14][16][17][18][19][20][21][22].…”

“…ADRs in the included literature were rhabdomyolysis (n = 12) [7][8][9]11,13,[16][17][18][19][20][21][22], acute hepatitis(n = 1) [15], muscle weakness(n = 1) [14], tendinopathy of hip(n = 1) [10], and myopathy(n = 1) [12] (Table 2). CK was reported in 81%(n = 13) of the case reports with a range between 183 to 816,000 units/L, which all above the normal value for CK [7][8][9][12][13][14][16][17][18][19][20][21][22]. All patients were given statins, including simvastatin (n = 10) [9][10][11][12][15][16][18][19][20][21][22] at a dose range of 20-80mg/day and 66.7% of the remaining patients received 80 mg/day of oral atorvastatin (n = 4) [7,[13][14]17].…”

“…CK was reported in 81%(n = 13) of the case reports with a range between 183 to 816,000 units/L, which all above the normal value for CK [7][8][9][12][13][14][16][17][18][19][20][21][22]. All patients were given statins, including simvastatin (n = 10) [9][10][11][12][15][16][18][19][20][21][22] at a dose range of 20-80mg/day and 66.7% of the remaining patients received 80 mg/day of oral atorvastatin (n = 4) [7,[13][14]17]. And there were 2 patients with unspeci ed statin doses, separately using simvastatin and atorvastatin.…”