The Journal of the Arkansas Medical Society Med Journal Feb 2019 Final 2 | Page 20

CASE REPORT
Rhabdomyolysis From Atorvastatin and
Levofloxacin in an Elderly Patient With Renal Failure
Lilianna Hanefeld-Fox, MD; Sai Prasad Desikan, MD;
Caston Taylor, PA; Seth Barnes, MD; Raman Desikan, MD
White River Health System, Batesville
S
tatins are increasingly used to ef-
fectively lower low-density lipopro-
tein cholesterol (LDL) and improve
outcomes in coronary heart disease, both in
primary prevention of established coronary
heart disease and in secondary prevention
in established disease. 1,2 However, concerns
about muscle toxicity may prompt underutiliza-
tion of these effective agents. 3 Rhabdomyolysis
is a potentially fatal but rare complication of statin
therapy. Risk of statin-induced muscle damage is
increased by concomitant administration of drugs
that impair the metabolism of statins or other
drugs associated with intrinsic myotoxic poten-
tial. 4,5 Levofloxacin is widely prescribed for com-
munity-acquired respiratory infections; it has pre-
dominant renal elimination, and dose reductions
are necessary for renal impairment. Levofloxacin
has been reported to cause rhabdomyolysis in the
elderly, patients on hemodialysis, and post-renal
transplantation. 6-8 We report on acute rhabdomy-
olysis in an elderly patient with renal impairment
from concomitant administration of levofloxacin
and atorvastatin.
Case Report
An 83-year-old white female was admit-
ted for increasing weakness and myalgia. Her
past medical history was significant for aortic
stenosis, coronary artery disease, hypertension,
diabetes mellitus type 2, hyperlipidemia, gout,
breast cancer, chronic kidney disease, and en-
suing normocytic anemia. She had two recent
hospitalizations: pneumonia a month prior to this
admission and dyspnea with sinus symptoms two
weeks before this admission. She was treated
with a course of Levofloxacin on both visits. She
was switched to Atorvastatin from Simvastatin for
coronary artery disease 11 months earlier. She
had noticed increasing weakness over a month,
necessitating more help with activities of daily liv-
ing. She also noticed increasing left upper thigh
and hip pain in addition to significant muscular
weakness. Left extremity Doppler was unremark-
able. Workup revealed rhabdomyolysis with ele-
vated myoglobin of 14370 ng/ml, creatine kinase
(CK) of 20340 U/L, and creatine kinase, muscle
and brain (CK-MB) of 75.5 ng/ml. Transaminases
were also elevated with alanine aminotransferase
(ALT) of 320 U/L and aspartate aminotransferase
(AST) of 742 U/L. Creatinine of 1.3 mg/dl was not
significantly elevated from baseline at 1.3 mg/dl
and improved during hospitalization. Atorvastatin
was held; myoglobin levels and liver enzymes
showed progressive improvement. On last evalu-
ation four months from onset of rhabdomyolysis,
she reported continued improvement of muscle
weakness. In addition, myoglobin and creatinine
kinase showed continuing reduction, even though
values were still above normal at 429 ng/ml and
258 U/L respectively (Figure 1 and 2).
Discussion
Muscle-related symptoms are well recog-
nized, severe adverse effects of statin therapy;
the spectrum includes myalgia, myopathy, and
rhabdomyolysis. Myopathy, defined by muscle
symptoms and CK elevation of 10 fold above up-
per limit of normal, occurs in five patients per 100,
000 person years. Rhabdomyolysis, defined by
CK elevation above 10,000 IU/L or 10 folds above
upper limit of normal with increase in creatinine
value, is observed less often (1.6 per 100,000
person years). Less severe manifestations such
as myalgia and asymptomatic CK elevation (< 10
fold ULN) are much more common. On average,
statin-associated myopathy develops approxi-
mately 6.3 months from start of therapy, while
rhabdomyolysis is observed much earlier (mean
188 • THE JOURNAL OF THE ARKANSAS MEDICAL SOCIETY
time to onset of 9 days). Multiple factors are
known to predispose to rhabdomyolysis (fragility,
low body mass index, older age, female sex, hy-
pothyroidism, hypertension, and polypharmacy).
Drug interactions from concomitant medications
play a major part in development of rhabdomy-
olysis. Statins, especially lovastatin, simvastatin,
and atorvastatin are metabolized by CYP3A4
isoform of cytochrome P450. CYP3A4 is inhib-
ited by many commonly used drugs (antifungals,
macrolides, fusidic acid, cyclosporine, protease
inhibitors and calcium channel blockers) making
rhabdomyolysis more likely with these agents. Fi-
brates, when employed with statin, increase the
incidence of rhabdomyolysis. Fibrates have intrin-
sic myotoxic potential, causing rhabdomyolysis
when employed alone. Fibrates are not known to
inhibit CYP3A4. 4,5
Levofloxacin, a commonly employed anti-
biotic for respiratory infection, is mainly elimi-
nated by kidney and requires dose reduction
with renal impairment; acute rhabdomyolysis
has been reported in the elderly, patients on he-
modialysis, and after renal transplantation. Other
fluoroquinolones have also been associated with
rhabdomyolysis. 10. Levofloxacin is not known to
inhibit cytochromes CYP3A4 or CYP2C8, which
are important in metabolism of statins and active
metabolites. Levofloxacin is a potent inhibitor of
the P-glycoprotein mediated drug efflux system.
Levofloxacin is the drug most implicated in
causation of rhabdomyolysis in our patient on
account of recent exposure. However, she has
had multiple exposures to levofloxacin in the set-
ting of chronic renal impairment, despite which
she did not exhibit symptoms of rhabdomyolysis.
Atorvastatin has established myotoxic poten-
tial; however, she tolerated Atorvastatin for 11
months without any muscle-related symptoms.
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