1. Statin Myopathy: Massive Rhabdomyolysis from Inadvertent Use of Two Statins Dinesh Kadariya MD, Kamran Zahid MD, TS Dharmarajan MD, FACP, AGSF Dept. of Medicine, Montefiore Medical Center (North Division), Bronx, NY
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Abstract
Case Description
Discussion
Statin Myopathy: Massive Rhabdomyolysis from Inadvertent Use of Two Statins
Dinesh Kadariya MD, Kamran Zahid MD, TS Dharmarajan MD, FACP, AGSF Department of Medicine , Montefiore Medical Center (North Division), Bronx, NY
Introduction
Statins are commonly prescribed and the most effective medications for management of hyperlipidemia. Adequate patient education coupled with appropriate follow up helps minimize adverse effects.
The Case
57 year old female living alone in the community has hyperlipidemia and HIV disease on ART (CD4 721) and chronic HIV related neuropathic pain. She was brought to hospital for evaluation of severe whole body myalgias with inability to lift objects. She was now unable to care for herself and get up to go to the bathroom.  Evaluation demonstrated acute kidney injury (BUN/Cr 56/4.5), SGOT 392, SGPT 117, and rhabdomyolysis (CPK 13309, myoglobin ). EMG confirmed statin induced proximal muscle myopathy. She was managed in the ICU and discharged to subacute rehab.
Medications at home included: Kaletra (Lopinavir/ritonavir) 200/50mg BID, Truvada (emtricitabine/tenofovir 200/300) 1 tab daily, simvastatin 40 mg/d, pravastatin 40mg/d. gemfibrozil 600mg BID, ASA 81 mg daily, and gabapentin 300mg TID. Although the statin was changed to simvastatin, patient inadvertently continued to take both pravastatin and simvastatin.
Discussion
Thousands of patients are treated with statins, with minimal adverse effects. The most common adverse events include gastrointestinal disturbances (nausea, diarrhea,constipation), fatigue and muscle and joint pain. Serious adverse events reported include myopathy, elevated transaminase levels, and rhabdomyolysis. Reported incidence is lower in clinical trials than real world use. Serious muscle injury is more common when statins are combined with fibrates, especially in the presence of kidney disease. Alcoholism increases risk of myopathy, as also high doses (e.g. simvasatin 80 mg or higher daily). There is no data suggesting benefits or adverse effects from using more than one statin at the same time. Our patient was on 2 statin and a fibrate. Myalgias may occur on statin therapy although CPK levels may be normal. Thus CPK level testing by itself for statin-associated myopathy is unreliable.
Treatment options include discontinuing the statin, switching to a different statin, lowering the dose and intermittent use. Avoidance of alcohol and fibrates use with statins is helpful
Lessons learnt
Statins are generally favored medications because of their efficacy, safety and tolerability, but life-threatening adverse events including death can occur.
Although no proven markers predict toxicity, patient education and appropriate follow up help detect and minimize adverse effects.
References
Thompson PD, et al. Statin associated myopathy.JAMA.2003;289(13): .
Phillips PS, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med.2002; 137:581–585.
57 year old female from community with hyperlipidemia, HIV on ART(CD4 721) & HIV related Neuropathy was brought to hospital for evaluation of severe generalized body pains and inability to lift objects. Patient was unable to carry out activities of daily living. Laboratory evaluation revealed Acute kidney injury (BUN/Cr 56/4.5), Acute Liver failure (SGOT 392, SGPT 117), and rhabdomyolysis (CPK 13309, myoglobin ). EMG confirmed statin induced proximal muscle myopathy. She was admitted to ICU, treated with IV fluids and serial monitoring of renal functions, Liver enzymes and CPK level. Labs revealed progressive improvement, Patient was transferred to General Medical floor. She was seen by physical medicine and rehabilitation and discharged to sub-acute rehab for physical and occupational therapy.
Patient’s home medication list includes: Kaletra (Lopinavir/ritonavir) 200/50mg BID, Truvada (emtricitabine/tenofovir 200/300) 1 tab daily, simvastatin 40 mg/d, pravastatin 40mg/d. gemfibrozil 600mg BID, ASA 81 mg daily, and gabapentin 300mg TID.
History revealed that, although the pravastatin was switched to simvastatin, patient inadvertently continued to take both pravastatin and simvastatin along with gemfibrozil, that resulted in patient’s complaints requiring ICU admission.
Statin–fibrate /Statin-statin combination regimens have potential adverse effects on muscle, including myopathy. No large-scale, randomized, controlled trial has evaluated the safety and efficacy of statin–fibrate /Statin-statin combination therapy .
The onset of myopathy after initiation of therapy is weeks to months but can occur during anytime of treatment. Symptoms resolve over days to weeks (typically within one month to six months) after discontinuation of therapy.
There is little evidence of benefit of CoQ10 and vitamin supplemets for the treatment of myopathy.
Management includes discontinuation of therapy and supportive care.
Increased statin-associated myopathy occurs in patient with
Kidney Disease
Hypothyroidism
Obstructive Liver Disaease
Statins triggering myogenic symptoms more readily than in healthy persons
Myasthenia gravis
Mitochondrial myopathy
carnitine-palmitoyl transferase deficiency
myotonic dystrophy
Amyoltrophic lateral sclerosis
Common drugs that increase statin-associated-myopathy:-
Cyclosporin
Gemfibrozil
Amiodarone
Amlodipine,Verapamil, Diltiazem,
Itraconazole, Erythromycin
HIV protease inhibitors
Colchicine
Lessons
Clinicians need to consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic and other factors that can increase the toxic effects of statin on muscles.
Routine monitoring of CPK level and Liver enzymes is no longer recommended but having baseline CPK and Liver enzymes before initiation of therapy is useful for reference purpose.
Introduction
More than 20 million Americans take statins.
Patient receiving concurrent therapy with other drugs that inhibit CYP3A4 has increased risk of myopathy and rhabdomyolysis.
Bibliography
Thompson PD, et al. Statin associated myopathy.JAMA.2003;289(13):
Phillips PS, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med.2002; 137:581–585.