Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin

OBJECTIVE: To report a case of rhabdomyolysis resulting from concomitant use of clarithromycin and simvastatin. CASE SUMMARY: A 64-year-old African-American man was admitted to the hospital for worsening renal failure, elevated creatine phosphokinase, diffuse muscle pain, and severe muscle weakness. About three weeks prior to admission, the patient was started on clarithromycin for sinusitis. The patient had been receiving simvastatin for approximately six months. He was treated aggressively with intravenous hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy revealed necrotizing myopathy secondary to a toxin. The patient continued to receive intermittent hemodialysis until his death from infectious complications that occurred three months after admission. There were several factors that could have increased his risk for developing rhabdomyolysis, including chronic renal failure. DISCUSSION: Clarithromycin is a potent inhibitor of CYP3A4, the major enzyme responsible for simvastatin metabolism. The concomitant administration of macrolide antibiotics and other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have resulted in previous reports of rhabdomyolysis. Other factors may increase the risk of this drug interaction, including the administration of other medications that are associated with myopathy, underlying renal insufficiency, and administration of high doses of HMG-CoA reductase inhibitors. CONCLUSIONS: Macrolide antibiotics inhibit the metabolism of HMG-CoA reductase inhibitors that are metabolized by CYP3A4 (i.e., atorvastatin, cerivastatin, lovastatin, simvastatin). This interaction may result in myopathy and rhabdomyolysis, particularly in patients with renal insufficiency or those who are concurrently taking medications associated with myopathy.     

Rhabdomyolysis associated with gemfibrozil-colchicine therapy

OBJECTIVE: To report a case of rhabdomyolysis possibly due to combination therapy with colchicine and gemfibrozil. CASE SUMMARY: A 40-year-old man with amyloidosis and hepatitis B virus-related chronic liver disease was admitted to the university hospital because of fatigue, lack of appetite, dark brownish urine, and myalgia for 2 weeks. The patient was receiving colchicine and gemfibrozil. Elevations of serum creatine kinase, lactate dehydrogenase, and aspartate aminotransferase concentrations with myalgia were compatible with the diagnosis of rhabdomyolysis. DISCUSSION: To our knowledge, myopathy and rhabdomyolysis due to a combination of colchicine and gemfibrozil therapy have not been previously reported. Preexisting mild renal failure, hepatitis B-related chronic liver disease, and amyloidosis may be contributing risk factors for the development of rhabdomyolysis in this patient. An objective causality assessment revealed that the adverse drug event was possible. CONCLUSIONS: Patients receiving combination therapy with colchicine and gemfibrozil, especially those with renal and hepatic dysfunction, should be monitored for rhabdomyolysis, and concomitant colchicine and gemfibrozil therapy should be considered in the differential diagnosis of rhabdomyolysis.     

Rhabdomyolysis associated with simvastatin-nefazodone therapy

Simvastatin is a hydroxymethyl glutaryl coenzyme A reductase inhibitor commonly used to treat patients with hyperlipidemia. It is a safe and effective medication in most patients when used appropriately. A serious side effect known as rhabdomyolysis may rarely occur in patients who take simvastatin, especially at higher doses and with agents that interact and increase the level of simvastatin in the blood. We describe the case of a patient with rhabdomyolysis that occurred after the patient's simvastatin was titrated to 80 mg at approximately the same time that his antidepressant medication was switched to nefazodone. We found only two other similar cases in the literature, both of which were presented as letters to the editor in two different journals. We present this case to add to the literature and to assist practitioners by raising their awareness of this interaction so that it can be monitored.     

Rhabdomyolysis secondary to keyboard overuse: Occupational hazard of the computer age

A 33-year-old man presented with rhabdomyolysis with bilateral forearm pain and a profoundly elevated creatine phosphokinase. The cause of his illness appears to be computer keyboard overuse soon after a viral illness. This is the first case report directly linking rhabdomyolysis with keyboard overuse.     

Pneumothorax secondary to acupuncture therapy

A 27-year-old medical student seeking acupuncture therapy for a right levator scapular muscle spasm developed acute dyspnea, chest pain, and nonproductive cough within minutes following the treatment. The patient was later diagnosed with a 30% pneumothorax of the right lung. Pneumothorax is a well-known adverse effect of medical procedures such as central line placement, thoracocentesis and transbronchial lung biopsy. This case illustrates another iatrogenic cause of pneumothorax--acupuncture-induced pneumothorax. A review of the literature since 1985 reveals nine case reports of acupuncture-induced pneumothorax.     

Rhabdomyolysis and pancreatitis associated with coadministration of danazol 600 mg/d and lovastatin 40 mg/d

BACKGROUND: Danazol is a steroid analogue with anabolic and androgenic effects and is indicated for the treatment of endometriosis, fibrocystic diseases of the breast, and hereditary angioedema. Lovastatin has been prescribed to lower total cholesterol and low-density lipoprotein cholesterol, reducing cardiovascular-related morbidity and mortality in patients with hypercholesterolemia. As monotherapies, both danazol and lovastatin have been reported to induce myopathy and pancreatitis. CASE SUMMARY: A 59-year-old Asian woman (height, 155 cm; weight, 54 kg; and body mass index, 22.5 kg/m2) presented to the outpatient neurology clinic with acute progressive quadriparesis and generalized myalgia (without focal sensory loss, numbness, dizziness, diplopia, dysarthria, dysphagia, or sphincter incontinence), lasting for 5 days. She was admitted to the National Cheng Kung University Hospital, Tainan, Taiwan. The patient's medical history revealed multiple comorbidities (eg, end-stage renal disease, hypertension, diabetes mellitus) for which she was receiving concomitant medication. Her medication history revealed that at the time the patient presented, she was also receiving calcium bicarbonate 1500 mg/d, labetalol 100 mg/d, and glipizide 10 mg/d in the treatment of her other comorbid illnesses. The patient was also receiving alprazolam 0.5 mg/d for insomnia. Her medical records also revealed that lovastatin 40 mg/d (a particularly high dose and not recommended) had been administered for 7 weeks, and danazol 600 mg/d was added ( approximately 15 days later) to treat thrombocytopenia due to hypoplastic bone marrow. Laboratory findings revealed elevated creatine kinase (68,193 U/L), elevated pancreatic enzymes (amylase/lipase, 361/2788 U/L), and elevated liver enzymes (aspartate/alanine aminotransferase, 1496/1493 U/L), consistent with rhabdomyolysis and pancreatitis. After discontinuation of both drugs, the symptoms improved 5 days after admission and completely disappeared 1 month after admission. In addition, laboratory abnormalities completely normalized approximately 2 months after admission.Danazol was resumed to treat persistent thrombocytopenia, while lovastatin was replaced with ezetimibe 10 mg QD to treat high cholesterol (dyslipidemia). CONCLUSION: The coadministration of high-dose lovastatin and danazol was probably associated with rhabdomyolysis and pancreatitis in this patient with multiple underlying comorbidities for which concomitant medications were being administered.     

Rhabdomyolysis

Rhabdomyolysis is a severe clinical symptom of variable etiology. Acquired factors of exogenous origin such as traumata and endogenous metabolic disturbances have to be separated from hereditary disease as causative mechanism. Most frequently, exertional stress during hyperthermia, traumatic damage or ethanol abuse are observed. Almost independent of the diverse initial events, the pathogenesis follows a common final pathway with intracellular calcium accumulation and ATP depletion. Clinical symptoms vary. Seldom, the classical triad of muscle pain, weakness, and dark urine is observed. Recurrent episodes should raise suspicion of an inherited disorder. Severe complications are hypovolemia, electrolyte disorders with hyperkalemia and hypocalcemia resulting in life threatening arrhythmias, a compartment syndrome, disseminated intravascular coagulation and acute renal failure, which is frequently oligo-anuric. In combination with often severe underlying disease, renal failure causes death in 1/5 of the patients. The diagnosis is made with the determination of serum creatine kinase and the myoglobin levels in plasma and urine. Therapeutic options are to correct the hypovolemia with sufficient fluid supply, the prevention of oliguria using loop diuretics, alkalinization of the urine, normalization of serum electrolytes with reduction of hyperkaemia, and decompression of compartment syndromes. An underlying disease should be evaluated to initiate specific therapeutical and preventative steps. Avoiding pre-disposing factors by identifying the mechanisms of disease will reduce the occurrence of rhabdomyolysis with its still high mortality.     

Rhabdomyolysis

Rhabdomyolysis is the dissolution of skeletal muscle. Breakdown of the myocyte causes the extravasation of intracellular constituents, leading to a clinical syndrome--the classic triad of brown urine, muscle pain, and weakness. The pathogenesis of rhabdomyolysis is presented.     

Rhabdomyolysis

Rhabdomyolysis is a potentially life-threatening syndrome resulting from the breakdown of skeletal muscle fibers with leakage of muscle contents into the circulation. The most common causes are crush injury, overexertion, alcohol abuse and certain medicines and toxic substances. Several inherited genetic disorders, such as McArdle's disease and Duchenne's muscular dystrophy, are predisposing factors for the syndrome. Clinical features are often nonspecific, and tea-colored urine is usually the first clue to the presence of rhabdomyolysis. Screening may be performed with a urine dipstick in combination with urine microscopy. A positive urine myoglobin test provides supportive evidence. Multiple complications can occur and are classified as early or late. Early complications include severe hyperkalemia that causes cardiac arrhythmia and arrest. The most serious late complication is acute renal failure, which occurs in approximately 15 percent of patients with the syndrome. Early recognition of rhabdomyolysis and prompt management of complications are crucial to a successful outcome.     

Pathogenesis of tendon rupture secondary to fluoroquinolone therapy

Tendon rupture related to trauma and corticosteroid injection, in and about tendon insertion sites, is well documented in the literature. Rupture of tendon after fluoroquinolone therapy has been identified in the recent past. Both short- and long-term courses of antibiotic treatment with fluoroquinolone may precipitate alteration in tendon matrix leading to tendinopathy with subsequent rupture. The pathogenesis of tendon rupture secondary to fluoroquinolone therapy is presented.     

Generalized seizures secondary to high-dose busulfan therapy.

Two patients without prior histories of neurologic disorders experienced generalized seizures while receiving high-dose busulfan (total dose 16 mg/kg) as part of a preparative regimen for allogeneic bone marrow transplantation. A review of the literature revealed 14 similar occurrences. Maintenance of therapeutic blood concentrations of phenytoin in subsequent patients at our institution has resulted in no further patients experiencing generalized seizures. Prophylactic anticonvulsant therapy should be considered in patients receiving high doses of busulfan.