Reactions 1236 - 24 Jan 2009

SAtorvastatin/lovastatin/niacin

Myotoxicity in a patient with an A3243G mutation:case report

A female adolescent [age not clearly stated] developedmyotoxicity on three separate occasions duringhypercholesterolaemia treatment with lovastatin,atorvastatin or niacin [nicotinic acid; times to reactiononsets not stated]. She was subsequently found to have anA3243G mutation.

Since the girl was 15 years old she had experiencedprogressive moderate to severe bilateral sensorineuralhearing loss. She presented at 16 years of age withproteinuria during routine screening. Over the subsequent4 months progression of renal dysfunction was noted; focalglomerulosclerosis and global sclerosis were evident uponrenal biopsy. She was started on lovastatin 20mg daily forpersistent hypercholesterolaemia. She developed muscleaches with a creatine kinase level of 334–833 U/L, analdolase level of 8.7 U/L and a myoglobin level of157 ng/mL. After about 2 months of administration,lovastatin was withdrawn and her muscle enzyme levelsreturned to normal.

The girl then began receiving atorvastatin [dosage notstated]. She developed muscle pain, lower limb swellingand a creatine kinase level of up to 397 IU/L. Atorvastatinwas discontinued. At this time an elevated arterial lactatelevel was also noted (5.8 mmol/L). A metabolic myopathywas suspected. Scattered ragged red fibers were evidentduring muscle biopsy, some of which showed decreasedcytochrome c oxidase staining.

The girl began receiving ubidecarenone [coenzyme-Q10]supplementation and niacin [dosage not stated]. Howeverniacin was discontinued due to a creatine kinase level of2223 U/L. She rapidly progressed to end stage renal failure.Creatine kinase levels following discontinuation of lipidlower agents were 57–78 U/L. Her family history wasremarkable for proteinuria and high-frequencysensorineural hearing loss in her younger sister and amaternal aunt who had seizures and hearing loss.Subsequent genetic analysis revealed an A3243G mutation,a common mutation in patients with MELAS syndrome(mitochondrial encephalopathy, lactic acidosis and strokelike episodes). [Patient outcome not clearly stated].

Author comment: "[T]he patient’s pre-existingmitochondrial dysfunction may have rendered her sensitive toeven low levels of statin drugs. In addition, her renaldysfunction may also have resulted in unexpectedly hightissue concentration of the drug in muscle. Conversely, it isunclear how much rhabdomyolysis and myoglobinuria mayhave contributed to her rapidly progressive renal failure."Tay SKH, et al. Myotoxicity of lipid-lowering agents in a teenager with MELASmutation. Pediatric Neurology 39: 426-428, No. 6, Dec 2008 -Singapore 801135259

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Reactions 24 Jan 2009 No. 12360114-9954/10/1236-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved