Gemfibrozil-Induced Myopathy

Magarian, Gregory J.; Lucas, Linda M.; Colley, Colleen A.

doi:10.1001/archinte.1991.00400090143027

Cited by 61 publications

(9 citation statements)

References 10 publications

(2 reference statements)

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“…Clofibrate clearly causes myopathy in a small number of patients [22]. A rare myopathy associated with gemfibrozil alone has also been described, especially in patients who may have elevated gemfibrozil metabolites due to renal insufficiency [23].…”

Section: Fibrate-statin Combination Therapymentioning

confidence: 99%

Combination drug therapy for combined hyperlipidemia

Guyton

1999

Curr Cardiol Rep

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Combination therapy for hyperlipidemia, especially combined hyperlipidemia, may have advantages over single drug therapy, affording better improvement in lipoprotein risk factors and possibly better prevention of atherothrombotic events. Although preliminary experience has been gained using treatment combinations of niacin with statins, and fibrates with statins, few studies have focused on angiographic or clinical outcomes. Both of these treatment combinations increase the risk of drug-induced myopathy and rhabdomyolysis. Current estimates of myopathy incidence are much lower than original estimates, but the relative safety of combined therapy might depend upon employing low or moderate statin doses. Safety depends critically upon educating the patient to respond appropriately to muscle symptoms, to intercurrent illness, and to concurrent use of certain other medications. Other useful drug combinations include those derived by addition of fish oil, bile acid binding resins, or stanol esters, as well as nonstatin combinations such as niacin-resin or fibrate-niacin.

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Section: Fibrate-statin Combination Therapymentioning

confidence: 99%

Combination drug therapy for combined hyperlipidemia

Guyton

1999

Curr Cardiol Rep

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“…These effects are due to two factors: activation of peroxisome proliferators-activated alpha and induction of the overexpression of genes containing a peroxisome proliferators *Address correspondence to this author at the Pharmacovigilance Unit, Second Chair of Pharmacology, School of Medicine, Universidad de Buenos Aires, Paraguay 2155 -Piso 16, C1121ABG, Buenos Aires, Argentina; Tel: +54 11 4961-0943; Fax: +54 11 4961-0943; E-mail: guillermokeller@gmail.com response element in their promoter [3]. Several severe pharmacokinetic interactions have been described with these agents [4]. Mycophenolate, an antimetabolite, has become one of the most common prescribed immunosuppressant.…”

Section: Introductionmentioning

confidence: 99%

Severe Neutropenia in a Renal Transplant Patient Suggesting an Interaction Between Mycophenolate and Fenofibrate

Álvarez¹,

Egozcue²,

Sleiman³

et al. 2012

CDS

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Objective: To describe a patient in whom initiation of micronized fenofibrate precipitated mycophenolate induced neutropenia.Case Summary: A 57-year-old man was admitted to the hospital because of febrile neutropenia. He had undergone kidney transplantation seventeen years ago. The patient's immunosuppressive maintenance regimen consisted of mycophenolate mofetil (MMF) 500 mg three times a day, and meprednisone 4 mg daily. His medical history included, hypertension treated with losartan 50mg daily, and dyslipidemia treated with ezetimibe 10mg /simvastatin 20mg for four years (until 2 weeks before admission when micronized fenofibrate 200 mg per day was started because of persistently elevated triglycerides levels. On presentation temperature was 37.8ºC and initial laboratory tests showed 3130 White Blood Cell Count(WBC)/μL with neutropenia (absolute neutrophil count (ANC) 313/μL) Fenofibrate and mycophenolate mofetil were discontinued, piperacillin tazobactam 4.5gr three times a day and granulocyte stimulation factor 300 μg/day were started. Three days after admission WBC was 7280/μL, neutrophils: 22%, ANC: 1160/mm 3 . Mycophenolate mofetil was restarted and granulocyte stimulation factor was discontinued. One month after discharge his WBC was 4480/μL and ANC 1926/μL. Discussion:The initiation of fenofibrate in a patient on stable and therapeutic doses of mycophenolate may have precipitated mycophenolate induced neutropenia, a well described, dose dependent phenomenon. Mycophenolic acid (MPA) displays a complex pharmacokinetic profile susceptible to potential significant interactions with fenofibrate. Since approximately 99% of MPA and fenofibrate bind to albumin, displacement may occur, leading to increased free MPA. Second competition of fenofibric acid for UGT1A9 an enzyme implicated in conjugation of MPA may have decreased its metabolism. The combination of these two effects may increase the risk of dose dependent neutropenia. Using the Interaction Probability Scale (DIPS), the interaction was designated as probable.Conclusions: Until further evidence is available, when fenofibrate is started in a renal transplant patient on mycophenolate careful monitoring should be considered to avoid potentially fatal complications.

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“…Most lipid-lowering therapies including statins, fibrates, and niacin may cause muscle toxicity [4][5][6][7][8]. Muscle pathology and abnormal excretion of urinary organic acids in patients who are intolerant of lipid-lowering drugs suggest altered fat metabolism [9,10].…”

Section: Introductionmentioning

confidence: 99%

Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids

Phillips

Ciaraldi

Kim

et al. 2008

Endocr

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Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.

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Gemfibrozil-Induced Myopathy

Cited by 61 publications

References 10 publications

Combination drug therapy for combined hyperlipidemia

Combination drug therapy for combined hyperlipidemia

Severe Neutropenia in a Renal Transplant Patient Suggesting an Interaction Between Mycophenolate and Fenofibrate

Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids

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