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GEMFIBROZIL


DIR Classification


Classification:Most-DIR concern
Severity Score:4

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

  • CONTRAINDICATIONS
  • 1. Combination therapy of gemfibrozil with cerivastatin due to the increased risk of myopathy and rhabdomyolysis (see WARNINGS).
  • 2. Hepatic or severe renal dysfunction, including primary biliary cirrhosis.
  • 3. Preexisting gallbladder disease (seeWARNINGS).
  • 4. Hypersensitivity to gemfibrozil.
  • WARNINGS
  • Concomitant therapy with gemfibrozil and an HMG-CoA reductase inhibitor is associated with an increased risk of skeletal muscle toxicity manifested as rhabdomyolysis, markedly elevated creatine kinase (CPK) levels and myoglobinuria, leading in a high proportion of cases to acute renal failure and death. Because of an observed marked increased risk of myopathy and rhabdomyolysis, the specific combination of gemfibrozil and cerivastatin is absolutely contraindicated (see CONTRAINDICATIONS). IN PATIENTS WHO HAVE HAD AN UNSATISFACTORY LIPID RESPONSE TO EITHER DRUG ALONE, THE BENEFIT OF COMBINED THERAPY WITH GEMFIBROZIL AND HMG-CoA REDUCTASE INHIBITORS OTHER THAN CERIVASTATIN DOES NOT OUTWEIGH THE RISKS OF SEVERE MYOPATHY, RHABDOMYOLYSIS, AND ACUTE RENAL FAILURE (refs. 8, 9, 10, 11) (seeDRUG INTERACTIONS). The use of fibrates alone, including gemfibrozil, may occasionally be associated with myositis. Patients receiving gemfibrozil and complaining of muscle pain, tenderness or weakness should have prompt medical evaluation for myositis, including serum creatine-kinase level determination. If myositis is suspected or diagnosed, gemfibrozil therapy should be withdrawn.
  • PRECAUTIONS
  • Drug Interactions
  • HMG-CoA reductase inhibitors: The risk of myopathy and rhabdomyolysis is increased with combined gemfibrozil and HMG-CoA reductase inhibitor therapy (seeCONTRAINDICATIONS). Myopathy or rhabdomyolysis with or without acute renal failure have been reported as early as three weeks after initiation of combined therapy or after several months (refs. 8, 9, 10, 11). (SeeWARNINGS.) There is no assurance that periodic monitoring of creatine kinase will prevent the occurrence of severe myopathy and kidney damage.
  • REFERENCES
  • 8. Pierce LR, Wysowski DK, Gross TP. Myopathy and rhabdomyolysis associated with lovastatin/gemfibrozil combination therapy. JAMA 1990;264:71-75.
  • 9. Bermingham RP, Whitsitt TB, Smart ML et al. Rhabdomyolysis in a patient receiving the combination of cerivastatin and gemfibrozil. Am J Health-Syst Pharm 2000;57:461-464.
  • 10. Duell PB, Connor WE, Illingworth DR. Rhabdomyolysis after taking atorvastatin with gemfibrozil. Am J Cardiol 1998;81:368-369.
  • 11. Tal A, Rajeshawari M, Isley W. Rhabdomyolysis associated with simvastatin/gemfibrozil therapy. South Med J 1997;90:546-547.

Postmarketing Surveillance

Contingency Table:

Current Drug
Other Drugs
Rhabdomyolysis
1096
41816
Other ADRs
1632
14115647

Odds Ratio = 226.699

Drug Property Information



ATC Code(s):
  • C10AB04 - gemfibrozil
    • C10AB - Fibrates
    • C10A - "LIPID MODIFYING AGENTS, PLAIN"
    • C10 - LIPID MODIFYING AGENTS
    • C - CARDIOVASCULAR SYSTEM
Active Ingredient:gemfibrozil
Active Ingredient UNII:Q8X02027X3
Drugbank ID:DB01241
PubChem Compound:3463
CAS Number:25812-30-0
Dosage Form(s):tablet
Route(s) Of Administrator:oral
Daily Dose:
  • 1200.0 mg/day C10AB04
Chemical Structure:
SMILE Code:
CC1=CC(=C(C=C1)C)OCCCC(C)(C)C(=O)O

Reference

COHORT STUDY:

N/A

OTHER REFERENCE(S):

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94: [Cerivastatin and gemfibrozil: a dangerous combination].

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95: [Fatal rhabdomyolysis caused by cerivastatin].

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97: Bayer pulls cerivastatin (Baycol) from market.

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98: [Severe rhabdomyolysis associated with cerivastatin and gemfibrozil].

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99: Baycol withdrawn from market.

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100: Bayer decides to withdraw cholesterol lowering drug.

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101: Statin-fibrate combination therapy.

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105: Rhabdomyolysis after cerivastatin-gemfibrozil therapy in an HIV-infected patient with protease inhibitor-related hyperlipidemia.

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114: Clinical pharmacology of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

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115: Rhabdomyolysis associated with the combined use of hydroxymethylglutaryl-coenzyme A reductase inhibitors with gemfibrozil and macrolide antibiotics.

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116: Dual hepatic metabolism of cerivastatin--clarifications.

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118: Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias.

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119: Rhabdomyolysis after taking atorvastatin with gemfibrozil.

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120: Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia.

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122: Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil.

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123: Rhabdomyolysis and acute renal failure associated with gemfibrozil therapy.

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126: Approaches to the treatment of hyperlipidemia in the solid organ transplant recipient.

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127: Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors.

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128: Pharmacokinetics of the combination of fluvastatin and gemfibrozil.

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130: Rhabdomyolysis and acute renal failure in a heart transplant recipient treated with hypolipemiants.

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132: Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias.

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133: Hyperlipidemia after heart transplantation: report of a 6-year experience, with treatment recommendations.

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134: Lovastatin-induced rhabdomyolysis in the absence of concomitant drugs.

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135: Gemfibrozil-induced myopathy.

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136: [Side effects of fibrates (except liver and muscle)].

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137: Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins.

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138: Hyperlipoproteinemia in chronic renal failure: pathophysiological and therapeutic aspects.

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139: Myopathy and rhabdomyolysis with lovastatin taken with gemfibrozil.


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141: Lovastatin-induced acute rhabdomyolysis.

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142: Rhabdomyolysis and acute renal failure induced by combination lovastatin and gemfibrozil therapy.

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143: The role of cholesterol-lowering agents in drug-induced rhabdomyolysis and polymyositis.

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