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U.S. Department of Health and Human Services

Safety

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Mevacor (lovastatin) Tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – February 2012

 

Summary View

 

CONTRAINDICATIONS

  • Concomitant administration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone)

 

WARNINGS

Myopathy/Rhabdomyolysis
  • Mevacor therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Mevacor therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.
  • Certain drugs which inhibit this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, and posaconazole, the macrolide antibiotics erythromycin and clarithromycin, and the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, or the antidepressant nefazodone…
  • Although not studied clinically, voriconazole has been shown to inhibit lovastatin metabolism in vitro (human liver microsomes). Therefore, voriconazole is likely to increase the plasma concentration of lovastatin. It is recommended that dose…
  • Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with lovastatin coadministered with colchicine…
  • Ranolazine: The risk of myopathy, including rhabdomyolysis, may be increased by concomitant administration of ranolazine
Liver Dysfunction
  • It is recommended that liver enzyme tests be obtained prior to initiating therapy with Mevacor and repeated as clinically indicated.
  • There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including lovastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Mevacor, promptly interrupt therapy. If an alternate etiology is not found do not restart Mevacor.

 

Information for patients
  • It is recommended that liver enzymes be checked before starting therapy, and if signs or symptoms of liver injury occur. All patients treated with Mevacor should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
Drug Interactions/CYP3A4 Interaction
  • Strong inhibitors of CYP3A4 (below)e.g., itraconazole, ketoconazole, posaconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, and erythromycin), and large quantities of grapefruit juice (>1 quart daily) increase the risk of myopathy by reducing the elimination of lovastatin.
  • In vitro studies have demonstrated that voriconazole inhibits the metabolism of lovastatin. Adjustment of the lovastatin dose may be needed to reduce the risk of myopathy, including rhabdomyolysis, if voriconazole must be used concomitantly with lovastatin.
Other Drug Interactions
  • Cyclosporine: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of cyclosporine
  • Danazol, Diltiazem, or Verapamil: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol, diltiazem, or verapamil particularly with higher doses of lovastatin
  • Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with lovastatin coadministered with colchicine.
  • Ranolazine: The risk of myopathy, including rhabdomyolysis, may be increased by concomitant administration of ranolazine.
Endocrine Function
  • Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including Mevacor.

 

ADVERSE REACTIONS

Concomitant Therapy
  • Caution should be used when prescribing other fibrates or lipid-lowering doses (≥1 g/day) of niacin with lovastatin
Neurological:
  • There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Gastrointestinal:
  • fatal and non-fatal hepatic failure