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Medication Safety Issues
Sound-alike/look-alike issues:
Lopid® may be confused with Levbid®, Lipitor®, Lodine®, Lorabid®, Slo-bid™
Pronunciation
(jem FI broe zil)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hypertriglyceridemia in Fredrickson types IV and V hyperlipidemia for patients who are at greater risk for pancreatitis and who have not responded to dietary intervention; to reduce the risk of CHD development in Fredrickson type IIb patients without a history or symptoms of existing CHD who have not responded to dietary and other interventions (including pharmacologic treatment) and who have decreased HDL, increased LDL, and increased triglycerides
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in animal reproduction studies. There are no adequate and well-controlled studies in pregnant women. Use only if benefits outweigh the risks.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to gemfibrozil or any component of the formulation; hepatic or severe renal dysfunction; primary biliary cirrhosis; pre-existing gallbladder disease; concurrent use with repaglinide
Warnings/Precautions
Concerns related to adverse effects:
• Cholelithiasis: May increase risk of cholelithiasis; discontinue if gallstones are found upon gallbladder studies.
• Elevated transaminases: Elevations in serum transaminases may be seen with use; periodic monitoring recommended.
• Hematologic effects: May cause mild decreases in hemoglobin, hematocrit, and WBC upon initiation which usually stabilizes with long-term therapy. Anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have rarely been reported. Periodic monitoring recommended during the first year of therapy.
• Malignancy: Possible increased risk of malignancy.
• Myopathy/rhabdomyolysis: Has been associated with rare myositis or rhabdomyolysis; patients should be monitored closely. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine.
Disease-related concerns:
• Renal impairment: Use with caution in patients with mild-to-moderate renal impairment; contraindicated in patients with severe impairment. Deterioration eterioration has been seen when used in patients with a serum creatinine >2 mg/dL.
Concurrent drug therapy issues:
• HMG-CoA reductase inhibitors: Use caution with HMG-CoA reductase inhibitors; may lead to myopathy, rhabdomyolysis.
• Warfarin: Use with caution in patient taking warfarin; adjustments in warfarin therapy may be required.
Other warnings/precautions:
• Appropriate use: Secondary causes of hyperlipidemia should be ruled out prior to therapy. Be careful in patient selection, this is not a first- or second-line choice; other agents may be more suitable. Discontinue if lipid response not seen.
Adverse Reactions
>10%: Gastrointestinal: Dyspepsia (20%)
1% to 10%:
Cardiovascular: Atrial fibrillation (1%)
Central nervous system: Fatigue (4%), vertigo (2%)
Dermatologic: Eczema (2%), rash (2%)
Gastrointestinal: Abdominal pain (10%), nausea/vomiting (3%)
<1% or case reports with probable causation (limited to important or life-threatening): Alkaline phosphatase increased, anemia, angioedema, arthralgia, bilirubin increased, blurred vision, bone marrow hypoplasia, cholelithiasis, cholecystitis, cholestatic jaundice, creatine phosphokinase increased, depression, dermatitis, dermatomyositis/polymyositis, dizziness, eosinophilia, exfoliative dermatitis, headache, hypoesthesia, hypokalemia, impotence, laryngeal edema, leukopenia, libido decreased, myalgia, myasthenia, myopathy, nephrotoxicity, painful extremities, paresthesia, peripheral neuritis, pruritus, Raynaud's phenomenon, rhabdomyolysis, somnolence, synovitis, taste perversion, transaminases increased, urticaria
Reports where causal relationship has not been established: Alopecia, anaphylaxis, cataracts, colitis, confusion, decreased fertility (male), drug-induced lupus-like syndrome, extrasystoles, hepatoma, intracranial hemorrhage, pancreatitis, peripheral vascular disease, photosensitivity, positive ANA, renal dysfunction, retinal edema, seizure, syncope, thrombocytopenia, vasculitis, weight loss
Metabolism/Transport Effects
Substrate of CYP3A4 (minor); Inhibits CYP1A2 (moderate), 2C8 (strong), 2C9 (strong), 2C19 (strong)
Drug Interactions
Antidiabetic Agents (Thiazolidinedione): Gemfibrozil may decrease the metabolism of Antidiabetic Agents (Thiazolidinedione). Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Fibric Acid Derivatives. Management: Separate doses by at least 2 hours to minimize this interaction; fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant. Exceptions: Colesevelam. Risk D: Consider therapy modification
Carvedilol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk X: Avoid combination
Colchicine: Fibric Acid Derivatives may enhance the myopathic (rhabdomyolysis) effect of Colchicine. Risk C: Monitor therapy
CycloSPORINE: May enhance the nephrotoxic effect of Fibric Acid Derivatives. Fibric Acid Derivatives may decrease the serum concentration of CycloSPORINE. Management: Careful consideration of the risks and benefits should be undertaken prior to use of this combination; extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary. Risk D: Consider therapy modification
CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP2C8 Substrates (High risk): CYP2C8 Inhibitors (Strong) may decrease the metabolism of CYP2C8 Substrates (High risk). Risk D: Consider therapy modification
CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
Ezetimibe: Fibric Acid Derivatives may increase the serum concentration of Ezetimibe. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors: Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Gemfibrozil may increase the serum concentration of HMG-CoA Reductase Inhibitors. Exceptions: Fluvastatin. Risk D: Consider therapy modification
Repaglinide: Gemfibrozil may increase the serum concentration of Repaglinide. The addition of itraconazole may augment the effect of gemfibrozil on repaglinide. Risk X: Avoid combination
Sulfonylureas: Fibric Acid Derivatives may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Treprostinil: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Treprostinil. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Fibric Acid Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol to decrease triglycerides.
Food: When given after meals, the AUC of gemfibrozil is decreased.
Storage
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light and moisture.
Mechanism of Action
The exact mechanism of action of gemfibrozil is unknown, however, several theories exist regarding the VLDL effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels; increases HDL-cholesterol; the mechanism behind HDL elevation is currently unknown
Pharmacodynamics/Kinetics
Onset of action: May require several days
Absorption: Well absorbed
Protein binding: 99%
Metabolism: Hepatic via oxidation to two inactive metabolites; undergoes enterohepatic recycling
Half-life elimination: 1.5 hours
Time to peak, serum: 1-2 hours
Excretion: Urine (~70% primarily as conjugated drug); feces (6%)
Dosage
Adults: Oral: 600 mg twice daily; administer 30 minutes before breakfast and dinner
Dosage adjustment in renal impairment:
Mild-to-moderate impairment: Use caution; deterioration of renal function has been reported in patients with baseline serum creatinine >2 mg/dL
Severe impairment: Use is contraindicated
Hemodialysis: Not removed by hemodialysis; supplemental dose is not necessary
Dosage adjustment in hepatic impairment: Use is contraindicated
Administration: Oral
Administer 30 minutes prior to breakfast and dinner.
Monitoring Parameters
Serum cholesterol, LFTs periodically, CBC periodically (first year)
Dietary Considerations
Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3-6 months and the diet should be continued during drug therapy. Should be taken 30 minutes prior to breakfast and dinner
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Should be taken 30 minutes before meals. Take with milk or meals if GI upset occurs. Avoid alcohol. Follow dietary recommendations of prescriber. You will need check-ups and blood work to assess effectiveness of therapy. You may experience loss of appetite and flatulence (small, frequent meals may help); or diarrhea. Report severe stomach pain, nausea, vomiting; headache; persistent diarrhea; or vision changes. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.
Geriatric Considerations
Gemfibrozil is the drug of choice for the treatment of hypertriglyceridemia and hypoalphaproteinemia in the elderly; it is usually well tolerated; myositis may be more common in patients with poor renal function. The definition of and, therefore, when to treat hyperlipidemia in the elderly is a controversial issue. The National Cholesterol Education Program recommends that all adults maintain a plasma cholesterol <160 mg/dL. Older adults with one additional risk factor, goal LDL would be <130 mg/dL. It is the authors' belief that pharmacologic treatment be reserved for those who are unable to obtain a desirable plasma cholesterol concentration by diet alone and for whom the benefits of treatment are believed to outweigh the potential adverse effects, drug interactions, and cost of treatment.
Anesthesia and Critical Care Concerns/Other Considerations
Gemfibrozil increases HDL, decreases total cholesterol and triglycerides. A recent study (VA-HIT), showed that gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with CHD and with low HDL-cholesterol (Rubins, 1999). These findings suggest that the rate of coronary events is reduced by raising HDL-cholesterol levels and lowering triglyceride levels. The treatment of low HDL in the general population, is not established.
Cardiovascular Considerations
Fibric acids decrease triglycerides (TGs) by 20% to 50%, and increase HDL-cholesterol (HDL-C) by 10% to 20%. They decrease LDL-cholesterol (LDL-C) by 5% to 20%, however, LDL-C actually may increase by 10% to 30% when fibrates are initiated in patients with high TGs (>400 mg/dL). Although combination therapy with statins has been used in patients with resistant hyperlipidemias, keep vigilant for signs and symptoms of myopathy.
A recent study (VA-HIT) showed that gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with CHD and isolated low HDL-C ?40 mg/dL (average: 32 mg/dL) with LDL-C ?140 mg/dL (average: 111 mg/dL) and TGs ?300 mg/dL (average: 161 mg/dL) (Rubins, 1999). These findings suggest that the rate of coronary events is reduced by raising HDL-cholesterol levels in patients with isolated low HDL-C levels. The treatment of isolated low HDL-C in the general population is usually reserved for patients at high risk for developing CAD with therapy focused on addressing the other risk factors. At present, minimal if any, data are available on how to use medications in patients with low HDL-C and no risk factors.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause sedation or depression
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other pharmacological agents patient may be taking (eg, increased risk of myopathy, rhabdomyolysis, hypoglycemia, and toxicity). Assess results of laboratory tests (serum cholesterol and LFTs), therapeutic effectiveness (decreased lipid levels), and adverse reactions (eg, gastrointestinal disturbances) periodically during therapy. Teach proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 600 mg
Lopid®: 600 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Gemfibrozil)
600 mg (60): $15.99
Tablets (Lopid)
600 mg (60): $142.20
References
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, 57:461-4.
Duell PB, Connor WE, and Illingworth DR, “Rhabdomyolysis After Taking Atorvastatin With Gemfibrozil,” Am J Cardiol, 1998, 81:368-9.
“Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III),” JAMA, 2001, 285(19):2486-97.
Frick MH, Heinonen OP, Huttunen JK, et al, “Efficacy of Gemfibrozil in Dyslipidaemic Subjects With Suspected Heart Disease. An Ancillary Study in the Helsinki Heart Study Frame Population,” Ann Med, 1993, 25(1):41-5.
Mahley RW and Bersot TP, “Drug Therapy for Hypercholesterolemia and Dyslipidemia,” Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed, Hardman JE and Limbird LE, eds, New York, NY: McGraw-Hill, 2001, 993-5.
Pierce LR, Wysowski DK, and Gross TP, “Myopathy and Rhabdomyolysis Associated With Lovastatin/Gemfibrozil Combination Therapy,” JAMA, 1990, 264(1):71-5.
Rubins HB, Robbins SJ, Collins D, et al, “Gemfibrozil for the Secondary Prevention of Coronary Heart Disease in Men With Low Levels of High-Density Lipoprotein Cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group,” N Engl J Med, 1999, 341(6):410-8.
Tal A, Rajeshawari M, and Isley W, “Rhabdomyolysis Associated With Simvastatin/Gemfibrozil Therapy,” South Med J, 1997, 90(5):546-7.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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