Lopid (Gemfibrozil) - Summary

LOPID SUMMARY

LOPID® (gemfibrozil tablets, USP) is a lipid regulating agent. It is available as tablets for oral administration. Each tablet contains 600 mg gemfibrozil.

LOPID (gemfibrozil tablets, USP) is indicated as adjunctive therapy to diet for:

1. Treatment of adult patients with very high elevations of serum triglyceride levels (Types IV and V hyperlipidemia) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them. Patients who present such risk typically have serum triglycerides over 2000 mg/dL and have elevations of VLDL-cholesterol as well as fasting chylomicrons (Type V hyperlipidemia). Subjects who consistently have total serum or plasma triglycerides below 1000 mg/dL are unlikely to present a risk of pancreatitis. LOPID therapy may be considered for those subjects with triglyceride elevations between 1000 and 2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. It is recognized that some Type IV patients with triglycerides under 1000 mg/dL may, through dietary or alcoholic indiscretion, convert to a Type V pattern with massive triglyceride elevations accompanying fasting chylomicronemia, but the influence of LOPID therapy on the risk of pancreatitis in such situations has not been adequately studied. Drug therapy is not indicated for patients with Type I hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of very low density lipoprotein (VLDL). Inspection of plasma refrigerated for 14 hours is helpful in distinguishing Types I, IV, and V hyperlipoproteinemia (ref. 5).
2. Reducing the risk of developing coronary heart disease only in Type IIb patients without history of or symptoms of existing coronary heart disease who have had an inadequate response to weight loss, dietary therapy, exercise, and other pharmacologic agents (such as bile acid sequestrants and nicotinic acid, known to reduce LDL- and raise HDL-cholesterol) and who have the following triad of lipid abnormalities: low HDL-cholesterol levels in addition to elevated LDL-cholesterol and elevated triglycerides (see WARNINGS, PRECAUTIONS, and CLINICAL PHARMACOLOGY). The National Cholesterol Education Program has defined a serum HDL-cholesterol value that is consistently below 35 mg/dL as constituting an independent risk factor for coronary heart disease (ref. 6). Patients with significantly elevated triglycerides should be closely observed when treated with gemfibrozil. In some patients with high triglyceride levels, treatment with gemfibrozil is associated with a significant increase in LDL-cholesterol. BECAUSE OF POTENTIAL TOXICITY SUCH AS MALIGNANCY, GALLBLADDER DISEASE, ABDOMINAL PAIN LEADING TO APPENDECTOMY AND OTHER ABDOMINAL SURGERIES, AN INCREASED INCIDENCE IN NON-CORONARY MORTALITY, AND THE 44% RELATIVE INCREASE DURING THE TRIAL PERIOD IN AGE-ADJUSTED ALL-CAUSE MORTALITY SEEN WITH THE CHEMICALLY AND PHARMACOLOGICALLY RELATED DRUG, CLOFIBRATE, THE POTENTIAL BENEFIT OF GEMFIBROZIL IN TREATING TYPE IIA PATIENTS WITH ELEVATIONS OF LDL-CHOLESTEROL ONLY IS NOT LIKELY TO OUTWEIGH THE RISKS. LOPID IS ALSO NOT INDICATED FOR THE TREATMENT OF PATIENTS WITH LOW HDL-CHOLESTEROL AS THEIR ONLY LIPID ABNORMALITY.

In a subgroup analysis of patients in the Helsinki Heart Study with above-median HDL-cholesterol values at baseline (greater than 46.4 mg/dL), the incidence of serious coronary events was similar for gemfibrozil and placebo subgroups (see Table I).

The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. Excess body weight and excess alcohol intake may be important factors in hypertriglyceridemia and should be managed prior to any drug therapy. Physical exercise can be an important ancillary measure, and has been associated with rises in HDL-cholesterol. Diseases contributory to hyperlipidemia such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy is sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia. In such cases, discontinuation of estrogen therapy may obviate the need for specific drug therapy of hypertriglyceridemia. The use of drugs should be considered only when reasonable attempts have been made to obtain satisfactory results with nondrug methods. If the decision is made to use drugs, the patient should be instructed that this does not reduce the importance of adhering to diet.

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NEWS HIGHLIGHTS

Media Articles Related to Lopid (Gemfibrozil)

AHA: FDA Drops Clopidogrel Bomb at AHA
Source: MedPage Today Gastroenterology [2009.11.17]
ORLANDO (MedPage Today) -- The FDA has issued a public health advisory warning patients and physicians that concommitant use of clopidogrel (Plavix) and omeprazole (Prilosec and Prilosec OTC) blunts the antiplatelet effect of clopidogrel, so the combination should be avoided.

ticlopidine, Ticlid
Source: MedicineNet Claudication Specialty [2009.09.10]
Title: ticlopidine, Ticlid
Category: Medications
Created: 12/31/1997
Last Editorial Review: 9/10/2009

FDA Announces New Warning On Plavix: Avoid Use With Prilosec/Prilosec OTC
Source: Health News from Medical News Today [2009.11.19]
Patients should avoid using the stomach acid reducer Prilosec/Prilosec OTC (omeprazole) with the anti-clotting drug Plavix (clopidogrel), the U.S. Food and Drug Administration warned on Nov. 17. New data suggest that when patients take both Prilosec and Plavix, Plavix's ability to block platelet aggregation (anti-clotting effect) may be reduced by about half.

AHA: Low Bleeding Rates Observed in Dabigatran Dose-Ranging Trial (CME/CE)
Source: MedPage Today Cardiovascular [2009.11.19]
ORLANDO (MedPage Today) -- The oral anticoagulant dabigatran did not appear to markedly increase major bleeding rates among post-MI patients who were already being treated with aspirin and clopidogrel (Plavix), researchers said here.

AHA: Prasugrel Incorporated into New STEMI Guidelines (CME/CE)
Source: MedPage Today Cardiovascular [2009.11.18]
ORLANDO (MedPage Today) -- A 60-milligram loading dose of prasugrel (Effient) is now a recommended alternative to clopidogrel for patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention, according to updated guidelines.

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Published Studies Related to Lopid (Gemfibrozil)

Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial. [2009.05]
BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) activators reduce inflammation and oxidative stress. Inflammation plays an important role in the initiation and maintenance of atrial fibrillation (AF). It has been suggested that PPARalpha activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARalpha activator gemfibrozil prevents or delays the development of AF in patients with coronary heart disease... CONCLUSIONS: In this post hoc analysis of a multicenter, double-blinded, randomized controlled trial, the PPARalpha activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease.

Effect of combination nicotinic acid and gemfibrozil treatment on intermediate density lipoprotein, and subclasses of low density lipoprotein and high density lipoprotein in patients with combined hyperlipidemia. [2009.02.01]
The goal of this study was to determine, using analytic ultracentrifugation, the effect of nicotinic acid alone or nicotinic acid added to gemfibrozil on lipoprotein subclass distribution, including intermediate-density lipoprotein (IDL; low-density to very low density flotation rate [S(f)] 12 to 20); low-density lipoprotein (LDL) subfractions LDL-I (S(f) 7 to 12), LDL-II (S(f) 5 to 7), LDL-III (S(f) 3 to 5), and LDL-IV (S(f) 0 to 3); and high-density lipoprotein (HDL) subfractions HDL(2) (high-density flotation rate 3.5 to 9.0) and HDL(3) (high-density flotation rate 0 to 3.5)...

Effects of gemfibrozil and atorvastatin on the pharmacokinetics of repaglinide in relation to SLCO1B1 polymorphism. [2008.10]
In a randomized crossover study, 24 SLCO181-genotyped healthy volunteers were given daily doses of 1,200 mg gemfibrozil, 40 mg atorvastatin, or placebo, followed by 0.25 mg of repaglinide on day 3. The mean increase in the repaglinide area under the plasma concentration-time curve from 0 h to infinity (AUC(0-infinity)) produced by gemfibrozil was larger in individuals with the SLCO1B1 c.521CC genotype (n = 6) than in those with the c.521TC (n = 6) and c.521TT (n = 12) genotypes, by factors of 1.56 (P = 0.004) and 1.54 (P = 0.002), respectively...

The effect of gemfibrozil on repaglinide pharmacokinetics persists for at least 12 h after the dose: evidence for mechanism-based inhibition of CYP2C8 in vivo. [2008.09]
Repaglinide is metabolized by cytochrome P450 (CYP) 2C8 and 3A4...

Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). [2008.02]
CONCLUSIONS: In VA-HIT, gemfibrozil resulted in weight loss associated with reductions in insulin. With weight loss gemfibrozil produced a significant reduction in CHD events that did not occur in the absence of weight loss.

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Clinical Trials Related to Lopid (Gemfibrozil)

Drug-Drug Interaction Study of Mitiglinide and Gemfibrozil [Completed]

Drug Interaction Study of Lopinavir/Ritonavir and Gemfibrozil [Active, not recruiting]
This study will determine whether the protease inhibitor lopinavir/ ritonavir (Kaletra™ (Trademark)), which is used to treat HIV disease, lowers blood levels of the lipid-regulating drug gemfibrozil (Lopid™ (Trademark)) in HIV-negative healthy volunteers. Many patients with HIV infection who take protease inhibitors have abnormally high lipids (cholesterol and triglycerides). Gemfibrozil, commonly used to treat high triglycerides, often is not effective in HIV-infected patients taking protease inhibitors, possibly because of an interaction between the two medicines that causes a lowering of gemfibrozil's levels in the blood. Results from this study will give researchers information on whether lopinavir/ ritonavir affects the blood levels of gemfibrozil.

Healthy, normal volunteers between 18 and 65 years old who test negative for HIV may be eligible for this study.

On study day 1, subjects have a blood sample drawn from a catheter inserted into a vein in the arm to determine pre-dosing blood levels of gemfibrozil. They then take a gemfibrozil tablet and are given breakfast 30 minutes after taking the drug. Blood samples are obtained through the catheter at 0, 1, 1. 5, 2, 3, 4, 6, 8, 12, and 24 hours after dosing to determine gemfibrozil levels at those intervals. At the end of 12 hours, the catheter is removed and the subject is discharged from the clinic. The next morning subjects return to the clinic for another blood sample, collected through a vein in the arm.

Subjects begin taking lopinavir/ ritonavir between 7 and 35 days after their first dose, depending on their schedule and the clinic schedule. On the fourteenth day of dosing subjects come to the clinic and are given a single dose of gemfibrozil, as on study day 1, and have breakfast 30 minutes later. Blood samples are collected to determine gemfibrozil levels just like on study days 1 and 2. An additional sample is collected for routine lab tests.

Study Evaluating Potential Interaction Between SAM-531 And Gemfibrozil When Co-Administered [Recruiting]

Effect of Gemfibrozil on Serum Glycosylphosphatidylinositol (GPI) Phospholipase D and Triglycerides [Completed]

The VA HDL Intervention Trial [Completed]
This was a double-blind randomized trial comparing 1200 mg per day of gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL-C of 40mg/dl or less, an LDL-C of 140 mg/dl or less, and triglycerides of 300mg/dl or less. The primary outcome was nonfatal myocardial infarction(MI) or death from coronary causes. The midian follow-up was 5. 1 years. There was a risk reduction of 22% in the primary outcome (p=.0006) and 24% risk reduction in the combined endpoint of stroke, MI, and CHD death. The rate of events was reduced by raising HDL-C and lowering triglycerides without lowering LDL-C (N Engl J Med 1999;341: 410-418).

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