The P-I-E-N-O Parkinsn's List Drug Database

gemfibrozil / Lopid^TM

CHOLESTEROL CONTROL

Description: Gemfibrozil is a fibric acid antilipemic agent similar to clofibrate. Gemfibrozil possesses biologic actions distinct from those of clofibrate. Gemfibrozil effectively lowers serum triglycerides and also produces favorable changes in lipoproteins, but the HMG-CoA reductase inhibitors are more effective in hyperlipoproteinemia. The Helsinki Heart Study, published in 1987, found gemfibrozil effective in reducing the risk of coronary heart disease in men.¥ Gemfibrozil was approved by the FDA in 1981.

Mechanism of Action: The exact mechanism of action has not been fully defined. Gemfibrozil has been shown to inhibit peripheral lipolysis and to decrease hepatic extraction of free fatty acids, which, in turn, decreases hepatic triglyceride production. Gemfibrozil also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. Gemfibrozil may also accelerate turnover and removal of cholesterol from the liver and increase excretion of cholesterol into the feces. Gemfibrozil's effects on triglyceride concentrations and HDL fraction have been shown to be greater than those of clofibrate, to which it is structurally related.

Gemfibrozil has variable effects on LDL cholesterol. Although it causes moderate reductions in patients with type IIa hyperlipoproteinemia, changes in patients with either type IIb or type IV hyperlipoproteinemia are unpredictable. In general, the HMG-CoA reductase inhibitors are more effective than gemfibrozil in reducing LDL cholesterol.

Pharmacokinetics: Gemfibrozil is rapidly and completely absorbed from the GI tract and undergoes enterohepatic recirculation. Plasma concentrations correlate with dose but not response. Protein binding is approximately 95%. Gemfibrozil is metabolized by the liver and excreted by the kidneys, mainly as metabolites; fecal elimination is about 6%. One of the metabolites possesses pharmacologic activity. Elimination half-life is approximately 1.5 hours.

CONTRAINDICATIONS/PRECAUTIONS: Gemfibrozil should be used cautiously in patients with hepatic disease, especially primary biliary cirrhosis, since it can decrease clearance of the drug. In patients with biliary cirrhosis, further elevations of serum cholesterol can occur.

Gemfibrozil elimination is reduced in patients with renal impairment. Lower doses should be considered in these patients.

Gemfibrozil is related to clofibrate, which has been associated with gallbladder disease. Although the association between gemfibrozil and gallbladder disease is less defined, gemfibrozil should be used cautiously in this patient group because these patients had a higher mortality.

Since safety and efficacy in children under 18 years of age has not been demonstrated, gemfibrozil is contraindicated in pediatric patients.

Gemfibrozil has been shown to have detrimental effects on fetal growth and development in laboratory animals. Adequate or well-controlled studies have not been done in humans. Use of gemfibrozil during pregnancy should be avoided unles the potential benefits justify the potential risks to the fetus.

DRUG INTERACTIONS: Like clofibrate, gemfibrozil can potentiate warfarin's effects. This interaction may be magnified in patients with hyperthyroidism. While warfarin may be added to the regimen of patients already receiving gemfibrozil, prothrombin times should be carefully monitored if gemfibrozil is added to the regimen of patients receiving warfarin.

Concurrent use of gemfibrozil and lovastatin may be associated with increases in creatine kinase (CK), an increased risk of rhabdomyolysis, and myoglobinuria leading to acute renal failure. These effects can occur from 3 weeks to several months after initiating the combined therapy. In a small study of 70 patients with normal renal function, the incidence of elevated CK concentrations was 7.1% during combined therapy. Although these two drugs may be used together safely, CK levels should be monitored closely during the initial weeks of therapy.

Colestipol can reduce the oral bioavailability of gemfibrozil if these agents are administered together. Although the clinical significance of this interaction is uncertain, it would be prudent to stagger the administration times of these agents by at least 2 hours to avoid affecting the bioavailability of gemfibrozil.

ADVERSE REACTIONS: Adverse GI effects are the most frequently reported side effects and occasionally are severe enough to require discontinuance of the drug. These effects include abdominal pain, dyspepsia, nausea/vomiting, diarrhea, and cholestasis with jaundice. Cholelithiasis can occur during gemfibrozil therapy as a result of increased biliary excretion of cholesterol. This problem is a serious concern with clofibrate, a related agent. Although gallbladder disease does not appear to be as serious with gemfibrozil, therapy should be discontinued if any signs of cholelithiasis occur. Elevated liver-function tests have also been associated with gemfibrozil.

A variety of nervous system effects have been reported with gemfibrozil. These include headache, dizziness, drowsiness, blurred vision, dysgeusia, peripheral neuropathy, mental depression, impotence, and libido decrease.

Concomitant use of gemfibrozil with lovastatin is associated with a risk of myopathy and rhabdomyolysis (see Drug Interactions). Therapy should be discontinued if elevated CK levels or myalgia (muscle pain) occur.

There is a probable causal relationship between gemfibrozil use and anemia, leukopenia, bone marrow hyperplasia, and eosinophilia. The effect on hemoglobin, hematocrit, and white blood cell counts is generally mild. In controlled clinical trials, incidence of viral and bacterial infection was more common in patients treated with gemfibrozil than with placebo. Infection was manifested as the common cold, cough, and urinary tract infection. Periodic blood counts are recommended during the first twelve months of treatment.

PATIENT INFORMATION:

What do gemfibrozil tablets do?

Gemfibrozil (Lopid^TM ) can help prevent cholesterol clogging blood vessels. It lowers blood fats and cholesterol for patients who are at risk of getting heart disease or a stroke. It is only for patients whose cholesterol level is not controlled by diet. It is not a cure. Generic gemfibrozil tablets are not yet available.

What should my doctor, dentist, or pharmacist know before I take gemfibrozil?

They need to know if you have any of these conditions:

• gallbladder disease
• kidney disease
• liver disease
• an unusual or allergic reaction to gemfibrozil, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I take this medicine?

Take gemfibrozil tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses twice a day, 30 minutes before the morning and evening meal unless otherwise directed. Take your doses at regular intervals. Do not take your medicine more often than directed.

Special precautions for use in children:

This medicine is not for children.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What other medicines can interact with gemfibrozil?

• colestipol
• lovastatin
• warfarin

Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.

What side effects may I notice from taking gemfibrozil?

Serious side effects with gemfibrozil include:

• cough or hoarseness
• dark yellow or brown urine
• fever or chills
• lower back or side pain
• stomach pain with nausea and vomiting
• muscle pain
• pain or difficulty passing urine
• unusual tiredness
• yellowing of the eyes or skin

Call your doctor as soon as you can if you get any of these side effects.

Minor side effects with gemfibrozil include:

• blurred vision
• drowsiness, dizziness
• headache
• sexual dysfunction (loss of sexual desire)
• stomach gas, heartburn

Let your doctor know about these side effects if they do not go away or if they annoy you.

What do I need to watch for while I take gemfibrozil?

Gemfibrozil will not cure your condition, but taken regularly it will help keep down your cholesterol level. Visit your doctor for regular checks on your progress. Do not stop taking gemfibrozil, except on your doctor's advice.

Gemfibrozil is only part of a total cholesterol-lowering program. Your doctor or dietician can suggest a low-cholesterol and low-fat diet that will reduce your risk of getting heart and blood vessel disease. Avoid alcohol and smoking, and keep a proper exercise schedule.

If you are going to have surgery tell your doctor or dentist that you are taking gemfibrozil.

If you are diabetic, the dose of your antidiabetic medicine may need to be changed. Gemfibrozil can increase your blood sugar levels. Check with your doctor or pharmacist before you change the dose of your diabetic medicine.

You may get drowsy or have blurred vision; until you know how gemfibrozil affects you, do not drive, use machinery, or do anything that needs mental alertness.

Where can I keep my medicine?

Keep out of the reach of children in a container that small children cannot open.

Store at room temperature below 30C (86F). Keep container tightly closed. Throw away any unused medicine after the expiration date.

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