Lopid

Gemfibrozil helps reduce cholesterol and triglycerides (fatty acids) in the blood. High levels of these types of fat in the blood are associated with an increased risk of atherosclerosis (clogged arteries).

Gemfibrozil is used to treat very high cholesterol and triglyceride levels in people with pancreatitis.

Gemfibrozil is also used to lower the risk of stroke, heart attack, or other heart complications in people with high cholesterol and triglycerides who have not been helped by other treatment methods.

Gemfibrozil may also be used for purposes not listed in this medication guide.

You should not use this medication if you are allergic to gemfibrozil, if you are also taking repaglinide (Prandin), or if you have gallbladder disease, liver disease, or severe kidney disease.

Call your doctor at once if you have a serious side effect such as sharp pain in your upper stomach (especially after eating), jaundice (yellowing of your skin or eyes), blurred vision, eye pain, or seeing halos around lights, or pain or burning when you urinate.

Avoid eating foods that are high in fat or cholesterol. Gemfibrozil will not be as effective in lowering your cholesterol if you do not follow a cholesterol-lowering diet plan.

Avoid drinking alcohol. It may interfere with your treatment.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. Your liver and kidney function may also need to be tested. Visit your doctor regularly.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Lopid falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

• Store Lopid at room temperature.
• Keep this and all medications out of the reach of children.

You should not use gemfibrozil if you are allergic to it, if you have:

• severe liver disease;

• severe kidney disease;

• gallbladder disease; or

• if you are also taking repaglinide (Prandin), dasabuvir (Viekira Pak), or simvastatin (Zocor, Vytorin, Juvisync, Simcor).

To make sure gemfibrozil is safe for you, tell your doctor if you have:

• a history of gallstones; or

• if you take a blood thinner (warfarin, Coumadin, Jantoven).

It is not known whether gemfibrozil will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether gemfibrozil passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking gemfibrozil.

Contraindications

• Hepatic impairment, including primary biliary cirrhosis; severe renal impairment; or preexisting gallbladder disease.1

• Known hypersensitivity to gemfibrozil or any ingredient in the formulation.1

Warnings/Precautions

Warnings

May increase cholesterol excretion in bile,1 34 61 resulting in cholelithiasis.1 26 34 Cholecystitis and cholelithiasis reported.1 Discontinue therapy if gallbladder studies indicate the presence of gallstones.1

Use may be associated with myositis.1 Myalgia, myopathy, myasthenia, painful extremities, arthralgia, synovitis, and rhabdomyolysis reported.1 Myopathy, rhabdomyolysis, and other complications also reported in patients receiving gemfibrozil concomitantly with certain other antilipemic agents.1

Monitor creatine kinase (CK, creatine phosphokinase, CPK) concentrations in patients reporting adverse musculoskeletal effects.1 108 116 Discontinue therapy if myositis is suspected or diagnosed.1

Effect on cardiovascular mortality not established.1 Because gemfibrozil is chemically, pharmacologically, and clinically similar to other fibric acid derivatives, some adverse effects of clofibrate (no longer commercially available in the US) such as increased incidence of cholelithiasis, cholecystitis requiring surgery, postcholecystectomy complications, malignancy, pancreatitis, appendectomy, gallbladder disease, and increased overall mortality may also apply to gemfibrozil,1 and the usual precautions associated with fibrate therapy should be observed.1

Possible subcapsular bilateral and unilateral cataracts.1

Sensitivity Reactions

Angioedema, laryngeal edema, urticaria, rash, dermatitis, and pruritus reported.1

Major Toxicities

Mild decreases in hemoglobin,1 2 hematocrit,1 2 38 and leukocyte counts1 2 reported; these counts usually normalize during long-term therapy.1 Severe anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have occurred rarely; eosinophilia also reported.1

Monitor blood cell counts periodically during the first 12 months of therapy.1

General Precautions

Possible elevations in serum concentrations of aminotransferase (i.e., AST, ALT),1 2 24 25 47 LDH,1 2 bilirubin,1 and alkaline phosphatase.1 2 15 25 47 Serum aminotransferase concentrations usually return slowly to pretreatment values following discontinuance of gemfibrozil.1 Cholestatic jaundice reported.1

Perform liver function tests periodically.1 Discontinue therapy if abnormalities persist.1

Carcinogenicity (e.g., hepatic, Leydig cell tumors) demonstrated in animals.1

Specific Populations

Category C.1

Not known if gemfibrozil is distributed into milk.1 102 Discontinue nursing or the drug.1

Safety and efficacy not established.1

Possible exacerbation of renal insufficiency in patients with baseline Scr >2 mg/dL.1 Consider use of alternative antilipemic therapy against the risks and benefits of a lower dose of gemfibrozil.1

Common Adverse Effects

GI disturbances (e.g., dyspepsia, abdominal pain, diarrhea, nausea, vomiting, constipation, acute appendicitis, gallbladder surgery), adverse CNS effects (headache, hypesthesia, paresthesias, dizziness, somnolence, peripheral neuritis, depression), fatigue, eczema, vertigo, taste perversion, blurred vision, decreased libido, impotence.1

Specific Drugs

Absorption

Bioavailability

Rapidly and completely absorbed from the GI tract.1 2 7 76

Peak plasma concentrations occur within 1–2 hours.1 2 7 9 Plasma concentrations do not appear to correlate with therapeutic response.29 102

Food

Rate and extent of absorption increased when administered 30 minutes before meals.1

Distribution

Extent

Highest tissue concentrations observed in the liver and kidneys in animals.2

Gemfibrozil crosses the placenta;2 not known if it is distributed into milk.1 102

Plasma Protein Binding

About 95%.2

Elimination

Metabolism

Appears to be metabolized in the liver to 4 major metabolites produced via 3 metabolic pathways.2 7 102 A phenol derivative (metabolite I)2 7 is pharmacologically active.102

Elimination Route

Excreted in urine (70%) in the form of metabolites and in feces (approximately 6%).1

Half-life

1.3–1.5 hours.1 7 9 10

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Heartburn.
• Belly pain.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

There have been reported cases of overdosage with Lopid. In one case, a 7-year-old child recovered after ingesting up to 9 grams of Lopid. Symptoms reported with overdosage were abdominal cramps, abnormal liver function tests, diarrhea, increased CPK, joint and muscle pain, nausea and vomiting. Symptomatic supportive measures should be taken, should an overdose occur.