CONTRAINDICATIONS:

Hepatic or severe renal dysfunction, including primary biliary cirrhosis, preexisting gallbladder disease,  hypersensitivity to Gemfibrozile.

CLINICAL PHARMACOLOGY:

Gemfibrozile capsule is a lipid regulating agent which decreases serum triglycerides and very low density lipoprotein (VLDL) cholesterol, and increases high density lipoprotein (HDL) cholesterol.

Further information is available from a 3.5 year (8.5 year cumulative) follow-up of all subjects who had participated in the helsinki heart study. A 20% relative decrease in cardiac events in the group originally randomized to Gemfibrozile versus the originally randomized placebo group.

The mechanism of action of Gemfibrozile has not been definitely established. In man, Gemfibrozile has been shown to inhibit peripheral lipolysis and to decrease the hepatic extraction of free fatty acids, thus reducing hepatic triglyceride production. Gemfibrozile inhibits synthesis and increases clearance of VLDL carrier apolipoprotein B, leading to a decrease in VLDL production.

Gemfibrozile is completely absorbed after oral administration of Gemfibrozile capsules, reaching peak plasma concentrations 1 to 2 hours after dosing. In one study, both the rate and extent of absorption of the drug were significantly increased when administered 0.5 hour before meals.

Gemfibrozile mainly undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and a carboxyl metabolite. Approximately seventy percent of the administered human dose is excreted in the urine. Gemfibrozile is highly bound to plasma proteins and there is potential for displacement interactions with other drugs.

WARNINGS:

A greater prevalence of gallstones during the Helsinki Heart study within the Gemfibrozile treatment group (7.5% vs 4.9% for the placebo group, a 55% excess for the Gemfibrozile group). If a significant serum lipid response is not obtained, Gemfibrozile should be discontinued. Concomitant Anticoagulants-Caution should be exercised when anticoagulants are given in conjunction with Gemfibrozile. The dosage of the anticoagulant should be reduced to maintain the prothrombin time at the desired level to prevent bleeding complications. Concomitant therapy with Gemfibrozile and an HMG-CoA reductase inhibitor is associated with an increased risk of skeletal muscle toxicity manifested as rhabdomyolysis, markedly elevated creatine kinase (CPK) levels and myoglobinuria, leading in a high proportion of cases to acute renal failure and death.

PRECAUTIONS:

Periodic determination of serum lipids should be obtained, and the drug withdrawn if lipid response is inadequate after three months of therapy.

Pregnancy: Category C

Nursing Mothers: a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Hematologic changes: Mild hemoglobin, hematocrit and white blood cell decreases have been observed in occasional patients following initiation of Gemfibrozile therapy. However, these levels stabilize during long-term administration.

Liver Function: Abnormal liver function tests have been observed occasionally during Gemfibrozile administration, including elevations of AST (SGOT), ALT (SGPT), LDH, bilirubin, and alkaline phosphatase.

Kidney Function: There have been reports of worsening renal insufficiency upon the addition of Gemfibrozile therapy in individuals with baseline plasma creatinine >2.0 mg/dL.

Pediatric Use: Safety and efficacy in pediatric patients have not been established.

Drug Interactions:

HMG-CoA reductase inhibitors, Anticoagulants

SIDE EFFECTS:

Gastrointestinal: cholestatic jaundice

Central nervous system: dizziness, somnolence, paresthesia,  peripheral neuritis, decreased libido, depression, headache

Eye: blurred vision,

Genitourinary: impotence

Musculoskeletal: myopathy, myasthenia, myalgia, painful extremities, arthralgia

, synovitis, rhabdomyolysis

Clinical laboratory: increased creatine phosphokinase, increased bilirubin

increased liver transaminases (AST [SGOT], ALT [SGPT])

increased alkaline phosphatase

Hematopoietic: anemia, leucopenia, bone marrow hypoplasia, eosinophilia

Immunologic: angioedema, laryngeal edema, urticaria,

Skin: exfoliative dermatitis, Rash, dermatitis, pruritus

OVERDOSAGE:

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.

DOSAGE AND ADMINISTRATION:

The recommended dose for adults is 1200 mg administered in two divided doses 30 minutes before the morning and evening meal.

How Supplied: Each pack of Ruz-Gemfibrozile 300 mg capsules contains 100 capsules in 10 blisters.

storage: Store below 30°C. Protect from light and humidity.

Reference: PDR 2000, page 2264-7

                  USPDI for Professional Health Care, 2004, Page 1461-3

                  Martindale 2005, Page 923