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LOPID 600

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

LOPID 600
(tablet)

COMPOSITION:
Tablets containing 600 mg gemfibrozil.

PHARMACOLOGICAL CLASSIFICATION:
A: 7.5 Serum-cholesterol reducers.

PHARMACOLOGICAL ACTION:
LOPID is a lipid-regulating agent which produces an increase in the cholesterol content of the high density lipoprotein (HDL) fraction and lowers elevated total serum cholesterol and triglyceride concentrations due to decreases in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions.
The mechanism by which these actions occur has not been firmly established.
In animal studies LOPID has been shown to reduce the incorporation of long-chain fatty acids into rat liver triglycerides and to inhibit adipose tissue lipolysis.
In humans LOPID inhibits peripheral lipolysis and decreases the hepatic uptake of plasma-free fatty acids leading to reduced hepatic triglyceride production. It also inhibits the production and increases the turnover rate of the beta-apoprotein moiety of VLDL, the resulting decrease in VLDL providing the basis for the drug's ability to reduce total lipid levels. LOPID increases plasma HDL levels by stimulating the synthesis of the major apolipoproteins of HDL.
Pharmacokinetics and metabolism:
Gemfibrozil is absorbed from the gastro-intestinal tract after oral administration. Peak plasma levels occur in one to two hours with a plasma half-life of 1,5 hours following multiple doses.
Gemfibrozil undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and a carboxyl metabolite. Approximately 70% of the administered human dose is excreted in the urine, mostly as the glucuronide conjugate, with less than 2% excreted as the unchanged gemfibrozil. Six percent of the dose is accounted for in the faeces.

INDICATIONS:
LOPID is indicated as adjunctive therapy to diet and weight loss in the treatment of the following hyperlipidaemias:

1.	Fredrickson Type IIb (mixed hyperlipidaemia)
2.	Fredrickson Type IV

NOTE: LOPID should be prescribed only for patients with a potentially responsive lipid or lipoprotein abnormality where appropriate dietary therapy alone is insufficient to correct the condition.
The potential benefit of LOPID in treating Type IIa patients with elevation of LDL-only is not likely to outweigh the risks.
LOPID therapy may be considered in those Type IIb patients who have low HDL levels in addition to elevated LDL and triglyceride levels and who have had inadequate response to non-drug therapy, or other agents such as bile acid sequestrants or nicotinic acid.
Excess body weight and excessive alcohol intake may be important factors in hypertriglyceridaemia and should be addressed prior to any drug therapy. Appropriate physical exercise may be a valuable ancillary measure. Contributory underlying pathology should be adequately treated e.g. hypothyroidism and diabetes mellitus.

CONTRA-INDICATIONS:

(1)	Hepatic and/or severe renal dysfunction, including primary biliary cirrhosis
(2)	Gall-stones
(3)	Hypersensitivity to gemfibrozil.

Safe use in pregnancy has not been established. It is not known whether or not gemfibrozil is secreted in human milk. Gemfibrozil should be avoided during pregnancy and lactation.
Safety and efficacy in children have not been established.

WARNING:
There have been reports of severe myositis with markedly elevated creatine kinase and myoglobinuria (rhabdomyolysis) when LOPID and the HMG-CoA reductase inhibitor, Lovastatin were used concomitantly. In most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefit of combined therapy with a HMG-CoA reductase inhibitor and gemfibrozil does not outweigh the risks of severe myopathy, rhabdomyolysis, and acute renal failure.

DOSAGE AND DIRECTIONS FOR USE:
1 200 mg daily in two divided doses 30 minutes before the morning and evening meals, is the usual dose.
900 mg daily in two divided doses will prove sufficient in some patients and should be tried in cases of intolerance at normal dosage.
When maximal triglyceride reduction is desired up to 1 500 mg daily in divided doses may be needed.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-Effects:
The most frequently occurring side-effects are gastro-intestinal and include abdominal and epigastric pain, diarrhoea, dyspepsia and flatulence, nausea and vomiting.
Other important side-effects include headache, fatigue, rash, dermatitis, pruritus, urticaria, vertigo, impotence, myositis manifesting as painful extremities, myalgia accompanied by an increase in creatine kinase, acute appendicitis and atrial fibrillation.
Other possibly related side-effects to which the physician should be alerted include dry mouth, constipation, anorexia, blurred vision, drowsiness, depression, paraesthesia and tinnitus, insomnia, malaise and syncope, arthralgia, swollen joints and muscle cramps, back pain, hypokalaemia, cholestatic jaundice, pancreatitis, dizziness, somnolence, peripheral neuritis, synovitis, myopathy, myasthenia, exfoliative dermatitis, decreased libido, angioedema, laryngeal edema and rhabdomyolysis.
Photosensitivity has also been reported.
Special Precautions:
Diabetes Mellitus:
As gemfibrozil may elevate the fasting blood sugars during treatment, periodic blood sugar determinations are advisable in diabetics receiving LOPID to assure adequate control.
Cholelithiasis:
Because LOPID may increase cholesterol excretion into the bile leading to cholelithiasis, gallbladder studies are indicated if cholelithiasis is suspected. LOPID therapy should be discontinued if gallstones are found.
Interactions:

A.	HMG-CoA reductase inhibitors: There have been reports of severe myositis with markedly elevated creatine kinase and myoglobinuria (rhabdomyolysis) when LOPID and the HMG-CoA reductase inhibitor, Lovastatin were used concomitantly. In most subjects who have had an unsatisfactory lipid response to either medicine alone, the possible benefit of combined therapy with a HMG-CoA reductase inhibitor and gemfibrozil does not outweigh the risks of severe myopathy, rhabdomyolysis and acute renal failure.
B.	Anticoagulants: As prothrombin time may be increased if coumarin-type anticoagulants are administered in conjunction with LOPID, caution should be exercised. The dosage of the anticoagulant should be reduced to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the prothrombin level has stabilized.
C.	Anion exchange resin medicines: Reduced bioavailability of LOPID may result when given simultaneously with resin-granule medicines such as colestipol. Administration of the medicines two hours or more apart is recommended.

General:
Because long-term administration of LOPID may be needed, all baseline values including lipid profile, blood count and liver function tests, should be reliably measured before treatment and periodic determinations of serum lipids should be obtained. The medicine should be withdrawn after 3 months if the response is inadequate. A paradoxical elevation of serum lipids has occasionally been observed, usually in patients with alcoholic hepatic disease.
Mild haemoglobin, haematocrit and white blood cell decreases have been observed in occasional patients following initiation of LOPID therapy. However, these levels stabilize during long-term administration. Less frequently, severe anaemia, leukopenia, thrombocytopenia, eosinophilia and bone marrow hypoplasia have been reported. Therefore, periodic blood counts are recommended during the first 12 months of LOPID administration.
Abnormal liver function tests have been observed occasionally during LOPID administration, including elevations of AST(SGOT), ALT(SGPT), LDH, and alkaline phosphatase. These are usually reversible when LOPID is discontinued. Therefore periodic liver function studies are recommended and LOPID therapy should be terminated if abnormalities persist.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptomatic and/or supportive treatment.

IDENTIFICATION:
White, film-coated, oval, biconvex tablet.

PRESENTATION:
Tablets in blisters of 60.

STORAGE INSTRUCTIONS:
Store in a cool (below 25°C), dry place. KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
Y/7.5/245

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pfizer Laboratories (Pty) Ltd
102 Rivonia Road
SANDTON, 2196

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
26 July 1991

        Revised: OCT97

Updated on this site: February 2005
Source: Pharmaceutical Industry
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