Components:
Gemfibrozil
Method of action:
Lipid Modifying Agents
Available in countries
Medically reviewed by Oliinyk Elizabeth Ivanovna, Pharmacy Last updated on 2019.06.26

Name of the medicinal product

Gemfibrozil Sandoz

Qualitative and quantitative composition

Gemfibrozil

Therapeutic indications

The information provided in Therapeutic indications of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Therapeutic indications in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Capsule, hard
Film-coated tablet

Gemfibrozil Sandoz is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following:

- Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol.

- Mixed hyperlipidaemia when a statin is contraindicated or not tolerated.

- Primary hypercholesterolaemia when a statin is contraindicated or not tolerated.

Primary prevention

Reduction of cardiovascular morbidity in males with increased non-HDL cholesterol and at high risk for a first cardiovascular event when a statin is contraindicated or not tolerated.

Lopid is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following:

- Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol.

- Mixed hyperlipidaemia when a statin is contraindicated or not tolerated.

- Primary hypercholesterolaemia when a statin is contraindicated or not tolerated.

Primary prevention

Reduction of cardiovascular morbidity in males with increased non-HDL cholesterol and at high risk for a first cardiovascular event when a statin is contraindicated or not tolerated.

Dosage (Posology) and method of administration

The information provided in Dosage (Posology) and method of administration of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Dosage (Posology) and method of administration in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Capsule, hard
Film-coated tablet

Prior to initiating gemfibrozil, other medical problems such as hypothyroidism and diabetes mellitus must be controlled as best as possible and patients should be placed on a standard lipid-lowering diet, which should be continued during treatment. Gemfibrozil Sandoz should be taken orally.

Posology

Adult

The dose range is 900 mg to 1200 mg daily.

The only dose with documented effect on morbidity is 1200 mg daily.

The 1200 mg dose is taken as 600 mg twice daily, half an hour before breakfast and half an hour before the evening meal.

The 900 mg dose is taken as a single dose half an hour before the evening meal.

Elderly (over 65 years old)

As for adults

Children and adolescents

Gemfibrozil therapy has not been investigated in children. Due to the lack of data the use of Gemfibrozil Sandoz in children is not recommended.

Renal impairment

In patients with mild to moderate renal impairment (Glomerular filtration rate 50 - 80 and 30 - < 50 ml/min/1.73 m2, respectively), start treatment at 900 mg daily and assess renal function before increasing dose. Gemfibrozil Sandoz should not be used in patients with severely impaired renal function.

Hepatic impairment

Gemfibrozil is contraindicated in hepatic impairment.

Prior to initiating gemfibrozil, other medical problems such as hypothyroidism and diabetes mellitus must be controlled as best as possible and patients should be placed on a standard lipid-lowering diet, which should be continued during treatment. Lopid should be taken orally.

Posology

Adult

The dose range is 900 mg to 1200 mg daily.

The only dose with documented effect on morbidity is 1200 mg daily.

The 1200 mg dose is taken as 600 mg twice daily, half an hour before breakfast and half an hour before the evening meal.

The 900 mg dose is taken as a single dose half an hour before the evening meal.

Elderly (over 65 years old)

As for adults

Children and adolescents

Gemfibrozil therapy has not been investigated in children. Due to the lack of data the use of Lopid in children is not recommended.

Renal impairment

In patients with mild to moderate renal impairment (Glomerular filtration rate 50 - 80 and 30 - < 50 ml/min/1.73 m2, respectively), start treatment at 900 mg daily and assess renal function before increasing dose. Lopid should not be used in patients with severely impaired renal function.

Hepatic impairment

Gemfibrozil is contraindicated in hepatic impairment.

Contraindications

The information provided in Contraindications of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Contraindications in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Capsule, hard
Film-coated tablet

Hepatic impairment.

Severe renal impairment.

History of/or pre-existing gall bladder or biliary tract disease, including gallstones

Concomitant use of repaglinide or dasabuvir or simvastatin

Patients with previous history of photoallergy or phototoxic reaction during treatment with fibrates

Hepatic impairment

Severe renal impairment

History of/or pre-existing gall bladder or biliary tract disease, including gallstones

Concomitant use of repaglinide or dasabuvir or simvastatin

Patients with previous history of photoallergy or phototoxic reaction during treatment with fibrates

Special warnings and precautions for use

The information provided in Special warnings and precautions for use of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Special warnings and precautions for use in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Film-coated tablet

Muscle disorders (myopathy/rhabdomyolysis)

There have been reports of myositis, myopathy and markedly elevated creatine phosphokinase associated with gemfibrozil. Rhabdomyolysis has also been reported rarely.

Muscle damage must be considered in any patient presenting with diffuse myalgia, muscle tenderness and/or marked increase in muscle CPK levels (>5x ULN); under these conditions treatment must be discontinued.

Concomitant HMG CoA reductase inhibitors

The concomitant administration of gemfibrozil with simvastatin is contraindicated.) and dosage adjustments may be necessary.

The benefit of further alterations in lipid levels by the combined use of gemfibrozil and HMG-CoA reductase inhibitors should be carefully weighed against the potential risks of such combinations and clinical monitoring is recommended.

A creatine phosphokinase (CPK) level should be measured before starting such a combination in patients with pre-disposing factors for rhabdomyolysis as follows:

- renal impairment

- hypothyroidism

- alcohol abuse

- age > 70 years

- personal or family history of hereditary muscular disorders

- previous history of muscular toxicity with another fibrate or HMG-CoA reductase inhibitor

In most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefits of combined therapy with HMG-CoA reductase inhibitors and gemfibrozil does not outweigh the risks of severe myopathy, rhabdomyolysis and acute renal failure.

Use in patients with gallstone formation

Gemfibrozil may increase cholesterol excretion into the bile raising the potential for gallstone formation. Cases of cholelithiasis have been reported with gemfibrozil therapy. If cholelithiasis is suspected, gallbladder studies are indicated. Gemfibrozil therapy should be discontinued if gallstones are found.

Monitoring serum lipids

Periodic determinations of serum lipids are necessary during treatment with gemfibrozil. Sometimes a paradoxical increase of (total and LDL) cholesterol can occur in patients with hypertriglyceridaemia. If the response is insufficient after 3 months of therapy at recommended doses treatment should be discontinued and alternative treatment methods considered.

Monitoring liver function

Elevated levels of ALAT, ASAT, alkaline phosphatase, LDH, CK and bilirubin have been reported. These are usually reversible when gemfibrozil is discontinued. Therefore liver function tests should be performed periodically. Gemfibrozil therapy should be terminated if abnormalities persist.

Monitoring blood counts

Periodic blood count determinations are recommended during the first 12 months of gemfibrozil administration. Anaemia, leucopenia, thrombocytopenia, eosinophilia and bone marrow hypoplasia have been reported rarely.

<5).

Concomitant use with CYP2C8, CYP2C9, CYP2C19, CYP1A2, UGTA1, UGTA3 and OATP1B1 substrates.

The interaction profile of gemfibrozil is complex resulting in increased exposure of many medicinal products if administered concomitantly with gemfibrozil.

Gemfibrozil potently inhibits CYP2C8, CYP2C9, CYP2C19, CYP1A2, and UDP glucuronyltransferase (UGTA1 and UGTA3) enzymes and also inhibits organic anion-transporting polypeptide 1B1 (OATP1B1). In addition, gemfibrozil is metabolised to gemfibrozil 1-O-β-glucuronide which also inhibits CYP2C8 and OATP1B1.

Concomitant use with hypoglycaemic agents

There have been reports of hypoglycaemic reactions after concomitant use with gemfibrozil and hypoglycaemic agents (oral agents and insulin). Monitoring of glucose levels is recommended.

Concomitant anticoagulants

Gemfibrozil may potentiate the effects of coumarin type vitamin K antagonist anticoagulants such as warfarin, acenocoumarol, or phenprocoumon. The concomitant administration of gemfibrozil with these anticoagulants necessitates careful monitoring of prothrombin time (INR - International Normalised Ratio). Caution should be exercised when such a coumarin type vitamin K antagonist anticoagulant is given concomitantly with gemfibrozil. The dosage of the anticoagulant may need to be reduced to maintain desired prothrombin time levels.

Muscle disorders (myopathy/rhabdomyolysis)

There have been reports of myositis, myopathy and markedly elevated creatine phosphokinase associated with gemfibrozil. Rhabdomyolysis has also been reported rarely.

Muscle damage must be considered in any patient presenting with diffuse myalgia, muscle tenderness and/or marked increase in muscle CPK levels (>5x ULN); under these conditions treatment must be discontinued.

Concomitant HMG CoA reductase inhibitors

The concomitant administration of gemfibrozil with simvastatin is contraindicated.) and dosage adjustments may be necessary.

The benefit of further alterations in lipid levels by the combined use of gemfibrozil and HMG-CoA reductase inhibitors should be carefully weighed against the potential risks of such combinations and clinical monitoring is recommended.

A creatine phosphokinase (CPK) level should be measured before starting such a combination in patients with pre-disposing factors for rhabdomyolysis as follows:

- renal impairment

- hypothyroidism

- alcohol abuse

- age > 70 years

- personal or family history of hereditary muscular disorders

- previous history of muscular toxicity with another fibrate or HMG-CoA reductase inhibitor

In most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefits of combined therapy with HMG-CoA reductase inhibitors and gemfibrozil does not outweigh the risks of severe myopathy, rhabdomyolysis and acute renal failure.

Use in patients with gallstone formation

Gemfibrozil may increase cholesterol excretion into the bile raising the potential for gallstone formation. Cases of cholelithiasis have been reported with gemfibrozil therapy. If cholelithiasis is suspected, gallbladder studies are indicated. Gemfibrozil therapy should be discontinued if gallstones are found.

Monitoring serum lipids

Periodic determinations of serum lipids are necessary during treatment with gemfibrozil. Sometimes a paradoxical increase of (total and LDL) cholesterol can occur in patients with hypertriglyceridaemia. If the response is insufficient after 3 months of therapy at recommended doses treatment should be discontinued and alternative treatment methods considered.

Monitoring liver function

Elevated levels of ALAT, ASAT, alkaline phosphatase, LDH, CK and bilirubin have been reported. These are usually reversible when gemfibrozil is discontinued. Therefore liver function tests should be performed periodically. Gemfibrozil therapy should be terminated if abnormalities persist.

Monitoring blood counts

Periodic blood count determinations are recommended during the first 12 months of gemfibrozil administration. Anaemia, leucopenia, thrombocytopenia, eosinophilia and bone marrow hypoplasia have been reported rarely.

5).

Concomitant use with CYP2C8, CYP2C9, CYP2C19, CYP1A2, UGTA1, UGTA3 and OATP1B1 substrates.

The interaction profile of gemfibrozil is complex resulting in increased exposure of many medicinal products if administered concomitantly with gemfibrozil.

Gemfibrozil potently inhibits CYP2C8, CYP2C9, CYP2C19, CYP1A2, and UDP glucuronyltransferase (UGTA1 and UGTA3) enzymes and also inhibits organic anion-transporting polypeptide 1B1 (OATP1B1). In addition, gemfibrozil is metabolised to gemfibrozil 1-O-β-glucuronide which also inhibits CYP2C8 and OATP1B1.

Concomitant use with hypoglycaemic agents

There have been reports of hypoglycaemic reactions after concomitant use with gemfibrozil and hypoglycaemic agents (oral agents and insulin). Monitoring of glucose levels is recommended.

Concomitant anticoagulants

Gemfibrozil may potentiate the effects of coumarin type vitamin K antagonist anticoagulants such as warfarin, acenocoumarol, or phenprocoumon. The concomitant administration of gemfibrozil with these anticoagulants necessitates careful monitoring of prothrombin time (INR - International Normalised Ratio). Caution should be exercised when such a coumarin type vitamin K antagonist anticoagulant is given concomitantly with gemfibrozil. The dosage of the anticoagulant may need to be reduced to maintain desired prothrombin time levels.

Effects on ability to drive and use machines

The information provided in Effects on ability to drive and use machines of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Effects on ability to drive and use machines in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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No studies on the effects on the ability to drive and use machines have been performed. In isolated cases dizziness and visual disturbances can occur which may negatively influence driving.

Undesirable effects

The information provided in Undesirable effects of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Undesirable effects in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Most commonly reported adverse reactions are of gastrointestinal character and are seen in approximately 7% of the patients. These adverse reactions do not usually lead to discontinuation of the treatment.

Adverse reactions are ranked according to frequency using the following convention: Very common (>1/10), Common (>1/100, <1/10), Uncommon (>1/1,000, <1/100), Rare (>1/10,000, <1/1,000), Very rare (<1/10,000), including isolated reports:

System Organ Class

Undesirable effect

Blood and lymphatic system disorders

Rare

Bone marrow failure, severe anaemia, thrombocytopenia, leukopenia, eosinophilia

Psychiatric disorders

Rare

Depression, decreased libido

Nervous system disorders

Common

Vertigo, headache

Rare

Neuropathy peripheral, paraesthesia, dizziness, somnolence

Eye disorders

Rare

Vision blurred

Cardiac disorders

Uncommon

Atrial fibrillation

Respiratory, thoracic and mediastinal disorders

Rare

Laryngeal oedema

Gastrointestinal disorders

Very common

Dyspepsia

Common

Diarrhoea, vomiting, nausea, abdominal pain constipation, flatulence

Rare

Pancreatitis, appendicitis

Hepatobiliary disorders

Rare

Jaundice cholestatic, hepatitis, cholelithiasis, cholecystitis, hepatic function abnormal

Skin and subcutaneous tissue disorders

Common

Eczema, rash

Rare

Angioedema, dermatitis exfoliative, urticaria, dermatitis, alopecia, photosensitivity reaction, pruritus

Musculoskeletal and connective tissue disorders

Rare

Rhabdomyolysis, myopathy, myositis, muscular weakness, synovitis, myalgia, arthralgia, pain in extremity

Reproductive system and breast disorder

Rare

Erectile dysfunction

General disorders and administration site conditions

Common

Fatigue

Investigations

Rare

Haemoglobin decreased, haematocrit decreased, white blood cell count decreased, blood creatine phosphokinase increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Overdose

The information provided in Overdose of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Overdose in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Overdose has been reported. Symptoms reported with overdosage were abdominal cramps, abnormal LFT's, diarrhea, increased CPK, joint and muscle pain, nausea and vomiting. The patients fully recovered. Symptomatic supportive measures should be taken if overdose occurs.

Pharmacodynamic properties

The information provided in Pharmacodynamic properties of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Pharmacodynamic properties in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Capsule, hard
Film-coated tablet

Pharmacotherapeutic group: Serum-lipid lowering agent

Chemical subgroup: Fibrates

ATC code: C10A B04

Gemfibrozil is a non-halogenated phenoxypentanoic acid. Gemfibrozil is a lipid regulating agent which regulates lipid fractions.

Gemfibrozil's mechanism of action has not been definitively established. In man, gemfibrozil stimulates the peripheral lipolysis of triglyceride rich lipoproteins such as VLDL and cholymicrons (by stimulation of LPL). Gemfibrozil also inhibits synthesis of VLDL in the liver. Gemfibrozil increases the HDL2 and HDL3 subfractions as well as apolipoprotein A-I and A-II.

Animal studies suggest that the turnover and removal of cholesterol from the liver is increased by gemfibrozil.

There is evidence that treatment with fibrates may reduce coronary heart disease events but they have not been shown to decrease all cause mortality in the primary or secondary prevention of cardiovascular disease.

In the Helsinki Heart Study, which was a large placebo-controlled study with 4081 male subjects, 40 to 55 years of age, with primary dyslipidaemia (predominantly raised non-HDL cholesterol +/- hypertriglyceridaemia), but no previous history of coronary heart disease, gemfibrozil 600 mg twice daily, produced a significant reduction in total plasma triglycerides, total and low density lipoprotein cholesterol and a significant increase in high density lipoprotein cholesterol. The cumulative rate of cardiac end-points (cardiac death and non-fatal myocardial infarction) during a 5 year follow-up was 27.3/1000 in the gemfibrozil group (56 subjects) and 41.4/1000 in the placebo group (84 subjects) showing a relative risk reduction of 34.0% (95% confidence interval 8.2 to 52.6, p<0.02) and an absolute risk reduction of 1.4% in the gemfibrozil group compared to placebo. There was a 37% reduction in non-fatal myocardial infarction and a 26% reduction in cardiac deaths. The number of deaths from all causes was, however, not different (44 in the gemfibrozil group and 43 in the placebo group). Diabetes patients and patients with severe lipid fraction deviations showed a 68% and 71% reduction of CHD endpoints, respectively.

The VA-HIT study was a double-blind study comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with a history of coronary heart disease, HDL-C levels of < 40 mg/dL (1.0 mmol/L), and normal LDL C levels. After one year, the mean HDL-C level was 6% higher and the mean triglyceride level was 31% lower in the gemfibrozil group than in the placebo group. The primary event of non-fatal myocardial infarction or cardiac death occurred in 17.3% of gemfibrozil-treated and 21.7% of placebo-treated patients (reduction in relative risk 22%; 95% CI, 7 to 35 %; P=0.006). Among secondary outcomes, patients treated with gemfibrozil experienced relative risk reductions of 25% (95% CI -6-47%, p=0.10) for stroke, 24% (95% CI 11-36%, p< 0.001) for the combined outcome of death from CHD, non-fatal myocardial infarction, or confirmed stroke, 59% (95% CI 33-75%, p< 0.001) for transient ischaemic attack, and 65% (95% CI 37-80%, p< 0.001) for carotid endarterectomy.

Pharmacotherapeutic group: Serum-lipid lowering agent

Chemical subgroup: Fibrates

ATC code: C10A B04

Gemfibrozil is a non-halogenated phenoxypentanoic acid. Gemfibrozil is a lipid regulating agent which regulates lipid fractions.

Gemfibrozil's mechanism of action has not been definitively established. In man, gemfibrozil stimulates the peripheral lipolysis of triglyceride rich lipoproteins such as VLDL and cholymicrons (by stimulation of LPL). Gemfibrozil also inhibits synthesis of VLDL in the liver. Gemfibrozil increases the HDL2 and HDL3 subfractions as well as apolipoprotein A-I and A-II.

Animal studies suggest that the turnover and removal of cholesterol from the liver is increased by gemfibrozil.

There is evidence that treatment with fibrates may reduce coronary heart disease events but they have not been shown to decrease all cause mortality in the primary or secondary prevention of cardiovascular disease.

In the Helsinki Heart Study, which was a large placebo-controlled study with 4081 male subjects, 40 to 55 years of age, with primary dyslipidaemia (predominantly raised non-HDL cholesterol +/- hypertriglyceridaemia), but no previous history of coronary heart disease, gemfibrozil 600 mg twice daily, produced a significant reduction in total plasma triglycerides, total and low density lipoprotein cholesterol and a significant increase in high density lipoprotein cholesterol. The cumulative rate of cardiac end-points (cardiac death and non-fatal myocardial infarction) during a 5 year follow-up was 27.3/1000 in the gemfibrozil group (56 subjects) and 41.4/1000 in the placebo group (84 subjects) showing a relative risk reduction of 34.0% (95% confidence interval 8.2 to 52.6, p<0.02) and an absolute risk reduction of 1.4% in the gemfibrozil group compared to placebo. There was a 37% reduction in non-fatal myocardial infarction and a 26% reduction in cardiac deaths. The number of deaths from all causes was, however, not different (44 in the gemfibrozil group and 43 in the placebo group). Diabetes patients and patients with severe lipid fraction deviations showed a 68% and 71% reduction of CHD endpoints, respectively.

The VA-HIT study was a double-blind study comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with a history of coronary heart disease, HDL-C levels of < 40 mg/dL (1.0 mmol/L), and normal LDL C levels. After one year, the mean HDL-C level was 6% higher and the mean triglyceride level was 31% lower in the gemfibrozil group than in the placebo group. The primary event of non-fatal myocardial infarction or cardiac death occurred in 17.3% of gemfibrozil-treated and 21.7% of placebo-treated patients (reduction in relative risk 22%; 95% CI, 7 to 35 %; P=0.006). Among secondary outcomes, patients treated with gemfibrozil experienced relative risk reductions of 25% (95% CI -6-47%, p=0.10) for stroke, 24% (95% CI 11-36%, p< 0.001) for the combined outcome of death from CHD, non-fatal myocardial infarction, or confirmed stroke, 59% (95% CI 33-75%, p< 0.001) for transient ischaemic attack, and 65% (95% CI 37-80%, p< 0.001) for carotid endarterectomy.

Pharmacokinetic properties

The information provided in Pharmacokinetic properties of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Pharmacokinetic properties in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Absorption

Gemfibrozil is well absorbed from the gastro-intestinal tract after oral administration with a bioavailability close to 100%. As the presence of food alters the bioavailability slightly gemfibrozil should be taken 30 minutes before a meal. Peak plasma levels occur in one to two hours. After administration of 600 mg twice daily a Cmax in the range 15 to 25 mg/ml is obtained.

Distribution

Volume of distribution at steady state is 9-13 l. The plasma protein binding of gemfibrozil and its main metabolite are at least 97%.

Biotransformation

Gemfibrozil undergoes oxidation of a ring methyl group to form successively a hydroxymethyl and a carboxyl metabolite (the main metabolite). This metabolite has a low activity compared to the mother compound gemfibrozil and an elimination half-life of approximately 20 hours. Glucuronidation to gemfibrozil 1-O-β-glucuronide is another important elimination pathway for gemfibrozil in man.

The enzymes involved in the metabolism of gemfibrozil are not known. The interaction profile of gemfibrozil and its metabolites is complex. In vitro and in vivo studies have shown that gemfibrozil inhibits CYP2C8, CYP2C9, CYP2C19, CYP1A2, UGTA1, UGTA3 and OATP1B1. Gemfibrozil 1-O-β-glucuronide also inhibits CYP2C8 and OATP1B1.

Elimination

Gemfibrozil is eliminated mainly by metabolism. Approximately 70% of the administered human dose is excreted in the urine, mainly as conjugates of gemfibrozil and its metabolites. Less than 6% of the dose is excreted unchanged in the urine. Six percent of the dose is found in faeces. The total clearance of gemfibrozil is in the range 100 to 160 ml/min, and the elimination half-life is in the range 1.3 to 1.5 hours. The pharmacokinetics is linear within the therapeutic dose range.

Special patient groups

No pharmacokinetic studies have been performed in patients with impaired hepatic function.

There are limited data on patients with mild, moderate and non-dialysed severe renal impairment. The limited data support the use of up to 1200 mg a day in patients with mild to moderate renal failure not receiving another lipid lowering drug.

Pharmacotherapeutic group

The information provided in Pharmacotherapeutic group of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Pharmacotherapeutic group in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Serum-lipid lowering agent

Preclinical safety data

The information provided in Preclinical safety data of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Preclinical safety data in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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In a 2-year study of gemfibrozil, subcapsular bilateral cataracts occurred in 10%, and unilateral in 6.3%, of male rats treated at 10 times the human dose.

In a mouse carcinogenicity study at dosages corresponding to 0.1 and 0.7 times the clinical exposure (based on AUC), there were no significant differences from controls in the incidence of tumours. In a rat carcinogenicity study at dosages corresponding to 0.2 and 1.3 times the clinical exposure (based on AUC), the incidence of benign liver nodules and liver carcinomas was significantly increased in high dose males, and the incidence of liver carcinomas increased also in the low dose males, but this increase was not statistically significant.

Liver tumours induced by gemfibrozil and other fibrates in small rodents are generally considered to be related to the extensive proliferation of peroxisomes in these species and, consequently, of minor clinical relevance.

In the male rat, gemfibrozil also induced benign Leydig cell tumours. The clinical relevance of this finding is minimal.

In reproductive toxicity studies, administration of gemfibrozil at approximately 2 times the human dose (based on body surface area) to male rats for 10 weeks resulted in decreased fertility. Fertility was restored after a drug-free period of 8 weeks. Gemfibrozil was not teratogenic in either rats or rabbits. Administration of 1 and 3 times the human dose (based on body surface area) of gemfibrozil to female rabbits during organogenesis caused a dose-related decrease in litter size. Administration of 0.6 and 2 times the human dose (based on body surface area) of gemfibrozil to female rats from gestation Day 15 through weaning caused dose-related decreases in birth weight and suppression of pup growth during lactation. Maternal toxicity was observed in both species and the clinical relevance of decreases in rabbit litter size and rat pup weight is uncertain.

Incompatibilities

The information provided in Incompatibilities of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Incompatibilities in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Capsule, hard
Film-coated tablet

Not applicable.

Not applicable.

Special precautions for disposal and other handling

The information provided in Special precautions for disposal and other handling of Gemfibrozil Sandoz is based on data of another medicine with exactly the same composition as the Gemfibrozil Sandoz of the medicine (Gemfibrozil). Be careful and be sure to specify the information on the section Special precautions for disposal and other handling in the instructions to the drug Gemfibrozil Sandoz directly from the package or from the pharmacist at the pharmacy.
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Not applicable.