Drugs List

Therapeutic Indications

Uses

As an adjunct to diet modification and other non-pharmacological treatment such as exercise and weight reduction in the following conditions:

Severe hypertriglyceridaemia with or without low HDL-cholesterol.

Mixed hyperlipidaemia when a statin is contraindicated or not tolerated.

Primary hypercholesterolaemia (in particular when a statin is considered inappropriate or is not tolerated).

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

Administration

For oral administration.

Contraindications

Severe renal impairment (see Renal Impairment )
Gall bladder disease and history of gall bladder disease
Gallstones
Biliary tract disease and history of biliary tract disease
Hepatic impairment (see Hepatic Impairment )
History of photoallergy with fibrates
History of phototoxic reaction with fibrates
Pregnancy (see Pregnancy )
Breastfeeding (see Lactation )
Alcoholism
Children under 18 years
Creatine kinase levels over 5 times the upper limit of normal
Myopathy

Precautions and Warnings

Dietary restrictions should be maintained.

Myositis, myopathy and significantly elevated creatine phosphokinase levels have been reported with gemfibrozil. Rhabdomyolysis has also been reported rarely.

Any patient presenting with diffuse myalgia, muscle tenderness and/or significant increases in CPK levels greater than 5 times the upper limit of normal should have their treatment discontinued due to the possibility of muscle damage.

The risk of muscle damage is increased if gemfibrozil is used in combination with an HMG-CoA reductase inhibitor. Dosage adjustments may also be necessary. Evaluate the benefit of lipid level alteration against the potential risk of combination therapy and monitor the patient closely.

Creatine phosphokinase levels should be measured before therapy in patients with risk factors for rhabdomyolysis such as:
Moderate renal impairment (see Renal Impairment );
Hypothyroidism-correct before initiating treatment;
Alcohol abuse;
Patients greater than 70 years;
Family or personal history of hereditary muscular disorders;
History of muscular toxicity with another fibrate or HMG-CoA reductase inhibitor;
History of non-traumatic rhabdomyolysis;
Major surgery;
Severe infection;
Severe trauma;

Monitor serum lipids during treatment with gemfibrozil. In patients with hypertriglyceridaemia a paradoxical increase of total and LDL cholesterol can occur. If there is an insufficient response after 3 months discontinue treatment and consider alternative treatment methods.

Determine blood counts periodically in first year of therapy. Anaemia, leucopenia, thrombocytopenia, eosinophilia and bone marrow hypoplasia have been reported rarely.

Monitor hepatic function. Elevated levels of ALAT, ASAT, alkaline phosphatase, LDH, CK and bilirubin levels have been reported. If abnormalities persist discontinue therapy.

Hypoglycaemic reactions have been reported after concurrent use of gemfibrozil and oral hypoglycaemic agents or insulin. Monitor blood glucose levels.

Gemfibrozil may increase cholesterol excretion into the bile raising the potential for the formation of gallstones. Cases of cholelithiasis have been reported. If gallstones are found discontinue treatment.

Pregnancy and Lactation

Pregnancy

The potential risk to foetal development is unknown, as there is insufficient data on the use of gemfibrozil in pregnancy.

Gemfibrozil has been studied in rats and rabbits. In male and female rats gemfibrozil was tumorigenic. The treatment of female rats with 0.6 and 2 times the human dose before and during gestation produced a dose related decrease in conception rate, birth weight and increased skeletal variations. Anophthalmia was also observed. Rabbits that were given 1 and 3 times the human dose had a decreased litter size and increased incidence of parietal bone variations. Therefore gemfibrozil should not be used during pregnancy unless the benefits out weigh the risks to the foetus (Briggs, 2011).

Schaefer (2007) concludes that inadvertent treatment with gemfibrozil during pregnancy does not necessitate either termination of pregnancy or invasive diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

To date there have been limited reports on the use of gemfibrozil during breastfeeding. Due to the low molecular weight of about 250 it would be expected that gemfibrozil would be excreted into breastmilk (Briggs, 2011). Because of a concern with disruption of infant lipid metabolism, the consensus is that gemfibrozil should not be used during breastfeeding as safety has not been established.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Pruritus
Urticaria
Rash
Headache
Dizziness
Blurred vision
Painful extremities
Myalgia
Impotence
Cholestatic jaundice
Myopathy
Rhabdomyolysis
Atrial fibrillation
Pancreatitis
Alopecia
Thrombocytopenia
Anaemia
Leucopenia
Eosinophilia
Bone marrow hypoplasia
Vertigo
Somnolence
Paraesthesia
Peripheral neuritis
Reduced libido
Dyspepsia
Diarrhoea/loose stools
Flatulence
Nausea
Vomiting
Constipation
Hepatitis
Eczema
Exfoliative dermatitis
Arthralgia
Synovitis
Myasthenia
Fatigue
Photosensitivity
Laryngeal oedema
Acute appendicitis
Creatine kinase increased
Liver function disturbances
Myositis
Haemoglobin decrease
Decrease in haematocrit
White blood cell count decreased
Depression
Dermatitis
Abdominal pain
Angioedema
Cholelithiasis
Cholecystitis

Drugs List

Therapeutic Indications

Uses

As an adjunct to diet modification and other non-pharmacological treatment such as exercise and weight reduction in the following conditions:

Severe hypertriglyceridaemia with or without low HDL-cholesterol.

Mixed hyperlipidaemia when a statin is contraindicated or not tolerated.

Primary hypercholesterolaemia (in particular when a statin is considered inappropriate or is not tolerated).

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

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration.

Contraindications

Severe renal impairment (see Renal Impairment )
Gall bladder disease and history of gall bladder disease
Gallstones
Biliary tract disease and history of biliary tract disease
Hepatic impairment (see Hepatic Impairment )
History of photoallergy with fibrates
History of phototoxic reaction with fibrates
Pregnancy (see Pregnancy )
Breastfeeding (see Lactation )
Alcoholism
Children under 18 years
Creatine kinase levels over 5 times the upper limit of normal
Myopathy

Precautions and Warnings

Dietary restrictions should be maintained.

Myositis, myopathy and significantly elevated creatine phosphokinase levels have been reported with gemfibrozil. Rhabdomyolysis has also been reported rarely.

Any patient presenting with diffuse myalgia, muscle tenderness and/or significant increases in CPK levels greater than 5 times the upper limit of normal should have their treatment discontinued due to the possibility of muscle damage.

The risk of muscle damage is increased if gemfibrozil is used in combination with an HMG-CoA reductase inhibitor. Dosage adjustments may also be necessary. Evaluate the benefit of lipid level alteration against the potential risk of combination therapy and monitor the patient closely.

Creatine phosphokinase levels should be measured before therapy in patients with risk factors for rhabdomyolysis such as:
Moderate renal impairment (see Renal Impairment );
Hypothyroidism-correct before initiating treatment;
Alcohol abuse;
Patients greater than 70 years;
Family or personal history of hereditary muscular disorders;
History of muscular toxicity with another fibrate or HMG-CoA reductase inhibitor;
History of non-traumatic rhabdomyolysis;
Major surgery;
Severe infection;
Severe trauma;

Monitor serum lipids during treatment with gemfibrozil. In patients with hypertriglyceridaemia a paradoxical increase of total and LDL cholesterol can occur. If there is an insufficient response after 3 months discontinue treatment and consider alternative treatment methods.

Determine blood counts periodically in first year of therapy. Anaemia, leucopenia, thrombocytopenia, eosinophilia and bone marrow hypoplasia have been reported rarely.

Monitor hepatic function. Elevated levels of ALAT, ASAT, alkaline phosphatase, LDH, CK and bilirubin levels have been reported. If abnormalities persist discontinue therapy.

Hypoglycaemic reactions have been reported after concurrent use of gemfibrozil and oral hypoglycaemic agents or insulin. Monitor blood glucose levels.

Gemfibrozil may increase cholesterol excretion into the bile raising the potential for the formation of gallstones. Cases of cholelithiasis have been reported. If gallstones are found discontinue treatment.

Pregnancy and Lactation

Pregnancy

The potential risk to foetal development is unknown, as there is insufficient data on the use of gemfibrozil in pregnancy.

Gemfibrozil has been studied in rats and rabbits. In male and female rats gemfibrozil was tumorigenic. The treatment of female rats with 0.6 and 2 times the human dose before and during gestation produced a dose related decrease in conception rate, birth weight and increased skeletal variations. Anophthalmia was also observed. Rabbits that were given 1 and 3 times the human dose had a decreased litter size and increased incidence of parietal bone variations. Therefore gemfibrozil should not be used during pregnancy unless the benefits out weigh the risks to the foetus (Briggs, 2011).

Schaefer (2007) concludes that inadvertent treatment with gemfibrozil during pregnancy does not necessitate either termination of pregnancy or invasive diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

To date there have been limited reports on the use of gemfibrozil during breastfeeding. Due to the low molecular weight of about 250 it would be expected that gemfibrozil would be excreted into breastmilk (Briggs, 2011). Because of a concern with disruption of infant lipid metabolism, the consensus is that gemfibrozil should not be used during breastfeeding as safety has not been established.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

Advise patient of the following side effects dizziness and visual disturbances and if affected they should not drive or operate any machinery.

Side Effects

Pruritus
Urticaria
Rash
Headache
Dizziness
Blurred vision
Painful extremities
Myalgia
Impotence
Cholestatic jaundice
Myopathy
Rhabdomyolysis
Atrial fibrillation
Pancreatitis
Alopecia
Thrombocytopenia
Anaemia
Leucopenia
Eosinophilia
Bone marrow hypoplasia
Vertigo
Somnolence
Paraesthesia
Peripheral neuritis
Reduced libido
Dyspepsia
Diarrhoea/loose stools
Flatulence
Nausea
Vomiting
Constipation
Hepatitis
Eczema
Exfoliative dermatitis
Arthralgia
Synovitis
Myasthenia
Fatigue
Photosensitivity
Laryngeal oedema
Acute appendicitis
Creatine kinase increased
Liver function disturbances
Myositis
Haemoglobin decrease
Decrease in haematocrit
White blood cell count decreased
Depression
Dermatitis
Abdominal pain
Angioedema
Cholelithiasis
Cholecystitis

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store below 25 degrees C.

Storage requirements may vary between formulations. See specific product literature for storage requirements.

Reference Sources

British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Lopid 300mg hard capsules and 600mg film-coated tablets. Pfizer limited. Revised May 2011.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Gemfibrozil Last revised: August 6, 2009
Last accessed: March 8, 2012.