Drugs List

Therapeutic Indications

Uses

Mixed hyperlipidaemia when statin is contraindicated or not tolerated
Severe hypertriglyceridaemia with or without low HDL cholesterol

Bezafibrate 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.

Contraindications

Children under 10 years
Creatine kinase levels over 5 times upper limit of normal
Hypoalbuminaemia
Photoallergic or phototoxic reactions to fibrates
Breastfeeding
Gallbladder disease
Myopathy
Nephrotic syndrome
Pregnancy
Renal dialysis
Renal impairment - creatinine clearance below 15ml/minute
Renal impairment in children 10 to 18 years - eGFR <15ml/minute/1.73m sq
Severe hepatic impairment

Precautions and Warnings

Children aged 10 to 18 years
Family history of hereditary muscular disorders
High alcohol intake
Major surgery
Patients over 65 years
Severe infection
Severe trauma
Diabetes mellitus
Electrolyte imbalance
Hereditary muscular disorder
History of muscular toxicity secondary to fibrates
History of muscular toxicity secondary to HMG-CoA reductase inhibitors
History of non-traumatic rhabdomyolysis
Hypothyroidism
Renal impairment - creatinine clearance 15-60ml/minute

Reduce dose in patients with creatinine clearance of 15-60 ml/min
Advise ability to drive/operate machinery may be affected by side effects
Correct hypothyroidism before treatment
Exclude/correct secondary causes of dyslipidaemia prior to treatment
If cholelithic symptoms occur perform appropriate diagnostic procedures
Monitor antidiabetic drug treatment
Monitor creatine kinase levels in patients at risk of rhabdomyolysis
Monitor diabetic patients during initiation of therapy
Advise patients to report muscle pain/tenderness/weakness
Discontinue if myopathy is suspected
Discontinue if an adequate response not achieved within 3 months
Discontinue if creatine kinase concentration increases significantly
Discontinue immediately if rhabdomyolysis occurs
Dietary restrictions should be maintained
Female: Ensure adequate contraception during treatment

Bezafibrate should be used as an adjunct to diet and measures such as physical activity, weight loss and adequate treatment of other metabolic disorders (e.g. diabetes, gout).

Secondary causes of dyslipidaemia, such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephritic syndrome, dysproteinaemia, obstructive liver disease, pharmacological treatment, alcoholism should be adequately treated before bezafibrate therapy is initiated.

Bezafibrate is known to alter the composition of bile and isolated reports of gallstones have been reported.

Oestrogens may lead to a rise in lipid levels, prescribing of bezafibrate in patients taking oestrogens or oestrogen-containing contraceptives must be critically considered on an individual basis.

Pregnancy and Lactation

Pregnancy

Bezafibrate is contraindicated in pregnancy.

At the time of writing there is limited data from the use of bezafibrate in pregnant women.

Bezafibrate is not recommended during pregnancy and in women of childbearing potential not using contraception.

Schaefer (2007) states inadvertent treatment with bezafibrate does not necessitate termination of pregnancy or requirement for invasive diagnostic procedures. It is unknown if it crosses the placenta.

Animal studies are sufficient with respect to reproductive toxicity.

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 to 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

Bezafibrate is contraindicated in breastfeeding.

At the time of writing there is insufficient information on the excretion of bezafibrate or its metabolites in human milk. A risk to the infant cannot be excluded.

A decision must be made whether to discontinue breastfeeding or to discontinue bezafibrate therapy taking into account the benefit of breastfeeding for the infant and the benefit of therapy for the women.

Schaefer (2007) suggests that there is no disadvantage to the mother if treatment is stopped during breastfeeding.

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

Abdominal distension
Abdominal pain
Acute renal failure
Alopecia
Anaphylactic reaction
Anorexia
Cholelithiasis
Cholestasis
Constipation
Creatine phosphokinase increased
Decreased alkaline phosphatase
Decreased appetite
Depression
Diarrhoea
Dizziness
Dyspepsia
Erectile dysfunction
Erythema multiforme
Gamma glutamyl transferase (GGT) decreased
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal disturbances
Haemoglobin decrease
Headache
Hypersensitivity reactions
Increase in serum transaminases
Increased platelet count
Insomnia
Interstitial lung disease
Muscle cramps
Muscle weakness
Myalgia
Nausea
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Photosensitivity
Pruritus
Rash
Rhabdomyolysis
Serum creatinine increased
Stevens-Johnson syndrome
Thrombocytopenic purpura
Toxic epidermal necrolysis
Urticaria
White blood cell count decreased

Presentation

Oral standard release formulations of bezafibrate

Drugs List

Therapeutic Indications

Uses

Mixed hyperlipidaemia when statin is contraindicated or not tolerated
Severe hypertriglyceridaemia with or without low HDL cholesterol

Bezafibrate 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.

Dosage

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 10 years
Creatine kinase levels over 5 times upper limit of normal
Hypoalbuminaemia
Photoallergic or phototoxic reactions to fibrates
Breastfeeding
Gallbladder disease
Myopathy
Nephrotic syndrome
Pregnancy
Renal dialysis
Renal impairment - creatinine clearance below 15ml/minute
Renal impairment in children 10 to 18 years - eGFR <15ml/minute/1.73m sq
Severe hepatic impairment

Precautions and Warnings

Children aged 10 to 18 years
Family history of hereditary muscular disorders
High alcohol intake
Major surgery
Patients over 65 years
Severe infection
Severe trauma
Diabetes mellitus
Electrolyte imbalance
Hereditary muscular disorder
History of muscular toxicity secondary to fibrates
History of muscular toxicity secondary to HMG-CoA reductase inhibitors
History of non-traumatic rhabdomyolysis
Hypothyroidism
Renal impairment - creatinine clearance 15-60ml/minute

Reduce dose in patients with creatinine clearance of 15-60 ml/min
Advise ability to drive/operate machinery may be affected by side effects
Correct hypothyroidism before treatment
Exclude/correct secondary causes of dyslipidaemia prior to treatment
If cholelithic symptoms occur perform appropriate diagnostic procedures
Monitor antidiabetic drug treatment
Monitor creatine kinase levels in patients at risk of rhabdomyolysis
Monitor diabetic patients during initiation of therapy
Advise patients to report muscle pain/tenderness/weakness
Discontinue if myopathy is suspected
Discontinue if an adequate response not achieved within 3 months
Discontinue if creatine kinase concentration increases significantly
Discontinue immediately if rhabdomyolysis occurs
Dietary restrictions should be maintained
Female: Ensure adequate contraception during treatment

Bezafibrate should be used as an adjunct to diet and measures such as physical activity, weight loss and adequate treatment of other metabolic disorders (e.g. diabetes, gout).

Secondary causes of dyslipidaemia, such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephritic syndrome, dysproteinaemia, obstructive liver disease, pharmacological treatment, alcoholism should be adequately treated before bezafibrate therapy is initiated.

Bezafibrate is known to alter the composition of bile and isolated reports of gallstones have been reported.

Oestrogens may lead to a rise in lipid levels, prescribing of bezafibrate in patients taking oestrogens or oestrogen-containing contraceptives must be critically considered on an individual basis.

Pregnancy and Lactation

Pregnancy

Bezafibrate is contraindicated in pregnancy.

At the time of writing there is limited data from the use of bezafibrate in pregnant women.

Bezafibrate is not recommended during pregnancy and in women of childbearing potential not using contraception.

Schaefer (2007) states inadvertent treatment with bezafibrate does not necessitate termination of pregnancy or requirement for invasive diagnostic procedures. It is unknown if it crosses the placenta.

Animal studies are sufficient with respect to reproductive toxicity.

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 to 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

Bezafibrate is contraindicated in breastfeeding.

At the time of writing there is insufficient information on the excretion of bezafibrate or its metabolites in human milk. A risk to the infant cannot be excluded.

A decision must be made whether to discontinue breastfeeding or to discontinue bezafibrate therapy taking into account the benefit of breastfeeding for the infant and the benefit of therapy for the women.

Schaefer (2007) suggests that there is no disadvantage to the mother if treatment is stopped during breastfeeding.

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

Abdominal distension
Abdominal pain
Acute renal failure
Alopecia
Anaphylactic reaction
Anorexia
Cholelithiasis
Cholestasis
Constipation
Creatine phosphokinase increased
Decreased alkaline phosphatase
Decreased appetite
Depression
Diarrhoea
Dizziness
Dyspepsia
Erectile dysfunction
Erythema multiforme
Gamma glutamyl transferase (GGT) decreased
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal disturbances
Haemoglobin decrease
Headache
Hypersensitivity reactions
Increase in serum transaminases
Increased platelet count
Insomnia
Interstitial lung disease
Muscle cramps
Muscle weakness
Myalgia
Nausea
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Photosensitivity
Pruritus
Rash
Rhabdomyolysis
Serum creatinine increased
Stevens-Johnson syndrome
Thrombocytopenic purpura
Toxic epidermal necrolysis
Urticaria
White blood cell count decreased

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 ).

Further Information

Last Full Review Date: August 2016

Reference Sources

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

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

Summary of Product Characteristics: Bezalip 200mg tablets. Actavis UK Ltd. Revised October 2015.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 21 June 2017