Drugs List

Therapeutic Indications

Uses

Heterozygous familial hypercholesterolaemia: Adjunct to diet
Mixed dyslipidaemia (type IIb) - adjunct to diet
Primary hypercholesterolaemia (type IIa) resistant to diet
Secondary prevention of coronary events post percut. coronary intervention

Contraindications

Children under 9 years
Creatine kinase levels over 5 times upper limit of normal
Breastfeeding
Elevated serum transaminases - if persistent and unexplained
Myopathy
Pregnancy
Serum transaminases above 3 times upper limit of normal
Severe hepatic impairment

Precautions and Warnings

Children aged 9 to 18 years
Family history of hereditary muscular disorders
Females of childbearing potential
High alcohol intake
Major surgery
Patients over 70 years
Severe trauma
Within 7 days of discontinuing fusidic acid
Galactosaemia
Glucose-galactose malabsorption syndrome
Hereditary muscular disorder
History of hepatic impairment
History of muscular toxicity secondary to fibrates
History of muscular toxicity secondary to HMG-CoA reductase inhibitors
History of non-traumatic rhabdomyolysis
Hypothyroidism
Lactose intolerance
Renal impairment - creatinine clearance below 30 ml/minute

Homozygous familial hypercholesterolaemia patients unlikely to benefit
Correct hypothyroidism before treatment
Exclude secondary causes of hypercholesterolaemia before treatment
Not all available brands are licensed for all age groups
Some brands contain lactose
Administer 2 hours before or > 4 hours after any bile acid sequestrant
Exclude pregnancy prior to initiation of treatment
Measure creatine kinase levels prior to treatment if risk of rhabdomyolysis
Perform liver function tests before commencing therapy
Monitor creatine kinase levels in patients at risk of rhabdomyolysis
Monitor creatine kinase levels in patients reporting myalgia
Monitor patients with existing or tendency towards diabetes mellitus
Repeat liver function tests within 3 months and at 12 months
Advise patient to report any symptoms of interstitial lung disease
Advise patients to report muscle pain/tenderness/weakness
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Discontinue if myopathy is suspected
Advise patient to seek advice at first indications of pregnancy
Discontinue if ALT or AST persistently exceed 3 x ULN
Discontinue if creatine kinase levels >5 times upper limit of normal
Discontinue if evidence of interstitial lung disease
Discontinue if muscular symptoms are severe
Not licensed for all indications in all age groups
Dietary restrictions should be maintained
Female: Contraception required during and for 3 months after treatment

Patients with unexplained diffuse myalgias, muscle tenderness or muscle weakness, and/or marked elevation of creatine kinase (CK) should be considered for myositis, myopathy and rhabdomyolysis.

There is no current evidence to require monitoring of plasma CK in asymptomatic patients. If patients require creatine kinase measurement do not measure following strenuous exercise or in the presence of other factors affecting CK levels. If CK levels are significantly elevated at baseline, they should be re-measured 5 to 7 days later. If they remain elevated do not start treatment.

If creatinine kinase levels return to normal and symptoms of myopathy resolve, treatment can be reinitiated at the lowest dose under close monitoring.

Some evidence suggests that statins raise blood glucose and in some patients at risk of diabetes may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (raised fasting glucose, raised body mass index at baseline, history of hypertension and raised triglycerides) should be monitored both clinically and biochemically according to national guidelines.

Pregnancy and Lactation

Pregnancy

Fluvastatin is contraindicated during pregnancy.

At the time of writing there is limited published data regarding the use of fluvastatin during pregnancy. The manufacturer does not recommend using fluvastatin during pregnancy.

Schaefer (2015) suggests that statins used for primary prevention should be discontinued when planning a pregnancy or when pregnancy is diagnosed. However, for women with severe metabolic disease a decision should be made by weighing up the risks and benefits. After statin exposure during the first trimester, a detailed ultrasound should be offered to ascertain normal foetal development. Briggs (2015) suggests that due to the requirement of cholesterol and products synthesized from cholesterol for the development of the foetus the use of fluvastatin is contraindicated.

Lactation

Fluvastatin is contraindicated during breastfeeding.

At the time of writing, there is limited data regarding the use of fluvastatin during breastfeeding. The manufacturer does not recommend breastfeeding whilst taking fluvastatin. It is expected that fluvastatin is excreted into human milk.

Side Effects

Abdominal pain
Anaphylactic reaction
Anaphylaxis
Angioedema
Creatine kinase increased
Depression
Dermatitis
Diarrhoea
Disturbances of sensation
Dysaesthesia
Dyspepsia
Eczema
Erectile dysfunction
Exanthema
Facial oedema
Headache
Hepatitis
Hypersensitivity reactions
Hypoaesthesia
Immune mediated necrotizing myopathy
Increase of liver transaminases
Insomnia
Interstitial lung disease
Joint pain
Lupus erythematosus-like syndrome
Memory loss
Muscle weakness
Myalgia
Myopathy
Myositis
Nausea
Nightmares
Pancreatitis
Paraesthesia
Precipitation of diabetes
Rash
Rhabdomyolysis
Sexual dysfunction
Skin reactions
Sleep disturbances
Tendinopathy
Thrombocytopenia
Urticaria
Vasculitis

Presentation

Oral formulations of fluvastatin sodium.

Drugs List

Therapeutic Indications

Uses

Heterozygous familial hypercholesterolaemia: Adjunct to diet
Mixed dyslipidaemia (type IIb) - adjunct to diet
Primary hypercholesterolaemia (type IIa) resistant to diet
Secondary prevention of coronary events post percut. coronary intervention

Dosage

Adults

Children

Contraindications

Children under 9 years
Creatine kinase levels over 5 times upper limit of normal
Breastfeeding
Elevated serum transaminases - if persistent and unexplained
Myopathy
Pregnancy
Serum transaminases above 3 times upper limit of normal
Severe hepatic impairment

Precautions and Warnings

Children aged 9 to 18 years
Family history of hereditary muscular disorders
Females of childbearing potential
High alcohol intake
Major surgery
Patients over 70 years
Severe trauma
Within 7 days of discontinuing fusidic acid
Galactosaemia
Glucose-galactose malabsorption syndrome
Hereditary muscular disorder
History of hepatic impairment
History of muscular toxicity secondary to fibrates
History of muscular toxicity secondary to HMG-CoA reductase inhibitors
History of non-traumatic rhabdomyolysis
Hypothyroidism
Lactose intolerance
Renal impairment - creatinine clearance below 30 ml/minute

Homozygous familial hypercholesterolaemia patients unlikely to benefit
Correct hypothyroidism before treatment
Exclude secondary causes of hypercholesterolaemia before treatment
Not all available brands are licensed for all age groups
Some brands contain lactose
Administer 2 hours before or > 4 hours after any bile acid sequestrant
Exclude pregnancy prior to initiation of treatment
Measure creatine kinase levels prior to treatment if risk of rhabdomyolysis
Perform liver function tests before commencing therapy
Monitor creatine kinase levels in patients at risk of rhabdomyolysis
Monitor creatine kinase levels in patients reporting myalgia
Monitor patients with existing or tendency towards diabetes mellitus
Repeat liver function tests within 3 months and at 12 months
Advise patient to report any symptoms of interstitial lung disease
Advise patients to report muscle pain/tenderness/weakness
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Discontinue if myopathy is suspected
Advise patient to seek advice at first indications of pregnancy
Discontinue if ALT or AST persistently exceed 3 x ULN
Discontinue if creatine kinase levels >5 times upper limit of normal
Discontinue if evidence of interstitial lung disease
Discontinue if muscular symptoms are severe
Not licensed for all indications in all age groups
Dietary restrictions should be maintained
Female: Contraception required during and for 3 months after treatment

Patients with unexplained diffuse myalgias, muscle tenderness or muscle weakness, and/or marked elevation of creatine kinase (CK) should be considered for myositis, myopathy and rhabdomyolysis.

There is no current evidence to require monitoring of plasma CK in asymptomatic patients. If patients require creatine kinase measurement do not measure following strenuous exercise or in the presence of other factors affecting CK levels. If CK levels are significantly elevated at baseline, they should be re-measured 5 to 7 days later. If they remain elevated do not start treatment.

If creatinine kinase levels return to normal and symptoms of myopathy resolve, treatment can be reinitiated at the lowest dose under close monitoring.

Some evidence suggests that statins raise blood glucose and in some patients at risk of diabetes may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (raised fasting glucose, raised body mass index at baseline, history of hypertension and raised triglycerides) should be monitored both clinically and biochemically according to national guidelines.

Pregnancy and Lactation

Pregnancy

Fluvastatin is contraindicated during pregnancy.

At the time of writing there is limited published data regarding the use of fluvastatin during pregnancy. The manufacturer does not recommend using fluvastatin during pregnancy.

Schaefer (2015) suggests that statins used for primary prevention should be discontinued when planning a pregnancy or when pregnancy is diagnosed. However, for women with severe metabolic disease a decision should be made by weighing up the risks and benefits. After statin exposure during the first trimester, a detailed ultrasound should be offered to ascertain normal foetal development. Briggs (2015) suggests that due to the requirement of cholesterol and products synthesized from cholesterol for the development of the foetus the use of fluvastatin is contraindicated.

Lactation

Fluvastatin is contraindicated during breastfeeding.

At the time of writing, there is limited data regarding the use of fluvastatin during breastfeeding. The manufacturer does not recommend breastfeeding whilst taking fluvastatin. It is expected that fluvastatin is excreted into human milk.

Side Effects

Abdominal pain
Anaphylactic reaction
Anaphylaxis
Angioedema
Creatine kinase increased
Depression
Dermatitis
Diarrhoea
Disturbances of sensation
Dysaesthesia
Dyspepsia
Eczema
Erectile dysfunction
Exanthema
Facial oedema
Headache
Hepatitis
Hypersensitivity reactions
Hypoaesthesia
Immune mediated necrotizing myopathy
Increase of liver transaminases
Insomnia
Interstitial lung disease
Joint pain
Lupus erythematosus-like syndrome
Memory loss
Muscle weakness
Myalgia
Myopathy
Myositis
Nausea
Nightmares
Pancreatitis
Paraesthesia
Precipitation of diabetes
Rash
Rhabdomyolysis
Sexual dysfunction
Skin reactions
Sleep disturbances
Tendinopathy
Thrombocytopenia
Urticaria
Vasculitis

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: April 2019

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Cadaff XL 80mg prolonged-release tablets. Torrent Pharma (UK) Ltd. Revised April 2017.
Summary of Product Characteristics: Dorisin XL prolonged-release tablets. Aspire Pharma Ltd. Revised February 2019.
Summary of Product Characteristics: Fluvastatin capsules 20mg. Teva UK Ltd. Revised October 2018.
Summary of Product Characteristics: Fluvastatin capsules 40mg. Teva UK Ltd. Revised October 2018.
Summary of Product Characteristics: Fluvastatin capsules 20mg. Gen UK Ltd. Revised October 2017.
Summary of Product Characteristics: Fluvastatin capsules 40mg. Gen UK Ltd. Revised October 2017.
Summary of Product Characteristics: Lescol XL 80mg. Novartis Pharmaceuticals UK Ltd. Revised December 2018.
Summary of Product Characteristics: Sinfatix XL 80mg Prolonged release Tablets. Accord Healthcare Ltd. Revised April 2016.

Drug Safety Update. MHRA Volume 5, issue 6 January 2012.
Available at https://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON140667
Last accessed: 28 March 2019

NAPOS: The Drug Database for Acute Porphyria
Available at: https://www.drugs-porphyria.org/languages/UnitedKingdom/selsearch.php?l=gbr
Last accessed: 28 March 2019

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 March 2019

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
Fluvastatin. Last revised: 31 October 2018
Last accessed: 26 March 2019