Drugs List

Therapeutic Indications

Uses

History of MI or unstable angina: reduce risk of cardiovascular events
Mixed dyslipidaemia (type IIb) - adjunct to diet
Post-transplantation hyperlipidaemia: patients on immunosuppressive therapy
Reduction of cardiac events in hypercholesterolaemia
Treatment of primary hypercholesterolaemia resistant to diet

Contraindications

Children under 8 years
Creatine kinase levels over 5 times upper limit of normal
Breastfeeding
Galactosaemia
Myopathy
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Serum transaminases above 3 times upper limit of normal
Severe hepatic impairment

Precautions and Warnings

Family history of hereditary muscular disorders
Females of childbearing potential
High alcohol intake
Major surgery
Patients over 70 years
Severe trauma
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 30-60ml/minute

Advise ability to drive/operate machinery may be affected by side effects
Correct hypothyroidism before treatment
Exclude secondary causes of hypercholesterolaemia before treatment
Contains lactose
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 lipids periodically and adjust dose accordingly
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 level exceed 3 times the upper limit of normal & persist
Discontinue if AST level exceed 3 times the upper limit of normal & persist
Discontinue if creatine kinase levels >5 times upper limit of normal
Discontinue if evidence of interstitial lung disease
Discontinue if muscular symptoms are severe
Discontinue if significant/persistent hepatic function abnormalities occur
Not licensed for all indications in all age groups
Dietary restrictions should be maintained
Female: Contraception required during and for 3 months after treatment

Advise patient to report any signs of liver toxicity such as yellow colour to the skin or eyes or generalised itching.

Statin therapy has been associated with the development of myalgia, myopathy and rhabdomyolysis, which can rarely be fatal. Myopathy is dose related.

Do not measure creatine kinase levels following strenuous exercise or in the presence of other factors affecting CK levels. If CK is greater than 5 times the upper limit of normal (ULN) levels prior to treatment, re-measure 5 to 7days later.
If symptoms of myopathy resolve and levels of creatinine kinase reduce, treatment can be reinitiated at the lowest dose and with close monitoring.

Some evidence suggests that statins as a class raise blood glucose and in some patients, at a high risk of future 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

Pravastatin is contraindicated in pregnancy.

A mixture of human malformations have been reported with the used of statins in the first trimester, these include; VATER-association, neural tube defects, holoprosencephaly, other CNS malformations and limb abnormalities (Schaefer, 2007). None of these malformations have occurred in significant enough quantities to enable causality to be concluded. However, the theoretical risks of reducing cholesterol availability during embryo development should be considered since pravastatin may reduce the foetal levels of mevalonate which is a precursor of cholesterol biosynthesis. The suspension of treatment throughout pregnancy is not considered likely to have a detrimental effect on the long term course of hyperlipidaemia. For these reasons pravastatin should not be used during pregnancy. Schaefer (2007) concludes that inadvertent treatment with a statin during pregnancy, does not require a termination of pregnancy, however, treatment should be stopped immediately and a detailed ultrasound examination should considered.

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

Pravastatin is contraindicated in breastfeeding.

At the time of writing, there is little published experience concerning the use of statins during breastfeeding. Due to the possible inhibition of cholesterol biosynthesis by statins, there is a theoretical risk posed to the neonate. The products of cholesterol biosynthesis, including cholesterol are essential for neonatal development. Therefore, the use of statins is contraindicated while breastfeeding. The suspension of treatment while breastfeeding is not considered likely to detrimentally affect the long term course of hyperlipidaemia, therefore pravastatin use during breastfeeding is not recommended.

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 pain
Abnormal vision
Alopecia
Altered liver function tests
Amnesia
Anaphylaxis
Angioedema
Arthralgia
Blurred vision
Changes in scalp or body hair
Constipation
Cough
Creatine kinase increased
Depression
Diarrhoea
Diplopia
Dizziness
Dyspepsia
Dyspnoea
Dysuria
Fatigue
Flatulence
Fulminant hepatic necrosis
Headache
Heartburn
Hepatitis
Hypersensitivity reactions
Increase in serum transaminases
Insomnia
Interstitial lung disease
Jaundice
Lupus erythematosus-like syndrome
Muscle weakness
Muscular cramps
Myalgia
Myoglobinaemia
Myopathy
Myositis
Nausea
Nightmares
Nocturia
Pancreatitis
Paraesthesia
Peripheral neuropathy
Polymyositis
Polyneuropathy
Precipitation of diabetes
Pruritus
Rash
Rhabdomyolysis
Sexual dysfunction
Sleep disturbances
Tendon disorder
Tendon rupture
Urinary frequency
Urticaria
Vomiting
Weight loss

Presentation

Oral formulations of pravastatin

Drugs List

Therapeutic Indications

Uses

History of MI or unstable angina: reduce risk of cardiovascular events
Mixed dyslipidaemia (type IIb) - adjunct to diet
Post-transplantation hyperlipidaemia: patients on immunosuppressive therapy
Reduction of cardiac events in hypercholesterolaemia
Treatment of primary hypercholesterolaemia resistant to diet

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 8 years
Creatine kinase levels over 5 times upper limit of normal
Breastfeeding
Galactosaemia
Myopathy
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Serum transaminases above 3 times upper limit of normal
Severe hepatic impairment

Precautions and Warnings

Family history of hereditary muscular disorders
Females of childbearing potential
High alcohol intake
Major surgery
Patients over 70 years
Severe trauma
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 30-60ml/minute

Advise ability to drive/operate machinery may be affected by side effects
Correct hypothyroidism before treatment
Exclude secondary causes of hypercholesterolaemia before treatment
Contains lactose
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 lipids periodically and adjust dose accordingly
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 level exceed 3 times the upper limit of normal & persist
Discontinue if AST level exceed 3 times the upper limit of normal & persist
Discontinue if creatine kinase levels >5 times upper limit of normal
Discontinue if evidence of interstitial lung disease
Discontinue if muscular symptoms are severe
Discontinue if significant/persistent hepatic function abnormalities occur
Not licensed for all indications in all age groups
Dietary restrictions should be maintained
Female: Contraception required during and for 3 months after treatment

Advise patient to report any signs of liver toxicity such as yellow colour to the skin or eyes or generalised itching.

Statin therapy has been associated with the development of myalgia, myopathy and rhabdomyolysis, which can rarely be fatal. Myopathy is dose related.

Do not measure creatine kinase levels following strenuous exercise or in the presence of other factors affecting CK levels. If CK is greater than 5 times the upper limit of normal (ULN) levels prior to treatment, re-measure 5 to 7days later.
If symptoms of myopathy resolve and levels of creatinine kinase reduce, treatment can be reinitiated at the lowest dose and with close monitoring.

Some evidence suggests that statins as a class raise blood glucose and in some patients, at a high risk of future 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

Pravastatin is contraindicated in pregnancy.

A mixture of human malformations have been reported with the used of statins in the first trimester, these include; VATER-association, neural tube defects, holoprosencephaly, other CNS malformations and limb abnormalities (Schaefer, 2007). None of these malformations have occurred in significant enough quantities to enable causality to be concluded. However, the theoretical risks of reducing cholesterol availability during embryo development should be considered since pravastatin may reduce the foetal levels of mevalonate which is a precursor of cholesterol biosynthesis. The suspension of treatment throughout pregnancy is not considered likely to have a detrimental effect on the long term course of hyperlipidaemia. For these reasons pravastatin should not be used during pregnancy. Schaefer (2007) concludes that inadvertent treatment with a statin during pregnancy, does not require a termination of pregnancy, however, treatment should be stopped immediately and a detailed ultrasound examination should considered.

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

Pravastatin is contraindicated in breastfeeding.

At the time of writing, there is little published experience concerning the use of statins during breastfeeding. Due to the possible inhibition of cholesterol biosynthesis by statins, there is a theoretical risk posed to the neonate. The products of cholesterol biosynthesis, including cholesterol are essential for neonatal development. Therefore, the use of statins is contraindicated while breastfeeding. The suspension of treatment while breastfeeding is not considered likely to detrimentally affect the long term course of hyperlipidaemia, therefore pravastatin use during breastfeeding is not recommended.

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 pain
Abnormal vision
Alopecia
Altered liver function tests
Amnesia
Anaphylaxis
Angioedema
Arthralgia
Blurred vision
Changes in scalp or body hair
Constipation
Cough
Creatine kinase increased
Depression
Diarrhoea
Diplopia
Dizziness
Dyspepsia
Dyspnoea
Dysuria
Fatigue
Flatulence
Fulminant hepatic necrosis
Headache
Heartburn
Hepatitis
Hypersensitivity reactions
Increase in serum transaminases
Insomnia
Interstitial lung disease
Jaundice
Lupus erythematosus-like syndrome
Muscle weakness
Muscular cramps
Myalgia
Myoglobinaemia
Myopathy
Myositis
Nausea
Nightmares
Nocturia
Pancreatitis
Paraesthesia
Peripheral neuropathy
Polymyositis
Polyneuropathy
Precipitation of diabetes
Pruritus
Rash
Rhabdomyolysis
Sexual dysfunction
Sleep disturbances
Tendon disorder
Tendon rupture
Urinary frequency
Urticaria
Vomiting
Weight loss

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: February 2014

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.

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.

Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on [February 11, 2014]].

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

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

Paediatric Formulary Committee. BNF for Children 2013-2014. London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; 2013. Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com [Accessed on [February 11, 2014]].

Summary of Product Characteristics: Lipostat 10mg, 20mg and 40mg Tablets. Bristol-Myers Squibb Pharmaceuticals Ltd. Revised April 2013.

Summary of Product Characteristics: Pravastatin Sodium 10mg Tablets. Accord Healthcare Ltd. Revised June 2012.
Summary of Product Characteristics: Pravastatin Sodium 20mg Tablets. Accord Healthcare Ltd. Revised June 2012.
Summary of Product Characteristics: Pravastatin Sodium 40mg Tablets. Accord Healthcare Ltd. Revised June 2012.

Summary of Product Characteristics: Pravastatin Sodium 20mg Tablets (Arrow). Actavis UK Ltd. Revised May 2012.
Summary of Product Characteristics: Pravastatin Sodium 40mg Tablets (Arrow). Actavis UK Ltd. Revised May 2012.

Summary of Product Characteristics: Pravastatin Sodium 10mg Tablets. Sandoz Ltd. Revised December 2012.
Summary of Product Characteristics: Pravastatin Sodium 20mg Tablets. Sandoz Ltd. Revised December 2012.
Summary of Product Characteristics: Pravastatin Sodium 40mg Tablets. Sandoz Ltd. Revised December 2012.

Drug safety update. Volume 1, issue 7, February 2008
https://www.mhra.gov.uk/home/groups/pl-p/documents/publication/con2033918.pdf
Last accessed: February 11, 2014.

Drug Safety Update. MHRA Volume 5, issue 6 January 2012.
Available at https://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON140667
Last accessed: February 11, 2014.

National Institute for Health and Care Excellence, NICE 71, Identification and management of familial hypercholesterolaemia, issued August 2008.
Available at: https://www.nice.org.uk/nicemedia/pdf/CG071NICEGuideline.pdf
Accessed: February 11, 2014.

NAPOS, The Drug Database for Acute Porphyria.
Available at: https://www.drugs-porphyria.com/monograph.php?id=1561
Pravastatin last revised: June 7, 2013.
Last accessed: February 11, 2014.

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
Pravastatin Last revised: September 07, 2013.
Last accessed: February 11, 2014.