Drugs List

Therapeutic Indications

Uses

Adjunctive therapy in patients with primary hypercholesterolaemia to further reduce LDL-cholesterol levels who are not adequately controlled by a statin alone.

As monotherapy in patients in whom a statin is either inappropriate or not well tolerated.

Combination therapy with ezetimibe, with or without a statin, in patients with both primary and familial hypercholesterolaemia.

Administration

For oral administration.
Take with a meal and liquid.

Contraindications

Bowel obstruction

Biliary obstruction

Children under 18 years

Precautions and Warnings

Exclude and treat secondary causes of hypercholesterolaemia prior to initiating therapy, for example:
Poorly controlled diabetes mellitus,
Hypothyroidism,
Nephrotic syndrome,
Dysproteinaemias,
Obstructive liver disease.

Caution when treating patients with triglyceride levels higher than 3.4 mmol/L as colesevelam increases triglyceride levels. Safety and efficacy has not been established in these patients.

Periodically measure serum total cholesterol, LDL cholesterol and triglyceride levels to confirm adequate response from this medication.

Caution should be exercised when considering treating the following patients as safety and efficacy has not been established:
Dysphagia,
Swallowing disorders,
Severe gastrointestinal motility disorders,
Inflammatory bowel disease,
Liver failure,
Major gastrointestinal tract surgery.

Colesevelam can induce or worsen constipation. This should be especially considered in patients with coronary heart disease or angina pectoris.

Use with caution in patients with a susceptibility to vitamin K or fat-soluble vitamin deficiencies e.g. those with malabsorption. Monitor vitamin A, D and E levels and assess vitamin K status via the measurement of coagulation parameters and consider supplemental vitamins in these patients if necessary.

Pregnancy (see Pregnancy ).

Breastfeeding (see Lactation ).

Colesevelam can affect the bioavailability of the oral contraceptive pill when administered simultaneously. Colesevelam should be administered at least 4 hours after the oral contraceptive pill to minimise the risk of any interaction.

Pregnancy and Lactation

Pregnancy

Use with caution when treating pregnant women.

There is limited data available on the use of colesevelam during human pregnancy.

There is no direct adverse affect from colesevelam to the embryo or foetus as the drug is not absorbed, therefore no direct embryo or fetal exposure will occur (Briggs, 2011).

Reproduction studies in pregnant rats and rabbits identified that doses of between 50 and 17 times, respectively, the maximum human dose (MHD) revealed no evidence of foetal harm.

Animal studies carried out indicate that more than 30 times the MHD resulted in a decrease in the concentration of the fat soluble vitamin, vitamin K, and haemorrhage. The effect on the absorption of fat the soluble vitamins, A, D, E, and, in particular, K, was not significantly impaired in pregnant women (Briggs, 2011).

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 ).

Known human teratogen? - No

Lactation

Use with caution in breastfeeding women.

The safety of colesevelam has not been established.

Colesevelam is a non-absorbable resin, therefore will not enter the bloodstream after oral administration and therefore the nursing infant will not be exposed to colesevelam via breast milk (Briggs, 2011). It is acceptable for use during breastfeeding.

Although the effects of colesevelam on level of fat soluble vitamins in the nursing mother have not been carried out, there is a theoretical risk of reduced concentrations of vitamins, A, D, E, and, in particular, K, within the milk resulting complications in the infant (Briggs, 2011).

Cholesterol is an important component of infant neurodevelopment and colesevelam results in a decrease in the maternal plasma cholesterol concentration and also the concentration of cholesterol in the expressed milk (Hale, 2010).

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

Drug excreted in breast milk? - No

Side Effects

Constipation
Dyspepsia
Diarrhoea
Nausea
Vomiting
Headache
Elevated triglyceride levels
Increase in serum transaminases
Myalgia
Gastro-intestinal discomfort
Increased bleeding tendency
Flatulence
Abnormal stools
Abdominal pain
Abdominal distension
Dysphagia
Pancreatitis

Drugs List

Therapeutic Indications

Uses

Adjunctive therapy in patients with primary hypercholesterolaemia to further reduce LDL-cholesterol levels who are not adequately controlled by a statin alone.

As monotherapy in patients in whom a statin is either inappropriate or not well tolerated.

Combination therapy with ezetimibe, with or without a statin, in patients with both primary and familial hypercholesterolaemia.

Administration

For oral administration.
Take with a meal and liquid.

Contraindications

Bowel obstruction

Biliary obstruction

Children under 18 years

Precautions and Warnings

Exclude and treat secondary causes of hypercholesterolaemia prior to initiating therapy, for example:
Poorly controlled diabetes mellitus,
Hypothyroidism,
Nephrotic syndrome,
Dysproteinaemias,
Obstructive liver disease.

Caution when treating patients with triglyceride levels higher than 3.4 mmol/L as colesevelam increases triglyceride levels. Safety and efficacy has not been established in these patients.

Periodically measure serum total cholesterol, LDL cholesterol and triglyceride levels to confirm adequate response from this medication.

Caution should be exercised when considering treating the following patients as safety and efficacy has not been established:
Dysphagia,
Swallowing disorders,
Severe gastrointestinal motility disorders,
Inflammatory bowel disease,
Liver failure,
Major gastrointestinal tract surgery.

Colesevelam can induce or worsen constipation. This should be especially considered in patients with coronary heart disease or angina pectoris.

Use with caution in patients with a susceptibility to vitamin K or fat-soluble vitamin deficiencies e.g. those with malabsorption. Monitor vitamin A, D and E levels and assess vitamin K status via the measurement of coagulation parameters and consider supplemental vitamins in these patients if necessary.

Pregnancy (see Pregnancy ).

Breastfeeding (see Lactation ).

Colesevelam can affect the bioavailability of the oral contraceptive pill when administered simultaneously. Colesevelam should be administered at least 4 hours after the oral contraceptive pill to minimise the risk of any interaction.

Pregnancy and Lactation

Pregnancy

Use with caution when treating pregnant women.

There is limited data available on the use of colesevelam during human pregnancy.

There is no direct adverse affect from colesevelam to the embryo or foetus as the drug is not absorbed, therefore no direct embryo or fetal exposure will occur (Briggs, 2011).

Reproduction studies in pregnant rats and rabbits identified that doses of between 50 and 17 times, respectively, the maximum human dose (MHD) revealed no evidence of foetal harm.

Animal studies carried out indicate that more than 30 times the MHD resulted in a decrease in the concentration of the fat soluble vitamin, vitamin K, and haemorrhage. The effect on the absorption of fat the soluble vitamins, A, D, E, and, in particular, K, was not significantly impaired in pregnant women (Briggs, 2011).

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 ).

Known human teratogen? - No

Lactation

Use with caution in breastfeeding women.

The safety of colesevelam has not been established.

Colesevelam is a non-absorbable resin, therefore will not enter the bloodstream after oral administration and therefore the nursing infant will not be exposed to colesevelam via breast milk (Briggs, 2011). It is acceptable for use during breastfeeding.

Although the effects of colesevelam on level of fat soluble vitamins in the nursing mother have not been carried out, there is a theoretical risk of reduced concentrations of vitamins, A, D, E, and, in particular, K, within the milk resulting complications in the infant (Briggs, 2011).

Cholesterol is an important component of infant neurodevelopment and colesevelam results in a decrease in the maternal plasma cholesterol concentration and also the concentration of cholesterol in the expressed milk (Hale, 2010).

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

Drug excreted in breast milk? - No

Side Effects

Constipation
Dyspepsia
Diarrhoea
Nausea
Vomiting
Headache
Elevated triglyceride levels
Increase in serum transaminases
Myalgia
Gastro-intestinal discomfort
Increased bleeding tendency
Flatulence
Abnormal stools
Abdominal pain
Abdominal distension
Dysphagia
Pancreatitis

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: May 2012

Reference Sources

British National Formulary, 63rd Edition (2012) Pharmaceutical Press, 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.

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.

Summary of Product Characteristics: Cholestagel 625mg film coated tablets. Genzyme therapeutics. Revised February 2012.

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
Colesevelam Last revised: August 6, 2009
Last accessed: May 10, 2012