Drugs List

Therapeutic Indications

Uses

Homocystinuria

Adjunctive treatment of homocystinuria involving deficiencies or defects in:

- Cystathionine beta-synthase

- 5,10-methylene-tetrahydrofolate reductase

- Cobalamin cofactor metabolism

Betaine should be used in addition to other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), folate and a specific diet.

Contraindications

None known

Precautions and Warnings

Breastfeeding
Pregnancy

Treatment to be initiated and supervised by a specialist
Allow 30minutes between intake of amino acid, vigabatrin and GABA analogues
Monitor plasma methionine at start of therapy & annually/biannually after
Withdraw treatment if cerebral oedema occurs

The plasma methionine concentration should be kept below 1000 micromole/litre. If methionine increases particularly above the first safety threshold of 700 micromole/litre, the patient should be monitored more frequently and compliance with diet should be checked.

If symptoms of cerebral oedema occur, check plasma methionine level and ensure that the recommended diet for the patient is adhered to. Treatment with betaine should be interrupted until symptoms resolve.

If these symptoms re-occur after the re-introduction of betaine therapy, treatment should be discontinued indefinitely.

Pregnancy and Lactation

Pregnancy

Use betaine with caution in pregnancy.

At the time of writing, there is very little published experience concerning exposed pregnancies and their outcomes.

No adverse effects on pregnancy or foetal/neonatal health have been seen in a limited number of exposed pregnancies. No other epidemiological data is available.

No animal reproduction studies have been conducted.
During pregnancy, the administration of betaine in addition to pyridoxine, folate, an anticoagulant, a controlled diet, and close monitoring of plasma homocysteine levels, is considered compatible with good maternal and foetal outcomes.

The manufacturer advises that betaine should not be used during pregnancy unless clearly necessary.

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

Use betaine with caution during breastfeeding.

At the time of writing, there is no published experience concerning the use of betaine 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 discomfort
Agitation
Anorexia
Cerebral oedema
Depression
Diarrhoea
Gastrointestinal disorder
Glossitis
Hair loss
Hives
Hypermethioninaemia
Irritability
Nausea
Personality disorder
Skin odour changes
Sleep disturbances
Tooth disorder
Urinary incontinence
Vomiting

Presentation

Oral powder containing betaine anhydrous.

Drugs List

Therapeutic Indications

Uses

Homocystinuria

Adjunctive treatment of homocystinuria involving deficiencies or defects in:

- Cystathionine beta-synthase

- 5,10-methylene-tetrahydrofolate reductase

- Cobalamin cofactor metabolism

Betaine should be used in addition to other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), folate and a specific diet.

Dosage

The aim of therapy is to maintain plasma levels of total homocysteine below 15 micromole/litre or as low as possible.

Adults

Elderly

Children

Contraindications

None known

Precautions and Warnings

Breastfeeding
Pregnancy

Treatment to be initiated and supervised by a specialist
Allow 30minutes between intake of amino acid, vigabatrin and GABA analogues
Monitor plasma methionine at start of therapy & annually/biannually after
Withdraw treatment if cerebral oedema occurs

The plasma methionine concentration should be kept below 1000 micromole/litre. If methionine increases particularly above the first safety threshold of 700 micromole/litre, the patient should be monitored more frequently and compliance with diet should be checked.

If symptoms of cerebral oedema occur, check plasma methionine level and ensure that the recommended diet for the patient is adhered to. Treatment with betaine should be interrupted until symptoms resolve.

If these symptoms re-occur after the re-introduction of betaine therapy, treatment should be discontinued indefinitely.

Pregnancy and Lactation

Pregnancy

Use betaine with caution in pregnancy.

At the time of writing, there is very little published experience concerning exposed pregnancies and their outcomes.

No adverse effects on pregnancy or foetal/neonatal health have been seen in a limited number of exposed pregnancies. No other epidemiological data is available.

No animal reproduction studies have been conducted.
During pregnancy, the administration of betaine in addition to pyridoxine, folate, an anticoagulant, a controlled diet, and close monitoring of plasma homocysteine levels, is considered compatible with good maternal and foetal outcomes.

The manufacturer advises that betaine should not be used during pregnancy unless clearly necessary.

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

Use betaine with caution during breastfeeding.

At the time of writing, there is no published experience concerning the use of betaine 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 discomfort
Agitation
Anorexia
Cerebral oedema
Depression
Diarrhoea
Gastrointestinal disorder
Glossitis
Hair loss
Hives
Hypermethioninaemia
Irritability
Nausea
Personality disorder
Skin odour changes
Sleep disturbances
Tooth disorder
Urinary incontinence
Vomiting

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: September 2014.

Reference Sources

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com. Accessed on August 26 2014.

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

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com. Accessed on August 26 2014.

Summary of Product Characteristics: Cystadane 1 g oral powder. Orphan Europe (UK) Ltd. Revised December 2016.