Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Adjunctive treatment of homocystinuria, involving deficiencies or defects in:

• cystathionine beta-synthase (CBS)
• 5,10-methylene-tetrahydrofolate reductase (MTHFR)
• cobalamin cofactor metabolism (cbl). Cystadane should be used as supplement to other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), folate and a specific diet.

Adult Dosage

Cystadane treatment should be supervised by a physician experienced in the treatment of patients with homocystinuria.

The recommended total daily dose in adult and paediatric patients over 10 years of age is 6 g per day administered orally in divided doses of 3 g two times per day. However, dose titration may be preferable in paediatric patients.

In paediatric patients less than 10 years of age, the usual effective dose regimen is 100 mg/kg/day given in 2 doses daily; increasing the frequency above twice daily and/or the dose above 150 mg/kg/day does not improve the homocysteine-lowering effect.

Use in hepatic or renal impairment

Experience with betaine therapy in patients with renal insufficiency or non-alcoholic hepatic steatosis has demonstrated no need to adapt the dose regimen of Cystadane.

The bottle should be lightly shaken before opening. Three measuring spoons are provided which dispense either 100 mg, 150 mg or 1 g of betaine anhydrous. It is recommended that a heaped measuring spoon is removed from the container and a flat surface e.g. base of a knife is drawn across the top of the measure. This will give the following doses: small measure 100 mg, middle size measure 150 mg and large measure 1 g of betaine anhydrous.

The powder should be mixed with water, juice, milk, formula or food until completely dissolved and ingested immediately after mixing.

Therapeutic monitoring:

The aim of treatment is to keep plasma levels of total homocysteine below 15 μM or as low as possible. The steady-state response usually occurs within a month.

Contra Indications

Hypersensitivity to betaine.

Special Precautions

Uncommon cases of severe cerebral oedema and hypermethioninemia were reported within 2 weeks to 6 months of starting betaine therapy. Complete recovery was seen after treatment discontinuation:

- Plasma methionine level should be monitored, at start of treatment and periodically thereafter. The plasma methionine concentrations should be kept below 1000 μM.

- If any symptoms of cerebral oedema like morning headaches with vomiting and/or visual changes appear, plasma methionine level and compliance to the diet should be checked and treatment with Cystadane interrupted.

- If symptoms of cerebral oedema recur after re-introduction of treatment then betaine therapy should be discontinued indefinitely.

To minimize the risk of potential drug interactions, it is advisable to leave 30 minutes between the intake of betaine and amino acids mixtures and/or medicinal products containing vigabatrin and GABA analogues.

Interactions

No interaction studies have been performed.

Based on in vitro data, betaine might interact with amino acids mixtures and medicinal products containing vigabatrin and GABA analogues.

Adverse Reactions

Experience derived from exposure to betaine in about 1,000 patients.

Reported adverse reactions are listed below, by system organ class and by frequency.

Frequencies are defined as: very common ( 1/10), common ( 1/100, < 1/10), uncommon ( 1/1,000, < 1/100), rare ( 1/10,000, < 1/1,000), very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

*Uncommon cases of severe cerebral oedema and hypermethioninemia were reported within 2 weeks to 6 months of starting betaine therapy, with complete recovery after treatment discontinuation. High increases in plasma methionine levels in a range from 1,000 to 3,000 μM were noted in these patients. As cerebral oedema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to betaine therapy has been postulated as a possible mechanism of action.

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