Consumer medicine information

Cystadane

Betaine

BRAND INFORMATION

Brand name

Cystadane

Active ingredient

Betaine

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cystadane.

What is in this leaflet

This leaflet answers some of the more common questions about Cystadane.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Cystadane against the benefits he/she expects it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read this again.

What CYSTADANE is used for

Cystadane is used to decrease high levels of homocysteine in the blood, referred to as homocystinuria. Homocysteine is a breakdown product of the amino acid methionine that forms part of proteins present in food. The high levels of homocysteine in the blood may be caused by the various deficiencies in enzymes that break down proteins, specifically called cystathionine beta synthase (CBS) or from 5, 10- methylenetetrahydrofolate reductase deficiency (MTHFR deficiency) or cobalamin cofactor metabolism defect (CBL defect).

High levels of homocysteine in the blood can be toxic and may cause problems in the skeleton and the eyes, as well as mental retardation and cardiovascular disease.

Some people are born with inherited diseases that cause some of the body’s natural enzymes of metabolism to be missing or defective. CBS deficiency, MTHFR deficiency and CBL defects are all rare disorders that result in patients not being able to perform the conversion of methionine to cysteine. This disorder presents at early childhood and persists for life, so therefore this treatment is lifelong.

Cystadane together with other treatments such as vitamin B6, vitamin B12 and folate helps the body effectively process homocysteine by triggering the enzymes required to convert it to methionine. This results in a decrease of plasma homocysteine levels.

Ask your doctor if you have any questions about why Cystadane has been prescribed for you.

This medicine is available only with a doctor’s prescription.

Before your doctor gives you CYSTADANE

Tell your doctor if you:

  • Have allergies to any medicines
  • Are taking or using any other medicines. These include medicines bought from pharmacies, supermarkets and health food stores
  • Have any other medical conditions
  • Are pregnant or breast feeding.

Do not take this medicine after the expiry date printed on the bottle.

If you want further information, consult your doctor.

How to take CYSTADANE

Follow all directions given to you by your doctor and pharmacist carefully. These directions may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

Your doctor will evaluate your individual responsiveness to Cystadane before initiating any long term treatment.

The dose will be individually adjusted in order to maintain normal blood levels of homocysteine.

How much to take

The initial dose given to children under 3 years of age is 100mg per kilogram of body weight per day. Dosage in all patients can be gradually increased until plasma homocysteine is undetectable or present only in small amounts.

In pediatric and adults patients, the usual dose of Cystadane is 6 grams per day administered orally in divided doses of 3 grams two times per day.

Always consult your doctor with questions about your prescribed dose.

How to take it

Cystadane powder should be measured using the measuring scoops provided and then dissolved in 120 – 180 mL of water and then drunk immediately after.

Cystadane may be taken along with with one or more of the following treatments:

  • Vitamin B6 (Pyridoxine)
  • Vitamin B12 (Cobalamin)
  • Folic acid
  • Methionine restriction
  • Cysteine supplements

Your doctor will advise on the most appropriate treatment.

How long to take it

Take Cystadane for as long as your doctor tells you.

Cystadane helps to lower your levels of homocysteine in the blood, but it does not cure your condition.

If you forget to take it

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, talk to your doctor or pharmacist.

If you take too much of it (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 764 766) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Cystadane. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking CYSTADANE

Things you must do

Your blood homocysteine levels should be checked regularly while you are taking this medicine.

If you become pregnant while you are taking Cystadane, contact your doctor immediately.

If you are about to be started on any new medication, remind your doctor and pharmacist that you are taking Cystadane.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

Things you must not do

Do not give Cystadane to anyone else even if they have the same condition as you.

Do not take Cystadane to treat any other complaints unless your doctor tells you.

Side Effects

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • Vomiting;
  • Gastrointestinal discomfort;
  • Diarrhoea.

After taking CYSTADANE

Storage

Keep the powder in the bottle until it is time for administration.

If you pour the powder out of the bottle it may not keep well.

Do not freeze the powder.

Once the container has been opened, the bottle can be stored in a cool dry place out of direct sunlight, at below 25 °C.

At this temperature, an unopened bottle has a lifespan of 4 years and an open bottle has a lifespan of 3 months.

Keep the bottle somewhere that children cannot reach it.

Disposal

If your doctor tells you to stop taking Cystadane, or it has passed its expiry date, ask your pharmacist what to do with the powder that is left over.

Product Description

What it looks like

Cystadane is a white, granular powder.

It is supplied in a bottle containing 180 grams of betaine anhydrous. The powder is stored in a re-sealable container. Three measuring scoops are provided to dispense either 100 mg (green scoop), 150 mg (blue scoop) or 1 g (pink scoop) of betaine anhydrous.

Ingredients

The active ingredient of Cystadane is anhydrous betaine. There are no other ingredients present in the product.

This medicine does not contain lactose or gluten.

Supplier

Cystadane is supplied in Australia by:

Recordati Rare Diseases
Australia Pty. Ltd.
Suite 1802, Level 18, 233
Castlereagh Street,
Sydney, NSW, 2000
Australia
Phone: +61 (0) 408 061 403
[email protected]

Date of preparation

This leaflet was prepared in April 2022.

AUST R: 57379

® Cystadane is a registered trademark of Recordati Orphan Drugs.

Published by MIMS August 2022

BRAND INFORMATION

Brand name

Cystadane

Active ingredient

Betaine

Schedule

Unscheduled

 

1 Name of Medicine

Betaine anhydrous.

2 Qualitative and Quantitative Composition

1 g of powder contains 1 g of betaine anhydrous.
It contains no ingredient other than anhydrous betaine. Betaine anhydrous powder is soluble in water, methanol and ethanol. It is sparingly soluble in ether.

3 Pharmaceutical Form

Cystadane (betaine anhydrous powder) for oral administration is a white, granular powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Cystadane is indicated as an adjunct in the treatment of homocystinuria.
Cystadane is also indicated to decrease elevated homocysteine blood levels in patients of all age groups with:
1. cystathionine beta-synthase (CBS deficiency) type of homocystinuria, or
2. 5, 10-methylenetetrahydrofolate reductase deficiency (MTHFR deficiency), or
3. cobalamin cofactor metabolism defect (cbl defect) type of homocystinuria.
Cystadane is also indicated to increase methionine and S-adenosylmethionine blood levels in patients with 5, 10-methylenetetrahydrofolate reductase deficiency (MTHFR deficiency) and cobalamin cofactor metabolism defect (cbl defect) types of homocystinuria.
Patient response to Cystadane can be monitored by homocysteine plasma levels (see Section 4.2 Dose and Method of Administration). Response usually occurs within a week and steady state within a month.
Methionine blood levels may become greatly elevated in CBS deficiency type patients. However, monitoring of patients with high methionine blood levels for many years has not revealed any toxicities or other clinical problems.
Cystadane can be administered along with folate, vitamin B6 and vitamin B12 (cobalamin).

4.2 Dose and Method of Administration

The usual dose used in adults and paediatric patients is 6 g per day administered orally in divided doses of 3 g two times per day. Dosages of up to 20 g per day have been necessary to control homocysteine levels in some patients. In paediatric patients less than 3 years of age, dosage may be started at 100 mg/kg/day and then increased weekly by 100 mg/kg increments. Dosage in all patients can be gradually increased until plasma homocysteine is undetectable or present only in small amounts.
The prescribed amount of Cystadane powder should be measured using one of the measuring scoops provided and then dissolved in 120-180 mL of water for immediate ingestion. Three measuring scoops are provided which dispense either 100 mg (green scoop), 150 mg (blue scoop) or 1 g (pink scoop) of betaine anhydrous. It is recommended that a heaped measuring scoop 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.

4.3 Contraindications

None known.

4.4 Special Warnings and Precautions for Use

Hypermethioninemia.

Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations. Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine. Cerebral oedema has been reported in patients with hypermethioninemia including a few patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 micromol/L through dietary modification and, if necessary, a reduction of Cystadane dose.

Information for patients.

1. Measure with the scoops provided.
2. Mix with 120-180 mL of water and drink immediately.
Always replace the cap tightly after using.

Use in the elderly.

No data available.

Paediatric use.

The majority of cases of homocystinuria patients treated with betaine have been paediatric patients. The disorder, in its most severe form, can be manifested within the first months or years of life by lethargy, failure to thrive, development delays, seizures or eye lens displacement. Patients have been treated successfully without adverse effects within the first months or years of life with dosages of 6 g per day or more of betaine, with resultant biochemical and clinical improvement. However, dosage titration may be preferable in paediatric patients (see Section 4.2 Dose and Method of Administration).

Effects on laboratory tests.

Homocysteine plasma levels can be determined by utilisation of various commercially available amino acid analysers. See Section 5 Pharmacological Properties.

4.5 Interactions with Other Medicines and Other Forms of Interactions

None known.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Long term fertility studies have not yet been conducted on betaine.
(Category C)
Animal reproduction studies have not been conducted with betaine. It is also not known whether betaine can cause foetal harm when administered to a pregnant woman or can affect reproductive capacity. Cystadane should be given to a pregnant woman only if clearly needed.
 It is not known if betaine is excreted in human milk (although its metabolic precursor, choline, occurs in high levels in human milk). Because many drugs are excreted in human milk, caution should be exercised when Cystadane is administered to a nursing mother.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to betaine have been minimal. Possible adverse effects include nausea, gastrointestinal distress and diarrhoea.
A few cases of cerebral oedema have been reported secondary to severe hypermethioninemia in patients with cystathionine beta-synthase (CBS) deficiency treated with Cystadane. See Section 4.4 Special Warnings and Precautions for Use, Hypermethioninemia.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

No incidence of overdosage has been reported.
For information on the management of overdose, contact the Poison Information Centre on 131 126 (Australia) or the National Poisons Centre on 0800 POISON (0800 764 766) in New Zealand.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Betaine occurs naturally in the body. It is a metabolite of choline and present in small amounts in foods such as beets, spinach, cereals, and seafood.
When administered in recommended oral dosage to children or adults, Cystadane acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. As a result, toxic blood levels of homocysteine are reduced in these patients, usually to 20-30 percent or less of pre-treatment levels.
Elevated homocysteine blood levels are considered to cause serious clinical problems in patients such as cardiovascular thrombosis leading to premature death, osteoporosis, skeletal abnormalities, and optic lens dislocation. Studies have demonstrated that homocysteine plasma levels decreased in 98% of patients taking betaine. Clinical improvement was observed in 77% of patients, and in an additional 21% of patients, disease progression was prevented. Many of these patients had not responded to previous therapies including vitamin B6, vitamin B12 (cobalamin) and folate.

Clinical trials.

Studies have demonstrated betaine to be effective in the three types of homocystinuria, i.e. cystathionine beta-synthase deficiency (CBS deficiency); 5,10-methylenetetrahydrofolate reductase deficiency (MTHFR deficiency); and cobalamin cofactor metabolism defect (cbl defect).
Betaine has also been demonstrated to increase plasma methionine and S-adenosylmethionine (SAM) in MTHFR deficiency and cbl defect patients who have low levels of methionine and SAM, which are thought to be the cause of demyelination and other neurologic problems.
In CBS deficient patients, increases in methionine levels have been marked. However, these have not been of clinical consequence as evidenced by treatment of CBS deficient patients with betaine for up to 11 years with no adverse effect.

5.2 Pharmacokinetic Properties

Pharmacokinetic studies of betaine are not available. However, pharmacodynamic measurements, i.e. monitoring of plasma homocysteine levels, have demonstrated the onset of action of betaine is within several days and that steady state in response to dosage is achieved within several weeks. Patients have taken betaine for many years without evidence of tolerance.

5.3 Preclinical Safety Data

Long-term toxicology studies of betaine in animals have not been conducted. In an acute toxicology study in rats, the LD50 was 11,179 mg/kg.

Genotoxicity.

No evidence of mutagenic potential was demonstrated in the following tests: Metaphase analysis of human lymphocytes; bacterial reverse mutation assay and mouse micronucleus test.

Carcinogenicity.

Long term carcinogenicity studies have not yet been conducted on betaine.

6 Pharmaceutical Particulars

6.1 List of Excipients

None.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG).
The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Storage conditions.

Store below 25°C.

6.5 Nature and Contents of Container

Cystadane is available in bottles of 180 grams. Three measuring scoops are included in each pack. Three measuring scoops (pink, blue, green) dispense, respectively, 1 g, 150 mg and 100 mg of betaine anhydrous powder.

6.6 Special Precautions for Disposal

Any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

The chemical name of betaine anhydrous powder is trimethylglycine.

Chemical structure.


CAS number.

107-43-7.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes