ities, and urinary incontinence.
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C: Animal reproduction studies have not been conducted with Cystadane. It is also not known whether Cystadane can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cystadane should be given to a pregnant woman only if clearly needed.
8.3 Nursing Mothers
It is not known whether Cystadane is excreted in human milk. Use only if clearly needed.
8.4 Pediatric Use
The majority of case studies of homocystinuria patients treated with Cystadane have been pediatric patients, including patients ranging in age from 24 days to 17 years [see Clinical Studies (14)]. Children younger than 3 years of age may benefit from dose titration [see Dosage and Administration (2)].
Overdosage
In an acute toxicology study in rats, death occurred frequently at doses equal to or greater than 10 g/kg.
Cystadane Description
Cystadane (betaine anhydrous for oral solution) is an agent for the treatment of homocystinuria. It contains no ingredients other than anhydrous betaine. Cystadane is a white, granular, hygroscopic powder, which is diluted in water and administered orally. The chemical name of betaine anhydrous powder is trimethylglycine. It has a molecular weight of 117.15. The structural formula is:
Cystadane - Clinical Pharmacology
12.1 Mechanism of Action
Cystadane acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. Cystadane occurs naturally in the body. It is a metabolite of choline and is present in small amounts in foods such as beets, spinach, cereals, and seafood.
12.2 Pharmacodynamics
Cystadane was observed to lower plasma homocysteine levels in three types of homocystinuria, including CBS deficiency; MTHFR deficiency; and cbl defect. Patients have taken Cystadane for many years without evidence of tolerance. There has been no demonstrated correlation between Cystadane levels and homocysteine levels.
In CBS-deficient patients, large increases in methionine levels over baseline have been observed. Cystadane has also been demonstrated to increase low plasma methionine and S-adenosylmethionine (SAM) levels in patients with MTHFR deficiency and cbl defect.
12.3 Pharmacokinetics
Pharmacokinetic studies of Cystadane are not available. Plasma levels of Cystadane have not been measured in patients and have not been correlated to homocysteine levels.
Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term carcinogenicity and fertility studies have not been conducted with Cystadane. No evidence of genotoxicity was demonstrated in the following tests: metaphase analysis of human lymphocytes; bacterial reverse mutation assay; and mouse micronucleus test.
Clinical Studies
Cystadane was studied in a double-blind, placebo-controlled, crossover study in 6 patients with CBS deficiency, ages 7 to 32 years at enrollment. Cystadane was administered at a dosage of 3 grams twice daily, for 12 months. Plasma homocystine levels were significantly reduced (p<0.01) compared to placebo. Plasma methionine levels were variable and not significantly different compared to placebo. No adverse events were r |
