(120 to 180 mL) of water, juice, milk, or formula, or mixed with food for immediate ingestion.
Dosage Forms and Strengths
Cystadane is a white, granular, hygroscopic powder for oral solution available in bottles containing 180 grams of betaine anhydrous.
Contraindications
None.
Warnings and Precautions
5.1 Risk of Hypermethioninemia in Patients with CBS Deficiency
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 edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.
Adverse Reactions
6.1 Adverse Reactions in Clinical Studies
The most serious adverse reaction reported with Cystadane treatment is the development of hypermethioninemia and cerebral edema in patients with CBS Deficiency [see Warnings and Precautions (5.1)].
The assessment of clinical adverse reactions is based on a survey study of 41 physicians, who treated a total of 111 homocystinuria patients with Cystadane. Adverse reactions were retrospectively recalled and were not collected systematically in this open-label, uncontrolled, physician survey. Thus, this list may not encompass all types of potential adverse reactions, reliably estimate their frequency, or establish a causal relationship to drug exposure. The following adverse reactions were reported (Table 1):
Table 1: Number of Patients with Adverse Reactions to Cystadane by Physician Survey
Adverse Reactions Number of Patients
Nausea 2
Gastrointestinal distress 2
Diarrhea 1
"Bad Taste" 1
"Caused Odor" 1
Questionable psychological changes 1
“Aspirated the powder” 1
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of Cystadane. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
In postmarketing experience with Cystadane, severe cerebral edema and hypermethioninemia have been reported within 2 weeks to 6 months of starting betaine therapy, with complete recovery after discontinuation of Cystadane. All patients who developed cerebral edema had homocystinuria due to CBS deficiency and had severe elevation in plasma methionine levels (range 1,000 to 3,000 mM). As cerebral edema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to betaine therapy has been postulated as a possible mechanism of action.
The following adverse reactions have been reported in patients during postmarketing use of Cystadane: anorexia, agitation, depression, irritability, personality disorder, sleep disturbed, dental disorders, diarrhea, glossitis, nausea, stomach discomfort, vomiting, hair loss, hives, skin odor abnormal
