Cystadane (betaine anhydrous)

A powder dissolved in a drink or mixed with food, taken twice a day to lower high homocysteine in homocystinuria. Cystadane was approved in 1996 for CBS deficiency, MTHFR deficiency and cobalamin (cbl) defects, in children and adults. The Cystadane label has no boxed warning, but in CBS deficiency the drug can push methionine higher, and brain swelling has been reported.

In homocystinuria, the body cannot process homocysteine, an amino acid made when the body breaks down methionine from protein, and homocysteine builds up in the blood. Betaine, also called trimethylglycine, is a natural substance the body makes from choline and that is found in small amounts in foods such as beets, spinach, cereals and seafood^[1]. Cystadane hands a methyl group, a small chemical tag, to homocysteine, which turns it back into methionine through a route that does not depend on the faulty enzyme^[1]. The label reports that this lowered homocysteine in all 3 types it covers, CBS deficiency, MTHFR deficiency and cbl defects, and that in MTHFR and cbl defects it can also raise low methionine and S-adenosylmethionine (SAM) levels^[1]. In CBS deficiency, the same reaction can drive methionine, which is often already high, even higher^[1].

Cystadane has no boxed warning and no contraindications^[1]. Its 1 warning covers patients with CBS deficiency, whose methionine is often already high: Cystadane can push methionine higher, and cerebral edema (brain swelling) has been reported in patients with high methionine, including patients on Cystadane^[1]. Since approval, severe brain swelling with high methionine has been reported within 2 weeks to 6 months of starting Cystadane, all in patients with CBS deficiency whose methionine was 1,000 to 3,000µmol/L, with complete recovery after Cystadane was stopped^[1]. The label says to monitor methionine in CBS deficiency and keep it below 1,000µmol/L through diet and, if needed, a lower dose^[1]. In a survey of 41 doctors treating 111 patients, the reported side effects were nausea (2 patients), stomach upset (2), diarrhea, bad taste, odor, possible psychological changes and breathing in the powder (1 each), and the label notes this recalled data cannot give reliable rates^[1]. Other reports since approval include loss of appetite, agitation, depression, irritability, personality changes, sleep problems, dental problems, sore tongue, vomiting, hair loss, hives, unusual skin odor and urine leakage^[1]. For pregnancy, the label says limited case reports have not shown a drug-linked risk of birth defects or miscarriage, and there are no data on betaine in breast milk^[1].

Cystadane is a white powder in 180-gram bottles with a measuring scoop; 1 level scoop (1.7mL) holds 1 gram^[1]. The powder is mixed with 4 to 6 ounces (120 to 180mL) of water, juice, milk or formula until fully dissolved, or mixed with food, and taken right away^[1]. For adults and children 3 and older, the label dose is 6 grams a day, given as 3 grams twice a day^[1]. For children under 3, the starting dose is 100mg/kg a day split into 2 doses, raised each week by 50mg/kg^[1]. Doses are raised gradually until plasma total homocysteine is undetectable or present only in small amounts; the label says some patients have needed up to 20 grams a day, while 1 simulation study suggested little added benefit above 150mg/kg a day or more than twice-daily dosing^[1]. The bottle is kept at room temperature, tightly capped and away from moisture^[1].

Yes, Betaine anhydrous (Cystadane) is FDA approved (1996) for the treatment of Homocystinuria.