Betaine (Monograph)

Drug class: Other Miscellaneous Therapeutic Agents
ATC class: A16AA06
VA class: HS900
Chemical name: 1-Carboxy-N, N, N-trimethylmethanaminium hydroxide
Molecular formula: C₅H₁₁NO₂
CAS number: 107-43-7

Medically reviewed by Drugs.com on Dec 23, 2024. Written by ASHP.

Introduction

Betaine is a methyl group donor that functions in the normal metabolic cycle of methionine and reduces homocystinuria in patients with inborn errors of methionine metabolism.

Uses for Betaine

Homocystinuria

Betaine is used in the management of homocystinuria, including forms of the disorder caused by cystathionine β-synthase (CBS) deficiency, 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency, or cobalamin cofactor metabolism (cbl) defect, and has been designated an orphan drug by the US Food and Drug Administration (FDA) for the management of this condition. Although betaine can correct biochemical abnormalities (e.g., reduce elevated plasma homocysteine concentrations) in these patients, the drug does not correct the underlying basic genetic disorder.

Effectiveness of betaine can be determined by monitoring the concentration of homocysteine in plasma. Therapy with betaine usually results in the plasma concentration of homocysteine decreasing within a week and reaching steady state within a month. Plasma homocysteine concentrations usually are reduced to 20–30% or less of pretreatment values. Correction of biochemical abnormalities usually is accompanied by clinical improvement or prevention of disease progression. Therefore, early detection of homocystinuria and initiation of betaine therapy (e.g., during infancy) are important in improving the long-term prognosis of the patient. In patients with homocystinuria secondary to MTHFR deficiency or cbl defect, the drug can increase depressed plasma concentrations of methionine and S-adenosylmethionine (SAM). Although marked increases in plasma methionine concentrations can occur during betaine treatment of homocystinuria in patients with CBS deficiency, such increases do not appear to be associated with clinically important adverse effects.

Patients have received betaine concomitantly with pyridoxine hydrochloride, vitamin B₁₂, and/or folic acid.

Betaine Dosage and Administration

Administration

Betaine is administered orally as a solution prepared from the anhydrous powder. The solution should be prepared immediately before administration by dissolving the appropriate amount of powder in 120–180 mL of water. The scoop provided by the manufacturer delivers 1 g of betaine anhydrous powder per level scoopful, which apportions 1.7 mL. The solution should not be administered if it is colored or the powder does not dissolve completely.

Dosage

Dosage of betaine is expressed in terms of anhydrous drug.

The usual dosage of betaine for the management of homocystinuria in adults and children is 6 g daily administered in 2 equally divided doses. Although children ranging in age from several months to years have been treated successfully and without unusual adverse effects with 6 g daily, dosage titration may be preferable in children. Children younger than 3 years of age may receive an initial betaine dosage of 100 mg/kg daily that is subsequently increased at weekly intervals in increments of 100 mg/kg daily.

All patients may receive gradual increases in betaine dosage until the concentration of homocysteine in plasma is undetectable or present only in small amounts. Some patients have required up to 20 g daily to control concentrations of homocystine in plasma.

Description

Betaine, a methyl group donor that functions in the normal metabolic cycle of methionine, occurs naturally in the body as a metabolite of choline and is present in foods such as beets, spinach, cereals, and seafood. However, natural dietary sources provide betaine in amounts insufficient to be therapeutic in patients with homocystinuria.

In patients with inborn errors of methionine metabolism and resultant homocystinuria, oral administration of betaine at recommended pharmacologic dosages results in reduction of elevated plasma concentrations of homocysteine through the action of betaine functioning as a methyl group donor in the remethylation of homocysteine to methionine. Remethylation of homocysteine to methionine is catalyzed by betaine-homocysteine S-methyltransferase and does not require 5-methyltetrahydrofolate or methylcobalamin cofactors. Because this reaction does not depend on these cofactors, betaine is effective in all 3 primary forms of homocystinuria (i.e., cystathionine β-synthase [CBS] deficiency, 5,10-methylenetetrahydrofolate reductase [MTHFR] deficiency, and cobalamin cofactor metabolism [cbl] defect). Betaine also can increase low plasma methionine and S-adenosylmethionine (SAM) concentrations in patients with MTHFR deficiency or cbl defect. Elevations in plasma homocysteine concentrations in conditions other than homocystinuria also have been reported.

Betaine is commercially available as an anhydrous powder, and potency of the drug is expressed on the anhydrous basis.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cystadane is available through a specialty distribution system via Chronimed, Inc, by calling (800) 900-4267 or a drug wholesaler.

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