CurrentNeighborhood Health Plan of Rhode IslandPolicy 2988-A

Betaine anhydrous (Cystadane) — Coverage Criteria for Homocystinuria and Related Disorders

This policy governs prior authorization and coverage criteria for betaine anhydrous (Cystadane) used to treat homocystinuria and methylmalonic acidemia with homocystinuria for members of Neighborhood Health Plan of Rhode Island (as administered by CVS Caremark). It affects prescribers and pharmacy benefit adjudication.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyBetaine anhydrous (Cystadane) — Coverage Criteria for Homocystinuria and Related Disorders

Policy CodePolicy 2988-A

Change TypeNo material changes

Effective Date

Next Review Date

Key ActionObtain prior authorization for up to 12 months when approval criteria are met and submit required diagnostic documentation (enzyme analysis or genetic testing) as evidence.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthsauthorization period granted for initial and continued treatment

1drug referenced (Cystadane)

<=1000plasma methionine monitoring threshold (CBS deficiency)

Coverage Criteria

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Initial therapy for homocystinuria: Member has one of the following types of homocystinuria and the diagnosis was confirmed by enzyme assay or genetic testing: cystathionine beta-synthase (CBS) deficiency; 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency; or cobalamin cofactor metabolism (cbl) defect.

For CBS deficiency, plasma methionine concentrations must be monitored and kept below 1,000 micromol/L through dietary modification and dose reduction if necessary.

inv-03: Reauthorization — Homocystinuria

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for homocystinuria when BOTH of the following are met:

Reauthorization — Homocystinuria: Total homocysteine level is undetectable or present only in small amounts, OR there is a substantial decrease in homocysteine levels and the dose will be increased until maximum tolerability or plasma total homocysteine is undetectable or present in only small amounts.

If CBS deficiency, plasma methionine must be monitored and kept below 1,000 micromol/L.

inv-04: Reauthorization — Methylmalonic acidemia with homocystinuria

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for methylmalonic acidemia with homocystinuria when:

Reauthorization — Methylmalonic acidemia with homocystinuria: Member is experiencing benefit from therapy as evidenced by disease stability or disease improvement.

Coding

Referenced drugmixed

Cystadane

betaine anhydrous (brand name listed)

inv-08: Plasma methionine — <= 1000 micromol/L

ThresholdPlasma methionine ≤ 1,000 micromol/L

Monitoring requirementFor members with CBS deficiency, plasma methionine concentrations must be monitored and maintained below 1,000 micromol/L through dietary modification and dose reduction if necessary.

ApplicationApplies to initial authorization and reauthorization for homocystinuria when CBS deficiency is present.

Provider Actions & Requirements

Documentation Required

Required diagnostic documentation

Submission of the following information is necessary to initiate the prior authorization review: For cystathionine beta‑synthase (CBS) deficiency, enzyme analysis of CBS activity or genetic testing results. For 5,10‑methylenetetrahydrofolate reductase (MTHFR) deficiency, enzyme analysis of MTHFR activity or genetic testing results. For cobalamin cofactor metabolism (cbl) defect, genetic testing results.

CBS deficiency: enzyme analysis of CBS activity or genetic testing
MTHFR deficiency: enzyme analysis of MTHFR activity or genetic testing
cbl defect: genetic testing results

Prior Authorization

Prior authorization duration & monitoring

Authorization of 12 months may be granted for treatment of homocystinuria to decrease elevated homocysteine blood levels when approval criteria are met for initial therapy or reauthorization. For members with CBS deficiency, plasma methionine concentrations must be monitored and kept below 1,000 micromol/L through dietary modification and, if necessary, dose reduction of the requested medication.

Prior authorization duration: up to 12 months for initial therapy or reauthorization
Monitoring for CBS deficiency: plasma methionine < 1,000 micromol/L

Documentation Required

Prescriber specialty

This medication must be prescribed by or in consultation with a physician who specializes in the treatment of metabolic disease and/or lysosomal storage disorders.

Prescriber specialty requirement: metabolic disease and/or lysosomal storage disorder specialist

Denial Risk

Non‑covered indications

All other indications not listed (outside FDA‑approved and compendial uses) are considered experimental/investigational and not medically necessary.

Non‑covered indications: any indication outside listed diagnoses

Background

Betaine anhydrous (Cystadane) is indicated to decrease elevated homocysteine blood concentrations in patients with homocystinuria, including recognized inherited metabolic disorders such as cystathionine beta‑synthase (CBS) deficiency, MTHFR deficiency, and cobalamin cofactor metabolism defects. Compendial use also includes treatment of methylmalonic acidemia with homocystinuria.

Definitions

inv-15: Homocystinuria — Inherited metabolic disorders characterized by elevated homocysteine; includes CBS deficiency, MTHFR deficiency, and cobalamin cofactor m...

DefinitionInherited metabolic disorders characterized by elevated homocysteine; includes CBS deficiency, MTHFR deficiency, and cobalamin cofactor metabolism defects.

Included conditionsCystathionine beta-synthase (CBS) deficiency; 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency; cobalamin cofactor metabolism (cbl) defect.

Clinical relevanceIndication for betaine anhydrous (Cystadane) to decrease elevated homocysteine blood concentrations in pediatric and adult patients.