Cigna penicillamine prior auth Step Therapy

Coverage Criteria

Initial Therapy — Cystinuria (capsules)

Penicillamine capsules (Cuprimine/generic) are covered as medically necessary for FDA‑approved indications when the specified criteria are met.

Cystinuria (capsules): Approve for 1 year if BOTH A and B are met

A) According to the prescriber, patient has tried increased fluid intake; restriction of sodium and protein; and urinary alkalinization; B) Patient meets ONE of the following: i. Generic penicillamine capsules are requested; OR ii. If brand Cuprimine is requested, patient has tried generic penicillamine capsules AND cannot take generic penicillamine capsules due to a formulation difference in the inactive ingredient(s) (e.g., difference in dyes, fillers, preservatives) which, per the prescriber, would result in a significant allergy or serious adverse reaction.

Wilson's disease (capsules): Approve for 1 year if ALL A, B, C, and D are met

A) Diagnosis confirmed by ONE of: i. Genetic testing confirming biallelic pathogenic ATP7B mutations; OR ii. At least TWO of: a) Kayser-Fleischer rings; b) Serum ceruloplasmin < 20 mg/dL; c) Liver biopsy consistent with Wilson's disease; d) 24-hour urinary copper > 40 mcg/24 hours. B) Patient meets ONE of: i. Tried Galzin (zinc acetate); ii. Tried another zinc product; iii. Prescriber states zinc is inappropriate; iv. Patient already started on penicillamine. C) Patient meets ONE of: i. Generic penicillamine capsules are requested; OR ii. If brand Cuprimine is requested, patient has tried generic capsules AND cannot take generic due to an inactive-ingredient–related allergy/serious adverse reaction. D) Medication is prescribed by or in consultation with a gastroenterologist, hepatologist, or liver transplant physician.

Initial Therapy — Wilson's disease (capsules)

Wilson's disease coverage criteria for penicillamine capsules.

Wilson's disease (capsules): Approve for 1 year if ALL A, B, C, and D are met

Initial Therapy — Cystinuria and Wilson's disease (tablets)

Penicillamine tablets (Depen/generic) are covered as medically necessary for FDA‑approved indications when the specified criteria are met.

Cystinuria (tablets): Approve for 1 year if BOTH A and B are met

A) According to the prescriber, patient has tried increased fluid intake; restriction of sodium and protein; and urinary alkalinization; B) Patient meets ONE of the following: i. Generic penicillamine tablets are requested; OR ii. If brand Depen is requested, patient has tried generic penicillamine tablets AND cannot take generic penicillamine tablets due to a formulation difference in the inactive ingredient(s) (e.g., difference in dyes, fillers, preservatives) which, per the prescriber, would result in a significant allergy or serious adverse reaction.

Wilson's disease (tablets): Approve for 1 year if ALL A, B, C, and D are met

A) Diagnosis confirmed by ONE of: i. Genetic testing confirming biallelic pathogenic ATP7B mutations; OR ii. At least TWO of: a) Kayser-Fleischer rings; b) Serum ceruloplasmin < 20 mg/dL; c) Liver biopsy consistent with Wilson's disease; d) 24-hour urinary copper > 40 mcg/24 hours. B) Patient meets ONE of: i. Tried Galzin (zinc acetate); ii. Tried another zinc product; iii. Prescriber states zinc is inappropriate; iv. Patient already started on penicillamine. C) Patient meets ONE of: i. Generic penicillamine tablets are requested; OR ii. If brand Depen is requested, patient has tried generic tablets AND cannot take generic due to an inactive-ingredient–related allergy/serious adverse reaction. D) Medication is prescribed by or in consultation with a gastroenterologist, hepatologist, or liver transplant physician.

Use of Cuprimine (penicillamine capsules), Depen (penicillamine tablets), or their generic equivalents for any indication other than the specified FDA‑approved uses is considered experimental, investigational, or unproven and is not covered. Criteria will be updated if new published data become available.

Coding

Coding (not provided)mixed

not specified

No CPT/HCPCS/ICD-10/NDC codes were provided in the policy text.

Laboratory thresholdsmixed

24-hour urinary copper	> 40 mcg/24 hours
Serum ceruloplasmin	< 20 mg/dL

inv-06: 24-hour urinary copper

Laboratory threshold> 40 mcg/24 hours

Context of useUsed as one of the diagnostic criteria for Wilson's disease (counts toward meeting at least two clinical features).

Source guideline referenceAASLD diagnostic criteria referenced in policy guidance

inv-07: Serum ceruloplasmin

Laboratory threshold< 20 mg/dL

Context of useLow serum ceruloplasmin is one of the clinical features used to confirm Wilson's disease (counts toward meeting at least two features).

Source guideline reference

Provider Actions / Requirements

Prior Authorization

Prior Authorization Required / Step Therapy Applies

Prior Authorization is required for penicillamine products. This policy includes a Step Therapy component: when clinically appropriate, members should try generic penicillamine (Step 1) prior to approval of brand Cuprimine or Depen (Step 2). If a brand is requested but the Step Therapy requirement has not been met, approval for generic penicillamine will be authorized instead. Approvals are provided for the duration specified in the policy.

Prior authorization required for penicillamine products (generic and brand).
Step therapy: generic penicillamine is Step 1; brand Cuprimine or Depen is Step 2.

Step Therapy

Step Therapy Requirement

Step therapy requires trial of a generic penicillamine product before brand Cuprimine or Depen will be authorized. Exceptions to the Step Therapy requirement may be granted when the prescriber documents that the member cannot tolerate the generic due to a formulation-related allergy or serious adverse reaction (e.g., difference in inactive ingredients) or when clinical reasons make generic therapy inappropriate.

Definitions

inv-14: Wilson's disease diagnostic confirmation

DefinitionWilson's disease diagnostic confirmation is either genetic confirmation of biallelic pathogenic ATP7B variants OR at least two clinical features among: Kayser-Fleischer rings; serum ceruloplasmin <20 mg/dL; liver biopsy findings consistent with Wilson's disease; 24-hour urinary copper >40 mcg/24 hours.

Acceptable genetic evidenceGenetic testing demonstrating biallelic pathogenic ATP7B mutations (symptomatic or asymptomatic individuals).

Acceptable clinical feature combinationsAny two of: Kayser-Fleischer rings; serum ceruloplasmin <20 mg/dL; liver biopsy consistent with Wilson's disease; 24-hour urinary copper >40 mcg/24 hours.

Policy useRequired documentation for Wilson's disease coverage under penicillamine criteria — must meet genetic OR clinical-feature criteria to qualify for approval.

Initial Therapy and Step Therapy Criteria

Initial therapy and step therapy

Initial authorization for FDA‑approved indications; step therapy requires trial of generic penicillamine before brand product is authorized.

Formulation/brand step therapy: Generic penicillamine (capsule or tablet as appropriate) must be tried first. If brand (Cuprimine or Depen) is requested, trial of generic is required unless the prescriber documents that the patient cannot take the generic due to an inactive-ingredient–related allergy or serious adverse reaction.

If brand is requested but the step therapy requirement is not met, an approval may be issued for generic penicillamine instead.

FDA‑approved indications (summary): Approve covered indications for 1 year when respective indication-specific criteria are met

Covered indications include cystinuria (document prior conservative measures) and Wilson's disease (diagnostic confirmation per policy).

Continuation / Duration Criteria

Continuation/Duration

Approval duration and requirements for continued coverage.

Approval duration: Approvals are provided for 1 year for covered indications.

Because of specialized skills required for Wilson's disease, therapy should be prescribed by or in consultation with an appropriate specialist.

Step Therapy Details

Step	Requirement	Exception / Documentation Required	Coverage Action
Step 1
Trial of generic penicillamine (capsule or tablet as appropriate) must be attempted before pursuing a brand product (Cuprimine or Depen).
If generic cannot be used due to an inactive‑ingredient–related allergy or a serious adverse reaction, the prescriber must document the specific formulation difference and the clinical rationale (e.g., dyes, fillers, preservatives).
If step met (generic trial completed), brand may be considered per other coverage criteria. If step not met and brand requested, approval will be issued for generic penicillamine instead.

Background

Penicillamine is a chelating agent provided as capsules (Cuprimine and generics) and tablets (Depen and generics). It is indicated for several FDA‑listed conditions including cystinuria, Wilson’s disease, and for severe, active rheumatoid arthritis after failure of conventional therapy. Clinical guidance recognizes penicillamine and other chelators as standard initial therapy for symptomatic Wilson’s disease, while zinc may be used in presymptomatic or maintenance settings.

OpenPayer

Penicillamine (Cuprimine, Depen) prior authorization with step therapy