Trientine & Cystine-Depleting Agents - NC Standard

Restricted Product(s)

• Cuprimine® (penicillamine 250 mg capsule)
• CuvriorTM (trientine tetrahydrochloride)
• Depen® (penicillamine 250mg tablet)
• penicillamine 250mg capsule (generic Cuprimine®)
• Syprine® (trientine)
• tiopronin (generic Thiola)
• Thiola® (tiopronin)
• tiopronin delayed release (generic Thiola EC®)
• Thiola EC® (tiopronin delayed release)
• trientine (generic Syprine®)
• Venxxiva (tiopronin delayed release tablet)

FDA Approved Use

• Cuprimine, Depen
  • For the treatment of Wilson's disease 
  • For the treatment of cystinuria
• Syprine, Trientine
  • For the treatment of Wilson’s disease in patients who are intolerant of penicillamine.
• Cuvrior
  • For the treatment of adult patients with stable Wilson’s disease who are de-coppered and tolerant of penicillamine.
• Thiola, tiopronin, Thiola EC, tiopronin delayed release, Venxxiva
  • In combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adult and pediatric patients (20 kg and greater) with severe homozygous cystinuria, who are not responsive to these measures alone.  

Criteria for Approval of Restricted Product(s)

1. The request is for Cuprimine, penicillamine capsule (generic Cuprimine) or Depen; AND
   1. The patient has a confirmed diagnosis of Wilson’s disease (medical record documentation required); AND
      1. The patient has tried and failed or has a clinical contraindication/intolerance to generic trientine (medical record documentation required); AND
      2. The patient has tried and failed generic penicillamine 250 mg tablets (medical record documentation required); OR
         1. The patient has a clinical contraindication to the inactive ingredients of generic penicillamine 250 mg tablets (medical documentation required); OR
   2. The patient has a confirmed diagnosis of Cystinuria (medical record documentation required); AND
      1. The patient had stone formation while on a urinary alkalinizers (such as potassium citrate); OR
         1. The patient has a clinical contraindication to the use of urinary alkalinizers; AND
      2. The patient has tried and failed (had stone formation) while on tiopronin (generic tiopronin, Thiola or Thiola EC) (medical record documentation required); OR
         1. The patient has a clinical contraindication to the use of tiopronin (generic tiopronin, Thiola or Thiola EC); (medical record documentation required); AND
      3. The patient has tried and failed generic penicillamine 250 mg tablets (medical record documentation required); OR
         1. The patient has a clinical contraindication to the inactive ingredients of generic penicillamine 250 mg tablets (medical documentation required); AND
   3. The patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., hepatologist, nephrologist, urologist); OR
2. The request is for Syprine or generic trientine; AND
   1. The patient is 6 years of age or older; AND
   2. The patient has a confirmed diagnosis of Wilson’s disease (medical record documentation required); AND
   3. The patient has documented failure, intolerance, or clinical contraindication to penicillamine (medical record documentation required); AND
   4. If the request is for brand Syprine,
      1. The patient has tried and failed generic trientine (medical record documentation required); OR
         1. The patient has a clinical contraindication to the inactive ingredients of generic trientine (medical documentation required); AND
   5. The patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., hepatologist); OR
3. The request is for Cuvrior; AND
   1. The patient is 18 years of age or older; AND
   2. The patient has a confirmed diagnosis of Wilson’s disease (medical record documentation required); AND
   3. The patient has documented failure or clinical contraindication to penicillamine (medical record documentation required); AND 
   4. The patient has tried and failed generic trientine (medical record documentation required); OR
      1. The patient has a clinical contraindication to the inactive ingredients of generic trientine (medical documentation required); AND
   5. The patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., hepatologist); OR
4. The request is for Thiola, generic tiopronin (Thiola), Thiola EC, generic tiopronin DR (Thiola EC) or Venxxiva; AND
   1. The patient is 9 years of age or older; AND
   2. The patient has a diagnosis of cystinuria (medical record documentation required); AND
   3. The patient had stone formation while on a urinary alkalinizers (such as potassium citrate); OR
      1. The patient has a clinical contraindication to the use of urinary alkalinizers; AND
   4. The patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., nephrologist, urologist); AND
5. The prescribed dose and quantity are appropriate based on intended use and FDA labeling; AND
6. Indications outside of FDA labeling will be subject to medical necessity review in accordance with specific strong endorsement or support by nationally recognized compendia, when such recommendation is based on strong/high levels of evidence, and/or uniform consensus of clinical appropriateness has been reached. Medical records and references / evidence must be provided; AND
7. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.
   
   Duration of Approval: 365 days (1 year)

Quantity Limit Exception Criteria

1. The quantity (dose) requested is for documented titration purposes at the initiation of therapy (authorization for a 90 day titration period); AND
2. The prescribed dose cannot be achieved using a lesser quantity of a higher strength; AND
3. The quantity (dose) requested does not exceed the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert; OR
4. If the quantity (dose) requested exceeds the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert, then the prescriber must submit documentation in support of therapy with a higher dose for the intended diagnosis (submitted documentation may include medical records OR fax form which reflects medical record documentation that shows the length of time the requested dose has been used, and what other medications and doses have been tried and failed).
   
   Duration of Approval: 365 days (1 year)

References

All information referenced is from FDA package insert unless otherwise noted below.

Pearle M, Goldfarb D, Assimos D, et al. Medical Management of Kidney Stones: AUA Guideline. J Urol. [Internet] 2014 Aug [cited 2016 Aug 23]: 192(2):316-324. 

Schilsky M, Roberts E, Bronstein J, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: Executive summary of the 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology 77(4):p 1428-1455, April 2023. | DOI: 10.1002/hep.32805

Policy Implementation/Update Information

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q2 annually.

January 2025: Criteria update: Added Venxxiva (tiopronin delayed release tabs) to policy.

March 2024: Criteria update: Added tiopronin delayed release tabs (generic Thiola EC) to policy.

October 2023 (v2): Criteria update: Removed Clovique from policy. Added P&T review statement to policy.

October 2023: Criteria update: Added trientine 500mg capsules to policy.

April 2023 (v2): Criteria update: Added Cuvrior to policy.

April 2023: Criteria change: Formatting changes and criteria review. Updated requirements to remove penicillamine capsules as an option of t/f medication. Added quantity limitations section. Added patient must be managed by or in consultation with a specialist in the area of the patient’s diagnosis.

January 2023: Criteria update: Formatting changes. Clarified restriction applies to all brand and generic products. Decreased duration of approval to one year.

June 2021: Criteria update: Added tiopronin (generic Thiola) to policy.

April 2021: Criteria change: Added Clovique, Depen, Thiola, Thiola EC and Syprine to policy. Remove Rheumatoid Arthritis from policy as this is now an unsupported use for Cuprimine & Depen.

April 2020: Criteria change: Applied criteria to Net Results formulary. Removed Simponi and added Rinvoq to tried and failed list for Rheumatoid arthritis.

Jan 2020: Criteria change: Updated criteria to prefer generic penicillamine tablets.

May 2019: Criteria update: Updated criteria format, updated non-formulary statement

Oct 2018: Annual review; No change

January 2017: Original utilization management criteria issued.