ph-1182
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Penicillamine Step Therapy Program Summary

Policy Number: PH-1182

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE                                                                                                                                                

Effective Date

Date of Origin   

1/1/2023

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

Cuprimine®

(penicillamine)

Capsule

Treatment of Wilson’s disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy

Generic equivalent available

1

Depen®

(penicillamine)

Tablet

Treatment of Wilson’s disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy

Generic equivalent available

2

See package insert for FDA prescribing information:  https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Wilson's Disease

Wilson’s disease is an autosomal recessive genetic disorder that leads to impairment of cellular copper transport and affects about one in 30,000 people worldwide. Wilson’s disease can present clinically as liver disease, as a progressive neurological disorder (hepatic dysfunction being less apparent or occasionally absent), or as psychiatric illness. Wilson’s disease presents with liver disease more often in children and younger adult patients than in older adults. Symptoms at any age are frequently nonspecific.  It is fatal unless it is detected and treated before serious illness from copper poisoning develops.(3-5)

 

Copper is present in most foods, and healthy individuals excrete any excess copper. Patients with Wilson’s disease cannot eliminate the extra copper, possibly because the liver lacks the mechanism to excrete free copper into the bile, and it accumulates in the liver or brain. Copper accumulation begins immediately after birth when hepatocytes begin to store excess copper, but as their capacity is exceeded, copper is released into the blood and is taken up into extrahepatic sites. Symptoms usually appear in late adolescence and patients may experience hepatitis, psychiatric, or neurologic manifestations. Signs may include jaundice, abdominal swelling, vomiting of blood, abdominal pain, tremors, difficulty walking, difficulty talking and difficulty swallowing. Other symptoms may include mental illness, and may consist of homicidal or suicidal behavior, depression and aggression. Women may experience menstrual irregularities, absent periods, infertility, or multiple miscarriages. The disease is always fatal if not diagnosed and treated.(3-5)

 

Wilson’s disease is diagnosed by relatively simple tests including:

  • Ophthalmic slit lamp examination of Kayser-Fleischer rings
  • Serum ceruloplasmin test
  • 24 hour urine copper test
  • Liver biopsy for histology and histochemistry and copper quantification
  • Genetic testing, haplotype analysis for sibling and mutation analysis

 

Wilson’s disease should be considered in any individual between 3 and 55 years of age with liver abnormalities of uncertain cause and should be excluded in any patient with unexplained liver disease along with neurological or neuropsychiatric disorder. Diagnostic testing may include an extremely low ceruloplasmin level (less than 5 mg/dL), basal 24-hour urinary copper excretion greater than 40 mcg, hepatic parenchymal copper concentration greater than 250 mcg/g dry weight, neurological evaluation and radiological imaging of the brain may provide evidence to support diagnosis, generic studies, or a penicillamine challenge study may also be completed for the purpose of diagnosis.(3,4)

 

Treatment is lifelong and includes a low copper diet and chelation therapy aimed at removing excess copper and preventing its reaccumulation. With proper therapy, disease progress can be halted and often symptoms can be improved. It is recommended that patients avoid the foods that are highest in copper (organ meats, shellfish, chocolate, nuts, and mushrooms), multivitamins or other dietary supplements that may contain copper, and consume only drinking water that testing has shown has less than 0.1 ppm of copper. In addition, chelation therapy drugs approved for treating Wilson’s disease act by binding of copper causing increased urinary excretion and include penicillamine (Cuprimine and Depen) and trientine. Guidelines support the view that initial therapy in a symptomatic patient should be a chelating agent (penicillamine or trientene). Galzin (zinc acetate) is a mettalothionein inducer drug approved for treating Wilson’s disease and acts by blocking the absorption of copper in the intestinal tract which depletes accumulated copper and prevents its reaccumulation. Some patients with severe hepatitis or liver failure may require a liver transplant.(4,6)

Safety (1,2)

Penicillamine is contraindicated in the following:  

  • Pregnancy, except for the treatment of Wilson’s disease or certain patients with cystinuria
  • Breastfeeding
  • Patients with a history of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine
  • Rheumatoid arthritis patients with a history or other evidence of renal insufficiency

REFERENCES                                                                                                                                                              

Number

Reference

1

Cuprimine prescribing information. Bausch Health US LLC. October 2020.

2

Depen prescribing information. Meda Pharmaceuticals. July 2018.

3

Wilson’s Disease Association. http://www.wilsonsdisease.org.

4

Roberts, E.A., Schilsky, M.L. Diagnosis and treatment of Wilson disease: An update. Hepatology. 2008; 47: 2089-2111. https://doi.org/10.1002/hep.22261.

5

EASL Clinical Practice Guidelines: Wilson’s disease. Journal of Hepatology. 2012; 56(3):671-685. doi: 10.1016/j.jhep.2011.11.007. PMID: 22340672.

6

Saroli Palumbo C, Schilsky ML. Clinical practice guidelines in Wilson disease. Ann Transl Med. 2019 Apr;7(Suppl 2):S65. doi: 10.21037/atm.2018.12.53. PMID: 31179302; PMCID: PMC6531645.

 

POLICY AGENT SUMMARY STEP THERAPY

Agent Names

Strength

Targeted MSC

Available MSC

Preferred Status

Effective Date

CUPRIMINE*Penicillamine Cap 250 MG

250 MG

M ; N ; O ; Y

O ; Y

01-01-2023

DEPEN TITRATABS*Penicillamine Tab 250 MG

250 MG

M ; N ; O

O ; Y

01-01-2023

CLIENT SUMMARY – STEP THERAPY

STEP THERAPY CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

TARGET AGENT(S)

Cuprimine® (penicillamine)*

Depen® (penicillamine)**

* - available as a generic; included as a target in the step therapy program

** - available as a generic; generic included as a prerequisite in the step therapy program

 

Target Agent(s) will be approved when ONE of the following is met:

  1. The patient’s medication history includes use of generic penicillamine tablets within the past 90 days OR
  2. The patient has an intolerance or hypersensitivity to generic penicillamine tablets that is not expected to occur with the requested agent OR
  3. The patient has an FDA labeled contraindication to generic penicillamine tablets that is not expected to occur with the requested agent

Length of Approval: 12 months

 

 This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

 

Commercial _ PS _ Penicillamine Step Therapy _ProgSum_ 1/1/2023  _ © Copyright Prime Therapeutics LLC. November 2022 All Rights Reserved