Category Filter
- Advanced Imaging
- Autism Spectrum Mandate
- Behavioral Health
- Blue Advantage Policies
- Chronic Condition Management
- Genetic Testing
- HelpScript Program
- Hemophilia Drugs
- Medical Policies
- Pre-Service Review (Predetermination/Precertification)
- Provider-Administered Drug Policies
- Radiation Therapy
- Self-Administered Drug Policies
- Transgender Services
Asset Publisher
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 |
07-01-2024 |
|
FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Cuprimine® 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 available |
1 |
Depen® 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 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), as a psychiatric illness or as a combination of these. Wilson’s disease presents with isolated 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.(7) Copper is present in many 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, brain and other organs. 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:(3)
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.(4,7) 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 state that all patients with a newly established diagnosis of Wilson's disease should initiated on lifelong medical therapy. Initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientene). Treatment of asymptomatic patients with Wilson's disease can be a chelating agent or zinc. 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.(4,6,7) |
Rheumatoid Arthritis |
Rheumatoid arthritis (RA) is the most common inflammatory autoimmune arthritis in adults. The main goal of therapy is to achieve remission, but additional goals include decrease inflammation, relieve symptoms, prevent joint and organ damage, improve physical function/overall well-being, and reduce long term complications.(10,11) The choice of therapy depends on several factors, including the severity of disease activity when therapy is initiated and the response of the patient to prior therapeutic interventions.(10) American College of Rheumatology (ACR) guidelines list the following guiding principles in the treatment of RA:(10)
D‐penicillamine is a penicillin derived compound originally used to treat patients with rheumatoid arthritis (RA) in the 1950's. Although frequently used in the past, its use has declined because of concerns over its safety and due to the increasing use of other disease modifying anti‐rheumatic drugs (DMARDs) such as methotrexate.(8) |
Cystinuria |
Cystinuria is the most common genetic cause of recurrent kidney stones. As the result of a genetic defect in proximal tubular reabsorption of filtered cystine, increased urine levels of the poorly soluble amino acid result in recurrent cystine nephrolithiasis. Recurrent cystine stones not only adversely affect the quality of patients suffering from cystinuria but also may result in chronic kidney disease (CKD) from recurrent renal injury. Thus, the mainstay of medical management revolves around prevention of stones.(9) Medical management of cystinuria begins with a series of core conservative measures aimed at stone prevention—high fluid intake, minimizing intake of dietary sodium and animal protein, and urinary alkalinization. Patients should consume enough fluids to maintain 24-h urine cystine concentrations of less than 250 mg/L (1 mmol/L), usually equating to greater than 3 L urine output each day in adults. Pharmacotherapy for cystinuria should be escalated in a stepwise fashion, with pharmacotherapy with cystine binding thiol drugs (CBTD) added for patients who continue to have recurrent cystine nephrolithiasis despite implementation of and adherence to conservative therapy. These drugs, alpha-mercaptopropionylglycine (tiopronin) and D-penicillamine, work through the reduction of the disulfide bond of cystine, yielding a more soluble drug-cysteine complex and reducing free urinary cystine levels. The use of CBTDs has been demonstrated to be effective in reducing cystine stone growth, new stone formation, and incidence of urologic intervention in retrospective studies. However, their use is limited to cases refractory to conservative therapy given their high cost, adverse effect profile, including drug sensitivity reactions, nephrotic range proteinuria secondary to membranous nephropathy, and very rare liver abnormalities and hematologic disturbances, such as neutropenia and thrombocytopenia.(9) |
Safety |
Penicillamine is contraindicated in the following:(1,2)
|
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. |
7 |
Schilsky, M, Roberts, E, 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 ():p n/a, December 07, 2022. | DOI: 10.1002/hep.32805 |
POLICY AGENT SUMMARY STEP THERAPY
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Cuprimine |
Penicillamine Cap 250 MG |
250 MG |
M ; N ; O ; Y |
O ; Y |
|
|
Depen titratabs |
Penicillamine Tab 250 MG |
250 MG |
M ; N ; O |
O ; Y |
|
|
CLIENT SUMMARY – STEP THERAPY
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Cuprimine |
Penicillamine Cap 250 MG |
250 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Depen titratabs |
Penicillamine Tab 250 MG |
250 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
STEP THERAPY CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
||||
|
*available as a generic Target Agent(s) will be approved when ONE of the following is met:
Length of Approval: 12 months *Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required. |
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.
ALBP _ Commercial _ CSReg _ Penicillamine__ST _ProgSum_ 07-01-2024 _ © Copyright Prime Therapeutics LLC. May 2024 All Rights Reserved