Effective Date

Date of Origin   

10-01-2024           

Elmiron®

(pentosan polysulfate sodium)

Capsule

The relief of bladder pain or discomfort associated with interstitial cystitis

1

Interstitial cystitis

Interstitial cystitis (IC) is a chronic, or long-lasting, condition that causes painful urinary symptoms. There is no known exact cause of IC. IC can cause repeat discomfort, pressure, tenderness or pain in the bladder, lower abdomen, and pelvic area.(5)

IC varies so much in symptoms and severity that most researchers believe it is not one, but several diseases. In recent years, bladder pain syndrome (BPS) or painful bladder syndrome (PBS) has been used to describe cases with painful urinary symptoms that may not meet the strictest definition of IC. The term IC/BPS includes all cases of urinary pain that can’t be attributed to other causes, such as infection or urinary stones. The term interstitial cystitis, or IC, is used alone when describing cases that meet all of the IC criteria established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The diagnosis of IC/PBS in the general population is based on:(5)

• Presence of pain related to the bladder, usually accompanied by frequency and urgency of urination
• The absence of other diseases and conditions that could cause similar symptoms, such as urinary tract infections (UTIs), bladder cancer, endometriosis (women), or prostatitis (men) - infection or inflammation of the prostate

There is not medical test to confirm a diagnosis of IC/BPS. Methods to assist in diagnosing IC/BPS include:(6)

• Medical History
• Baseline Pain and Voiding Tests
• Urine exam
• Urodynamic Tests
• Cystoscopy

Clinical Guidelines - European Association of Urology (EAU)- Guidelines on Treatment of Chronic Pelvic Pain (2022)

Bladder pain syndrome (BPS) is the occurrence of persistent or recurrent pain perceived in the urinary bladder region, accompanied by at least one other symptom, such as pain worsening with bladder filling and day-time and/or night-time urinary frequency. There is no proven infection or other obvious local pathology. BPS is often associated with cognitive, behavioral, sexual or emotional consequences, as well as with symptoms suggestive of lower urinary tract and sexual dysfunction. BPS is believed to represent a heterogeneous spectrum of disorders. There may be specific types if inflammation as a feature in subsets of patients.(3)

Localization of the pain can be difficult by examination, and consequently, another localization symptom of the pain is required. Cystoscopy with hydrodistension and biopsy may be indicated to define phenotypes. Other terms for BPS that have been used include interstitial cystitis, painful bladder syndrome, and PBS/IC or BPS/IC. These terms are no longer recommended.(3)

Recommendations with 1 to 2a or strong strength rating for treatment of BPS:(3)

• Offer subtype and phenotype-oriented therapy for the treatment of BPS
• Multimodal behavioral, physical and psychological techniques alongside oral or invasive treatments of BPS
• Amitriptyline
• Oral pentosan polysulphate sodium
• Oral pentosan polysulphate plus subcutaneous heparin in low responders to pentosan polysulphate alone
• Do not recommend oral corticosteroids for long-term treatment
• Administer submucosal injection of Botulinum toxin type A plus hydrodistension if intravesical instillation therapies have failed
• All ablative organ surgery should be the last resort for experienced and BPS knowledgeable surgeons only
• Transurethral resection (or coagulation or laser) of bladder lesions, but in BPS type 3 C only

Clinical Guidelines - American Urologic Association [AUA] - Guidelines on Treatment of Interstitial Cystitis/Bladder Pain Syndrome [IC/BPS] (2022)

The body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed.(4)

Treatment decisions should typically be made after shared decision-making, with the patient informed of the risks, potential benefits, and alternatives. Except for patients with Hunner lesions, initial treatment should be nonsurgical. Treatment is categorized into:(4)

• Behavioral/non-pharmacologic treatments:
  • Patients should be educated about normal bladder function, what is known and not known about IC/BPS, benefits vs risks/burdens of the available treatment alternatives, the fact that no single treatment has been found effective for the majority of patients and the fact that acceptable symptom control may require trials of multiple therapeutic options (including combination therapy) before it is achieved. (Clinical Principle)
  • Self-care practices and behavioral modifications that can improve symptoms should be discussed and implemented as feasible. (Clinical Principle)
  • Patients should be encouraged to implement stress management practices to improve coping techniques and manage stress-induced symptom exacerbations. (Clinical Principle)
  • Appropriate manual physical therapy techniques (e.g., maneuvers that resolve pelvic, abdominal and/or hip muscular trigger points, lengthen muscle contractures, and release painful scars and other connective tissue restrictions), if appropriately trained clinicians are available, should be offered to patients who present with pelvic floor tenderness. Pelvic floor strengthening exercises (e.g., Kegel exercises) should be avoided. (Evidence Strength: Grade A)
• Oral Medications:
  • Clinicians may prescribe pharmacologic pain management agents (e.g., urinary analgesics, acetaminophen, NSAIDs, opioid/non-opioid medications) after counseling patients on the risks and benefits. Pharmacological pain management principles for IC/BPS should be similar to those for management of other chronic pain conditions. (Clinical Principle)
  • Amitriptyline, cimetidine, hydroxyzine, or pentosan polysulfate may be administered as oral medications (listed in alphabetical order; no hierarchy is implied, Evidence Strength: Grades B, B, C, and B)
  • Clinicians should counsel patients who are considering pentosan polysulfate about the potential risk for macular damage and vision-related injuries. (Clinical Principle)
  • Oral cyclosporine A may be offered particularly for patients with Hunner lesions refractory to fulguration and/or triamcinolone. (Evidence Strength: Grade C)

The treatments below appear to lack efficacy and/or appear to be accompanied by unacceptable adverse event profiles:(4)

• Long-term oral antibiotic administration should not be offered. Standard (Evidence Strength: Grade B)
• Intravesical instillation of bacillus Calmette-Guerin should not be offered outside of investigational study settings. Standard (Evidence Strength: Grade B)
• High-pressure, long-duration hydrodistension should not be offered. Recommendation (Evidence Strength: Grade C)
• Systemic (oral) long-term glucocorticoid administration should not be offered. Recommendation (Evidence Strength: Grade C)

Efficacy

Elmiron was evaluated in two clinical trials for the relief of pain in patients with chronic interstitial cystitis (IC). All patients met the NIH definition of IC based upon the results of cystoscopy, cytology, and biopsy.(1)

Patients had unblinded evaluations every 3 months for the patient's rating of overall change in pain in comparison to baseline and for the difference calculated in "pain/discomfort" scores. At baseline, pain/discomfort scores for the original 2499 patients were severe or unbearable in 60%, moderate in 33% and mild or none in 7% of patients.(1)

At 3 months, 722/2499 (29%) of the patients originally in the study had pain scores that improved by one or two categories. By 6 months, in the 892 patients who continued taking Elmiron, an additional 116/2499 (5%) of patients had improved pain scores. After 6 months, the percent of patients who reported the first onset of pain relief was less than 1.5% of patients who originally entered in the study.(1)

Safety

Elmiron is contraindicated in patients with known hypersensitivity to the drug, structurally related compounds, or excipients. It is important to note that clinical value or risks of continued treatment in patients whose pain has not improved by 6 months is not known.(1)

Clinicians should counsel patients who are considering Elmiron on the potential risk for macular damage and vision-related injuries A detailed ophthalmologic history should be obtained in all patients prior to starting treatment with Elmiron.(4)

A baseline retinal examination (including OCT and auto-fluorescence imaging) is suggested for all patients within six months of initiating treatment and periodically while continuing treatment. If pigmentary changes in the retina develop, then risks and benefits of continuing treatment should be reevaluated, since these changes may be irreversible. Follow-up retinal examinations should be continued given that retinal and vision changes may progress even after cessation of treatment.(1)

1

Elmiron Prescribing Information. Janssen Pharmaceuticals, Inc. November 2022.

2

Hanno, Philip, MD. "Interstitial Cystitis/Painful Bladder Syndrome." Interstitial Cystitis/Painful Bladder Syndrome. National Kidney and Urologic Diseases Information Clearinghouse, 29 June 2012. Web. 05 July 2013. Reference no longer used.

3

European Association of Urology (EAU, 2022). Guidelines on treatment of chronic pelvic pain. Available at: https://uroweb.org/guideline/chronic-pelvic-pain/#1

4

Clemens JQ, Erickson DR, Varela NP et al: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome (2022):AUA guideline amendment. J Urol 2022;208(1):34-42. Published 2011. Updated 2022. Available at: https://www.auanet.org/guidelines/guidelines/interstitial-cystitis-(ic/bps)-guideline

5

Interstitial Cystitis (Painful Bladder Syndrome). National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Available at: https://www.niddk.nih.gov/health-information/urologic-diseases/interstitial-cystitis-painful-bladder-syndrome

6

What is Interstitial Cystitis(IC)/Bladder Pain Syndrome? - Urology Care Foundation. (n.d.). https://www.urologyhealth.org/urology-a-z/i/interstitial-cystitis

Elmiron

pentosan polysulfate sodium cap delayed release  ; pentosan polysulfate sodium caps

100 MG ; 150 MG ; 200 MG

M ; N ; O ; Y

N

Elmiron

pentosan polysulfate sodium cap delayed release  ; pentosan polysulfate sodium caps

100 MG ; 150 MG ; 200 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The requested agent will be used for the relief of bladder pain or discomfort associated with interstitial cystitis AND
2. The patient has tried and had an inadequate response to behavioral modification or self-care practices AND
3. ONE of the following:
   1. The patient has tried and had an inadequate response to amitriptyline, cimetidine, or hydroxyzine OR
   2. The patient has an intolerance or hypersensitivity to amitriptyline, cimetidine, or hydroxyzine OR
   3. The patient has an FDA labeled contraindication to amitriptyline, cimetidine, and hydroxyzine AND
4. The patient has had an eye exam with an eye specialist (e.g., optometrist, ophthalmologist) prior to starting the requested agent AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent AND
6. The requested quantity (dose) does not exceed the FDA labeled dose for the requested indication

Length of Approval:  6 months

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved for renewal when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent (e.g., decreased bladder pain, decreased frequency or urgency of urination) AND
3. The patient has had an eye exam with an eye specialist (e.g., optometrist, ophthalmologist) within the last 12 months AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent AND
5. The requested quantity (dose) does not exceed the FDA labeled dose for the requested indication

Length of Approval:  12 months