Effective Date

Date of Origin 

10/1/2022              

Elmiron^®

(pentosan polysulfate sodium)

Capsule

The relief of bladder pain or discomfort associated with interstitial cystitis

1

Interstitial cystitis

Interstitial cystitis (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).(2) The diagnosis of IC/PBS in the general population is based on: 1.) presence of pain related to the bladder, usually accompanied by frequency and urgency of urination, and 2.) absence of other diseases that could cause the symptoms.(2) 

Clinical Guidelines - European Association of Urology (EAU)- Guidelines on Treatment of Chronic Pelvic Pain (2020) [3]

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.

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.

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

• Multimodal behavioural, physical and psychological techniques alongside oral or invasive treatments of BPS
• Amitriptyline
• Pentosan polysulphate sodium
• Administer submucosal injection of BTX-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

Clinical Guidelines - American Urologic Association [AUA] - Guidelines on Treatment of Interstitial Cystitis/Bladder Pain Syndrome [IC/BPS] (June 2011, amended 2014) [4]

AUA categorizes body of evidence strength as: Grade A (well-conducted RCTs or exceptionally strong observational studies), Grade B (RCTs with some weaknesses of procedure, generalizability, or generally strong observational studies), or Grade C (observational studies that are inconsistent, have small sample sizes, or have other problems that potentially confound interpretation of data).

First-, second-, third-, fourth-, fifth-, and sixth-line treatment hierarchy was derived by balancing the potential benefits to the patient with the invasiveness of the treatment, the duration and severity of potential adverse events, and the reversibility of potential adverse events. It is important that this hierarchy was not established based on evidence strength.

• • First-line treatments should be performed on all patients (Evidence Grade A).
    • 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.
    • Self-care practices and behavioral modifications that can improve symptoms should be discussed and implemented as feasible.
    • A trial of over-the-counter products (phenazopyridine [Pyridium], nutraceuticals [Quercetin], or calcium glycerophosphate [Prelief]) is commonly initiated by patients themselves and, although data in the literature are limited, individual patients may find some to be worthwhile in alleviating symptoms.

• • Second-line treatments: Appropriate manual physical therapy techniques, if appropriately trained clinicians are available, should be offered. Pelvic floor strengthening exercises (e.g., Kegel exercises) should be avoided.
    • Multimodal pain management approaches (e.g., pharmacological, stress management, manual therapy if available) should be initiated. 
    • These medications are grouped together as second line treatments because their administration is associated with minor adverse events and efficacy for any individual is unpredictable (listed in alphabetical order; no hierarchy implied).
    • Amitriptyline, cimetidine, hydroxyzine or pentosan polysulfate may be administered as second line oral medications. All have an evidence grade of B, except hydroxyzine, which has a C.
    • Dimethyl sulfoxide, heparin or lidocaine may be administered as second line intravesical treatments. Lidocaine has an evidence grade of B, the others have C.
• Third-line treatments: Cystoscopy under anesthesia with short-duration (less than 10 minutes), low pressure (60 to 80 cm of water) hydrodistension. Hunner’s lesions can be taken off with electrodes, laser, or injected with the steroid triamcinolone (Kenalog). Evidence grade of C.

• Fourth-line treatments: Neurostimulation may be done for frequency/urgency relief but has not shown evidence of effectiveness. Evidence grade of C.
• Fifth-line treatments: Cyclosporine when justified as the risk of side effects is high. Botulinum toxin A (Botox) injections into bladder muscle when justified as side effects can be difficult such as painful urination and required catheterization. Evidence grade of C.
• Sixth-line treatment: Major surgery of bladder removal, enlargement, or urinary diversion when all else has failed. Evidence grade of C.

Efficacy (1)

Pentosan polysulfate sodium is a low molecular weight heparin-like compound. It has anticoagulant and fibrinolytic effects. The mechanism of action of pentosane polysulfate sodium in IC is unknown.

Safety (1)

Elmiron (pentosan polysulfate sodium) 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

Elmiron Prescribing Information. Janssen Pharmaceuticals, Inc. February 2021.

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.

3

European Association of Urology (EAU, 2020). Guidelines on treatment of chronic pelvic pain. Available at: https://uroweb.org/guideline/chronic-pelvic-pain/#1

4

Hanno PM, Erickson D, Moldwin R et al: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol 2015; 193: 1545. Published 2011. Updated 2014. Available at: https://www.auanet.org/guidelines/guidelines/interstitial-cystitis-(ic/bps)-guideline

ELMIRON*pentosan polysulfate sodium caps  ; PENTOSAN*pentosan polysulfate sodium cap delayed release

100 MG ; 150 MG ; 200 MG

M ; N ; O ; Y

N

ELMIRON*pentosan polysulfate sodium caps  ; PENTOSAN*pentosan polysulfate sodium cap delayed release

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 patient has a diagnosis of interstitial cystitis (IC) or interstitial cystitis/bladder pain syndrome (IC/BPS) or interstitial cystitis/painful bladder syndrome (IC/PBS) 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 after therapy with 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 does NOT have any FDA labeled contraindications to the requested agent AND
5. The requested quantity (dose) does not exceed the maximum FDA labeled dose for the requested indication

Length of Approval:  6 months

Renewal Evaluation

Target Agent(s) will be approved 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 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 does NOT have any FDA labeled contraindications to the requested agent AND
4. The requested quantity (dose) does not exceed the maximum FDA labeled dose for the requested indication

Length of Approval:  12 months