New Approaches in Managing Interstitial Cystitis/Bladder Pain Syndrome

Amber Jerauld, PharmD, BCACP; Lyndsay Wormuth, PharmD, BCACP; Brent Carlson, PharmD, BCPS, BCCCP

Disclosures

US Pharmacist. 2016;41(9):29-33. 

In This Article

Treatment Options

Since the etiology and pathogenesis are not well understood and there is no curative treatment, the goal of management is to provide relief of symptoms to improve quality of life. The Interstitial Cystitis Data Base study showed that there is no treatment consistently effective in providing relief. In this study, there were 581 women with IC/BPS who underwent 183 different types of treatment over the follow-up period and no single therapy was successful in the majority of study participants.[10]

IC/BPS is treated in a stepwise approach, and treatments are identified by risk of adverse effects and invasiveness of the treatment (Table 1). The management approaches are organized in the order of increasing risk, and clinicians should move from one level to the next when the less risky approach has failed or been found to be ineffective.[3]

First-line

Initial treatment should be based on symptom severity, clinician judgment, and patient preferences. Patients should be counseled on reasonable expectations for the treatment outcomes. First-line treatment options consist of patient education, self-care/behavioral modification, general relaxation and stress management, and pain management.[3]

Patient education on normal bladder function, what is and is not known about IC/BPS, risks and benefits of the available treatment options, the fact that no single agent has been found effective for the majority of patients, and that acceptable symptom control may require trials of multiple options (including combination therapy) before symptom control is achieved is of utmost importance.[3]

Behavioral modification and self-care practices are also important educational points. These may include altering the volume or concentration of urine by increasing hydration or fluid restriction; applying local heat or cold over the perineum or bladder; avoiding foods known to be irritants; trying an elimination diet to determine which foods may be contributing; use of OTC products (e.g., Pyridium, nutraceuticals, calcium glycerophosphate); mind-body strategies to manage flare-ups (e.g., meditation, imagery); pelvic floor muscle relaxation; and bladder training.[3]

These strategies have been shown to be effective according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) trial that focused on treatment-naïve IC/BPS patients.[11] Patients in this trial completed a standardized education and behavioral modification program (EBMP). Forty-five percent of patients (n = 136) assigned to the EBMP with placebo group were markedly or moderately improved on the Global Response Assessment.[11]

Another first-line treatment option is general relaxation and stress management. Yoga, acupuncture, and hypnosis have been used with variable results.[3]

Second-line

Second-line treatment options consist of appropriate manual physical therapy techniques; oral agents such as amitriptyline, cimetidine, hydroxyzine, or pentosan polysulfate sodium (PPS) (Table 2); intravesical therapies, including dimethylsulfoxide (DMSO), heparin, or lidocaine; and pain management.[3]

Amitriptyline. One randomized, controlled trial reported oral amitriptyline, a tricyclic antidepressant (TCA), to be superior to placebo when titrated from 25 mg daily to 100 mg daily over several weeks as tolerated.[12] Amitriptyline showed a clinically significant improvement in pain and urgency intensity when compared with placebo (P < .001). The most common adverse effects were anticholinergic in nature (i.e., sedation, drowsiness, nausea) and occurred in 92% of patients in the amitriptyline group and 21% in the placebo group.[12] If a TCA is used for treatment of IC/BPS, it is important to start with a low dose and titrate slowly, and patients should be educated that it may take several weeks to see a benefit.[3]

Cimetidine. A histamine[2]-receptor antagonist (H2RA), cimetidine 400 mg twice daily, was found to be statistically significant to placebo in improving total symptoms of pain and nocturia after 3 months in a randomized, controlled trial.[13] There were two other observational studies (300 mg twice daily or 200 mg three times daily) that resulted in 44% to 57% of patients reporting clinically significant improvement in symptoms. No significant adverse effects were reported.[14,15] There is a lack of long-term follow-up data, and it is well known that cimetidine has the potential to interact with many other medications.

Hydroxyzine. There is mixed data with the use of hydroxyzine for treatment of IC/BPS. There was a randomized controlled trial that resulted in 23% of patients in the treatment group experiencing clinically significant improvement in pain and urgency compared with 13% in the placebo group over a 6-month period.[16] This difference was not found to be statistically significant. Patients were started on 10 mg daily and titrated to 50 mg daily over several weeks.[16] There was some improvement in an observational study, in which patients were started on hydroxyzine 25 mg daily and titrated to 75 mg daily over several weeks.[17] This study reported 92% of patients experiencing clinically significant improvement in urinary symptoms. Of note, the patients in this study had systemic allergies, which may have resulted in the response to hydroxyzine. Adverse events were common in both studies, and overall they were not serious (e.g., sedation, weakness). It is recommended to give hydroxyzine at bedtime in patients who may have insomnia due to voiding frequently at night. The hypnotic effect of hydroxyzine may be helpful in these patients.[17]

PPS. This agent, available under the brand-name Elmiron, is the most-studied drug for treatment of IC/BPS, and it is the only oral medication approved by the FDA for treatment of bladder pain or discomfort associated with IC/BPS.[18] It has anticoagulant and fibrinolytic properties, and the proposed mechanism of action is acting as a buffer to control cell permeability because it adheres to the mucosal membrane of the bladder wall. This may prevent irritating solutes in the urine from reaching the cells in the bladder wall.[18] Per the AUA guideline, PPS receives the highest grade of evidence due to the greatest number of studies, which included more than 500 patients.[3]

Pentosan polysulfate sodium (PPS, Elmiron) is the only oral medication approved by the FDA for treatment of bladder pain or discomfort associated with IC/BPS.

It is important to keep in mind that the trials were fairly high quality but showed mixed results.[3] For example, in one randomized, placebo-controlled study of 155 patients, 38% of patients who received PPS (100 mg three times a day for 3 months) and 18% of those who received placebo showed >50% improvement in bladder pain (P = .005).[19] However, another randomized, controlled trial reported no significant differences in total symptom scores between PPS (200 mg twice daily for 4 months) and placebo. Both groups had similar rates of clinically significant improvement in symptoms, 56% and 49%, respectively.[20]

The recommended dosage of PPS is 100 mg three times daily, and it may take 3 to 6 months for relief of symptoms.[19] The adverse-effect profile for PPS is favorable (see Table 2>), making it a good treatment option for patients who have sedation with amitriptyline or antihistamines.[19] However, there is currently no generic version of PPS, so it is more costly compared with other oral agents that also have generics available such as TCAs.

Intravesical Treatments. Intravesical drug instillations are second-line options per the AUA guidelines and consist of DMSO, heparin, or lidocaine. Intravesical administration of drugs directly into the bladder allows a high concentration of medication to reach the target area with few systemic side effects. Disadvantages of this method of delivery include cost, risk of infection, and pain from intermittent catheterization.[1]

DMSO is the only drug approved by the FDA for intravesical drug instillation.[3] It is thought to provide relief by having anti-inflammatory, analgesic, smooth muscle relaxation, and mast-cell inhibition effects. It is often given as a cocktail that may include heparin, sodium bicarbonate, a local steroid, and/or a lidocaine preparation. A catheter is placed in the bladder, and DMSO is then passed through the catheter and held for 10 to 15 minutes before normal voiding takes place.[3] An example of a cocktail regimen is: 50% DMSO (50 mL), 100 mg hydrocortisone (5 mL), 10,000 units of heparin sulfate (10 mL), and 0.5% bupivacaine (10 mL).[21] Treatments are usually given every 1 to 2 weeks for 6 to 8 weeks and repeated as needed.[3,7]

Pain Management. Options for pain management should be continually assessed because pain plays an important role in quality of life. If pain is not controlled, a multidisciplinary approach should be taken. If patients experience treatment flares, a pain regimen with breakthrough pain management strategies should be considered. The goal is to design a pain regimen that provides significant relief without side effects. Urinary analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, narcotics, and a variety of non-narcotic agents for chronic pain can be used.[3]

Urinary analgesics consist of phenazopyridine and methenamine. These should be used short term, as long-term use may cause renal or liver dysfunction. Intravesical lidocaine with heparin and/or sodium bicarbonate may be used for those who have acute episodes of severe bladder pain. Because this requires bladder catheterization, it should only be utilized in patients who have not found sufficient relief from other agents.[3]

Third- to Sixth-line

If first- and second-line treatments have not helped or patients' symptoms are worsening, then third-line treatments may be considered. Third-line treatments include cystoscopy under anesthesia with short duration, low-pressure hydrodistention, pain management, and treatment of Hunner lesions, if found.[3]

Fourth-line treatment options include botulinum toxin A (Botox) injections into the bladder muscle, neuromodulation, and pain management. Botox can cause significant adverse effects, including urinary retention and painful urination. Neurostimulation is not effective for pain but may be useful for urinary frequency/urgency. Fifth-line treatments consist of cyclosporine A with pain management, and sixth-line options are diversion with or without cystectomy, pain management, and substitution cystoplasty.[3]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....