What medications are used to treat interstitial cystitis?

Medications for Interstitial Cystitis/Bladder Pain Syndrome

For interstitial cystitis/bladder pain syndrome (IC/BPS), treatment should begin with behavioral modifications and oral medications, with pentosan polysulfate, amitriptyline, cimetidine, and hydroxyzine being the primary oral pharmacologic options, though pentosan polysulfate carries important vision-related risks that must be discussed before initiation. 1

Treatment Framework

The 2022 American Urological Association guideline fundamentally changed the approach to IC/BPS treatment by eliminating the previous tiered system (first-line through sixth-line) and instead categorizing treatments into behavioral/non-pharmacologic, oral medicines, bladder instillations, procedures, and major surgery. 1 This reflects the heterogeneous nature of IC/BPS and emphasizes that treatment must be tailored to individual patient characteristics, particularly noting that patients with Hunner lesions represent a distinct subgroup requiring different management. 1

Oral Medications

Pentosan Polysulfate (PPS)

• PPS is the only FDA-approved oral medication for IC/BPS, dosed at 100 mg three times daily taken with water at least 1 hour before or 2 hours after meals. 1, 2
• Evidence shows contradictory results: some trials demonstrate significant improvement in pain, urgency, and frequency compared to placebo (with number needed to treat of 6-7), while other trials show no difference. 1, 3, 4
• Critical safety concern: Clinicians must counsel patients about potential macular damage and vision-related injuries before initiating or continuing PPS. 1
• Long-term data indicates only 6.2-18.7% of patients benefit from PPS on a sustained basis, with the only predictor of response being less constant pain at baseline. 5
• Common side effects include hair loss, diarrhea, nausea, blood in stool, headache, rash, upset stomach, abnormal liver function tests, dizziness, and bruising. 2
• PPS is a weak anticoagulant; avoid concurrent use with warfarin, heparin, high-dose aspirin, or NSAIDs without physician consultation. 2

Amitriptyline (Grade B Evidence)

• Amitriptyline has superior efficacy to placebo for improving IC/BPS symptoms, though adverse events are common and can substantially compromise quality of life. 1
• Recommended dosing: start at 10 mg and titrate gradually to 75-100 mg if tolerated. 1
• Common side effects include sedation, drowsiness, and nausea—not life-threatening but potentially bothersome. 1

Cimetidine (Grade B Evidence)

• Cimetidine demonstrates clinically significant improvement in IC/BPS symptoms, pain, and nocturia with no reported adverse events. 1

Hydroxyzine (Grade C Evidence)

• Oral hydroxyzine shows clinically significant improvement compared to placebo. 1
• Patients with systemic allergies may be more likely to respond to hydroxyzine. 1
• Common adverse events include short-term sedation and weakness. 1

Bladder Instillations

Dimethyl Sulfoxide (DMSO)

• RIMSO-50 is a sterile solution of 50% DMSO approved by the FDA for symptomatic relief of IC/BPS, administered via bladder instillation on an inpatient or outpatient basis. 6
• Patients typically experience a garlic-like taste within minutes of instillation that may last several hours, with breath and skin odor persisting up to 72 hours. 6
• Discomfort during administration usually becomes less prominent with repeated treatments. 6
• DMSO may alter the effectiveness of other medications; patients should disclose all current medications before treatment. 6
• Eye evaluations including slit lamp examinations should be performed prior to and periodically during treatment due to animal studies showing eye changes with prolonged high-dose DMSO. 6

Critical Clinical Approach

Initial Management

• Before initiating pharmacologic therapy, implement self-care practices and behavioral modifications: fluid management (either restriction or additional hydration to alter urine concentration/volume), dietary modifications avoiding bladder irritants, elimination diets, over-the-counter products (nutraceuticals, calcium glycerophosphates, phenazopyridine), heat/cold application to bladder or perineum, stress management, pelvic floor muscle relaxation, and bladder training with urge suppression. 1
• Address modifiable factors: certain exercises (especially pelvic floor exercises), sexual intercourse, tight-fitting clothing, and constipation. 1

Multimodal Strategy

• Pain management alone is insufficient for IC/BPS; combine pharmacologic agents with other therapies for optimal effectiveness. 1
• Treat underlying bladder-related symptoms, not just pain. 1
• Due to the opioid crisis, use chronic opioids judiciously only after informed shared decision-making with periodic follow-ups to assess efficacy, adverse events, compliance, and potential abuse; prioritize non-opioid alternatives. 1

Diagnostic Considerations

• Clinical diagnosis requires careful history, physical examination, and laboratory tests documenting symptoms present for at least six weeks with negative urine cultures. 1
• Document number of voids per day, constant urge sensation, and location/character/severity of pain, pressure, or discomfort. 1
• Note dyspareunia, dysuria, ejaculatory pain in men, and relationship of pain to menstruation in women. 1
• Perform brief neurological exam and evaluate for incomplete bladder emptying. 1
• Cystoscopy is indicated for patients with Hunner lesions or when clinical mimics (bladder cancer, stones, foreign bodies) are suspected. 1

Important Pitfalls

• Antibiotics provide no therapeutic benefit for IC/BPS despite symptom overlap with urinary tract infections, as there is no underlying infection. 7
• Do not use rifampin for IC/BPS treatment. 1
• Avoid assuming all IC/BPS patients respond similarly to treatment; the condition is heterogeneous with distinct phenotypes requiring individualized approaches. 1