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Intravesical Agents for IC/BPS

Intravesical instillation is an option for interstitial cystitis / bladder pain syndrome (IC/BPS). AUA 2022 removed the former numbered treatment tiers. DMSO (dimethyl sulfoxide) is the only FDA-approved intravesical agent for this indication.[25] The 2022 AUA guideline lists DMSO, heparin and/or lidocaine as bladder instillation options (Statement 17, Option; no hierarchy).[1] Other bladder instillations used or studied off-label with varying evidence include GAG-replenishment products (hyaluronic acid and chondroitin sulfate), oxybutynin and pentosan polysulfate.[2][3] Sustained-release systems are under investigation.[21][22] For refractory IC/BPS, the guideline treats onabotulinumtoxinA as an intradetrusor injection (Statement 20, Option).[1]

CUA 2025: evidence does not support choosing one intravesical agent or cocktail over all others. Refractory IC/BPS may be treated with botulinum toxin, with very low certainty of benefit.[23]

For the broader clinical condition and oral pharmacotherapy, see IC/PBS and Oral IC/BPS Agents. For the dedicated botulinum toxin article, see Botulinum Toxin.

Organizational Framework​

ClassAgentsMechanismAUA position
Anti-inflammatory / multimodalDMSO (Rimso-50)Anti-inflammatory, analgesic, collagen dissolution, muscle relaxant, mast-cell stabilizationOption (Grade C); FDA-approved[1]
Local anestheticLidocaine (± alkalinization)Direct urothelial anesthesiaOption (Grade B); EAU 2026 weak recommendation for lidocaine with sodium bicarbonate, level 1b for short-term effect[1][28]
GAG replenishmentHeparinRestores GAG layer, inhibits leukocytes, scavenges ROSOption (Grade C); EAU 2026 weak recommendation, level 3[1][28]
GAG replenishmentHyaluronic acid (HA), chondroitin sulfate (CS), HA/CS comboGAG-layer restoration, anti-inflammatoryNot listed as an AUA treatment option; widely used in Europe. EAU 2026 weakly recommends HA or CS before more invasive measures; its level 2b evidence summary addresses CS[3][4][5][6][28]
Neuromuscular blockadeOnabotulinumtoxinA (intradetrusor)Inhibits ACh and ATP release from nerve and urotheliumAUA: Option (Grade C) after other treatments are inadequate, for patients willing to accept possible intermittent self-catheterization. EAU 2026: Strong recommendation to consider bladder-wall/trigonal botulinum toxin A injection plus hydrodistension after failed instillations (level 1b for the combination).[1][14][15][16][28]
AnticholinergicOxybutyninReduces detrusor spasm; local anesthetic effectNot in AUA guideline; in 2025 Global Consensus[2][4]
GAG replenishmentPentosan polysulfate (intravesical)Reduces mucosal permeabilityNot listed among AUA Statement 17 intravesical options; EAU 2026 rates it effective on limited data and possibly enhancing oral treatment (level 1b)[1][7][17][28]
Vanilloid agonistsResiniferatoxin, capsaicinC-fiber TRPV1 desensitizationNot recommended[8][18]
ImmunomodulatoryBCGImmunological modulationAUA: not to be offered outside investigational settings[1]
Combination cocktailsDMSO + heparin + steroid + lidocaine / bupivacaineMultimodalCommonly used in practice[1][11]

DMSO (Rimso-50) — the FDA-approved agent​

DMSO has been available since the 1970s and remains the reference intravesical therapy.[9]

Multiple mechanisms[4]​

  • Anti-inflammatory inhibition of inflammatory mediators
  • Direct analgesic effect
  • Collagen dissolution (may reduce mural fibrosis)
  • Detrusor smooth-muscle relaxation
  • Mast-cell stabilization (relevant to mast-cell–mediated IC/BPS pathophysiology)
  • Membrane permeation enhancer. Rapidly absorbed across the bladder wall and enhances absorption of co-administered agents (a safety point for cocktails)

Dosing protocol (FDA label)[9]​

  • Formulation: sterile Rimso-50, 50% w/w DMSO in water; do not interpret the labeled concentration as a 50:50 volume-mixing recipe
  • Dose: 50 mL by catheter[9]
  • Dwell time: 15 minutes on the label (the AUA suggests 15–20 minutes); longer dwell times produce significant pain[1][9]
  • Frequency: every 2 weeks until maximum symptomatic relief, then increase the interval as appropriate
  • Pre-treatment: intraurethral lidocaine jelly; oral analgesics or B&O suppository for bladder spasm
  • Severe cases: initial 2–3 treatments may need anesthesia (saddle block)

Efficacy​

A 2025 review of 14 studies (554 patients; five RCTs, seven single-arm studies, and two cohorts) found lower symptom and pain scores after DMSO-containing instillations. Its pooled estimates compared follow-up with pretreatment, only four studies used DMSO alone, and follow-up was at most six months.[10]

A placebo-controlled trial randomized 96 Japanese patients with cystoscopy-defined bladder-centric IC/BPS to 50% DMSO or placebo every two weeks. At week 12, mean ICSI changes were −5.2 versus −3.4 (between-group difference −1.8, 95% CI −3.3 to −0.3).[30]

A 2023 open-label RCT randomized 83 women; 70 completed six weekly instillations (42 DMSO plus triamcinolone, 28 BTH). At visit 6, among patients with evaluable paired ICSI data, 19/30 (63%) in the DMSO plus triamcinolone arm versus 9/21 (43%) in the BTH arm achieved the prespecified >29.5% symptom-score reduction (p=0.15). Pain scores favored DMSO plus triamcinolone at visits 5 and 6; nocturia improved within that arm, but the between-arm nocturia difference at visit 6 was not significant.[11]

Adverse effects[9][10]​

  • Garlic-like taste within minutes of instillation, lasting hours
  • Garlic-like body / breath odor lasting up to 72 hours, a major patient-acceptance barrier
  • Transient chemical cystitis discomfort during instillation
  • Hypersensitivity, including possible anaphylactoid symptoms (DMSO can liberate histamine)[9]
  • Overall AE rate about 38% in meta-analysis, mostly mild[10]
  • Eye evaluation including slit lamp before treatment and periodically (lens opacities seen in animals at high chronic doses)
  • Liver function, renal function, CBC approximately every 6 months

Cautions[9]​

The label lists no absolute contraindications, but warns as follows.

  • Urinary tract malignancy. The label warns that DMSO-induced vasodilation may be harmful
  • Pregnancy. Insufficient controlled human data; the label calls for use only when potential benefit justifies fetal risk
  • Lactation. Excretion in human milk is unknown; use caution during nursing.[9]
  • Children. Safety and effectiveness are not established.[9]
  • Drug interactions. DMSO may enhance absorption of co-administered drugs, including lidocaine.[1][9]

Lidocaine​

Mechanism: direct local anesthetic on the urothelium and submucosal afferents.[4]

Evidence: AUA Option, Grade B (Statement 17). In the multicenter placebo-controlled trial of alkalinized lidocaine, 30% versus 10% reported moderate or marked improvement on the global response assessment three days after completing the five-day course (significant), and 24% versus 11.5% did so at ten days (not significant). The guideline judges the relief short-term (less than two weeks), and instillation can itself be painful.[1]

Practical caution: when combined with DMSO, DMSO enhances lidocaine absorption and can produce systemic toxicity (perioral numbness, tinnitus, dizziness, seizures, cardiac effects). Use a pharmacy-validated regimen accounting for the total local-anesthetic dose, formulation and dwell time; simply shortening dwell does not establish safety. Counsel on toxicity symptoms.[1][9]

Heparin​

Mechanism: heparin is a naturally occurring GAG that augments the urothelial mucopolysaccharide layer, inhibits leukocyte function, and scavenges reactive oxygen species , proposed to supplement the urothelial GAG barrier.[4][12]

Evidence : observational data show clinically significant symptom improvement; one small bicarbonate-controlled crossover trial of heparin plus alkalinized lidocaine found greater pain reduction at 12 hours (42% versus 21%); a separate 14-patient pilot used alkalinized lidocaine alone as comparator. Regimens described in the AUA supporting text include 10,000 IU in 10 mL sterile water three times weekly with a 1-hour retention, and 25,000 IU in 5 mL distilled water twice weekly, each for three months.[1]

Dosing varies by protocol. Heparin alone and alkalinized-lidocaine combinations have different doses, volumes and dwell times. Use a documented institutional formulation; pharmacy should verify final pH and lidocaine stability because excessive alkalinization can precipitate lidocaine.[31] Selected patients may self-instill after catheterization training and a plan for infection, hematuria or worsening symptoms.[1][23]

Intravesical Cocktails​

Cocktails are used in practice, but formulations are not interchangeable. The following are the actual regimens in Moss 2023, shown to make that trial interpretable; neither is established as a universally preferred prescribing protocol.[11]

Trial armInstilled mixtureSchedule
DMSO plus triamcinoloneDMSO 50 mL plus triamcinolone 10 mg (1 mL of 10 mg/mL)Weekly for 6 weeks; 15-minute dwell
BTHBupivacaine 0.5%, 30 mL (150 mg); triamcinolone 20 mg (2 mL of 10 mg/mL); heparin 20,000 units (2 mL of 10,000 units/mL)Weekly for 6 weeks; 15-minute dwell

For clinical use, verify sterile preparation, compatibility, final concentration, local-anesthetic exposure and contraindications with pharmacy. DMSO increases absorption; bicarbonate also changes lidocaine penetration. A generic mixture assembled from doses in unrelated protocols is not a validated recipe.[1][9]

GAG Replenishment Therapy (HA, CS, HA + CS)​

GAG-replenishment is built on the model that IC/BPS reflects urothelial GAG-layer disruption that allows urinary solutes to penetrate the wall and trigger inflammation.[12]

Hyaluronic acid (HA)​

  • In a porcine urothelial cell model, HA influenced barrier-related responses through cell interactions rather than directly restoring the luminal GAG layer.[13]
  • A meta-analysis published online in 2025 (2026 journal issue) included 30 BPS studies, alongside separate recurrent-UTI and radiation-cystitis studies. It reported symptom improvement, but included uncontrolled studies and limited randomized evidence.[5]
  • Manufacturer-described CYSTISTAT regimen: 40 mg HA in a 50 mL vial, instilled weekly for 4–12 treatments, then monthly until symptoms resolve.[26] Retain the instillation as long as possible, at least 30 minutes (Cystistat manufacturer leaflet)[26]
  • Widely used in Europe (Cystistat, Ialuril); not FDA-approved in the US for IC/BPS
  • CYSTISTAT precautions. Do not administer with known hypersensitivity; the leaflet does not recommend treatment in children or during pregnancy or lactation.[26]

Chondroitin sulfate (CS)​

  • GAG-layer replenishment with anti-inflammatory effect[4]
  • In a placebo-controlled trial of 98 women, 38.0% receiving 2% CS versus 31.3% receiving vehicle reported moderate or marked improvement at week 11; the difference was not statistically significant.[24]
  • Network safety rankings are based on limited, heterogeneous comparisons.[3]
  • Trial regimens used a 2% sodium chondroitin sulfate solution: 20 mL weekly for 8 weeks (Nickel 2012) or weekly for 6 weeks against DMSO (Tutolo 2017); product volumes and maintenance schedules vary.[24][25]
  • In the 36-patient randomized comparison, 16/22 (72.7%) receiving CS versus 2/14 (14%) receiving DMSO reported moderate or marked GRA improvement at 12 weeks; 6/22 (27%) versus 8/14 (57%) withdrew, and the trial stopped early because of DMSO withdrawals.[25]

Combined HA + CS (Ialuril)​

  • Ialuril (HA 1.6% with CS 2.0%, 50 mL) has been given in a prospective series as four weekly instillations, then two every two weeks and two monthly (eight doses), with a 60-minute dwell.[27]
  • A randomized open-label multicenter study (n=110; 1.6% HA with 2.0% CS or 50% DMSO, 13 weekly instillations) reported improvement in both arms, fewer treatment-related AEs with HA/CS (1.35% versus 22.2%) and a greater pain reduction in the per-protocol analysis.[6]
  • Network rankings have suggested benefit.[3]

Botulinum Toxin A (intradetrusor)​

The dedicated Botulinum Toxin article covers OAB and NDO uses; the IC/BPS-specific notes:

  • AUA position: intradetrusor onabotulinumtoxinA may be administered after other treatments fail, with the patient willing to accept the possibility of clean intermittent self-catheterization (Statement 20, Option, Grade C)[1]
  • Mechanism in IC/BPS: inhibits ACh and ATP release from nerve and urothelium, leading to reduced hypersensitivity, pain signaling, and involuntary contractions[14]
  • Efficacy. A meta-analysis of 12 RCTs found significant improvements in ICSI (SMD −0.302), ICPI (SMD −0.430), and VAS pain (SMD −0.576); in a 19-patient pilot RCT, intratrigonal 100 U versus placebo achieved ≥ 50% pain reduction at week 12 in 60% versus 22%[15][16]
  • Older network analyses suggested improvement[7]
  • Dose: the 2022 guideline notes that studies now mainly use 100 U; 200 U has also been studied, with more adverse events. Injection sites vary (posterior and lateral walls, or intratrigonal). The pilot RCT used 100 U as 10 trigonal injections of 1 mL each[1][16]
  • AEs: dysuria, large PVR, need for CISC, UTI[1]
  • Decision point: shared decision-making weighs short-term efficacy against the meaningful possibility of CISC[1]
  • A randomized trial analyzed 47 women receiving either 100 U onabotulinumtoxinA or six weekly heparin–lidocaine–bicarbonate instillations. At two months, mean ICSI and ICPI scores favored toxin (6.3 versus 9.6; 5.9 versus 8.3), but those score differences did not persist at six to nine months; 2/25 toxin recipients required self-catheterization.[32]

Other Intravesical Agents​

Intravesical oxybutynin​

  • Anticholinergic with local anesthetic properties[4]
  • An older Cochrane review described possible benefit, but the evidence was limited[4]
  • The 36-woman IC/BPS trial used 10 mg oxybutynin in 500 mL saline for staged bladder filling and training; it did not test a 20–30 mL, 30-minute instillation.[19]
  • Listed in the 2025 Global Consensus update[2]

Intravesical pentosan polysulfate (PPS)​

  • A network meta-analysis of 16 randomized IC/PBS trials, including two PPS comparisons, reported an urgency estimate favoring intravesical PPS over placebo (SMD −0.78, p=0.016), whereas its urinary-frequency estimate favored placebo (SMD +1.91, 95% CI +1.17 to +2.66).[7] A 41-woman randomized trial compared intravesical PPS plus oral PPS with intravesical placebo plus oral PPS; median O'Leary-Sant symptom/problem score change at week 12 was −12 versus −5.5 (p = 0.04).[29]
  • Oral PPS is the only FDA-approved oral agent for IC/BPS, but PPS-associated pigmented maculopathy with chronic oral use has reshaped prescribing[17][1]

Bacillus Calmette-Guérin (BCG)​

  • Immunomodulation based on autoimmune theory[4]
  • Mixed evidence; Cochrane found a trend to less pain and fewer general symptoms; network meta-analysis suggested GRA improvement[4][7]
  • AUA. BCG should not be offered outside investigational study settings (Statement 24, Standard, Grade B). Two randomized trials showed response rates not significantly different from placebo (21% versus 12% at seven months in the larger trial, n=265); in that trial, 95% of patients in each arm reported at least one adverse event, and life-threatening events including sepsis are described in the bladder-cancer literature[1]

Vanilloid agonists (resiniferatoxin, capsaicin)​

  • TRPV1-mediated C-fiber desensitization[4]
  • The largest RCT (n = 163) of intravesical RTX found no improvement in symptoms, pain, urgency, frequency, nocturia, or void volume over 12 weeks; dose-dependent instillation pain[8]
  • A meta-analysis of seven controlled trials enrolled 355 patients with IC or detrusor overactivity; the pooled RTX–saline bladder-pain VAS difference favored RTX by 0.42 points, with an IC subgroup estimate of 0.35 points (95% CI 0–0.70, p=0.05). The mixed-population analysis found no statistically significant difference in frequency, nocturia or incontinence.[18]
  • A network meta-analysis paradoxically ranked low-dose RTX favorably, but this likely reflects small-study effects and heterogeneity[3][8]
  • Not recommended for routine clinical use[4]

Intravesical steroids (triamcinolone)​

  • Local anti-inflammatory; primarily used as a cocktail component (with DMSO or heparin)[4]
  • Intralesional triamcinolone for a Hunner lesion is distinct from a steroid-containing bladder instillation. The AUA states that fulguration and/or triamcinolone injection should be performed when Hunner lesions are present (Statement 19, Recommendation, Grade C).[1][23]
  • Steroid dose depends on the formulation; adding triamcinolone has not been shown to improve every cocktail.[23]

Emerging Therapies and Novel Delivery Systems​

Intravesical interferon​

A single-center, double-masked 2024 RCT randomized 52 women with IC to intravesical interferon alfa-2b or HA; at six months, pain-score change favored interferon by 1.3 points (95% CI 0.3–2.3, p=0.02). Interferon remains investigational.[20]

Sustained-release platforms​

Conventional bladder instillations can lose drug exposure through dilution and voiding, prompting study of sustained-release systems.[2][21][22]

  • TRG-100. Sustained-release lidocaine plus oxybutynin studied in an open-label pilot including IC/BPS, OAB and ureteral-stent populations.
  • Silk-elastinlike protein polymer (SELP). Preclinical delivery platform; the reported 24-hour analgesic response was in a mouse model.
  • Intravesical liposomes. Under investigation for sustained delivery and barrier protection

Systemic anti-TNF research and intravesical antiviral approaches​

A randomized pilot studied subcutaneous certolizumab pegol in women with refractory IC/BPS; intravesical interferon was studied separately. Both remain investigational, and BK-virus phenotyping remains a research proposal.[17][20][33]

Comparative Effectiveness Summary​

The 2020 Cochrane review found largely low- or very-low-certainty evidence across 81 small, heterogeneous trials.[19] Reassess symptoms and harms after an agreed trial, and discontinue ineffective treatment.[1]

Clinical Positioning​

  • DMSO is FDA-approved; its label uses treatment every two weeks until maximum relief, then longer intervals.[9] Counsel about odor and discomfort; the label does not mandate exactly six treatments[1][9]
  • Heparin–lidocaine cocktails may be selected according to response, tolerability and a verified local protocol; home use requires appropriate training and follow-up[1]
  • HA / CS. Some supportive comparative data, with remaining uncertainty; availability and regulatory status vary by product and country, and it is not FDA-approved for IC/BPS[5][6]
  • OnabotulinumtoxinA is reserved for refractory disease and only for patients willing to accept CISC; counsel and document[1]
  • Resiniferatoxin / capsaicin are not appropriate for clinical use[4][8]
  • DMSO enhances absorption of co-administered drugs ; verify total local-anesthetic exposure and compatibility instead of assuming that a short dwell prevents toxicity[1][9]
  • Hunner lesions warrant lesion-directed assessment and discussion of fulguration or intralesional triamcinolone.[1]

See Also​

References​

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2. Buford K, Peters KM, Riedl C, et al. "Global consensus on interstitial cystitis/bladder pain syndrome: an update on therapeutic treatments." Neurourol Urodyn. 2025. doi:10.1002/nau.70106

3. Liu S, Zhang C, Peng L, Lu Y, Luo D. "Comparative effectiveness and safety of intravesical instillation treatment of interstitial cystitis/bladder pain syndrome: a systematic review and network meta-analysis of randomized controlled trials." Int Urogynecol J. 2021;32(5):1061–1071. doi:10.1007/s00192-020-04490-3

4. Dawson TE, Jamison J. "Intravesical treatments for painful bladder syndrome / interstitial cystitis." Cochrane Database Syst Rev. 2007;(4):CD006113. doi:10.1002/14651858.CD006113.pub2

5. Corona G, Capogrosso P, Baldini S, et al. "Hyaluronic acid and chondroitin sulphate instillation in chronic bladder diseases: a meta-analysis." BJU Int. 2026;137(1):36–48 (online October 26, 2025). doi:10.1111/bju.70016

6. Cervigni M, Sommariva M, Tenaglia R, et al. "A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome / interstitial cystitis." Neurourol Urodyn. 2017;36(4):1178–1186. doi:10.1002/nau.23091

7. Zhang W, Deng X, Liu C, Wang X. "Intravesical treatment for interstitial cystitis / painful bladder syndrome: a network meta-analysis." Int Urogynecol J. 2017;28(4):515–525. doi:10.1007/s00192-016-3079-4

8. Payne CK, Mosbaugh PG, Forrest JB, et al. "Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial." J Urol. 2005;173(5):1590–1594. doi:10.1097/01.ju.0000154631.92150.ef

9. RIMSO-50 (dimethyl sulfoxide) US prescribing information. DailyMed, updated March 17, 2021; accessed September 11, 2026.

10. Li HR, Shen SH, Gao XS, Peng L, Luo DY. "The efficacy and safety of dimethyl sulfoxide into the bladder for the treatment of interstitial cystitis / bladder pain syndrome: a systematic review and meta-analysis." Neurourol Urodyn. 2025;44(5):1036–1046. doi:10.1002/nau.70036

11. Moss NP, Chill HH, Sand PK, et al. "A prospective, randomized trial comparing intravesical dimethyl sulfoxide (DMSO) to bupivacaine, triamcinolone, and heparin (BTH), for newly diagnosed interstitial cystitis / painful bladder syndrome (IC/PBS)." Neurourol Urodyn. 2023;42(3):615–622. doi:10.1002/nau.25142

12. Wyndaele JJJ, Riedl C, Taneja R, et al. "GAG replenishment therapy for bladder pain syndrome / interstitial cystitis." Neurourol Urodyn. 2019;38(2):535–544. doi:10.1002/nau.23900

13. van Ginkel CJ, Baars CDM, Tiemessen DM, et al. "Hyaluronic acid: function and location in the urothelial barrier for bladder pain syndrome / interstitial cystitis, an in vitro study." PLoS One. 2025;20(2):e0318277. doi:10.1371/journal.pone.0318277

14. Lin YH, Chiang BJ, Liao CH. "Mechanism of action of botulinum toxin A in treatment of functional urological disorders." Toxins. 2020;12(2):E129. doi:10.3390/toxins12020129

15. Giannantoni A, Gubbiotti M, Bini V. "Botulinum neurotoxin A intravesical injections in interstitial cystitis / bladder painful syndrome: a systematic review with meta-analysis." Toxins. 2019;11(9):E510. doi:10.3390/toxins11090510

16. Pinto RA, Costa D, Morgado A, et al. "Intratrigonal onabotulinumtoxinA improves bladder symptoms and quality of life in patients with bladder pain syndrome / interstitial cystitis: a pilot, single center, randomized, double-blind, placebo controlled trial." J Urol. 2018;199(4):998–1003. doi:10.1016/j.juro.2017.10.018

17. Chermansky CJ, Guirguis MO. "Pharmacologic management of interstitial cystitis / bladder pain syndrome." Urol Clin North Am. 2022;49(2):273–282. doi:10.1016/j.ucl.2022.01.003

18. Guo C, Yang B, Gu W, et al. "Intravesical resiniferatoxin for the treatment of storage lower urinary tract symptoms in patients with either interstitial cystitis or detrusor overactivity: a meta-analysis." PLoS One. 2013;8(12):e82591. doi:10.1371/journal.pone.0082591

19. Imamura M, Scott NW, Wallace SA, et al. "Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis." Cochrane Database Syst Rev. 2020;7:CD013325. doi:10.1002/14651858.CD013325.pub2

20. Shen SH, Peng L, Zeng X, et al. "Intravesical interferon therapy vs hyaluronic acid for pain among female individuals with interstitial cystitis: a randomized clinical trial." JAMA Netw Open. 2024;7(4):e244880. doi:10.1001/jamanetworkopen.2024.4880

21. Jensen MM, Jia W, Schults AJ, et al. "Temperature-responsive silk-elastinlike protein polymer enhancement of intravesical drug delivery of a therapeutic glycosaminoglycan for treatment of interstitial cystitis / painful bladder syndrome." Biomaterials. 2019;217:119293. doi:10.1016/j.biomaterials.2019.119293

22. Raisin G, Dothan D, Perez D, et al. "Open label, pilot evaluation of the safety and efficacy of intravesical sustained release system of lidocaine and oxybutynin (TRG-100) for patients with interstitial cystitis / bladder pain syndrome, overactive bladder and patients with retained ureteral stents following endourological interventions." Urology. 2023;178:42–47. doi:10.1016/j.urology.2023.05.016

23. Doiron RC, Tadayon B, Violette PD, et al. "2025 Canadian Urological Association Guideline: Selected treatment recommendations for interstitial cystitis/bladder pain syndrome." Can Urol Assoc J. 2025;19(4):90–103. doi:10.5489/cuaj.9182

24. Nickel JC, Hanno P, Kumar K, et al. "Second multicenter, randomized, double-blind, parallel-group evaluation of effectiveness and safety of intravesical sodium chondroitin sulfate compared with inactive vehicle control in subjects with interstitial cystitis/bladder pain syndrome." Urology. 2012;79(6):1220–1224. doi:10.1016/j.urology.2012.01.059

25. Tutolo M, Ammirati E, Castagna G, et al. "A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis." Int Braz J Urol. 2017;43(1):134–141. doi:10.1590/S1677-5538.IBJU.2016.0302

26. Mylan Institutional. CYSTISTAT (sterile sodium hyaluronate solution, 40 mg/50 mL) directions for use and leaflet. Revised April 2013; accessed September 24, 2026.

27. Sherif H, Sebay A, Kandeel W, et al. Safety and efficacy of Intravesical hyaluronic acid/chondroitin sulfate in the treatment of refractory painful bladder syndrome. Turk J Urol. 2019;45(4):296-301. doi:10.5152/tud.2018.63600

28. Engeler D, Baranowski AP, Berghmans B, et al. EAU Guidelines on Chronic Pelvic Pain. European Association of Urology; limited update March 2026. Guideline

29. Davis EL, El Khoudary SR, Talbott EO, Davis J, Regan LJ. "Safety and efficacy of the use of intravesical and oral pentosan polysulfate sodium for interstitial cystitis: a randomized double-blind clinical trial." J Urol. 2008;179(1):177–185. doi:10.1016/j.juro.2007.08.170

30. Yoshimura N, Homma Y, Tomoe H, et al. "Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: a multicenter, randomized, double-blind, placebo-controlled, clinical study." Int J Urol. 2021;28(5):545–553. doi:10.1111/iju.14505

31. Parsons CL, Koziol JA, Proctor JG, Zupkas P, Argade S. "Heparin and alkalinized lidocaine versus alkalinized lidocaine for treatment of interstitial cystitis symptoms." Can J Urol. 2015;22(2):7739–7744. PMID:25891339

32. Welch EK, Dengler KL, DiCarlo-Meacham AM, et al. "Bladder instillations vs onabotulinumtoxinA injection for interstitial cystitis/bladder pain syndrome: a randomized clinical trial." Am J Obstet Gynecol. 2024;231(5):528.e1–528.e11. doi:10.1016/j.ajog.2024.05.027

33. Bosch PC. "A randomized, double-blind, placebo-controlled trial of certolizumab pegol in women with refractory interstitial cystitis/bladder pain syndrome." Eur Urol. 2018;74(5):623–630. doi:10.1016/j.eururo.2018.07.026