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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. The 2022 AUA guideline lists DMSO, heparin, and / or lidocaine as intravesical treatment options (Statement 17) without imposing a hierarchy among them, and a wide range of additional agents — GAG-replenishment products (hyaluronic acid, chondroitin sulfate), botulinum toxin A, intravesical oxybutynin, intravesical pentosan polysulfate, and emerging sustained-release platforms — are used off-label with varying evidence.[1][2][3]

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.[24]

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)[1]
GAG replenishmentHeparinRestores GAG layer, inhibits leukocytes, scavenges ROSOption (Grade C)[1]
GAG replenishmentHyaluronic acid (HA), chondroitin sulfate (CS), HA/CS comboGAG-layer restoration, anti-inflammatoryNot in AUA guideline; widely used in Europe[3][4][5][6]
Neuromuscular blockadeOnabotulinumtoxinA (intradetrusor)Inhibits ACh and ATP release from nerve and urotheliumOption (Grade C); after other treatments are inadequate[1][14][15][16]
AnticholinergicOxybutyninReduces detrusor spasm; local anesthetic effectNot in AUA guideline; in 2025 Global Consensus[2][4]
GAG replenishmentPentosan polysulfate (intravesical)Reduces mucosal permeabilityNot in AUA guideline[7][17]
Vanilloid agonistsResiniferatoxin, capsaicinC-fiber TRPV1 desensitizationNot recommended[8][18]
ImmunomodulatoryBCGImmunological modulationNot recommended by AUA[4][7]
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 (key 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
  • Dwell time: ~ 15 minutes — longer dwell times produce significant pain[1]
  • 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 systematic review and meta-analysis (5 RCTs + 9 observational studies, 554 patients) found intravesical DMSO produced clinically meaningful improvements in IC symptom scores and pain.[10]

A 2023 open-label RCT randomized 83 women; 70 completed six weekly instillations (42 DMSO plus triamcinolone, 28 BTH). Among those with evaluable paired ICSI data, 63% vs 43% achieved the prespecified >29.5% symptom-score reduction (p=0.15). This is a responder proportion, not the mean change in score. Pain and nocturia changes favored DMSO plus triamcinolone, but the nonsignificant primary comparison does not establish equivalence.[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
  • Rare hypersensitivity (DMSO can liberate histamine)
  • Overall AE rate ~38% in meta-analysis, mostly mild

Required monitoring (FDA label)[9]​

  • Eye evaluation including slit lamp before treatment and periodically (lens opacities seen in animals at high chronic doses)
  • Liver function, renal function, CBC every ~6 months

Contraindications and cautions[9]​

  • 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
  • Drug interactions — potentiates absorption of co-administered drugs (the rationale for shorter dwell times in DMSO cocktails)

Lidocaine​

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

Evidence: AUA Grade B — short-term symptom relief (< 2 weeks); benefit durability beyond a single instillation is limited.[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 (AUA Grade C): observational data show clinically significant symptom improvement; trials of heparin combined with alkalinized lidocaine show significant improvement vs placebo.[1]

Dosing varies by protocol. Heparin alone and alkalinized-lidocaine combinations have different doses, volumes and dwell times. Use a documented institutional formulation with pharmacy compatibility checks. Selected patients may self-instill after catheterization training and a plan for infection, hematuria or worsening symptoms; this is not a default daily regimen for everyone.[1][24]

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)​

  • HA influences barrier integrity through urothelial-cell interactions rather than purely 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. Its recurrent-infection outcome should not be presented as an IC/BPS-specific infection-prevention effect.[5]
  • Typical dose: 40 mg HA in 50 mL saline weekly × 4–6, then monthly maintenance
  • Widely used in Europe (Cystistat, Ialuril); not FDA-approved in the US for IC/BPS

Chondroitin sulfate (CS)​

  • GAG-layer replenishment with anti-inflammatory effect[4]
  • Network safety rankings are based on limited, heterogeneous comparisons; they do not establish CS as the safest choice for an individual[3]
  • Typical dose: 0.2% solution, 40 mL weekly × 6, then monthly

Combined HA + CS (Ialuril)​

  • A randomized open-label multicenter study (n=110) reported improvement in both arms, fewer treatment-related AEs with HA/CS (1.35% vs 22.2%) and a greater pain reduction in the per-protocol analysis. The unblinded study and analysis limitations do not establish universal equivalence or superiority over DMSO[6]
  • Network rankings have suggested benefit, but are not a reliable treatment hierarchy[3]
  • The study's economic analysis was setting-specific; it does not establish present-day local costs or access[6]

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 (Option, Grade C)[1]
  • Mechanism in IC/BPS: inhibits ACh and ATP release from nerve and urothelium → reduces hypersensitivity, pain signaling, and involuntary contractions[14]
  • Efficacy — meta-analysis of 12 RCTs found significant improvements in ICSI (SMD −0.302), ICPI (SMD −0.430), and VAS pain (SMD −0.576); intratrigonal 100 U vs placebo achieved ≥ 50% pain reduction in 60% vs 22%[15][16]
  • Older network analyses suggested improvement, but ranking probabilities alone do not establish comparative superiority[7]
  • Dose: 100 U in 10–30 mL saline, intradetrusor at 20–30 sites; injection sites vary across studies (trigonal, lateral, or posterior wall)[1]
  • AEs: dysuria, large PVR, need for CISC, UTI[1]
  • Decision point: shared decision-making is essential — short-term efficacy traded against the meaningful possibility of CISC[1]

Other Intravesical Agents​

Intravesical oxybutynin​

  • Anticholinergic with local anesthetic properties[4]
  • An older Cochrane review described possible benefit, but the evidence was limited; it does not establish routine use or superiority[4]
  • Typical dose 5–10 mg in 20–30 mL saline; dwell 30 min
  • Listed in the 2025 Global Consensus update[2]

Intravesical pentosan polysulfate (PPS)​

  • Network meta-analysis: improves urinary frequency and urgency vs placebo; lidocaine combined with PPS yielded greater symptom relief than lidocaine alone[7][1]
  • 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 does not recommend BCG for IC/BPS — risks of granulomatous cystitis and systemic BCG infection[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 found RTX reduced bladder pain but did not improve 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. Lesion fulguration or injection is supported as an option; this should not be described as a proven head-to-head RCT advantage.[1][24]
  • Steroid dose depends on the formulation; adding triamcinolone has not been shown to improve every cocktail.[24]

Emerging Therapies and Novel Delivery Systems​

Intravesical interferon​

A small 2024 RCT compared interferon with hyaluronic acid. This remains investigational: the study does not establish a standard viral cause of IC/BPS or justify routine antiviral treatment.[20]

Sustained-release platforms​

A major limitation of every intravesical agent is rapid drug clearance with voiding. Several sustained-release systems are in development:[2][21][22]

  • TRG-100 — sustained-release lidocaine plus oxybutynin studied in an open-label pilot including IC/BPS, OAB and ureteral-stent populations; this is not a confirmatory IC/BPS trial
  • Silk-elastinlike protein polymer (SELP) — preclinical delivery platform; the reported 24-hour analgesic response was in a mouse model, not clinical evidence of durable patient benefit
  • Intravesical liposomes — under investigation for sustained delivery and barrier protection

Certolizumab pegol (anti-TNF) and antiviral approaches​

Anti-TNF biologics and intravesical antivirals are in early-phase clinical investigation; phenotyping by BK virus status may eventually guide selection.[17][20]

Comparative Effectiveness Summary​

The 2020 Cochrane review found largely low- or very-low-certainty evidence across 81 small, heterogeneous trials. Historical reviews and network rankings do not establish one best intravesical therapy or show that almost every patient benefits from combinations.[7][19][23] 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. 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; do not default to prolonged nonspecific instillations.[1]

See Also​

References​

1. Clemens JQ, Erickson DR, Varela NP, Lai HH. "Diagnosis and treatment of interstitial cystitis/bladder pain syndrome." J Urol. 2022;208(1):34–42. doi:10.1097/JU.0000000000002756

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. Dimitrakov J, Kroenke K, Steers WD, et al. "Pharmacologic management of painful bladder syndrome / interstitial cystitis: a systematic review." Arch Intern Med. 2007;167(18):1922–1929. doi:10.1001/archinte.167.18.1922

24. 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