Dimethyl Sulfoxide (DMSO)
DMSO is recognized in the AUA guidelines as a recommended instillation option for IC/BPS. This agent provides anti-inflammatory, pain-relieving, and muscle-relaxing properties. Practitioners sometimes administer it as part of a multi-agent mixture, often referred to as a “cocktail,” which may also contain heparin, methylprednisolone, or other compounds. Patients should be aware that DMSO can cause temporary bladder irritation upon initial instillation, produce a distinctive garlic-like taste or breath odor, and cause temporary discomfort. At present, there is no standardized protocol regarding the ideal concentration, treatment frequency, or total number of sessions.

Lidocaine
When instilled at a 2% concentration, lidocaine can offer rapid relief from bladder pain while also decreasing symptoms of urgency and frequency. This makes it especially valuable for managing acute IC/BPS flares or for patients whose symptoms have proven resistant to other interventions. The effectiveness of lidocaine instillations can be enhanced by alkalizing the solution, typically by adding a small amount of sodium bicarbonate (8.4%), which facilitates penetration of the drug through the bladder mucosa.

Heparin
Heparin provides dual benefits when instilled intravesically: it combats inflammation and creates a protective coating over the bladder surface. These properties help to decrease sensitivity, pain, urgency, and voiding frequency. Dosing protocols vary considerably, with regimens typically ranging from 20,000 to 50,000 units per instillation. Heparin may be used on its own or mixed with alkalinized lidocaine at concentrations between 1% and 4%. Clinical studies, both randomized and observational, have reported response rates ranging from 56% to 94%.
Chondroitin Sulfate (CS)
Chondroitin sulfate functions by forming a protective layer along the bladder surface, shielding the underlying tissue from potentially harmful substances in the urine that could trigger inflammation and pain. Beyond its barrier function, CS also possesses anti-inflammatory properties. Clinical experience suggests that outcomes are improved when CS is administered alongside hyaluronic acid.

Hyaluronic Acid (HA)
Like chondroitin sulfate, hyaluronic acid is a naturally occurring component of the GAG layer. Its therapeutic effects include reducing inflammatory processes and supporting tissue repair, in part by preventing mast cells from releasing their inflammatory contents. HA is versatile and can be administered alongside other intravesical agents, including chondroitin sulfate, PPS, heparin, or lidocaine. It is worth noting that while many clinicians report favorable outcomes with GAG-replenishing therapies in patients whose symptoms are predominantly bladder-centered, formal controlled trials have not uniformly demonstrated statistically significant benefits, a finding likely attributable to the diversity of patient populations studied and insufficient sample sizes in many trials.

Intravesical Tacrolimus
Tacrolimus is a calcineurin inhibitor, a class of immunosuppressive drugs most commonly associated with organ transplant medicine, that has been investigated as an intravesical treatment for patients with severe IC/BPS that has not responded to conventional therapies. In a pilot investigation, the drug was delivered directly into the bladder in 64 patients with treatment-resistant disease, and roughly half (31 patients) experienced a clinically meaningful response. Although the evidence base remains small and further studies are warranted, intravesical tacrolimus may represent a viable option for patients with the most refractory forms of the condition.