Bladder Instillations

Mixtures of medicines put directly into the bladder.

Bladder Instillations/Cocktails

The American Urological Association’s clinical guideline for IC/BPS indicates bladder installations as a treatment option when diet modification, stress management, and over-the-counter products are not enough. Bladder instillations or bladder cocktails are mixtures of medicines put directly into the bladder. Types of instillations include:

Alkalinized Lidocaine and Heparin

Alkalinized Lidocaine and Heparin is a patented, proprietary compounded bladder instillation that includes heparin and alkalinized lidocaine that is buffered to a specific pH level.


The pre-mixed instillation is provided in ready-to-use, pre-filled sterile syringes and can be administered in a physician’s office or be prescribed for the patient to use at home.

Potential Side Effects

As with any bladder instillation, a potential side effect is discomfort depending on the frequency of catheterization.

You or your healthcare provider can obtain more information by visiting or calling 800-985-8065.


Dimethyl sulfoxide (DMSO, brand name RIMSO-50) was the first and remains the only FDA-approved bladder instillation specifically for interstitial cystitis/bladder pain syndrome (IC/BPS). Approved in 1978, its exact mechanism of action is still not fully known, though it is thought to have several effects positive effects:

  • Reducing bladder irritation and pain (anti-inflammatory)
  • Helping to relax the bladder and pelvic muscles (antispasmodic)
  • Relieving pain by depleting the level of substance P levels from bladder nerves
  • Increasing bladder capacity by breaking down scar tissue by preventing the formation of collagen, a protein the body uses to create scar tissue

Because of its ability to penetrate the bladder lining, some healthcare providers add DMSO to “bladder cocktails” to aid the absorption of other bladder-instilled medicines, such as heparin, steroids, bicarbonate, and analgesics (pain medicines). However, as reported in the Fall 2009 Professional Perspectives, there are changes in practice regarding preference for medicines mixed in bladder cocktails.

Sodium Hyaluronate

To treat interstitial cystitis/bladder pain syndrome (IC/BPS), sodium hyaluronate solution (Cystistat and Hyacyst) is instilled directly into the bladder. Neither of these medicines are approved for use in the United States. However, they are approved for IC/BPS treatment in the Europe and Canada.

Clinical trials tested the effectiveness of sodium hyaluronate solution, also called hyaluronic acid, in treating IC/BPS. As a result, Cystistat is prescribed in more than 20 countries, including the United Kingdom, Canada, Austria, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Scandinavia, Spain, Switzerland, China, and others. Hyacyst is also available throughout Europe.

Dosage & Treatment Plan

Both of these products are instillations:

  • Hyacyst is available in two doses (40mg and 120mg) and instillations are administered weekly for four weeks until symptoms improve. For some patients, additional treatments are recommended.
  • Cystistat is usually instilled once a week for 4 to 6 weeks and then monthly thereafter. One treatment is given every one or two weeks for four to eight treatments, depending on the patient’s response to the medicine. Many patients begin to experience relief after the fifth or sixth instillation. Some patients who respond positively may be able to increase the interval between treatments once the symptoms have stabilized.

Potential Side Effects

Side effects are reported to be minimal, limited primarily to minor discomfort due to catheterization, resulting in initial exacerbation of urinary frequency and urgency.

Pregnancy & Children

Because adequate and well controlled studies have not been performed in pregnant women, the manufacturer does not recommend use of either medication during pregnancy. The safety and effectiveness of the use of these medications in children has not been established.

You or your healthcare provider can obtain more information about:



Heparin is a compound that has both anti-inflammatory and surface protective actions. Heparin can mimic the activity of the bladder’s mucous lining, temporarily “repairing” the GAG layer, which may be defective in interstitial cystitis/bladder pain syndrome (IC/BPS).

Clinical studies on the effectiveness of heparin are limited. In one uncontrolled investigation, intravesical heparin resulted in some improvement of symptoms in about 50 percent of patients. Another study of patients undergoing DMSO treatments indicated that heparin might help reduce their relapse rate. Patients treated with DMSO alone had a relapse rate of 52 percent, while those maintained with monthly instillations of heparin and followed for 12 months had a relapse rate of 20 percent.

Dosage & Treatment Plan

While this drug can be given either by injection or by bladder instillation, the method of choice for the treatment of IC is bladder instillation. It can be used as a primary treatment method, as a component of an instilled “bladder cocktail” or as a “maintenance medicine” to supplement other types of treatment. Heparin is also combined with alkalinized lidocaine to form a “rescue remedy” for use during IC/BPS flares.

A heparin solution of 10,000 units diluted with saline solution is instilled intravesically daily, and held in the bladder for 20 to 30 minutes. Patients can be taught to self-catheterize and administer the treatments at home. After 3 to 4 months the frequency of instillations is reduced to 3 to 4 times per week.

It takes 3 to 6 months to begin to see improvement, but therapy should continue for at least 12 months. If there is no improvement in symptoms after 3 months, the dosage is increased to 20,000 units. Therapy can be continued indefinitely.

Potential Side Effects

The side effects of bladder instillation of heparin are limited primarily to pain, irritation, or discomfort resulting from frequent catheterization.

Bladder Cocktails

Below are some ICA Medical Advisory Board members’ bladder cocktail recipes. Many patients may be able to do instillations of these cocktails at home, after in-office education. If a solution causes your patient dysuria, it can be drained by catheter. In that case, in-office administration is more practical.

Kristene Whitmore, MD—Drexel University College of Medicine

Whitmore Cocktail

  • 0.5% bupivacaine (Marcaine, 20 mL)
  • 10,000 IU heparin (10 mL)
  • 100 mg hydrocortisone (5 mL of normal saline)
  • 40 mL sodium bicarbonate 48 mmol

Try using with patients who self-administer at home. For patients who have had a documented UTI within three months of the instillation, add 80 mg gentamicin (5 mL of normal saline) to this mixture.

Usually, give six weekly instillations. For patients who have premenstrual flares, try giving monthly instillations during the flare.

Robert Moldwin, MD—Smith Institute for Urology & Long Island Jewish Medical Center

Anesthetic/Steroid cocktail

  • 1:1 mixture of 0.5% bupivacaine (Marcaine) and 2% lidocaine jelly (about 30 to 40 mL total)
  • 40 mg triamcinolone (usually use 80 mg for Hunner’s ulcer patients)
  • 10-20,000 IU heparin
  • 80 mg gentamicin

Perform this instillation weekly in the office, or up to three times a week by patients at home. Longer-lasting improvement in symptoms may take up to 12 weeks. Once symptoms have improved, increase the time between instillations. In instances where patients describe loss of cocktail efficacy, we usually switch to “DMSO cocktail” and may come back to the anesthetic cocktail at a later date, if needed.

Alkalinized lidocaine cocktail

  • 25 mL 2% lidocaine
  • 5 mL sodium bicarbonate
  • 10,000 IU heparin
  • 80 mg gentamicin

In studies with alkalinized lidocaine, bicarbonate was instilled after lidocaine, but mixing this solution and instilling it “fresh” should avoid problems with precipitation.

DMSO cocktail

  • 50 mL Rimso-50 (DMSO)
  • 10-20,000 IU heparin
  • 40 mg triamcinolone
  • 10 mL sodium bicarbonate
  • 80 mg gentamicin

Christopher Payne, MD

Payne Cocktail I

  • 10,000 IU of heparin
  • 10 mL of bupivacaine (Marcaine)

Usually prescribe for self-instillation daily or three times a week. Sometimes, use this cocktail as a weekly office treatment.

Payne Cocktail II

  • 50 mL of Rimso-50 (DMSO)
  • 100 mg hydrocortisone (Solu-Cortef) plus 10 mL bupivacaine (Marcaine)
  • 5 mL sodium bicarbonate
  • Heparin (may add heparin; however, heparin is usually reserved as a separate treatment)

Instill 30 to 50 mL of the above into the bladder and ask the patient to try to hold the solution for 30 minutes. Belladonna and opium (B & O Supprettes) rectal suppositories may be used to help hold the cocktail in the bladder for longer periods. Perform instillations each week for six to eight weeks. If there is improvement, decrease the time between instillations to two weeks, three weeks, one month, and then discontinue.

New Instillations Under Development

New approaches to instillation therapy for IC/BPS are being tried and tested, with a focus on longer-term results or even healing rather than “rescue.” These include:

PSD597 (Plethora Solutions)

This is the formulation of alkalinized lidocaine used in the clinical trial published earlier this year. It includes a delivery system and a proprietary formulation said to protect the active drug in the bladder and ensure that the drug remains in the optimal chemical form for transport across the bladder wall to its site of action.

URG101 (Urigen)

This is a formulation of alkalinized lidocaine and heparin for instillation. Interim analysis of a phase 2 trial showed significant improvement in average daytime pain, daytime urgency, and symptom score.

Uracyst (Stellar Pharmaceuticals)

This formulation of sterile sodium chondroitin sulfate solution (2.0%) is approved for marketing in Canada and Europe. It is thought to replace the damaged glycosaminoglycan layer of the bladder. In an uncontrolled, six-week Canadian trial in 53 patients with moderately severe IC received weekly instillations for six weeks, then monthly over 16 weeks for a total of 10 treatments. At 10 and 24 weeks, symptom and bother scores were significantly reduced.

Liposomes for instillation (Lipella)

The first human trial of liposomes for instillation was published online in August 2009 (Chuang YC et al. J Urol. 2009;182:1393-1400). In this small trial, liposomes instilled once a week for four weeks were compared with oral pentosan polysulfate (Elmiron) 100 mg three times a day for four weeks. Both reduced frequency and nocturia significantly, but patients who received liposomes also had significant decreases in pain, urgency, and O’Leary-Sant symptom scores.

Misoprostol (Cytotec) for instillation

This prostaglandin E1 analog is used orally to reduce the risk of NSAID-induced gastric ulcers. NSAIDs interfere with the NF-kappa B signaling pathway prevent production of prostaglandins. Because this pathway is damaged in IC cells, Raymond Rackley, MD, at the Cleveland Clinic, theorized that this drug may help heal IC bladder lining. It is being used experimentally only in patients with severe IC for whom treatments short of surgery have failed.

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