der mucosa. The GAG layer appears to be Interstitial cystitis: a retrospective a critical defensive layer of the urothelium, normally preventing diffusion of toxins, analysis of treatment bacteria, and irritating components of urine through the underlying bladder wall. with pentosan polysulfate and Loss of the GAG layer is postulated to be the inciting cause of the symptom com- follow-up patient survey plex of interstitial cystitis. In 1996, the US Food and Drug Admin- MICHAEL G. WATERS, DO; JON F. SULESKEY, DO, FACOS; istration approved release of pentosan poly- LISA J. FINKELSTEIN, DO; sulfate sodium (PPS) (Elmiron), a semisyn- MAUREEN E. VAN OVERBEKE, DO, FACOS; thetic sulfated polysaccharide that serves VINCENT J. ZIZZA, DO; MANFRED STOMMEL, PhD as a synthetic bladder mucosal gly- cosaminoglycan. It adheres to the bladder To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS) in reliev- surface, reinforcing the defective GAG ing symptoms of interstitial cystitis, the authors retrospectively reviewed charts of 260 layer.2 Additionally, PPS has a weak hep- patients in whom interstitial cystitis had been diagnosed. Subsequently, they conducted arin-like effect, stabilizing mast cells and a follow-up phone interview or mail survey of those patients who were treated inhibiting histamine release.3 Originally with PPS to investigate changes in the patients’ symptoms, adverse effects, and used as a bladder instillation treatment, PPS change in quality of life. The control group consisted of patients whose interstitial was found to have reportedly low toxicity cystitis had been diagnosed at cystoscopy and had a duration of at least 1 year and good tolerance when taken orally. and who had taken at least one or more oral medications for their sypmptoms. Minor adverse reactions to the drug The average length of treatment was 9.3 months among the 27 subjects on PPS include nausea, diarrhea, headache, dizzi- therapy. The mean length of time that they had diagnosed interstitial cystitis was 35.63 ness, skin rash, peripheral edema, and months and 48.78 months for the PPS-treated and control groups, respectively, hair loss. Rarely, severe thrombocytope- with no statistically significant difference. Changes in frequency, urgency, and pain nia, increased anticoagulant activity, and were greater in the treatment group and statistically significant (P.11, P.49, elevated transaminase levels are report- and P.004, respectively). No change occurred in the rate of nocturia in the PPS- ed. Intestinal absorption of PPS is approx- treated group compared with that in the control group. Symptoms of both groups imally 3%. It is taken daily for at least 2 improved over time, but improvement was statistically significantly greater in the treat- to 3 months to assess efficacy. ment group (P.001) over the treatment interval. The most common side effect A significant number of patients in our attributable to PPS was diarrhea in 15% of subjects. Pentosan proved to be an population with interstitial cystitis have efficacious option for reducing the debilitating symptoms of interstitial cystitis. been started on treatment with PPS. The (Key words: interstitial cystitis, urinary frequency, urinary urgency, nocturia, objective of our study was to evaluate the pentosan polysulfate sodium) efficacy and safety of oral PPS in relieving recurring symptoms of interstitial cystitis through retrospective chart review and nterstitial cystitis is a chronic, debilitat- spectrum, presumably multifactorial. Symp- detailed follow-up interview of patients. Iing disorder characterized by urinary toms often resemble those of patients with frequency (sometimes up to 60 times a overactive bladder. Up to 50% of patients Materials and methods day), urinary urgency, nocturia, and pain. with symptoms of interstitial cystitis will Study design and patient selection Patients have symptoms of interstitial cys- have spontaneous resolution in time. Control and PPS treatment groups were titis for an average of 7 years before diag- Typical cystoscopic appearance of the eligible for the study if they had had inter- nosis is made.1 Although anyone can be bladder after hydrodistension with the stitial cystitis diagnosed at least 1 year pre- affected, 90% of the afflicted are women patient under anesthesia demonstrates viously and had persisting symptoms of in their fifth and sixth decades of life. Diag- glomerulations or submucosal pinpoint frequency, nocturia, urgency, or pain, either nosis of interstitial cystitis is primarily one capillary hemorrhages, and occasionally, singly or in combination. They were of exclusion. The disorder does not repre- a fissure-type lesion known as Hunner’s required to have undergone at least one sent a single disease entity but a disease ulcers. Inflammation of the bladder is a cystocopy/hydrodistension procedure with predominant finding in patients with inter- anesthesia and to have had negative urine stitial cystitis. Patients with interstitial cys- cultures. The PPS-treated group had to be Dr Waters is a senior resident in urological titis repeatedly lack evidence of any ongo- on PPS therapy at least 8 weeks to be surgery, Botsford General Hospital, Farming- ing bacterial or viral infection. included in the treatment arm. Control ton Hills, Mich; Drs Suleskey, Finkelstein, and Several intriguing theories have been group patients had to be taking at least Van Overbeke are clinical professors at Michi- gan State University–College of Osteopathic suggested as possible etiologic mecha- one oral medication as a treatment for their Medicine (MSU-COM), East Lansing, Mich; Dr nisms for the disorder, including inflam- symptoms of interstitial cystitis. Exclusion Zizza is an attending urologist, Newport, RI; matory/autoimmune effect, mast cell infil- criteria were age less than 18 years, PPS and Dr Stommel is in the Division of Biostatistics, tration, urinary toxins, and reflex therapy for less than 8 weeks, interstitial Department of Nursing MSU-COM. Correspondence to Michael G. Waters, DO, sympathetic dystrophy. Another hypoth- cystitis diagnosed for less than 1 year, no 1906 E 13 Mile Rd, Madison Heights, MI 48071. esis is that there is a defect in the gly- previous cystoscopy/hydrodistension, and E-mail: [email protected] cosaminoglycan (GAG) layer of the blad- inability to complete the questionnaire.

Waters et al • Interstitial cystitis JAOA • Vol 100 • No 3 • Supplement to March 2000 • S13 Charts of 260 patients with intersti- Statistics barely reaching statistical significance tial cystitis from seven metropolitan Length of participation was calculated as (P.049). Severity of urgency was worse Detroit area urology clinics were reviewed. the length of time on PPS therapy for the in the PPS-treated group than in the con- As of May 1998, 27 patients with inter- treatment arm and the changes in symp- trol group initially. stitial cystitis treated with PPS and 27 toms during the preceding year up to time control group patients met the criteria for of interview in the control arm group. Pain or discomfort the study. The same investigator (M.G.W.) Because four means (frequency, urgency, Both the PPS-treated and the control asked all patients to answer a question- pain, and overall change) and one covari- groups were similar at the onset, with the naire documenting their disease-related ant (interval of change) were identified, the patients treated with PPS having closest to symptoms, which included frequency, Fischer test was used for statistical analy- severe pain levels. Change in pain or dis- nocturia, urgency, pain or discomfort, sis. In order to test whether the PPS inter- comfort over time was greater in the PPS- and overall change over time. The respons- vention group did better than the control treated study group, with strong statistical es to the questionnaire provided the data group, a repeated measures analysis of significance (P.004). This represented for the quantitative evaluation presented covariance model was run.5 This model the largest change in the four study param- here. Both groups were compared demo- allowed examination and comparison of eters. graphically in relation to average age, age the changes in the mean scores from range, length of time with the diagnosis of pretest to posttest in the intervention and Overall change interstitial cystitis, and average number the control group. We asked patients about their complete of previous drug treatments (Table 1). change in all parameters over time, with Results 1 being worse up to 6 representing total Evaluation Of the 260 charts reviewed, 27 patients improvement or complete abatement (or All patients had undergone a complete with interstitial cystitis who were taking both) of symptoms. Although both groups history and comprehensive physical assess- PPS and 27 control patients with inter- improved over time, there was a strong ment with baseline laboratory studies stitial cystitis met the criteria for the study. statistically significant change in the PPS- (complete blood cell count with platelet The average age of PPS-treated patients treated group versus the control group and differential counts and electrolyte, was 43.9 years (range, 23 to 83 years), (P.001). blood urea nitrogen, and serum creati- while the average age for the control nine levels, prothrombin time, partial group patients was 45.3 years (range, 18 Previous treatments thromboplastin time, and urine cultures). to 72 years), with no statistically significant Table 2 lists and compares the previous Complete treatment histories were difference between the two groups. The medical treatments of both study groups. obtained, including previous experimen- length of time the patients had had the Six (22%) of the patients in each group tal modes of therapy, over-the-counter diagnosis of interstitial cystitis was 35.63 were given intravesical DMSO during medications or herbal products, and months and 48.78 months for the PPS- their course of therapy. Spasmolytics were intravesical instillation with such agents as treated and control groups, respectively, given more frequently in the PPS-treated dimethyl sulfoxide (DMSO), chromium, with no statistically significant difference. group (74%) than in the control group chlorpactin, and heparin. Most of the The number of previous drug treatments (44%); whereas tricyclic antidepressants patients underwent bladder biopsy during for both groups was identical (2.3). had been used in 30% of patients in the at least one cystoscopy/hydrodistension control versus only 4% of the patients in procedure. Biopsy results, when available, Urinary frequency the PPS-treated group. A transcutaneous were categorized and calculated in relation Although urinary frequency in both electrical nerve stimulation (TENS) unit to those typically found in interstitial cys- groups improved over time, the PPS-treat- had been placed in one patient of each titis, but no correlations were made with ed group demonstrated a larger change study group but had been subsequently patients’ symptoms. Bladder capacity was (5.9 vs 2.7), with the difference of removed. One patient had received full- recorded in all patients. improvement being statistically signifi- course intravesical bacille Calmette-Guérin The detailed questionnaire was adapted cant (P.11). Frequency in both groups (BCG) vaccine as part of a study that has from a study by Hanno4 in 1997. Patients was nearly identical initially. since been published.6 None of the control on PPS therapy provided information based group patients had received heparin blad- on symptoms just before starting therapy Nocturia der instillation. and up to current use or at the point of Control group patients had slighly more cessation of therapy. Control group patients nocturia than the PPS-treated patients ini- Concomitant medications were asked to report change in symptoms tially. Patients’ levels of nocturia, repre- We investigated the use of concomitant during the 12 months preceding the time of senting the number of voids per night, medication in our study cohort (Table 3). interview. Responses to the questionnaire dropped 2.2 points in the PPS-treated Spasmolytics were being used more fre- provided the quantitative data. Patients group versus 1.2 points in the control quently in the PPS-treated group (88%) were asked to report any adverse effects group, but the difference was not statist- versus in the control group (48%). An regardless of what medication had been cally significant (P.054). equal number of patients in each group prescribed for them. All adverse effects were using phenazopyridine (30%) to attributed to PPS were categorized and cal- Urgency treat their symptoms, while slightly more culated over the entire study. Any causes for Similar to frequency, the change in urgen- control group patients were taking tri- discontinuance of treatment with PPS were cy was better in the PPS-treated group cyclic antidepressants (33%) or selective calculated and categorized. compared with that in the control group, serotonin-reuptake inhibitors (26%) than

S14 • JAOA • Vol 100 • No 3 • Supplement to March 2000 Waters et al • Interstitial cystitis thinning. Three (11%) of the patients Table 1 reported some degree of hair thinning or Demographic Data: Group Treated with Pentosan Polysulfate fallout. One stopped therapy because of Versus Control Group persistent hair fallout. Eight percent of patients had abdominal cramping. One Group treated Control patient reported weight gain, while two Variable with pentosan group patients had neurolgic symptoms includ- Average age, y 43.96 45.30 ing paresthesias or visual disturbances. Age range, y 23 to 38 18 to 72 Other side effects included shortness of Mean time having 35.63 48.78 breath in a nonasthmatic patient and gen- diagnosis, mo eralized morbilliform rash in another. Mean time on 9.3 NA* In all, 27% of patients on PPS therapy pentosan therapy Average No. of 2.3 2.3 had gastrointestinal symptoms or weight previous treatment modalities gain during their course of treatment. A number of patients discontinued PPS *NA not applicable.s during their course of treatment, but not all discontinuations were due to negative factors. Four patients (15%) stopped tak- ing the drug because of the previously Table 2 listed side effects (Table 5). Symptoms Treatment Modalities Previously Used in Group Treated with Pentosan Polysulfate and in Control Group worsened in 9% of the patients, forcing discontinuance. One patient’s symptoms Treatment Control totally abated on PPS therapy, and she Treatment modality group group stopped use of PPS before the interview. One male patient had a myocardial infarc- Dimethyl sulfoxide, No. (%) 6 (22) 6 (22) tion during his course of treatment, and Spasmolytics, No. (%) 20 (74) 12 (44) administration of the drug was stopped Tricylic antidepressants, No. (%) 1 (4) 8 (30) Transcutaneous electrical, 1 (4) 1 (4) although the incident was not related to nerve stimulation, No. (%) the drug use. Finally, one patient stopped Bacille Calmette-Guérin 1 (4) taking PPS for a planned pregnancy. In all, vaccine, No. (%) 33% of patients stopped taking PPS dur- Chromium instillation, No. (%) 1 (4) Heparin instillation, No. (%) 3 (11) ing their course of treatment. Steroids, No. (%) 1 (4) 2 (7) Other, No. (%) 10 (37) 13 (48) Cystoscopy/bladder biopsy results To be part of the study cohort, all patients were required to have had at least one cystoscopy/hydrodistension with bladder Table 3 mucosal biopsy. Hunner’s patch was iden- Concomitant Oral Medication: tified in two (7.4%) of the PPS-treated Group Treated with Pentosan Polysulfate Versus Control Group patients and in only one (4%) of the patients in the control group (Table 6). Treatment Control Type of medication group group No fissures were found during cystoscopic evaluation in either group. Glomerula- Spasmolytics, No. (%) 24 (88) 13 (48) tions were similarly prevalent in both Tricyclic antidepressants, No. (%) 6 (22) 9 (33) study groups, with 81% of the PPS-treat- Selective serotonin- 3 (11) 7 (26)reuptake ed group and 74% of the control group inhibitors, No. (%) Phenazopyridine, No. (%) 8 (30) 8 (30) having glomerulations. Similarly, bloody Anxiolytics, No. (%) 2 (7) effluent was slightly more prevalent in Antibiotics, No. (%) 1 (3) 3 (11) the PPS-treated group (74%) compared Antihistamines, No. (%) 3 (11) 1 (4) with the control group (66%), but this -Blockers, No. (%) 2 (7) 2 (7) Herbal or other 10 (37) 7 (26) difference was not statistically significant. products, No. (%) Average bladder capacity was measured in both groups and found to be similar at 540 mL and 574 mL in the PPS-treated the PPS-treated group (11%). -Blockers we inquired as to whether the PPS study and control groups, respectively. were used in 7% of patients in each par- group had any side effects develop during ticipant group. Ten (37%) of the PPS- their course of treatment. Most prevalent Discussion treated patients and 7 (26%) of the con- was diarrhea, with mild cases developing Of the 260 charts reviewed, 27 patients trol group patients were using herbal in 4 (15%) of the 27 PPS-treated patients with interstitial cystitis taking PPS and 27 products or over-the-counter remedies. after initiating therapy (Table 4). The sec- control patients with interstitial cystitis Because PPS is a relatively new drug, ond most frequent side effect was hair met the criteria for the study. Criteria

Waters et al • Interstitial cystitis JAOA • Vol 100 • No 3 • Supplement to March 2000 • S15 used to enter patients into the study were strict so as to stratify both groups and Table 4 reduce confounding variables. Although Adverse Effects of Pentosan Polysulfate: Nature and Incidence some investigators do not require cys- toscopy for diagnosis of interstitial cysti- Side effect No. % tis, we required all patients to have under- Diarrhea 4 15 gone at least one hydrodistension and Hair thinning 3 11 bladder biopsy. This requirement was to Abdominal cramping 2 8 ensure that each patient had a similar Weight gain 1 4 baseline treatment (hydrodistension) and Shortness of breath 1 4 ruled out carcinoma in situ, other neo- Visual disturbances 1 4 Rash 1 4 plasms, diverticula, or stones as a poten- Paresthesias 1 4 tial cause of their symptoms. Because it is well established that PPS takes up to 6 weeks or more to exert any symptomatic relief, the PPS-treated patients had to have been taking the drug Table 5 Discontination of Pentosan Polysulfate Treatment for at least 8 weeks. Average length of use of PPS was 9.3 months among the Cause No. % 27 subjects which provides more long- term results compared with studies eval- Side effects* 4 15 uating patients at 3 months. Because the Worsening of symptoms 2 9 PPS-treated patients were taking at least Remission of symptoms 1 4 one drug (PPS), we stratified the control Myocardial infarction 1 4 Planned pregnancy 1 4 group by selecting only those patients Total 9 33 who were currently taking at least one oral medication. All patients had to have *Includes diarrhea, abdominal cramping, nausea, hair thinning. established interstitial cystitis diagnosed no less than 1 year previously. Patients treated with PPS on average were younger than the the control group Table 6 patients, but not statistically significantly Results of Cystoscopy and Biopsy for Group so. The PPS-treated patients had a short- Treated with Pentosan Polysulfate and Control Group er duration of diagnosed interstitial cysti- tis, but the difference was not statistical- Treatment Control ly significantly different. Both groups had Finding group group the same average number of previous drug Hunner’s patch, No. (%) 2 (7.4) 1 (4.0) treatments. Cystoscopic evaluation Fissures, No. (%) 0 (0) 0 (0) revealed Hunner’s patch in two (7.4%) of Glomerulations, No. (%) 22 (81.0) 20 (74.0) the PPS-treated patients, but in only one Blood effluent, No. (%) 20 (74.0) 18 (66.0) control group patient (4.0%), comparing Bladder capacity, mL 540 574 closely with the rate found in studies by Koziol (7.0%)7 and Messing and col- leagues (11.3%).8 As in the latter study, over time, with the frequency in both coworkers,9 who found a 50% or greater the rate of glomerulations (91% of groups being nearly identical initially (15.3 reduction in nocturia in PPS-treated patients) was similar in both study groups vs 16.4). Patients treated with PPS had patients. (81% of the PPS-treated group and 74% nearly 6 voids fewer per day compared As with urinary frequency, the change of the control group). Although bloody with just less than 3 fewer voids per day in urgency was better in the PPS-treated effluent was slightly more prevalent in for the control group. Frequency in both group compared with that in the control the PPS-treated group compared with the groups improved over the time interval. group, barely reaching statistical signifi- control group, this difference was not sta- Control group patients had slightly cance (P.049). Severity of urgency was tistically significant and was nearly iden- more nocturia than the PPS-treated worse in the PPS-treated group than the tical to the findings of Messing and col- patients initially, but both groups control group initially. Severity of urgen- leagues.8 Average bladder capacity was improved over the time interval. Noc- cy was worse in the PPS-treated group measured in both groups and found to turia, representing the number of voids than in the control group initially. be similar in both groups. per night, dropped 2.2 points in the PPS- Both PPS-treated and control groups Interestingly, mean symptoms in both treated group versus 1.2 points in the con- had similar pain levels at the onset, with the groups improved over time (Table 7). The trol group, but the difference was not sta- PPS-treated patients being closest to severe PPS-treated group demonstrated a statis- tistically significant (P.054). Our results pain levels. Change in pain or discomfort tically significant (P.11) improvement are consistent with those of most studies, over time was greater in the PPS-treated in urinary frequency on the analog scale but not with those of Parsons and study group with strong statistical signifi-

S16 • JAOA • Vol 100 • No 3 • Supplement to March 2000 Waters et al • Interstitial cystitis Regarding the use of concomitant oral Table 7 medications in our study cohort, it is inter- Improvement in Interstitial Cystitis Symptoms in esting to note that 10 PPS-treated patients Pentosan Polysulfate (PPS)–Treated and Control Groups (37%) and 7 (26%) control group patients were using herbal products and over-the- Group counter remedies. Although this fact could create a bias in the study results, both Parameter PPS-treated Control groups were essentially equal in their use of such agents. The pattern of herbal use Frequency, No. of voids Pretest 15.3 16.4 among patients, including specific types, Posttest 9.4 13.7 did not appear to greatly affect the out- Change 5.9 2.7 come of the patients’ symptoms. No patients were found to taking only an Nocturia, No. of voids Pretest 4.7 5.8 herbal remedy. Posttest 2.5 4.5 Although 9 patients discontinued tak- Change 2.2 1.3 ing PPS during their course of treatment, 3 of them did so for reasons not related to Urgency, severity* negative causative factors. Four patients Pretest 2.3 2.2 Posttest 1.4 1.6 (15%) stopped taking the drug because of Change 0.9 0.6 side effects, mostly gastrointestinal dis- turbances and hair thinning. According Pain, severity* to the package insert,10 approximately Pretest 6.6 6.2 Posttest 3.3 4.7 4% of patients taking PPS will have hair 4 Change 3.3 1.5 thinning or alopecia. Hanno noted alope- cia in 3.91% of study subjects. Interest- *Change in all parameters over time, with 1 being the worst up to 6, representing total improvement or ingly, we found nearly three times the complete abatement of symptoms (or both). rate of hair thinning in our patients com- pared with that of other investigators. This difference may be due to our use of cance (P.004). This represented the largest their course of treatment. Most prevalent a stricter definition of hair loss in our change in the four study parameters. was diarrhea, with mild cases developing patients. We asked patients about their com- in 4 (15%) of the 27 PPS-treated patients Symptoms of interstitial cystitis actually plete change in all parameters over time, after initiating therapy. The second most worsened in 9% of the patients, forcing with 1 being the worst up to 6, repre- frequent side effect was hair thinning. 3 discontinuation of the drug’s use. One senting total improvement or complete (11%) of patients reported some degree of patient’s symptoms totally abated on PPS abatement of symptoms (or both). hair thinning or fallout. One stopped ther- therapy, and she stopped use of PPS before Although both groups improved over apy due to persistent fallout. Eight percent the interview. It is unknown whether her time, there was a strong statistically sig- of patients experienced abdominal cramp- symptoms have returned since cessation of nificant change in the PPS-treated group ing. One patient reported weight gain, the drug. A second patient was contem- versus the control (P.001). while two patients experienced neurolgi- plating discontinuation because of marked Twenty-two percent of patients in each cal symptoms, including paresthesias or improvement of symptoms, as well. group were given intravesical DMSO dur- visual disturbances. Other side effects A male patient’s myocardial infarction ing their course of therapy. Spasmolytics included shortness of breath in a nonasth- during his course of treatment was not were given more frequently in the PPS- matic patient and generalized morbilli- related to use of the drug, although use of treated group (74%) than in the control form rash in another. the drug was stopped. The patient’s symp- group (44%), while tricyclic antidepres- In all, 27% of patients on PPS therapy toms were returning at the time of inter- sants had been used in 9 (33%) of the had gastrointestinal symptoms or weight view. To date, it is unknown whether the patients in the control group versus only gain during their course of treatment. This patient who stopped taking PPS for a 1 patient (4%) of the PPS-treated group. compares poorly with the PPS package planned pregnancy plans to resume PPS A TENS unit had been placed in one insert, which states that approximately therapy postpartum. patient of each study group but had been 5% of patients will experience such symp- This study, which compares highly subsequently removed. One patient had toms. selected, treatment-stratified patients with received full-course intravesical BCG as As interstitial cystitis is a difficult, interstitial cystitis, is useful to the clini- part of a study that was published in mid- chronic disease to treat, patients often cian because it is difficult, indeed rare, to 1998.6 She admitted to having improved require multimodal approach to alleviate find a group of patients of this cohort symptoms. None of the control group their symptoms. Most studies investigat- type who respond only to one drug and patients had received bladder instillation ing PPS involve patients taking PPS exclu- are willing to stay on one therapy regard- of heparin. sively, but in a day-to-day clinical setting, less of symptoms. Realistically, many As PPS is a relatively new drug, we it makes sense to us to evaluate the use of patients with interstitial cystitis require inquired as to whether the PPS study PPS as an additional medication to a reg- several medications or modes of therapy group had any side effects develop during imen providing marginal results. (or both) to control their debilitating

Waters et al • Interstitial cystitis JAOA • Vol 100 • No 3 • Supplement to March 2000 • S17 symptoms. This study confirms that PPS although both groups improved over time. 5. Winer JB. Statistical Principles in Experimental is an effective, viable choice for patients Compared with agents used by the control Design, 3rd ed; 1991. with interstitial cystitis and can provide patients, PPS provides modest efficacy in 6. Peters KM, Diokno AC, Steinert BW, Gonzalez JA. measurable improvement even when treating symptoms of interstitial cystitis The efficacy of intravesical bacillus Calmette-Guérin added to a patient’s current medical reg- and should be considered a useful drug in in the treatment of interstitial cystitis: long-term follow- up. J Urol 1998;159:1483-1486; discussion 1486-1487. imen. the armamentarium of treatments for the patient in whom interstitial cystitis is diag- 7. Koziol JA. Epidemiology of interstitial cystitis. Urol Clin Comment nosed. North Am 1994;21(1):7-20. The response to oral PPS varied widely 8. Messing E, Pauk D, Schaeffer A, Nieweglowski M, in patients from worsening symptoms to References Nyberg LM Jr, Landis JR, et al. Associations among cys- toscopic findings and symptoms and physical exami- complete ablation. Pentosan polysulfate 1. Hwang P, Auclair B, Beechinor D, Diment M, Einar- son TR. Efficacy of pentosan polysulfate in the treatment nation findings in women enrolled in the Interstitial Cys- significantly hastened the decline in the of interstitial cystitis: a meta-analysis. Urology titis Data Base (ICDB) study. Urology 1997;49(Suppl scores for urinary frequency, urgency, and 1997;50:39-43. 5A):91-85 pain between the two groups. There was, 2. Elmiron Product Monograph. Palo Alto, Calif: Alza 9. Parsons CL, Mulholland SG. Successful therapy of however, no significant change in the Pharmaceuticals; 1996. interstitial cystitis with pentosanpolysulfate. J Urol urgency parameter between the two 1987;138:513-516. 3. Jepsen JV, Sall M, Rhodes PR, Schmidt D, Messing groups. E, Bruskewitz RC. Long-term experience with pen- 10. Elmiron (pentosan polysulfate sodium) prescribing Perception of overall improvement was tosanpolysulfate in interstitial cystitis. Urology information. In: Physicians’ Desk Reference, 52nd ed. better in PPS-treated patients as compared 1998;51:381-387. Montvale, NJ: Medical Economics Company; 1998; pp 592-594. with those patients in the control group, 4. Hanno PM. Analysis of long-term therapy for interstitial cystitis. Urology 1997;49(Suppl 5A):93-99.

S18 • JAOA • Vol 100 • No 3 • Supplement to March 2000 Waters et al • Interstitial cystitis