1. Management of PBS/IC (Painful Bladder Syndrome/Interstitial Cystitis)
Abbreviated Prescribing Information can be found on the last slide of this presentation.
PMR-SEP
Date of preparation: September 2010

2. Roadmap What is PBS/IC? Symptoms and impact of PBS/IC
Management of PBS/IC
Causes and diagnosis
Supporting patients

3. Roadmap What is PBS/IC? Symptoms and impact of PBS/IC
Management of PBS/IC
Causes and diagnosis
Supporting patients

4. Definition of PBS/IC* Suprapubic pain related to bladder filling
Increased daytime and night-time frequency
Absence of infection or other pathology
Interstitial cystitis (IC) is a chronic inflammatory disorder of the bladder that is notoriously difficult to manage and can result in considerable morbidity. It can cause symptoms of urinary frequency and urgency, with pain as a predominant feature in one or more regions of the pelvis (but typically perceived as being related to the bladder), leading to a poor quality of life.1
The International Continence Society (ICS) prefers the term painful bladder syndrome (PBS) which it defines as ‘the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology’. The ICS reserves the term interstitial cystitis as being a ‘specific diagnosis and requires confirmation by typical cystoscopic features’.1
1. Meijlink J. Interstitial cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
*The ICS reserves the term interstitial cystitis as being a ‘specific diagnosis and requires confirmation by typical cystoscopic features’.

5. PBS/IC Nomenclature Interstitial cystitis Painful Bladder Syndrome
Bladder Pain Syndrome
Hypersensitive Bladder Syndrome
Chronic Pelvic Pain Syndrome
PBS/IC
Many different names are used to describe the symptoms characteristic of IC. These include:
Painful Bladder Syndrome (PBS),
Bladder Pain Syndrome (BPS),
The umbrella term Hypersensitive Bladder Syndrome
Chronic Pelvic Pain Syndrome (CPPS)
These terms can be used either alone or in different combinations.
This lack of an internationally accepted, standard definition has led to each country adopting their own preferred terminology and guidelines for the diagnosis of IC.1
The International Continence Society (ICS) prefers the term painful bladder syndrome (PBS) which it defines as ‘the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology’. The ICS reserves the term interstitial cystitis as being a ‘specific diagnosis and requires confirmation by typical cystoscopic features’.1
In 2006 the European Society for the Study of Interstitial Cystitis/Painful Bladder Syndrome (ESSIC) designed a type classification system according to findings at cystoscopy and biopsy and announced that it preferred to use the term bladder pain syndrome (BPS). The ESSIC also proposed amending the wording of the ICS definition of interstitial cystitis to ‘by typical cystoscopic and/or histological features’.1,2
It has been decided (by the ICS and urology experts worldwide) to use the term painful bladder syndrome/interstitial cystitis (PBS/IC) for the time being.2,3,4
1. Meijlink J. Interstitial cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
2. European Society for the Study of IC/PBS (ESSIC) Consensus on criteria, classification, and nomenclature for PBS/IC
3. Hanno et al. Painful Bladder Syndrome (including interstitial cystitis). International Consultation on Incontinence 2005.
4. Meijlink J. Painful Bladder Syndrome/Interstitial cystitis. Diagnosis and evaluation guidelines

6. Prevalence of PBS/IC Incidence/ 100 000 10 Females 8 Males
All patients 6 4 2
There is great divergence in the estimation of the prevalence of PBS/IC, partly due to the lack of an internationally accepted standard definition.
Reports on the prevalence of PBS/IC conflict depending on the country of origin, and the criteria used for diagnosis:2
USA prevalence cases per 100,000 women
European prevalence - 18 cases per 100,000 women
Japanese prevalence cases per 100,000 women
However, another report concluded that the incidence of PBS/IC in the general population might be three fold greater in Europe than that previously reported, and actually stood at 67 cases per 100,000 head of population.3
The condition is mainly found in women, with 80-90% of sufferers being female. In women, aged years, the estimated prevalence is 3.8%.4
However, approximately 10-20% of PBS/IC patients are men, who may have in the past been incorrectly diagnosed as having non-bacterial prostatitis or prostodynia. This possibility of misdiagnosis in men means that more men may have PBS/IC than first thought.5
Although PBS/IC may occur in any race, 94% of patients are white.2
The median age at presentation is 40 years,2 but on average, the patient will have had the condition for more than five years before diagnosis.1
Patients see an average of five doctors about their symptoms before PBS/IC is eventually diagnosed.1
Patients with PBS/IC are more likely to have undergone gynaecological surgery and/or to have a history of recurrent UTIs, and are times more likely to report childhood bladder problems.2
PBS/IC can also occur in children, where the median age of onset is 4.5 years, with a mean age of diagnosis of 8.2 years.2
1. CME/CE articles: Diagnosis and management of interstitial cystitis/Painful Bladder Syndrome. Accessed 13th January 2009.
2. Rovner E and Lebed B. Interstitial cystitis Overview. Accessed 11th December 2008.
3. Interstitial cystitis survey Cystitis and Overactive Bladder Foundation. Accessed 13th January 2009.
4. Reimbursement position for Uracyst in the UK. Report on behalf of Galen Ltd by Translucency Ltd. September 2008.
5. Meijlink J. Interstitial cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
0-19
20-29
30-39
40-49
50-59
60-69
70-79
Age group, years
Age-specific incidence rates for males, females and all patients with interstitial cystitis1

7. RAND IC Epidemiology Study (RICE)
Based on “high sensitivity” definition, 6.5% (95% CI 6.1 – 6.8%) of U.S. women have symptoms of PBS/IC
Based on “high specificity” definition, 2.7% (95% CI 2.5 – 2.9%) of U.S. women have symptoms of PBS/IC
This translates to between 3,376,317 and 7,851,094 U.S. women age 18 and over with PBS/IC symptoms
In the UK this represents approximately 675,500 to 1,600,000 women over the age of 18 years
The RAND Interstitial Cystitis Epidemiology (RICE) Study was initiated by NIDDK and began in 2006.
In 2006, the study began with research to develop a definition of IC/painful bladder syndrome (PBS), based on the medical literature and the input of top IC experts. That was tested in a survey of 599 women. Men were not included because it’s harder to separate IC from other conditions in men based on questions about symptoms. No single definition worked to identify IC, so the researchers came up with two.
One high sensitivity and low specificity, meaning that it identified nearly all women with IC but also included a large number who didn’t have IC.
The other had low sensitivity but high specificity, meaning that it missed more women with IC but included very few who didn’t have it. These definitions developed the basis for the questions asked in telephone surveys.
Researchers called some 100,000 US households over the course of one year asking questions that would identify the households that might have one or more women living with IC. Those women were then asked to undergo a more intensive screening based on the two definitions, which would yield a range of the prevalence of IC in US women. The results of the survey that yielded an estimate of the prevalence were presented in 2009 at the American Urological Association’s annual meeting. Estimating prevalence was not the only purpose of RICE. The study also aims to describe the impact of IC on quality of life compared with other diseases. Some of those results have also been presented at American Urological Association meetings.
Two definitions
High Sensitivity Definition Criteria - Pain, pressure or discomfort in the pelvic area AND Daytime urinary frequency 10+ OR Urgency due to pain, pressure, or discomfort not fear of wetting.
High Specificity Definition Criteria - Pain, pressure or discomfort in the pelvic area AND Daytime urinary frequency 10+ OR Urgency due to pain, pressure, or discomfort not fear of wetting AND Symptoms did not resolve after treatment with antibiotics AND No treatment with Lupron for endometriosis.
Details of the RICE study are available at
NSO statistics estimate a UK population of just over 25 million females over the age of 18 years
– Last accessed 6th October 2010

8. Roadmap What is PBS/IC? Symptoms and impact of PBS/IC
Management of PBS/IC
Causes and diagnosis
Supporting patients

9. Cardinal Symptoms of PBS/IC
Pain
Frequency
Urgency
The characteristic symptoms of PBS/IC are pain, urinary frequency and urinary urgency.1
Specific bladder pain associated with the condition presents as:1
Increased pain on bladder filling, that may be temporarily relieved by bladder emptying
Can be perceived as arising from the bladder or urethra, but may also extend to the suprapubic and rectal areas, as well as the lower back and groin
In women, may be felt in the vagina, whilst in men it may be experienced in the penis, scrotum, testicles and perineum
May be experienced as a feeling of pressure, discomfort or heaviness, or as a burning or stabbing sensation
May occur in conjunction with sexual intercourse in both men and women (dyspareunia)
Urinary frequency –
Normal frequency of voiding is typically seven or eight times per 24 hours
A patient with PBS/IC can void with tremendous frequency (up to several times an hour), simply to relieve the pain. In the later stages of the condition, some patients may need to urinate up to 60 times a day. Also typical is the need to empty the bladder during the night. The amount of urine passed each time is typically small.1,2
Urinary urgency –
Patients may feel a pressing need to go to the toilet due to increasing pain or discomfort that becomes impossible to tolerate, and in some patients may be accompanied by a feeling of malaise and/or nausea. 1,2,3
Recently, the clinical characteristics of PBS/IC in the community have been estimated as part of a review in the US. The most common presenting symptoms were:4
frequency (70%),
dysuria (52%),
urgency (50%),
suprapubic pain (50%),
nocturia (35%),
dyspareunia (13%).
Galen Limited has conducted a similar survey with the Cystitis and Overactive Bladder Foundation. Results are available on request from
1. Meijlink J. Interstitial cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
2. European Society for the Study of IC/PBS (ESSIC) Consensus on criteria, classification, and nomenclature for PBS/IC
3. Parsons M and Toozs-Hobson P. The investigation and management of interstitial cystitis. Journal of the British Menopause Society. 2005; 11 (4):
4. Patel R et al. Incidence and clinical characteristics of interstitial cystitis in the community. Int Urogynecol J. 2008; 19:

10. Patient quote
“IC affects your family life so much. Even with the simple basic things like taking a shopping trip, you have to realise that you can no longer do what you like, when you like, as you have to plan on finding toilets. My children know that wherever we are ‘Mummy will have to find a toilet soon’.”
GALEN WOULD LIKE TO THANK MEMBERS OF THE CYSTITIS AND OVERACTIVE BLADDER FOUNDATION FOR SUPPLYING THESE QUOTES .

11. part-time, local to my home, as I couldn’t travel on public
Patient quote
“Having IC has completely changed my working life. I went from working in a full-time, well paid job to being forced to work
part-time, local to my home, as I couldn’t travel on public
transport anymore.”
GALEN WOULD LIKE TO THANK MEMBERS OF THE CYSTITIS AND OVERACTIVE BLADDER FOUNDATION FOR SUPPLYING THESE QUOTES .

12. partner who realises what you are going through.”
Patient quote
“IC alters your intimate relationships. It’s very difficult to continue to have a fulfilling relationship when you are suffering with so much pain and discomfort.You really do need to have a very understanding
partner who realises what you are going through.”
GALEN WOULD LIKE TO THANK MEMBERS OF THE CYSTITIS AND OVERACTIVE BLADDER FOUNDATION FOR SUPPLYING THESE QUOTES .

13. Impact on Quality of Life
Pain, urinary urgency, and urinary frequency
Limitations on
sexual intimacy
Curtailed
activities
Sleep
deprivation
Reduced ability
to work
PBS/IC is more than just a symptom complex, it affects the quality of life of the patient.1
Social isolation: When outside the confines of their own home, the PBS/IC patient’s life is dominated by the question ‘where am I going to find the next toilet?’. Before every outing the patient will carefully plan a network of toilets, known as ‘toilet-mapping’. Embarrassment, at having to use the toilet so frequently, may cause patients to restrict the frequency of their visits to family and friends, and their social life may be non-existent.1
Occupation and career. Some jobs are impossible with PBS/IC, and the frequent need to urinate may make it difficult for the patient to carry on working. The impact of PBS/IC on their work and career may cause PBS/IC patients and their families considerable financial loss.1
Physical and psychological impact of sleep deprivation. Some patients need to urinate times a day and may sleep no more than 20 minutes a time at night. Sleep deprivation can have a detrimental physical and psychological impact on the patient.1
Impact on family life and relationships. PBS/IC will have an impact on the entire family, as the patient may be tired and irritable from the lack of proper sleep, from coping with the pain, and from the constant trips to the bathroom. Members of the family may find it difficult to understand, or appreciate, the impact of PBS/IC as externally the patient appears perfectly healthy.1
Sexual relations. PBS/IC can have a big impact on sexual relationships since sexual intercourse may be painful for both male and female patients.1
In a UK-based postal questionnaire survey, 64% of respondents reported a ‘considerable impact’ or more on their lifestyle and 46% reported moderate depression or worse. Forty-nine per cent reported at least considerable difficulties with sexual intercourse.2
Galen Limited has conducted a similar survey with the Cystitis and Overactive Bladder Foundation. Results are available on request from
1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Clinical Proceedings. Association of Reproductive Health Professionals. April 2008.
2. Parsons M and Toozs-Hobson P. The investigation and management of interstitial cystitis. Journal of the British Menopause Society. 2005; 11 (4):
Reduced QoL

14. Economic Impact More data is required
NHS incurs a considerable cost in treating PBS/IC
Clemens et al (US):1
Direct cost per year per patient = $3,631
Indirect cost to the patient per year = $4,216
Figures from 2006/7 indicate that, in the UK, there were 4,138 consultant appointments (563 inpatients and 3,575 day cases) associated with a diagnosis of interstitial cystitis, thus the NHS incurs a considerable cost in treating PBS/IC.2
As well as direct medical costs, PBS/IC is associated with significant economic costs in terms of lost productivity. In the UK, it is estimated that a patient with PBS/IC will take, on average, 16.5 sick days per year.3
One study by Clemens et al in the US, estimated that the annualised direct cost per person with PBS/IC is $3,631. In addition, 19% of the PBS/IC patients studied reported lost wages in the previous 3 months as a result of the condition. The authors estimate that the average annual indirect cost to each patient with PBS/IC is $4,216 (equal to approximately £2,691).
1. Clemens JQ et al. Comparison of Economic Impact of Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Interstitial Cystitis/Painful Bladder Syndrome. Urology. 2009; 73:
2. Reimbursement position for Uracyst in the UK. Report on behalf of Galen Ltd by Translucency Ltd. September 2008.
3. Interstitial cystitis survey Cystitis and Overactive Bladder Foundation. Accessed 13th January 2009.

15. Roadmap What is PBS/IC? Symptoms and impact of PBS/IC
Management of PBS/IC
Causes and diagnosis
Supporting patients

16. Causes of PBS/IC Irritating solutes GAG layer Urothelium
Irritated nerve
GAG layer
Inflammation
Despite considerable research into many different aspects of PBS/IC, the cause of the condition is still unknown. Proposed etiologies include the following:1
Deficiency in the glycosaminoglycan (GAG) layer on the luminal surface of the bladder, resulting in increased permeability of the underlying submucosal tissues to toxic substances in the urine
Pathogenic role of mast cells in the detrusor and/or mucosal layers of the bladder
Infection with an unknown, poorly characterised agent e.g. a slow-growing virus
Production of a toxic substance in the urine
Neurogenic hypersensitivity or inflammation mediated locally at the bladder or at spinal cord level
The symptoms may be a manifestation of pelvic floor dysfunction or dysfunctional voiding
It is also thought that PBS/IC is potentially an autoimmune disorder
1. Rovner E and Lebed B. Interstitial cystitis Overview. Accessed 11th December 2008.

17. Associated conditions
An additional problem for many patients is that PBS/IC often occurs in association with other diseases. These include:
Allergies – In a survey study in the US, 40.6% of the patients with PBS/IC stated that they suffered from allergy and in a Swedish study 41-47%. This is twice as frequent as in the general population.1
Irritable bowel syndrome (IBS). IBS occurs in 3-15% of the general population, but in the US survey mentioned above, 25% of PBS/IC patients stated that they suffered from IBS.1
Fibromyalgia. Fibromyalgia occurs in 3% of the population, and is more common in women in men. 12.8% of PBS/IC patients stated that they suffered from the condition i.e. four times more frequent than in the general population.1
Inflammatory bowel disease (IBD). 7.3% of patients stated that they suffered from IBD, one hundred times more frequent than in the general population.1
Systemic lupus erythematosus (SLE). In the USA survey, 1.7% of PBS/IC patients stated that they suffered from SLE, which is three times more frequent than in the general population.1
Rheumatoid arthritis(RA). RA occurs in about 1% of the population, but it has been estimated to occur in about 13% of classic PBS/IC patients and in 4% of patients with non-ulcerative PBS/IC.1
Sjogren’s syndrome. Sjogren’s syndrome occurs in 0.6% of the adult population and, like PBS/IC, is ten times more common in females than males. A number of features of Sjogren’s syndrome are remarkably similar to those of PBS/IC, suggesting a possible link between the two conditions.1
Sensitive skin, vulvodynia, chronic fatigue syndrome, migraine and asthma have also all been reported to be more prevalent in patients with PBS/IC, as have Crohn’s disease and ulcerative colitis.1
1. Van de Merwe J. Interstitial cystitis and associated disorders. International Painful Bladder Foundation. Accessed 13th January 2009.

18. Challenges of diagnosis
Issues related to the diagnosis of PBS/IC No
biological
markers
Restrictive
research-based
criteria
Painful
invasive
techniques
The diagnosis of PBS/IC is challenging for a number of reasons:1
Currently available diagnostic criteria were developed for research rather than clinical use. The use of these somewhat restrictive criteria has been shown to miss many patients with the condition.
Painful, invasive techniques have been used for diagnosis, which some experts believe to be inaccurate and unnecessary.
To date, there are no specific biological markers which may be employed in the diagnosis of PBS/IC.
At the present time, therefore, the diagnosis of PBS/IC tends to be based on:2
Symptoms i.e. pain, urgency, and frequency, typically lasting for more than three months.
Exclusion of any identifiable infection, disease or disorder that may cause the symptoms.
1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.
2. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.

19. NIDDK inclusion criteria
Bladder pain or urinary urgency
Glomerulations or Hunner’s ulcer on cystoscopy
Specific findings after hydrodistension
In 1987, the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK) in the United States, put forth a definition of PBS/IC to provide researchers with guidelines for selecting comparable study populations. The NIDDK criteria include 18 exclusion requirements and three inclusion requirements i.e:1,2
Pain associated with the bladder, or urinary urgency
Hunner’s ulcer, or glomerulations, on cystoscopic examination
Hydrodistension (stretching of the bladder) under anaesthesia showing diffuse glomerulations present in at least three quadrants of the bladder, with at least ten lesions per quadrant
These criteria were purposely designed to be restrictive, to ensure that only patients with clearly defined cases of PBS/IC were included in research studies. However, due to a lack of any other useful diagnostic criteria, the NIDDK criteria have been used in the clinical setting.1
One study found that use of these criteria in the clinical setting misses 60% of patients with PBS/IC. Not only are the NIDDK criteria purposely restrictive, but they may also require the use of operating-room based diagnostic procedures that are not generally necessary in the clinical setting.1
Overall, therefore, although these criteria may have some place in the research setting, the general consensus is that they are not recommended for use in diagnosing individual patients.
1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.
2. Rovner E and Lebed B. Interstitial Cystitis: Overview. Accessed 11th December 2008.

20. Components of basic assessment
Medical
History
Urine
cultures
Symptom
scales
Physical
Examination
Voiding
diary
A detailed medical history of the patient should be taken, focusing on voiding symptoms, pelvic pain or discomfort, urinary frequency and urgency, and nocturia. A general physical examination should also be carried out. Women may have a vaginal examination and men a digital rectal examination.1,2
Urine cultures should be carried out to check for bacterial infection or infectious diseases. In men, prostatic fluid may also be examined for signs of infection.2
As part of their basic assessment, patients may be asked to fill in a voiding diary, which can be an important tool in the investigation of lower urinary tract symptoms. It may range in complexity from simple records of fluid intake and urine output, to more complex diaries that include symptoms, to facilitate history-taking about the degree of frequency, nocturia and volumes voided at each episode.1,2,3
In order for a voiding diary to have value, it must be completed correctly. If the diary is too long, then compliance is likely to be poor. It is thought that day-to-day variability of the symptoms of a PBS/IC patient may compromise records spanning only a day or two, so a three-day diary has been suggested as being optimal.3
1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.
2. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
3. Parsons M and Toozs-Hobson P. The investigation and management of interstitial cystitis. Journal of the British Menopause Society. 2005; 11 (4):

21. Differential diagnosis
There are a number of conditions that must be considered in the differential diagnosis of a patient with possible PBS/IC, including:1
Urinary tract infection (UTI)
Overactive bladder (OAB)
Endometriosis
Bladder carcinoma
Drug effects: cyclophosphamide, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), allopurinol.
Clinicians should be wary of making a diagnosis of PBS/IC in patients who have OAB, or a history of recurrent UTI, unless adequate treatment of involuntary detrusor contractions (for OAB), or infection (for recurrent UTI), fails to resolve symptoms. Also, clinicians should be aware that although urgency is a common symptom of PBS/IC, it is also characteristic of OAB.1
1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.

22. Roadmap What is PBS/IC? Symptoms and impact of PBS/IC
Management of PBS/IC
Causes and diagnosis
Supporting patients

23. Management of PBS/IC Diet Oral therapy Intravesical therapy
Treatment in PBS/IC is symptom-driven, so in order to maximise the effects of any treatment strategy, it is important to determine which symptom(s) are causing the most problems, at each stage of the condition, in each individual patient. However, effective evaluation of treatment is hampered by the spontaneous flares and remission of symptoms so characteristic of PBS/IC. It is, therefore, sometimes very difficult to assess whether an improvement has been caused by the treatment itself, or simply by a spontaneous remission.1
Treatment generally begins with the most conservative methods, such as dietary changes, physical exercise and bladder training, and oral medication.1,2
In a market research survey carried out amongst urologists and gynaecologists in 2008, 64% of respondents indicated that oral therapy would be their preferred, first-line, treatment option for the management of PBS/IC, with a further 26% opting for intravesical therapy in the first instance. Urologists were almost twice as likely to use intravesical therapy first line as compared to gynaecologists (34% vs. 17%). In the same survey, 3% of respondents suggested that a combination of both oral and intravesical therapy would be their choice of initial treatment strategy, whilst 11% thought that other options such as diet, surgery, neurostimulation etc may be more appropriate.3
1. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
2. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.
3. Painful Bladder Syndrome/Interstitial Cystitis Study. Market Research Report. Medix Intelligent Information. September 2008.

24. Diet
Many patients will find that certain foods and beverages appear to exacerbate their bladder symptoms. Every patient is different, and not all PBS/IC patients appear to be affected by diet, but by eliminating items known to cause irritation based on their own experience, a patient can at least avoid unnecessary exacerbation of their bladder symptoms. Patients with milder forms of the condition may even find that diet modification is the only treatment they need.1,2
Some common substances that can trigger PBS/IC symptom flares are shown above, including:
Alcohol
Citrus fruit
Fizzy drinks
Tomatoes
Caffeine
Spicy food
1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.
2. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.

25. Pharmacological management
Epithelial insult
Activation of C fibres
Release of
Substance P
More
inflammation
Mast cell
activation;
histamine release
Epithelial
layer damage
Potassium
leak into
bladder wall
GAG-like therapies
Inhibit neurological activity
Antihistamines
Anti-inflammatory drugs
Pharmacotherapy in PBS/IC is based on three principles:1,2
Controlling a dysfunctional urothelium by restoring the GAG layer with GAG or GAG-like drugs. Other treatments may be added to it, but GAG replenishment therapy is the foundation of any treatment plan. Only this mode of therapy offers a chance to reverse the course of the disease and actually correct the underlying pathophysiology. This may be achieved through the use of oral medication e.g. pentosan polysulfate sodium (PPS), or intravesical therapy may be necessary.
Inhibiting neurological activity. Drugs such as amitriptyline, may be employed, but it should be borne in mind that these drugs suppress symptoms, while the disease process will actually be progressing.
Suppression of allergies. e.g. hydroxyzine.
1. Parsons M and Toozs-Hobson P. The investigation and management of interstitial cystitis. Journal of the British Menopause Society. 2005; 11 (4):
2. Rosenberg M, Newman D and Page S. Interstitial cystitis/painful bladder syndrome: symptom recognition is key to early identification, treatment. Cleveland Clinic Journal of Medicine. 2007; 74 (S3): S54-S62.

26. Oral therapy Amitriptyline Analgesics Antihistamines
Anti-inflammatory agents
Anticholinergics
Various oral treatments are used for the management of PBS/IC. The main advantage of such treatment is that it is easy to administer and non-invasive. However, there are also disadvantages. Absorption of the drug into the bloodstream may mean that relatively little of the active ingredient may actually reach the bladder, and there is a greater likelihood of undesirable adverse effects.1
Although many of these agents are not licensed for use in this condition, oral treatment may consist of one or more of the following (in alphabetical order):
Amitriptyline, an oral tricyclic antidepressant, is used in PBS/IC patients to regulate pain and urgency in the bladder, by modulating neuronal dysfunction. In an early study, amitriptyline provided mild to moderate pain relief in 60-90% of patients with PBS/IC. A recent placebo-controlled, double-blind study showed that this drug was safe and effective in patients with PBS/IC, for up to four months.2
Analgesics. In those cases of extreme pain that fails to respond to other therapy, long-acting opioid analgesics may be necessary e.g. tramadol, morphine. Chronic opioid therapy is usually considered to be a last resort option only.1
Antihistamines e.g. hydroxyzine. Hydroxyzine may help to support mast cell degranulation, which is part of the inflammatory process. One open-label study found that hydroxyzine reduced symptom scores, in PBS/IC patients with a history of allergies, by 55% on average. However, a subsequent randomised, controlled, trial found that the drug did not reduce global assessment scores significantly more than placebo.3
Anti-inflammatory agents e.g. corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs)1
Anticholinergics e.g. oxybutynin. These drugs may be effective in some PBS/IC patients.1
1. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
2. Rosenberg M, Newman D and Page S. Interstitial cystitis/painful bladder syndrome: symptom recognition is key to early identification, treatment. Cleveland Clinic Journal of Medicine. 2007; 74 (S3): S54-S62.
3. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.

27. Oral therapy continued
Anticonvulsants
Cimetidine
Immunosuppressive agents
Pentosan polysulfate sodium
Anticonvulsants e.g. gabapentin, pregabalin. These agents may have good results in some PBS/IC patients with severe pain, allowing them to reduce their dependence on opioid analgesics.1
Cimetidine is a histamine H2 receptor antagonist, it appears to be useful in alleviating the pain and other symptoms of some PBS/IC patients.1
Immunosuppressive agents e.g. ciclosporin. Recent small studies with low dose ciclosporin have shown that it may be effective in some patients with PBS/IC, but should only be used in the most severe cases that have failed to respond to other therapy.1
Pentosan polysulfate sodium (PPS, brand name Elmiron). This is the only oral medication currently approved by the US Food and Drug Administration (FDA) for the management of PBS/IC, but is available on an unlicensed, named-patient basis only, in the UK. PPS is believed to provide the bladder with a compound structurally analogous to the bladder GAG layer, so facilitating its replenishment. In the trials that formed the basis of FDA approval, oral PPS was found to be beneficial in 32% of PBS/IC patients, compared to 16% of placebo-treated patients. More recent, open-label studies have, however, reported greater efficacy. Patients may be slow to respond to PPS, and treatment should continue for at least six months.2,3
1. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
2. Rosenberg M, Newman D and Page S. Interstitial cystitis/painful bladder syndrome: symptom recognition is key to early identification, treatment. Cleveland Clinic Journal of Medicine. 2007; 74 (S3): S54-S62.
3. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.

28. Intravesical therapy Chondroitin sulfate Sodium hyaluronate
Dimethyl sulfoxide
There are a variety of treatments that may be used in the UK for intravesical therapy for PBS/IC, including:1
Chondroitin sulfate (Uracyst). Chondroitin sulfate is a substance that occurs naturally in the bladder GAG layer, and studies have indicated that it is effective and well-tolerated in the management of PBS/IC. Uracyst is a 2% concentration of chondroitin sulfate in a 20ml vial. This provides 400mg of chondroitin sulfate.
Chondroitin sulfate (Gepan). Gepan is a 0.2% concentration in a 40ml vial. This provides 80mg of chondroitin sulfate.
Sodium hyaluronate (Cystistat). Sodium hyaluronate is also an glycosaminoglycan, and is present in all connective tissues in the body. It is not, however, naturally present in the surface GAG layer of the bladder wall.2
Sodium hyaluronate and chondroitin sulfate (iAluRil). A combination product of the two glycosaminoglycan constituents.
Dimethyl sulfoxide (DMSO, brand name Rimso-50) is one of the most commonly used drugs for bladder instillation and is available on a named-patient basis in the UK. It is a by-product of the wood pulp industry, and appears to have anti-inflammatory, analgesic, and some muscle relaxant properties.
Intravesical therapies such as chondroitin sulfate and sodium hyaluronate have a physical action on the bladder, and are not absorbed into the bloodstream resulting in a low risk of side-effects.
1. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.
2. Hurst RE. Structure, function, and pathology of proteoglycans and glycosaminoglycans in the urinary tract. World J Urol. 1994; 12: 3-10.

29. Patient perception of intravesical therapy for PBS/IC
Agent
Total no. of patients
Improved
Made worse
No effect
DMSO
159/750 (21.2%) 59
(37.1%) 57
(35.8%) 43
(27.1%)
Cystistat
28/750
(3.7%) 15
(53.6%) 3
(10.7%) 10
(35.7%)
Heparin sodium
25/750
(3.3%) 16
(64%) 5
(20%) 4
(16%)
Seven hundred and fifty patients with a diagnosis of PBS/IC completed a computerised, internet-based survey. Amongst other parameters, the questionnaire queried each patient about their perceived treatment outcomes. Specific information was obtained on the different procedures and medications used to treat PBS/IC and whether they perceived their condition as improved, not affected or deteriorated. Data was collected over a twelve month period.1
40.1% of respondents had received intravesical therapy. The most commonly used intravesical treatments were DMSO, Cystistat and heparin. The perceived efficacy of each of these agents is summarised in the table above.1
On the whole, bladder instillations were found to be beneficial 45.3% of the time; however 27.7% of patients were made worse by the treatment and 27% felt no effect.1
It is clear by looking at these outcomes for DMSO and Cystistat (heparin sodium is not commonly used in the UK) that an alternative option for intravesical therapy would be a welcome addition.
1. Hill J et al. Patient perceived outcomes of treatments used for interstitial cystitis. Urology. 2008; 71:

30. Surgery Usually last resort Bladder augmentation Urinary diversion
Cystectomy
Pelvic pain may continue even after the bladder is removed
In some patients with PBS/IC, the problems with their bladder are so extreme that surgery remains the only option. This is usually considered a last resort for the management of PBS/IC.1
1. Meijlink M. Interstitial Cystitis diagnosis & treatment: an overview. International Painful Bladder Foundation. September 2008.

31. Roadmap What is PBS/IC? Symptoms and impact of PBS/IC
Management of PBS/IC
Causes and diagnosis
Supporting patients

32. Supporting the patient1
Be understanding of the challenges facing the patient
Reassure the patient
Explore treatment options
Support self-care
As has been covered earlier in this presentation PBS/IC can be challenging for patients due to:
Severe pain
Disruption of life due to urgency, frequency, and nocturia
Delay in diagnosis and relief of symptoms — treatments can take time to be effective
Sexual intimacy issues
Living with associated diseases
Effects on family, employment or other elements affecting quality of life
Reassure the patient:
Explain that PBS/IC is a diagnosis of exclusion and that there are no specific markers
Reassure patients that symptoms can be treated.
Discuss the importance of the medical history, patient questionnaires, and a voiding history to set baselines and track/celebrate progress
Encourage patients to ask questions and seek additional sources of information
Explore treatment options:
Explain the oral therapy options
Discuss potential side effects of oral therapy
Reassure the patient that treatment can be tailored to suit his or her specific symptoms and needs
Describe the intravesical therapy options, the advantages and the procedure used for bladder instillation
Support self-care:
Dietary advice - each patient is unique but cutting down (or out) certain foods may help symptoms
Encourage the patient to avoid using fluid restriction to reduce urinary frequency
Discuss options for stress reduction, e.g. meditation, yoga, support from other patients
Refer to physical therapy if pelvic floor dysfunction is suspected
For some patients using intravesical treatment, self-catheterisation may help with controlling symptoms and flare-ups
1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Association of Reproductive Health Professionals Clinical Proceedings. April 2008.

33. Uracyst Prescribing Information
The full Prescribing Information should be consulted prior to use.
Uracyst® Abbreviated Prescribing Information.
Description: Each ml of Uracyst contains 20mg sodium chondroitin sulfate (400mg of chondroitin sulfate per 20ml vial). Chondroitin sulfate is an acidic mucopolysaccharide and is one of the glycosaminoglycans (GAGs). The luminal surface of the bladder is coated with a layer of GAGs that provide a protective impermeable barrier to the bladder. Damage to this GAG layer may result in deficiencies to its protective barrier, inducing irritations in the bladder wall. Chondroitin sulfate is an important component of the bladder GAGs that can replenish the deficient GAG layer on the bladder epithelium.
Indications: For replenishment of the glycosaminoglycan (GAG) layer in the bladder, for patients with damaged or GAG deficient bladder epithelium.
Dosage and administration: Instil 20ml into the bladder after any residual urine has been removed. For optimum results, Uracyst should be used full strength without dilution, and retained in the bladder as long as possible (not less than 30 minutes). Repeat the instillation of 20ml weekly for 4 to 6 weeks, then, monthly thereafter until symptoms are relieved. Most patients benefit from 6 weekly 20ml instillations, then monthly instillations thereafter depending on their symptomatic response.
Contraindications: Do not administer to patients with known hypersensitivity to the solution.
Warnings: For Bladder Instillation only. Uracyst contains neither preservatives nor antimicrobials; therefore, any unused portion must be discarded.
Precautions: Bring the contents of vial to room temperature before use.
Adverse effects: No known adverse effects. Short-term discomfort may be caused by the catheterisation process.
Legal category: Medical device.
CE Number: CE 0473.
CE Mark Holder: Stellar Pharmaceuticals Inc, 544 Egerton Street, London, Ontario, Canada N5W 3Z8.
Package quantities and price: Single-dose glass vial of 20ml. Packages of four: £260 (UK), €300 (Ireland).
Storage: Store 2 to 25oC. Do not freeze. Discard unused portions. Distributed by: Galen Limited. Date of preparation: May 2009.
Galen Limited, Seagoe Industrial Estate, Craigavon, BT63 5UA. Galen Ireland, c/o Allphar Services Ltd, 4045 Kingswood Road, Citywest Business Park, Co Dublin, Ireland. Telephone: +44 (0) Fax: +44 (0) Website:
Adverse incidents should be reported. Reporting forms and information can be found at or Adverse incidents should also be reported to Galen Limited on +44 (0) and select the customer services option, or Medical information enquiries should also be directed to Galen Limited.