Mamagement competition

Management of IBS

Keys to treatment of IBS

Education/reassurance

Lifestyle/diet modification

Communication between patient and physician

Appropriate drug therapy

Follow-up with patient

Adjustment of therapy if necessary

Patient education in IBS

Education and reassurance are essential elements of clinical management

Patients need information about the nature of their condition, such as its high prevalence, the causes and symptoms

Patients should be made aware of the available treatment options, e.g. pharmacologic andnon-pharmacologic therapies

Dietary and lifestyle modification

Stress management/reduction techniques have been shown to improve patient well-being1

Diet diaries may be used to identify dietary factors that tend to trigger IBS symptoms

– elimination or reduction in intake of these foods may reduce the frequency and severity

of symptoms2

1Leahy A et al. J R Coll Physicians London 1988;32:552–62Burden S. J Hum Nutr Diet 2001:14:231–41

Drugs for individual symptoms in IBS

Abdominal pain Bloating Altered bowel motility

Anticholinergic/ anti-–spasmodics

Tricyclic antidepressants

Selective serotonin reuptake inhibitors

Antispasmodics

Antiflatulents

Loperamide

Cholestyramine

Psyllium

Methylcellulose

Calcium polycarbophil

Lactulose

70% sorbitol

Polyethylene glycol solution

Serotonergic agents (e.g. tegaserod, alosetron)

Psychologic treatments for IBS

Some patients with IBS may also benefit from

– referral to a psychologist or psychiatrist

– hypnotherapy

– biofeedback

– psychodynamic therapy

– stress management/relaxation

– cognitive behavioural programs

Drossman DA et al. The Functional GI Disorders, 2000

A comprehensive multi-component approach

Treatment program is based on dominant symptoms and their severity, and on psychosocial factors

Medication directed at the predominant symptoms

Diet/lifestyle modifications

Psychologic or behavioural options– psychotherapy– stress management

Complementary/alternative therapies

AGA medical position statement: Irritable Bowel Syndrome, 2002

Levels of evidence and grading of recommendations

Level I: high-quality randomized clinical trials

– Grade A recommendation

Level II: intermediate quality randomized clinical trials

– Grade B recommendation

Level III–IV: evidence from non-randomized trials or case studies

– Grade C recommendation

ACG Functional GI Disorders Task Force. Am J Gastroenterol 2002;97:S1–S26

Recommendations on traditional approaches

Antispasmodic agents: (Grade B recommendation)– overall, trials were of short duration, suboptimal quality and

demonstrated inconsistent effectiveness– antispasmodics should be used with caution in patients with

constipation

Bulking agents: (Grade B recommendation)– overall, trials contained small numbers of patients and were of

suboptimal quality

– fiber has been shown to exacerbate common IBS symptoms (gas, bloating, abdominal discomfort)

– fiber is appropriate treatment for the treatment of constipation, but may not be recommended for the treatment of IBS


Recommendations on traditional approaches (cont’d)

Tricyclic antidepressants: (Grade B recommendation)

– overall, trials were of short duration, enrolled small numbers of patients, and were of suboptimal design

– the evidence is inadequate to support the effectiveness of TCAs for the improvement of global IBS symptoms

– there is limited evidence that TCAs may decrease abdominal pain

– TCAs may cause constipation and should be used with causation in IBS patients with constipation


Recommendation on tegaserod

Tegaserod: (Grade A recommendation)

– overall, tegaserod trials consistently demonstrated high quality study methodology and effectiveness for the treatment of IBS with constipation


THE IBS Market

Review

Defining an IBS Market

Many drugs prescribed Prescription data not available in all countries Created market (antispamodics + Laxatives)

Rationale behind the antispamodics

Relax smooth muscle of the colon Used with symptom of pain- May be used for the symptom of diarrhea

Antispasmodic drugs

Anticholinergic Muscle Relaxants Calcium channel blockers

Anticholinergic: Buscopan Hyoscine- B.Ingelheim

Advantages: Well established OTC use- cheap Well known Used in many indications

including dysmenorrhea Promoted by BI

Disadavantages Dry mouth Blurred vision May affect heart rhythm

Antispasmodic /Anticholinergic : Librax (clindinium+ chlordiazepoxide)

Advantages: Effective on the pain Well-established Inexpensive Generic forms available

Disadvantages Side effect profile (dry mouth

dizziness ) Constipation

Controlled prescription

Smooth Muscle relaxant: mebeverine

Duspatalin is the second most widely used drug on the market in UAE and Lebanon

Duspatalin from Solvay: number one brand in portfolio in Lebanon-

Number 2 in Portfolio in UAE

Duspatalin -Solvay

Present indication Symptomatic treatment of abdominal pain and discomfort and cramps, bowel disturbances and intestinal discomfort associated with IBS.

Planned indication NA

Formul./dosages 135mg (30 tabs) t.id200mg (30 tabs) given twice dailySyrup 10mg/ml available for children

PositioningKey Messages

Reminder detailing – sampling etc…

Others High on services to key customers – pharmacist deals

Overview:

Duspatalin

Advantages Relatively inexpensive Well- established Long term relationship in GI

field –supporting portfolio Sold directly from the

pharmacy Mainly sold through pharmacy

deals

Disadvantages Old No new supporting data Grade B –according to ACG Only provides relief of one

symptom – pain Not highly effective Doctors level of satisfaction May cause constipation in

some cases

Calcium channel Blockers: Dicetel pinaverium bromide (Solvay)

Advantages: Treatment of pain May reduce intestinal spasms Solvay is still active in GI field

Disadvantage: May reduce response to food

in the colon Not effective in C-IBS

Muscle relaxants and CCB’s- last note

A recent review of 26 controlled clinical trials on muscle relaxant and CCB’s:

Improve the pain

No effect on constipation No effect on the bloating

Laxative: A6

Key laxatives used in Lebanon and UAE: Duphalac (Lactulose) Solvay Dulcolax (Bisacodyl) BI

Laxatives –in general

Advantages Inexpensive Direct relief Natural alternative

Disadvantages May cause cramps and pains Development of tolerance Loss of fluids in most cases May cause flatulence

TCA & SSRI TCA & SSRI rationale & effectiveness rationale & effectiveness

Psychological co-morbidity Psychological co-morbidity

Major depressionMajor depression History of abuse (physical, sexual)History of abuse (physical, sexual) Serious impairment of daily functionSerious impairment of daily function somatizationsomatization

Multiple organs symptomsMultiple organs symptoms

Numerous specialists consultationsNumerous specialists consultations

Antidepressants - side effectsAntidepressants - side effects

Drug Main side effects

Tryptizol, Saroten: amitriptyline MSD/ Lundbeck

Sedation,orthostasis,dry mouth,constipation

Tofranil Imipramine Novartis

Diaphoresis, dry mouth, orthostasis

PROZAC: Fluoxetine E.Lilly cramping, mild hyperactivity, diarrhea

Faverin:Fluvoxamine Solvay Weight gain, hyperactivity, diarrhea

Zoloft: Sertraline Pfizer Mild hyperactivity, nausea

TCA & SSRI - DoseTCA & SSRI - Dose

Found to increase transit time Given in lower than usual doses

Ex- Prozac psychiatric dose is 10-20 mg , dose in IBS 5mg

No indication for these drugs but used off label –

Reality check: would you like to take a psychiatric drug for a problem in your gut?

FOR YOUR INFORMATION

The Story of Lotronex from GSK

This drug is alosteron introduced in few markets for D-IBS.

This drug is a 5 HT3 antagonist

Serious side effects: withdrawn in 2001 Severe constipation, ischemic colitis

The Story of Pruplsid (Gastroprokinetic)cisapride (J.Cilag)

5HT4 agonist and 5 HT3 Antagonist (weka) Indicated in GERD Used off- label in D-IBS

Caused QT prolongation - withdrawn

Documents

Mamagement competition