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Top Clinical Tips for Inflammatory Bowel Disease
Dr Ayesha Akbar Consultant Gastroenterologist Honorary Senior Lecturer
Job bag number: UK/AS/0165/07-13 Date of preparation: July 2013
Contents-focus on UC
Case study
Tests and history
Background
Treatment in relation to ECCO consensus
Data from 5-ASA studies
Summary
Case study
24 year old female
Presents with 5 week history of bloody diarrhoea
Mild weight loss
What do you want to ask?
What tests would you do?
What is the differential diagnosis?
History
Foreign travel
Antibiotic usage
Recurrent diarrhoea
Extra-intestinal manifestations
Family History
Smoking history
NSAIDs
Tests
Bloods
– FBC/haematinics
– CRP
– LFTs and albumin
– U&Es
Stool MC&S including CDT
?Faecal calprotectin
AXR if any tenderness or USS
Flexible sigmoidoscopy
Differential diagnoses
Post infective
Ulcerative colitis (or Crohn’s colitis)
Ischaemic colitis
Diverticulitis
Cancer
The Spectrum of Inflammatory Bowel Disease (IBD)
Ulcerative
colitis
Diarrhea
Abdominal pain
Relapsing course
Anemia
Extraintestinal
manifestations
Adapted from Satsangi J, et al. Inflammatory Bowel Diseases. Churchill Livingstone, 2003.
Crohn’s
disease
Indeterminate
colitis
Stenoses
Fistulae
Granuloma
Deep abscesses
Extracolonic
involvement
ASCA
Bloody
diarrhea
Continuous
involvement
pANCA
Mucosal
inflammation
Pathophysiology of IBD
Shanahan F, et al. Gastroenterology. 2001;120:622-635.
Genetic
Susceptibility
Environment
(microflora)
Host
(immune)
Response Inflammation
UC IL-5, IL-10
Crohn’s IL-1, IL-12,
TNFα, IFN-γ
Epidemiologic Risk Factors
UC CD
Appendectomy1 Negative (protective)
None
Smoking2 Negative Positive
Oral contraceptive use2 Questionable Positive
Breast feeding/adverse perinatal events2
Questionable Questionable
High level of sanitation in childhood2
Questionable Positive
1Koutroubakis I, et al. Inflamm Bowel Dis. 2002;8:277-286; 2Koutroubakis I, et al. Hepatogastroenterology.
1996;43:381-393.
Ulcerative Colitis Pathology
Confluent disease, beginning above the anus
Limited to mucosa
Never involves small bowel (backwash ileitis)
Rarely involves the anus
Ulcerative colitis
Ulcerative Colitis Symptoms
Rectal bleeding
Passage of mucus
Diarrhoea
– frequency
– consistency
Urgency
– incontinence
Abdominal cramping / pain
– usually related to bowel opening
Ulcerative Colitis Anatomical Extent
Proctitis
40%
Left sided
colitis 5%
Substantial 10%
Extensive
20%
Extends from just above anus
Procto-sigmoiditis
25%
Ulcerative Colitis Symptoms and Relationship to Extent
Proctitis
Extensive disease
Rectal blood and mucus, urgency
Loose motions, severe pain
Extent may vary with time
Extent defines treatment and cancer risk
Ulcerative Colitis Diagnosis
Establish diagnosis rigid or flexy sigmoidoscopy
Determine severity rigid or flexy sigmoidoscopy
Determine extent colonoscopy if needed
Caution with colonoscopy in very acute disease
If need to decide extent with severe disease, use
instant enema
Ulcerative Colitis Natural History
Relapsing - remitting course (90%)
– always exclude infection: stool for CDT
– extent usually constant
– presentation usually similar
Rarely severe colitis or toxic dilatation (10%)
Colectomy rate greatest initially
– first year 10%
– first 10 years 25%
Extra-Intestinal Manifestations Are Common in IBD Patients
Ocular inflammation 2%–13%
Oral ulceration 20%–30%
Satsangi J, et al. Inflammatory Bowel Diseases. Churchill Livingstone; 2003:669-684.
Ankylosing spondylitis 1%–6%
Peripheral arthritis 10%–20%
Erythema nodosum 6%–15%
Pyoderma gangrenosum 0.5%–2%
Inflammatory Bowel Disease Extra-intestinal Manifestations - Skin
Pyoderma gangrenosum
Inflammatory Bowel Disease Extra-intestinal Manifestations - Skin - Erythema nodosum
Inflammatory Bowel Disease Extra-intestinal Manifestations - Joints Large joint inflammation
– usually only one joint
– disease activity related
Polyarthropathy
– peripheral joints
– independent of disease activity
Sacroiliitis and ankylosing spondylitis
– “stiff back”
– independent of disease activity
Inflammatory Bowel Disease Extra-intestinal Manifestations - Eyes
Anterior uveitis, episcleritis, conjunctivitis
– independent of disease activity
– all cause painful, gritty red eye
Inflammatory Bowel Disease Extra-intestinal Manifestations - Liver Minor abnormalities of LFTs in 50%
Fatty liver in severe relapses
Chronic autoimmune hepatitis in 2.5%
Gallstones in 30%
Primary sclerosing cholangitis in 2.5%
– Progressive inflammatory disorder of biliary system
Cholangiocarcinoma in 0.1%
Inflammatory Bowel Disease Extra-intestinal Manifestations - Other
Thrombo-embolic disease
– especially in smokers, bed-bound, septic
– need maximal prophylactic anticoagulation
Amyloidosis
– rare
– terminal event
Osteoporosis...
Osteoporosis in IBD
Disease activity leads to loss of bone density
DEXA scanning osteopaenia T score (healthy controls) >1 s.d.
below mean
Osteoporosis T score >2.5 s.d. below mean
Osteoporosis in IBD Contributory factors
disease activity
steroid treatment
impaired Vitamin D and calcium absorption (especially Asians)
smoking (especially women)
sex hormone deficiency
malnutrition
genetic factors
Osteoporosis in IBD At-risk Patients
History of fractures
Recurrent courses of steroid
Postmenopausal with > 1 course steroid per year
T score below -1
Osteoporosis in IBD Treatment
Exclude osteomalacia (blood tests)
Check Calcium and Vit D levels
– if low, best is Calcium and Vit D supplements
– if normal, best is a bisphosphonate
– HRT of little value
Check bone density every 2 years
Prevention
Prognosis Ulcerative Colitis
75% relapsing-remitting
– 10% only one episode
20% chronic active
5% fulminant
Ulcerative Colitis Cancer Risk
Site of disease Risk vs generalpopulation
Distal X 1.5
Left-sided X 4
Total X 19
All patients X1.5
Population risk 1 in 30 for colorectal cancer
Ulcerative Colitis Cancer Risk
Risk greatest if
– disease more than 8 years
– disease greater than left-sided
– coexisting sclerosing cholangitis
– coexisting bowel polyps
– family history of colorectal cancer
Surveillance
– after 8 years if extensive disease or any of the above with less disease
– if find high-grade dysplasia, consider colectomy
Surveillance
BSG:
UC-pancolitis after 8 years; left sided
After 10 years
Annual if high risk e.g. PSC
3 years moderate risk
5 years in low risk
Corticosteroids have serious side effects (long-term)
Osteoporosis
Cataracts/glaucoma
Higher risk of infections
Growth retardation
Oedema/Cushing syndrome
Behavioral changes
Striae
Diabetes
Mild to moderate UC
Treat with 5-ASA-in flare escalate dose
Rule out infection-stool MC&S
Consider topical therapy
Lack of response at 14 days, consider steroids-use reducing regime. 30mg/day for 1 week; reduce by 5mg/day to zero
Concomitant Calcichew D3 (calcium carbonate, colecalciferol) with steroids
Benefits of St Mark’s hospital
Diagnosis
Patient education
Patient support-3 excellent IBD nurses at St Mark’s
Fast access if flare
Complex cases-weekly IBD MDM
Clinical trials-refractory patients
Multi disciplinary team-nutrition/surgeons
Weekly IBD MDM
Patient pathway Established diagnosis
Treat in community with increased 5-ASA dose (IBD
nurse support)
Mild to moderate flare
Resolution of symptoms
Failure of resolution after 10-14 days or worsening
symptoms
Hospital review
Job Number: UK/AS/0192/11-11. Date of preparation: January 2012. Job Number: UK/AS/0027/02-13. Date of preparation: February 2013. .
Management of moderately active ulcerative colitis (UC)
Prescribing information can be found at the end of this presentation.
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
What do patients need from their UC treatment?
• Fast symptom relief, among other attributes, is important to patients.
• Evidence shows that patients consider fast relief, relief from rectal bleeding, constant relief and prevention of flare to be among the most important attributes of treatment.
• In the most recent ECCO1 guidelines, it states that: • 10–14 days is a suitable time-point at which to assess
improvement in rectal bleeding, in line with one of the key treatment goals for patients.
• If rectal bleeding persists beyond 10–14 days, then the response can be said to be slow and therapy augmented.
1. Dignass A et al. J Crohn's Colitis 2012, http://dx.doi.org/10.1016/j.crohns.2012.09.002
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
What do patients want from their UC treatment?
• Overall, efficacy and safety-related attributes were more important to patients than those related to dosing regimen, cost and formulary coverage.1
Patient preference survey: treatment-related attributes rated by importance* (n=100)1
1. Gray et al. Aliment Pharmacol Ther 2009; 29: 1114-1120. 2. Data on file.
0
20
40
60
80
100
Patient preference survey attribute
Pa
tien
ts (
%)
Provides relief of
rectal bleeding
94%
Provides
consistent relief
94%
Prevents a
flare of UC
93%
Provides
fast relief
89%
*Percentage of patients rating attributes of 4 or 5 out of 5 on a scale of
importance, with 5 being most important
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
The ASCEND trials evaluated Asacol® (mesalazine) in patients with moderately active UC
• The ASCEND clinical trials (ASCEND I, II and III) are the only trials that have specifically evaluated Asacol® (mesalazine) in patients with moderately active UC1-3
• Other studies investigating the treatment of mesalazine have
combined mild and moderate UC populations4,5
1. Hanaeur SB et al. Can J Gastroenterol 2007; 21: 827–834. 2. Hanaeur SB et al. Am J Gastroenterol 2005; 100: 2478–2485.
3. Sandborn WJ et al. Gastroenterol 2009; 137: 1934–1943 e1931–1933. 4. Marteau P et al. Gut 2005; 54: 960–965.
5. Sandborn WJ et al. Aliment Pharmacol Ther 2007; 26: 205–215.
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
Time at which 50% of patients (median time) achieve symptom improvement* with Asacol® 800 mg MR tablets at 4.8 g/day
Symptom improvement
*Symptom improvement: a decrease of at least 1 point for rectal bleeding and stool frequency symptom score from
baseline
7
4
4
0 2 4 6
Both
Improvement of
stool frequency
Improvement of
rectal bleeding
Median time to symptom improvement (days)
n=161
n=160
n=133
Adapted from Orchard TR et al. Alim Pharmacol Ther 2011: 33(9); 1028-1035.
8
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
Time at which 50% of patients (median time) achieve symptom resolution* with Asacol® 800 mg MR tablets at 4.8 g/day
*Symptom resolution: cessation of rectal bleeding and normalisation of stool frequency
Symptom resolution
19
12
9
0 5 10 15 20
Both
Normalisation of
stool frequency
Absence of
rectal bleeding
Median time to symptom resolution (days)
n=161
n=160
n=133
Adapted from Orchard TR et al. Alim Pharmacol Ther 2011: 33(9); 1028-1035.
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
In the PINCE trial, 37% of patients responded to oral treatment alone within 2 weeks1
• Remission included patients who had some UC symptoms
(UC-DAI scores <2)2
1. Marteau P et al. ECCO, Feb 2010, Prague 2010; Abstract P122. 2. Marteau P et al. Gut 2005; 54 :960–965.
Pro
po
rtio
n o
f p
atie
nts
(%
)
0
20
40
60
80
30%
33%
37%
63%
Remission Improvement
P=0.842
P=0.032
100
Data from a post hoc analysis of efficacy at 2 weeks of the PINCE trial; patients with extensive mild to moderately active UC, N=127. The Intent to Treat (ITT) population consisted of 116 patients, who received at least one dose of study drug and had at least one efficacy evaluation after baseline.1,2
4 g/day oral Pentasa® (mesalazine) sachets plus 1 g mesalazine enema (n=63)
4 g/day oral Pentasa® (mesalazine) sachets plus placebo enema (n=53)
Remission = UC-DAI score of < 2
Improvement = a decrease in
UC-DAI of ≥ 2 points from
baseline
UC-DAI, ulcerative colitis
disease activity index
Job Number: UK/AS/0192/11-11. Date of preparation: January 2012. Job Number: UK/AS/0027/02-13. Date of preparation: February 2013. .
Mucosal healing
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
UC therapy should restore/maintain the bowel mucosa integrity as well as control symptoms1
• Published peer-reviewed papers recommend incorporating mucosal healing (along with symptom resolution) into the primary endpoints of therapeutic studies in mild to moderately active UC2,3
• The UC-DAI and the Mayo Score of Endoscopic Disease include clinical measures of UC as well as endoscopic measures3
1. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678. 2. D’Haens G et al. Gastroenterol 2007; 132: 763–786.
3. Lichtenstein GR et al. Inflamm Bowel Dis 2010; 16: 338–346. 4. Sutherland LR et al. Gastroenterol 1987; 92: 1894–1898.
5. Schroeder KW et al. N Eng J Med 1987; 317:1625–1629.
Score UC-DAI endoscopy score4 Mayo Score of Endoscopic Disease5
0 Normal Normal or inactive disease
1
Mild disease Mild friability
Erythema, decreased vascular pattern, mild friability
2
Moderate disease Moderate friability
Marked erythema, absent vascular pattern, friability and erosions
3
Severe disease Spontaneous bleeding and exudation Spontaneous bleeding, ulceration
UC-DAI, ulcerative colitis disease activity index
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
In ASCEND I and II, Asacol® demonstrated mucosal healing in 80% of patients by week 6
n=156
1. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678.
Defined by the Mayo Score of
Endoscopic Disease:
Mucosal healing = endoscopy
score of 0 or 1
Complete mucosal healing =
endoscopy score of 0
4.8 g/day Asacol® 800 mg MR tablet
• Mucosal healing was apparent across all disease extents (proctitis, proctosigmoiditis,
left-sided colitis and pancolitis; 73–86%)
Mucosal healing
80%
Pro
po
rtio
n o
f p
atie
nts
(%
)
0
20
40
80
60
100
Data from a post hoc analysis of combined ASCEND I and II data in patients with moderately active UC receiving 4.8 g/day Asacol® 800 mg MR tablets, N=213. This analysis included patients with an endoscopy subscore of ≥2 at baseline (N=182).
32%
Complete mucosal healing
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
Mucosal healing demonstrated across all disease extent
• Mucosal healing is becoming an objective marker for stable disease response1
1. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678.
73% (n=37)
79% (n=24)
Pancolitis Left-sided colitis Proctosigmoiditis Proctitis
86% (n=35)
82% (n=57)
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
Mezavant XL® (mesalazine) treatment for up to 8 weeks led to complete mucosal healing in 32% of patients
1. Kamm MA et al. Gastroenterol 2007; 132: 66–75. 2. Sandborn WJ et al. Aliment Pharmacol Ther 2007; 26: 205–215.
Complete
mucosal healing =
Modified UC-DAI
sigmoidoscopy
score of 0
• Patients with ulcerative proctitis (extent of inflammation 15 cm or less from the anus) were
excluded from these studies2
Data from a post hoc analysis of two 8-week randomised, double-blind, placebo-controlled trials of Mezavant XL®
in mild to moderately active UC, N=1742
4.8 g/day Mezavant XL® 1.2 g tablet
4.8 g/day Mezavant XL® 1.2 g tablet
Complete Mucosal Healing
32%
Pro
po
rtio
n o
f p
atie
nts
(%
)
0
20
40
80
60
100
UC-DAI, ulcerative
colitis disease
activity index
Data from an 8-week randomised, double-blind, placebo-controlled trial of Mezavant XL® in mild to moderately active UC, N=851
Pro
po
rtio
n o
f p
atie
nts
(%
)
0
20
40
80
60
100
Endoscopic
Remission =
Modified UC-DAI
sigmoidoscopy
score of ≤1 (with a
≥1-point decrease
from baseline) and
no mucosal
friability
UC-DAI, ulcerative
colitis disease
activity index
78%
36%
Endoscopic remission
(all patients; n=85)
Clinical & Endoscopic remission
(patients with moderately active disease; n=50)
Job Number: UK/AS/0192/11-11. Date of preparation: January 2012. Job Number: UK/AS/0027/02-13. Date of preparation: February 2013. .
Maintenance of Remission
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
The majority of patients with quiescent UC remain in remission at 12 months with Asacol® 800 mg MR tablets at
2.4 g/day in divided doses1,2
1. Hawthorne AB et al. Inflamm Bowel Dis 2012; 18: 1885–93.
2. Hawthorne AB et al. Poster presented at the British Society of Gastroenterology, Glasgow, UK. June 2013 (PTU-058)
Maintenance of remission at 1 year (per protocol population)
64%
80%
0%
20%
40%
60%
80%
100%
Once daily Three times daily
Pro
po
rtio
n (
%)
of
pat
ien
ts
46/72 63/79
p=0.03
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
Summary
• The majority of UC patients experience moderate to highly active disease within the first year of diagnosis.1
• Moderate disease should be distinguished from mild disease.2
• ECCO suggests that escalation of therapy should be considered for patients
in whom rectal bleeding persists beyond 10–14 days of treatment initiation.3
• In patients with moderately active disease, high-dose Asacol® (4.8 g/day)
provides: – Symptom improvement at 2 weeks in 73% of cases4
– Mucosal healing at 6 weeks in 80% of cases overall, across all disease extents (proctitis to pancolitis)5
1. Langholz E et al. Scand J Gastroenterol 1991; 26: 1247–1256. 2. Stange EF et al. J Crohn’s Colitis 2008; 2: 1–23.
3. Travis SPL et al. J Crohn’s Colitis 2008; 2: 24–62. 4. Orchard TR et al. Aliment Pharmacol Ther 2011; 33: 1028–1035.
5. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678.
ECCO, European Crohn's and Colitis Organisation
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
Summary
• Complex patients- surgical/medical discussion; IBD MDM
• Always involve patient
• Nutrition
Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.
Combined Abbreviated Prescribing Information: Asacol 400mg MR Tablet, Asacol 800mg MR Tablet, Asacol 250mg and 500mg Suppositories and Asacol Foam Enema
Presentation: Asacol 400mg MR Tablets, PL 10947/0011; each modified release tablet contains 400mg mesalazine (5-aminosalicylic acid). Bottles of 120, £39.21. Bottles of 90, £29.41. Asacol 800mg MR Tablets, PL 10947/0012; each modified release tablet contains 800mg mesalazine (5-aminosalicylic acid). Bottles of 180, £117.62. Asacol 250mg Suppositories, PL 10947/0013, each containing 250mg mesalazine. Packs of 20, £4.82. Asacol 500mg Suppositories, PL 10947/0014, each containing 500mg mesalazine. Packs of 10, £4.82. Asacol Foam Enema, PL 10947/0015, 1g mesalazine per metered dose. Carton containing can of 14 metered doses, 14 disposable applicators and 14 disposable plastic bags, £26.72.
Indications: Ulcerative colitis: Treatment of mild to moderate acute exacerbations. Maintenance of remission. Suppositories particularly appropriate for distal disease, Foam Enema for distal colon disease only. 400mg Tablets, 800mg Tablets, Suppositories: Maintenance of remission. 400mg Tablets and 800mg Tablets only: Crohn's ileo-colitis: Maintenance of remission.
Dosage and administration: ADULTS: 400mg Tablets: Acute disease: 6 tablets a day, in divided doses, with concomitant corticosteroid therapy where clinically indicated. Maintenance therapy: 3 to 6 tablets a day, in divided doses. 800mg Tablets: Mild acute exacerbations of ulcerative colitis: 3 tablets a day in divided doses. Moderate acute exacerbations of ulcerative colitis: 6 tablets a day in divided doses. Maintenance of remission of ulcerative colitis: Up to 3 tablets a day, once daily or in divided doses. Maintenance of remission of Crohn’s ileocolitis: Up to 3 tablets a day in divided doses. Suppositories: 250mg: 3 to 6 a day, in divided doses, with the last dose at bedtime. 500mg: A maximum of 3 a day, in divided doses, with the last dose at bedtime. Foam Enema: 1 (disease of rectosigmoid region) or 2 (disease of descending colon) metered doses as single daily dose for 4-6 weeks. ELDERLY: The normal adult dosage may be used unless renal function is impaired. CHILDREN: 800mg Tablets: Not recommended. 400mg Tablets, Suppositories, Foam Enema: No dosage recommendation.
Contra-indications: A history of sensitivity to salicylates or renal sensitivity to sulfasalazine. Confirmed severe renal impairment (GFR <20ml/min). 400mg Tablets, Suppositories and Foam Enema only: Children under 2 years of age. 800mg Tablets only: Hypersensitivity to any of the ingredients. Severe hepatic impairment. Gastric or duodenal ulcer, haemorrhagic tendency.
Precautions: Use in the elderly should be cautious and subject to patients having a normal renal function. Asacol should be used with extreme caution in patients with confirmed mild to moderate renal impairment. Renal function should be monitored (with serum creatinine levels measured) prior to start of treatment, and periodically during treatment, taking into account individual history & risk factors. Mesalazine should be discontinued if renal function deteriorates. If dehydration develops, normal fluid & electrolyte balance should be restored as soon as possible. Serious blood dyscrasias (some with fatal outcome) have been very rarely reported with mesalazine.
Haematological investigations including a complete blood count may be performed prior to therapy initiation, during therapy, and are required immediately if the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat. Stop treatment if suspicion or evidence of blood dyscrasia. Concurrent use of other known nephrotoxic agents, e.g. NSAIDs & azathioprine, may increase risk of renal reactions. 400mg Tablets and 800mg Tablets: Lactulose or similar preparations which lower stool pH should not be concomitantly administered. 400mg tablets, Suppositories, Foam Enema: Only use during pregnancy if benefits outweigh the risk. Avoid during lactation unless essential. 800mg Tablets only: Mesalazine should be used with caution during pregnancy and lactation when the potential benefit outweighs the possible hazards in the opinion of the physician. If neonate develops suspected adverse reactions consideration should be given to discontinuation of breast-feeding or discontinuation of treatment of the mother. Discontinue treatment immediately if acute symptoms of intolerance occur including vomiting, abdominal pain or rash. Patients with the rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine because of the presence of lactose monohydrate. Standard haematological indices (including the white cell count) should be monitored repeatedly in patients taking azathioprine, especially at the beginning of such combination therapy, whether or not mesalazine is prescribed.
Undesirable Effects: Common: Nausea, diarrhoea, abdominal pain, headache. Rare reports of leucopenia, neutropenia, agranulocytosis, aplastic anaemia, thrombocytopenia, peripheral neuropathy, pancreatitis, abnormalities of hepatic function and hepatitis, myocarditis, pericarditis, alopecia, lupus erythematosus-like reactions and rash (inc. urticaria), drug fever, interstitial nephritis and nephrotic syndrome with oral mesalazine treatment, usually reversible on withdrawal. Renal failure has been reported. Suspect nephrotoxicity in patients developing renal dysfunction. Very rarely, mesalazine may be associated with exacerbation of the symptoms of colitis, Stevens Johnson syndrome & erythema multiforme. 400mg Tablets, Suppositories, Foam Enema: Rare reports of allergic and fibrotic lung reactions. 800mg Tablets only: Common: vomiting, arthralgia / myalgia. Rare reports of vertigo, bronchospasm, eosinophilic pneumonia, bullous skin reactions. Very rarely, interstitial pneumonitis. Suppositories, Foam Enema: Rarely, local irritation may occur after use of rectal dosage forms of mesalazine.
Legal category: POM. Marketing Authorisation Holder: Warner Chilcott UK Ltd, Old Belfast Road, Millbrook, Larne, County Antrim, BT40 2SH, UK. Asacol is a trademark. Refer to Summary of Product Characteristics before prescribing.
Date of preparation April 2013
Job Bag Number: UK/AS/0095/04-13
Please refer to the SPC before prescribing, particularly in relation to side effects, precautions and contraindications
Adverse events should be reported
Reporting forms and information can be found at www.mhra.gov.uk/yellowcard
Adverse events should also be reported to Warner Chilcott UK Ltd on 0800 0328701
Combined Abbreviated Prescribing Information