Israel - English - Ministry of Health
Patient leaflet in accordance with the Pharmacists' Regulations (Preparations) - 1986
This medicine is dispensed with a doctor’s prescription only
mesalazine (5-aminosalicylic acid) 400 mg/tablet
mesalazine (5-aminosalicylic acid) 800 mg/tablet
Inactive ingredients and allergens: see section 2 ‘Important information about some of this
medicine’s ingredients’ and section 6 ‘Additional information’.
Read the entire leaflet carefully before you start using this medicine.
contains concise information about this medicine. If you have any further questions, consult
your doctor or pharmacist.
This medicine has been prescribed to treat your illness. Do not pass it on to others. It may
harm them, even if it seems to you that their illness is similar to yours.
1. What is this medicine intended for?
This medicine is intended for treating ulcerative colitis (acute exacerbation of colitis) and
Crohn’s disease (acute episodes) and for preventing recurrent episodes of ulcerative colitis.
2. Before using this medicine
Do not use this medicine if:
You are sensitive (allergic) to the active ingredient or to any of the other ingredients
in this medicine (listed in section 6 ‘Additional information’)
You are sensitive (allergic) to salicylates such as aspirin
You have severe kidney problems
You have severe liver problems
Children under two years old
Special warnings about using this medicine
Before starting treatment with Asacol, tell the doctor if:
- you have ever had any problems with your liver or kidneys, particularly if you are elderly
- you have any problems with the lungs, such as asthma
- you suffered an allergy to sulfasalazine in the past
- you have ever had allergic reactions of your heart such as inflammation of the heart muscle
or heart sac. If you have had previous allergic reactions of your heart that may have been
caused by mesalazine, do not take Asacol. You can take Asacol under supervision if you
have had a previous allergic reaction of the heart that was not caused by mesalazine.
- you have an ulcer of the stomach or intestine, you may take Asacol under supervision.
Kidney stones may develop with use of Asacol. Symptoms may include pain in the sides of
your abdomen and blood in your urine. Take care to drink sufficient amount of liquid during
treatment with Asacol.
Children and adolescents:
The safety and efficacy of Asacol tablets in children have not
been fully established.
Tests and follow-up
Before and during use of this medicine, your doctor may want to monitor you from time to
time, to check that your liver, kidneys, blood and lungs are all right.
There have been a few reports of intact tablets in the stool. What appear to be intact tablets
may sometimes be the remains of the tablet coating. If you often observe tablets or tablet
coating in the stool, you should consult your doctor.
Other medicines and Asacol
If you are taking or have recently taken other medicines, including nonprescription
medications and dietary supplements, tell your doctor or pharmacist.
your doctor or pharmacist if you are taking:
- medicines that affect the immune system such as azathioprine, 6-mercaptopurine, or
- medicines that prevent the formation of blood clots (anticoagulants such as warfarin)
Using this medicine and food
Take the medicine before meals. You may eat and drink normally (including alcohol), during
treatment with this medicine.
Pregnancy, breastfeeding, and fertility:
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a
baby, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines:
This medicine is not expected to affect your ability to drive or operate machines.
However, if you are affected in anyway, do not drive or operate machines.
Important information about some of this medicine’s ingredients
This medicine contains lactose (milk sugar).
Patients who are intolerant to lactose should note that this medicine contains a small amount
of lactose. If your doctor has told you that you have an intolerance to certain sugars, consult
your doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, i.e. is essentially
3. How to use this medicine?
Always use this medicine according to your doctor's instructions. Check with your doctor or
pharmacist if you are not sure about your dose or about how to take this medicine. Only your
doctor will determine your dose and how you should take this medicine.
The usually recommended dosage in adults is:
To treat ulcerative colitis:
Mild active disease: 2.4 grams (6 tablets of Asacol 400 or 3 tablets of Asacol 800) once daily
or in divided doses.
Moderate active disease: 2.4 grams (6 tablets of Asacol 400 or 3 tablets of Asacol 800) up to
4.8 grams (12 tablets of Asacol 400 or 6 tablets of Asacol 800) per day in divided doses.
You may take up to 2.4 grams once a day or in divided doses. If taking more than 2.4 grams a
day, take in divided doses.
To prevent recurrence of ulcerative colitis episodes:
1.2 grams (3 tablets of Asacol 400) up to 2.4 grams (6 tablets of Asacol 400 or 3 tablets of
Asacol 800) once daily or in divided doses.
For Crohn’s disease:
2.4 grams (6 tablets of Asacol 400 or 3 tablets of Asacol 800) per day in divided doses.
Asacol 400: Do not take more than 12 tablets a day and do not take more than 6 tablets at
Asacol 800: Do not take more than 6 tablets a day and do not take more than 3 tablets at
Do not exceed the recommended dose.
Take this medicine before meals; swallow it whole, preferably with some liquid. Do not chew,
crush or break the tablets before swallowing them. While you are taking this medicine make
sure you drink adequate fluids to avoid dehydration, especially after severe or prolonged
episodes of vomiting and/or diarrhoea, high fever or heavy sweating. This is to prevent
problems with your kidneys.
If you have accidentally taken a higher dose
If you have taken an overdose, or if a child has accidentally swallowed some medicine,
immediately see a doctor or go to a hospital emergency room and bring the medicine
package with you.
If you forget to take the medicine
If you forget to take a tablet at the scheduled time, take the next dose as soon as you
remember, unless it is nearly time to take the next dose. Do not take a double dose to make
up for a forgotten dose.
If you stop taking this medicine
Even if your health improves, do not stop taking this medicine without consulting your doctor
Do not take medicines in the dark! Check the label and dose every time you take
medicine. Wear glasses if you need them.
If you have any further questions about using this medicine, consult your doctor or
4. Side effects
Like with all medicines, using Asacol may cause side effects in some users. Do not be
alarmed by this list of side effects; you may not experience any of them.
Organ-specific side effects, affecting the heart, lungs, liver, kidneys, pancreas, skin and
subcutaneous tissue have been reported.
Stop taking the medicine immediately and consult your doctor right away:
if you develop unexplained bruising (without injury), bleeding under your skin, purple
spots or patches under your skin, anemia (feeling tired, weakness, and looking pale,
especially on lips, nails and inside of eyelids), high fever, abdominal pain, headache,
sore throat, rash or unusual bleeding (such as nose bleeds).
lung disease (scarring of lung tissue, allergic reaction) resulting in difficulty in
breathing, cough, wheezing and collection of fluids in the lungs, pneumonia
abnormal liver function tests, hepatitis (inflammation of the liver giving rise to flu-like
symptoms and jaundice)
inflammation of the heart with signs like chest pains or palpitations
disorder of the immune system (lupus-like syndrome) which can cause inflammation
of the heart sac or membranes around the lungs and heart, rash and/or joint pain
kidney problems (such as inflammation and scarring of the kidneys), kidney failure
which may be reversible if treatment is stopped early
reversible decrease in sperm production
Common side effects (may affect up to 1 in 10 people)
Uncommon side effects (may affect up to 1 in 100 people)
- high number of white blood cells called eosinophil granulocytes
- sensation of tingling, pricking and numbness
- hives, itching skin
- chest pain
Rare side effects (may affect up to 1 in 1,000 people)
- diarrhea, stomach pain, flatulence, unpleasant feeling and discomfort in the stomach with an
urge to vomit and vomiting
- increased sensitivity of your skin to sun and ultraviolet light (photosensitivity)
Very rare side effects (may affect up to 1 in 10,000 people)
- severe reduction in count of blood cells which can cause weakness, bruising or make
infections more likely, low blood cell counts; reduction in blood platelets which increase the
risk of bleeding
- allergic reactions such as rash or skin eruption
- fever that occurs while taking the medicine and which disappears when the medicine is
stopped (drug fever)
- immune system disease that can involve organs and joints
- ulcerative colitis involving the entire large intestine
- abnormal or damaged nerves that cause numbness or tingling
- inflamed pancreas (associated with pain in the upper abdomen and back and being
- hair loss
- muscle and joint pain
Side effects of unknown frequency (frequency cannot be estimated from available data)
- inflammation of the lung membrane (pleurisy)
- intolerance to mesalazine sometimes with worsening symptoms of the disease
- weight loss
- laboratory test results out of normal range
If you experience any side effect, if any side effect gets worse, or if you experience a
side effect not mentioned in this leaflet, consult your doctor.
You can report side effects to the Ministry of Health by following the link ‘Reporting Side
Effects of Drug Treatment’ on the Ministry of Health home page (www.health.gov.il) which
links to an online form for reporting side effects, or by using this link:
5. How to store the medicine?
Prevent poisoning! To prevent poisoning, keep this, and all other medicines, in a closed
place, out of the reach and sight of children and/or infants. Do not induce vomiting unless
explicitly instructed to do so by a doctor.
Do not use the medicine after the expiry date (exp. date) which is stated on the package. The
expiry date refers to the last day of that month.
Do not store above 25°C.
6. Additional information
In addition to the active ingredient, this medicine also contains:
sodium starch glycolate
methacrylic acid-methyl methacrylate copolymer (1:2)
ferric oxide red and yellow pigment
Each 400 mg tablet contains 76.40 mg lactose monohydrate.
Each 800 mg tablet contains 152.80 mg lactose monohydrate.
What the medicine looks like and contents of the pack
Oblong, reddish-brown tablets. The tablet are available in blister trays of 10 tablets in packs
Asacol 400 mg: 100 tablets per pack
Asacol 800 mg: 60 tablets per pack
Registration holder: Tradis Gat Ltd., 32 Shaham St., Petac Tikva.
Manufacturer: Tillotts Pharma, Rheinfelden, Switzerland.
Approved in March 2020.
Registration number of the medicine in the Ministry of Health’s National Drug Registry:
Asacol 400 mg: 659925654
Asacol 800 mg: 1333931029
NAME OF THE MEDICINAL PRODUCT
ASACOL® 400 mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each enteric coated tablet contains:
Mesalazine (5-aminosalicylic acid) 400 mg
Excipient with known effect: 76.4 mg lactose, see section 4.4.
For the full list of excipients, see section 6.1.
Enteric coated Tablet.
Reddish to brownish oblong tablets
4.1 Therapeutic indications
For the treatment of mild to moderate acute exacerbations. For the maintenance of
For the treatment of acute episodes.
Posology and method of administration
Mild acute disease: 2.4 g (six tablets) once daily or in divided doses, with concomitant
corticosteroid therapy to be taken when clinically indicated.
Moderate acute disease: 2.4 g to 4.8 g (six to twelve tablets) a day in divided doses, with
concomitant corticosteroid therapy where clinically indicated. 2.4 g may be taken once
daily or in divided doses. Above 2.4 g daily should be taken in divided doses.
The maximum adult dose should not exceed twelve tablets a day and not exceed six tablets
taken together at any one time.
Maintenance of remission:
1.2 to 2.4 g per day once daily or in divided doses.
2.4 g per day in divided doses.
Use in the elderly should be handled with caution and only for patients having a normal
There is no specific dose recommendation for children.
Method of administration
The tablets should be taken before meals and must be swallowed whole preferably with
some liquid. They must not be chewed, crushed or broken before swallowing
- Hypersensitivity to the active substance or to any of the excipients listed in section
Known hypersensitivity to salicylates
- Severe liver impairment.
- Severe renal impairment (GFR less than 30 mL/min/1.73 m2).
- Children under the age of 2 years.
4.4 Special warnings and precautions for use
Blood tests (differential blood count, liver function parameters such as ALT or AST; serum
creatinine) and urinary status (dip sticks) should be determined prior to and during
treatment, at the discretion of the treating physician. As a guideline, follow-up tests are
recommended 14 days after commencement of treatment and then every 4 weeks for the
following 12 weeks. If the findings are normal, follow-up tests should be carried out every
three months. If additional signs appear, these tests should be performed immediately.
Caution should be exercised in patients with raised serum creatinine or proteinuria.
The possibility of mesalazine-induced nephrotoxicity should be suspected in patients
developing impairment of renal function during treatment. Patients need to remain
well hydrated whilst taking Asacol to reduce the risk of crystalluria and consequential
Treatment with Asacol should be stopped immediately if there is evidence of renal
impairment and patients should seek immediate medical advice.
Cases of nephrolithiasis have been reported with the use of mesalazine including
stones with a 100% mesalazine content. It is recommended to ensure adequate fluid
intake during treatment.
Serious blood dyscrasia has very rarely been reported. Asacol therapy should be
stopped immediately if there is a suspicion or evidence of blood dyscrasia (signs of
unexplained bleeding, bruising, purpura, anemia, persistent fever or sore throat), and
patients should seek immediate medical advice.
administered to patients with liver impairment. Blood tests (liver function parameters
such as ALT or AST) should be performed prior to and during treatment, at the
discretion of the treating physician. As a guideline, follow-up tests are recommended
14 days after commencement of treatment, then a further two to three tests at intervals
of 4 weeks. If the findings are normal, follow-up tests should be carried out every 3
months. If additional symptoms occur, these tests should be performed immediately.
Cardiac hypersensitivity reactions
Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have
rarely been reported with Asacol. In case of a suspected mesalazine-induced cardiac
hypersensitivity, Asacol must not be reintroduced. Caution should be taken in patients
with previous myo- or pericarditis of allergic background regardless of its origin.
monitored during treatment with Asacol.
Adverse drug reactions to Sulphasalazine
Patients with a history of adverse drug reactions to sulphasalazine therapy should be
kept under close medical supervision. Treatment must be stopped immediately if acute
symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever,
severe headache and rash.
Gastric and duodenal ulcers
In case of existing gastric or duodenal ulcers treatment should begin with caution
based on theoretical grounds.
Tablets in stool
A limited number of reports of intact tablets in the stool have been received. What appear to
be intact tablets may in some cases represent largely empty shells of the coated tablets. If
intact tablets are observed in the stool repeatedly, the patient should consult his/her
Use in the elderly should be handled with caution and the product should only be
prescribed to patients having a normal or non-severely impaired liver and renal
function, see section 4.3.
Safety and effectiveness of Asacol tablets have not been fully established in paediatric
Pharmaceutical excipients of special interest
Intolerance to carbohydrates
With reference to the presence of lactose monohydrate in the formulation, patients with
rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-
galactose malabsorption should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, i.e. is
4.5 Interaction with other medicaments and other forms of interaction
No interaction studies have been performed.
There is weak evidence that mesalazine might decrease the anticoagulant effect of
In patients who are concomitantly treated with azathioprine, or 6-mercaptopurine or
thioguanine, a possible increase in the myelosuppressive effects of azathioprine, or 6-
mercaptopurine or thioguanine should be taken into account. As a result, life-
threatening infection can occur. Patients should be closely observed for signs of
infection and myelosuppression. Haematological parameters, especially the leucocyte,
thrombocyte, and lymphocyte cell counts should be monitored regularly (weekly),
especially at initiation of such combination therapy, see section 4.4. If white blood cells
are stable after 1 month, testing every 4 weeks for the following 12 weeks followed by
3 monthly monitoring intervals appears to be justified.
4.6 Fertility, pregnancy and lactation
There are no adequate data on the use of Asacol in pregnant women. However, data
on a limited number (627) of exposed pregnancies indicate no adverse effect of
mesalazine on pregnancy or on the health of the fetus/newborn child. To date no
other relevant epidemiologic data are available.
In one single case after long-term use of a high dose of mesalazine (2-4 g, orally)
during pregnancy, renal failure in a neonate was reported.
Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with
Asacol should only be used during pregnancy if the potential benefit outweighs the
N-acetyl-5-aminosalicylic acid and to a lesser degree, mesalazine are excreted in
breast milk. The clinical significance of this has not been determined. Only limited
experience during lactation in women is available to date. Hypersensitivity reactions
such as diarrhoea in the infant cannot be excluded. Therefore, Asacol should only be
used during breast-feeding, if the potential benefit outweighs the possible risk. If the
infant develops diarrhoea, the breast-feeding should be discontinued.
No effects on fertility have been observed.
4.7 Effects on ability to drive and use machines
Asacol has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
a) Summary of the safety profile
Organ specific adverse drug reactions affecting the heart, lungs, liver, kidneys,
pancreas, skin and subcutaneous tissue have been reported.
Treatment must be stopped immediately if acute symptoms of intolerance occur such
as abdominal cramps, acute abdominal pain, fever, severe headache and rash, see
b) Tabulated summary of adverse reactions
Undesirable effects relevant for the labeling reported from eight (8) double-blind and
five (5) open clinical studies with 739 patients treated with Asacol 400 mg enteric
coated tablets are listed below.
to < 1/10)
to < 1/100)
(≥ 1/10,000 to <
(as part of
reactions such as
drug fever, lupus
allergic and fibrotic
changes in liver
to < 1/10)
to < 1/100)
(≥ 1/10,000 to <
tissue and bone
well as rash and
Impairment of renal
acute and chronic
and renal failure
which may be
reversible on early
*see section c)
**see section 4.4 for further information
c) Description of selected adverse reactions
An unknown number of the above mentioned undesirable effects are probably associated
to the underlying IBD rather than Asacol/mesalazine medication. This holds true especially
for gastrointestinal undesirable effects, arthralgia, and alopecia.
To avoid blood dyscrasia resulting from developing bone marrow depression patients
should be monitored with care, see section 4.4.
azathioprine or 6-MP or thioguanine, life-threatening infection can occur, see section 4.5.
More severe reactions are reported in patients with pre-existing skin conditions such as
atopic dermatitis and atopic eczema.
d) Paediatric population
There is only limited safety experience with the use of Asacol tablets in the paediatric
population. It is expected that the target organs of possible adverse reactions in the
paediatric population are the same as for adults (heart, lungs, liver, kidneys, pancreas,
skin and subcutaneous tissue).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
Any suspected adverse events should be reported to the Ministry of Health according
to the National Regulation by using an online form
There are rare data on overdose (e.g. intended suicide with high oral doses of
mesalazine), which do not indicate renal or hepatic toxicity. There is no specific
antidote and treatment is symptomatic and supportive.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Intestinal anti-inflammatory agents, ATC code: A07EC02
Mechanism of Action
Asacol contains mesalazine also known as 5-aminosalicylic acid, which has an anti-
inflammatory effect through a mechanism that has not yet been fully clarified.
Mesalazine has been shown to inhibit LTB4-stimulated migration of intestinal macrophages
and thus may reduce intestinal inflammation by restricting migration of macrophages to
inflamed areas. The production of pro-inflammatory leukotrienes (LTB4 and 5-HETE) in
macrophages of the intestinal wall is inhibited. Mesalazine has been shown to activate
PPAR-γ receptors which counteract nuclear activation of intestinal inflammatory responses.
Under trial conditions mesalazine inhibited the cyclooxygenase and thus, the release of
and prostaglandin E
, but the clinical meaning of this effect is still unclear.
Mesalazine inhibits the formation of platelet activating factor (PAF). Mesalazine is also an
antioxidant; it has been shown to decrease formation of reactive oxygen products and to
capture free radicals.
Clinical efficacy and safety
Mild to moderate acute ulcerative colitis
Asacol 800 mg Tablets have been evaluated in 140 patients with mild to moderate
active ulcerative colitis in one controlled study lasting for 10 weeks comparing safety
and efficacy versus placebo. This indication was also investigated in seven controlled
and three open clinical trials including 787 patients, of whom 559 received Asacol 400
mg Modified Release Tablets. Three studies were placebo-controlled, one of which
also compared the efficacy of Asacol to another proprietary oral mesalazine product.
Five studies were performed without comparator. The studies included dose ranging
of Asacol. One study compared the efficacy of mesalazine versus sulfasalazine. The
studies included dose ranging of Asacol from 1.2 g/day to 4.8 g/day. One study used
prednisolone enema. These studies established the safety and efficacy of Asacol for
the treatment of mild to moderate acute UC at daily doses of 2.4 – 4.8 g mesalazine.
Maintenance of remission of ulcerative colitis
The efficacy of Asacol 400 was investigated in a double-blind randomised placebo-
controlled study including 264 patients. Treatment success in the two Asacol 400
groups (0.8 g/day and 1.6 g/day) was compared by endoscopic evaluation at the 6-
month endpoint with the placebo group by using the Fischer exact test. In the intention-
to-treat analysis of all patients, 42 of 87 patients (48.3%) in the placebo group
treatment success compared to 57 of the 90 patients (63.3% [CI, 52.8% to 73.8%]) in
the group receiving 0.8 g/day (P= 0.050) and 61 of the 87 patients (70.1% [CI, 59.9%
to 80.3%]) in the group receiving 1.6 g/day (P= 0.005). Asacol 400 mg GR Tablets
were safe and effective in maintaining remission in quiescent ulcerative colitis.
5.2 Pharmacokinetic properties
Asacol tablets are coated with a pH responsive polymer which enables the release of
mesalazine only at a pH above 7, i.e. within the terminal ileum and colon, which are
the main sites of inflammation in IBD. After any initial disruption of the coating
mesalazine will continue to be released irrespective of the pH. Asacol tablets have
been designed to minimise absorption in the digestive tract.
After a single dose of 2.4 g of mesalazine (6 Asacol 400 mg enteric coated Tablets) in
healthy volunteers under fasting conditions quantifiable amounts (> 2.00 ng/mL) of
mesalazine were observed in plasma after 4.5 h (median t
). The geometric mean
–value of mesalazine was 722.11 ng/mL with a median t
of about 9.5 h,
whereas that of N-acetyl mesalazine was 1437.90 ng/mL with a median t
of 12.0 h.
Based on the recovery of unchanged mesalazine and the main metabolite N-acetyl
mesalazine in collected urine after fasted oral administration approximately 25% of the
dose (more than 95 % as metabolite) was excreted renally within 60 h.
Following concomitant food intake in the same study a single dose of 2.4 g of
mesalazine resulted in quantifiable amounts of mesalazine after 9.0 h (median t
The geometric mean C
–value of mesalazine was 1725.93 ng/mL with a median t
of about 22.0 h, whereas that of N-acetyl mesalazine was 2235.32 ng/mL with a
of 24.0 h.
Based on the recovery of unchanged mesalazine and the main metabolite N-acetyl
mesalazine in collected urine after fed oral administration approximately 30% of the
dose (about 90 % as metabolite) was excreted renally within 60 h.
Following concomitant food intake the C
-values of mesalazine increased 2.39-fold,
and the extent of exposure (AUC
) increased 1.57-fold. Concerning N-acetyl
whereas its extent of exposure increased about 1.1-fold only.
About 43% mesalazine and about 78% N-acetyl mesalazine are bound to plasma
Approximately 75 % of the administered dose remains in the gut lumen and the
The mean apparent volume of distribution per kg of body weight (Vd
) was 59.07 L/kg
(geometric mean: 48.86 L/kg) after a single dose of 2.40 g of mesalazine (6 enteric
coated tablets of Asacol 400 mg) in healthy volunteers under fasting conditions. Based
upon the absorption of 24.8% of the administered dose, this parameter is equal to
14.65 L/kg (geometric mean: 12.12 L/kg).
Low concentrations of mesalazine and N-acetyl mesalazine have been detected in
human breast milk. The clinical significance of this has not been determined.
Mesalazine is metabolised both by the intestinal mucosa and the liver to the inactive
metabolite N-acetyl mesalazine. At least 90% of the drug recovered in the urine after
oral administration is found as the main metabolite N-acetyl-mesalazine.
The elimination of mesalazine is essentially urinary and faecal in the form of
mesalazine and its N-acetyl metabolite. The geometric mean of total apparent
clearance of mesalazine after administration of 2.40 g of mesalazine (6 enteric coated
tablets of Asacol 400 mg) in healthy volunteers under fasting conditions was about
135 L/h (geometric mean, CV% = 61.43%, intersubject). The median elimination half-
life was 20 h ranging from 5 to 77 h. About 25% of the total dose administered was
recovered in the urine within 60 h after fasted administration mainly as N-acetyl
mesalazine and as the parent compound (about 1 %).
In a cross-over design with 3 test periods and 3 ascending oral doses of Asacol 400
mg enteric coated Tablets administered 6 hourly over 4 consecutive doses (total daily
dose of mesalazine: 3200, 4800, 6400 mg) it was shown that the absorption and
elimination kinetics for mesalazine are dose independent for the 3 doses evaluated.
For each dose, about ¾ of the dose was available for the therapeutic activity for the
colon. Only about ¼ of each dose was absorbed and excreted in the urine, primarily
as the metabolite. Based on urine drug excretion, plasma drug C
’s and the
combined plasma AUC’s, there was a linear dose response for the 3 Asacol tablet
doses. The clinical performance of Asacol 400 should be similar for the range of doses
evaluated in this study.
Pharmacokinetic/ pharmacodynamics relationship(s)
No specific studies have been performed.
5.3 Preclinical safety data
Preclinical data with mesalazine reveal no special hazard for humans based on
conventional studies of safety pharmacology, genotoxicity, carcinogenicity or toxicity
Renal toxicity (renal capillary necrosis and epithelial damage in the proximal
convoluted tubule or the whole nephron) has been seen in repeat-dose toxicity
studies with high oral doses of mesalazine.
6.1 List of excipient(s)
sodium starch glycolate (type A)
methacrylic acid-methyl methacrylate copolymer (1:2)
ferric oxide red and yellow pigment (E172)
6.3 Shelf life
The expiry date of the product is indicated on the packaging materials.
6.4 Special precautions for storage
Do not store above 25° C.
6.5 Nature and contents of container
Pack of 100 tablets in a blister pack (PVC/aluminium).
6.6 Special precautions for disposal and other handling
Tillotts Pharma AG, SWITZERLAND
Registration Holder and Importer:
Tradis Gat Ltd. 32 Shacham St. Petach Tikva ISRAEL
Registration Number: 065-99-25654
Approved on March 2020
אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכדועמ( ןכדועמ(
םושירה רפסמו תילגנאב רישכת םש
___ םושירה לעב םש מ"עב תג סידרט
! דבלב תורמחהה טורפל דעוימ הז ספוט תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט
Posology, dosage &
Special Warnings and
Short monitoring intervals early after the
start of Asacol therapy will discover rare
acute renal reactions. In the absence of an
acute renal reaction monitoring intervals
can be extended to every 3 months and
then annually after 5 years. If additional
laboratory or clinical signs of renal
impairment appear, these tests should be
performed immediately. Treatment with
Asacol should be stopped immediately if
there is evidence of renal impairment and
patients should seek immediate medical
There have been reports of increased liver
Caution is recommended if Asacol is
impairment. Blood tests (liver function
parameters such as ALT or AST) should
treatment, at the discretion of the treating
physician. As a guideline, follow-up tests
commencement of treatment, then a
further two to three tests at intervals of 4
weeks. If the findings are normal, follow-
up tests should be carried out every 3
months. If additional symptoms occur,
Cardiac hypersensitivity reactions
pericarditis) have been reported rarely
with Asacol. In case of a suspected
hypersensitivity Asacol must not be
reintroduced. Caution should be taken in
regardless of its origin.
Gastric and duodenal ulcers
In case of existing gastric or duodenal
caution based on theoretical grounds.
Intolerance to carbohydrates
Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase
Tablets in stool
A limited number of reports of intact tablets
in stool have been received. What appear to
be intact tablets may in some cases represent
largely empty shells of the coated tablets.If
Use in the older people
should be handled with
caution and the product
should only be
prescribed to patients
having a normal and
intact tablets are observed in the stool
repeatedly, the patient should consult his/
Use in the older people should be handled with
caution and the product should only be
prescribed to patients having a normal or non-
severely impaired liver and renal function, see
Interaction with Other
Medicaments and Other
Forms of Interaction
Mesalazine decreases the
absorption of Digoxin
diuretic effect of
the activity of
can be increased.
should not be given
with lactulose or
which lower stool
pH and may
prevent release of
There is weak evidence that mesalazine might
decrease the anticoagulant effect of warfarin.
In patients who are concomitantly treated
with azathioprine, or 6-mercaptopurine or
thioguanine, a possible increase in the
myelosuppressive effects of azathioprine, or
6-mercaptopurine or thioguanine should be
taken into account. As a result, life-
threatening infection can occur. Patients
should be closely observed for signs of
infection and myelosuppression.
Fertility, pregnancy and
Hypersensitivity reactions such as
diarrhoea in the infant cannot be excluded.
Blood and lymphatic system disordersVery
Immune system disorder
Very rare: drug fever, pancolitis
Nervous system disorders
Respiratory, thoracic and mediastinal
Very rare: fibrotic lung reactions (including
dyspnoea, cough, bronchospasm, alveolitis,
pulmonary eosinophilia, lung infiltration,
pneumonitis), interstitial pneumonia,
flatulence, nausea, vomiting.
changes in liver function
parameters (increase in transaminases and
cholestasis parameters), hepatitis, cholestatic
Skin and subcutaneous tissue disorders
Uncommon: urticaria, pruritus.
Renal and urinary disorders
renal insufficiency, nephrotic
syndrome, renal failure which may be
reversible on early withdrawal.
General disorders and administration
pyrexia, chest pain.
blood creatinine increased,
decreased, amylase increased, red blood cell
increased, BUN increased.
Under co-administration of mesalazine with
azathioprine or 6-MP or thioguanine, life-
תושקובמה תורמחהה תונמוסמ ובש ,ןולעה ב"צמ בוהצ עקר לע
ונמוס תורמחה רדגב םניאש םייוניש )ןולעב( ב הנוש עבצ םייוניש אלו יתוהמ ןכות קר ןמסל שי . .טסקטה םוקימב ...ךיראתב ינורטקלא ראודב רבעוה
ןכרצל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכרצל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכדועמ( ןכדועמ(
םושירה רפסמו תילגנאב רישכת םש
___ םושירה לעב םש מ"עב תג סידרט
! דבלב תורמחהה טורפל דעוימ הז ספוט תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט תויוותה שמתשהל ןיא יתמ ?רישכתב תודחוימ תורהזא שומישל תועגונה :הפורתב רפס ,לוקאסאב לופיטה תלחתה ינפל :םא אפורל מ םעפ יא תלבס תובוגת בלב תויגרלא .בלה סיכ וא בלה רירש לש תקלד ןוגכ תלבס םא רבעב בלב תויגרלא תובוגתמ רשא יכ תודושח לאסמ ידי לע ומרגנ
,ןיז הז הרקמב לוטיל רוסא ןתינ .לוקאסא ךל התייה םא תוריהזב לוקאסא לוטיל רבעב אל רשא בלב תיגרלא הבוגת לאסמ ידי לע המרגנ
.ןיז שמתשהל ןיא ילבמ הפורתב ינפל אפורב ץעוויהל :לופיטה תלחתה ןיב תובוגת
תא ריבגהל יושע
חקורה :תויתופורת םרגנה
ןוסיחה תכרעמ יוכיד
ו ןירופוטפקרמ- ןינאוגוית
העפשהה תא ריבגהל לוכי ןיזאלאסמ .ןוסיחה תכרעמ תא תאכדמה
- ןירפראו תא תיחפהל לוכי ןיזאלאסמ .םדה תשירק תדגונ העפשהה :הקנהו ןוירה שמתשת דציכ :הפורתב :יאוול תועפות תוחיכש
לוכיע יישק תוחיכש יתלב
םיארקנה םינבל םד יאת לש הובג רפסמ םיליפוניזואא םיטיצולונרג
השוחת רסוחו רורקד ,ץוצקע תשוחת
רועב דוריג ,תדפרס
הזח באכ תורידנ םיזג דואמ תורידנ
תחרפת וא החירפ ןוגכ תויגרלא תובוגת תירוע
הפורתה תליטנ ןמזב עיפומה םוח ( התליטנ תא םיקיספמ רשאכ םלענהו
ברעל הלוכי רשא ןוסיחה תכרעמב הלחמ םיקרפמו םירביא
רסוחל םימרוגה םימוגפ וא םיניקת אל םיבצע ץוצקעל וא השוחת ,תוניקת אל דבכ ידוקפת תוקידב
הכיפה הניה רשא ערז רוצייב הדירי העודי אל תורידת
חווטהמ תוגרוח רשא הדבעמ תוקידב תואצות .ילמרונה תושקובמה תורמחהה תונמוסמ ובש ,ןולעה ב"צמ בוהצ עקר לע
( ונמוס תורמחה רדגב םניאש םייוניש ןולעב ב ) .הנוש עבצ םייוניש אלו יתוהמ ןכות קר ןמסל שי .טסקטה םוקימב ....ךיראתב ינורטקלא ראודב רבעוה