ASACOL - PACKAGE LEAFLET - LEAFLETS

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Asacol - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life

Active ingredients: Mesalazine

ASACOL 400 mg gastro-resistant tablets
ASACOL 800 mg gastro-resistant tablets

Asacol package inserts are available for pack sizes:

ASACOL 400 mg gastro-resistant tablets, ASACOL 800 mg gastro-resistant tablets
ASACOL 2g / 50ml rectal suspension, ASACOL 4g / 100ml rectal suspension
ASACOL® 2g granules for rectal suspension
ASACOL® 4g / 50ml Rectal suspension
ASACOL. 2 g rectal foam, ASACOL 4 g rectal foam
ASACOL 1g rectal foam
ASACOL 400 mg modified release capsules
ASACOL 500 mg suppositories
ASACOL 1g suppositories

Why is Asacol used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Aminosalicylic acid and analogues

THERAPEUTIC INDICATIONS

Ulcerative colitis and Crohn's disease.

Treatment of the active phases of the disease and prevention of relapses. In the severe active phase it is advisable to combine it with cortisone treatment.

Contraindications When Asacol should not be used

Hypersensitivity to the active substance, to closely related substances from a chemical point of view or to any of the excipients (in particular towards salicylates).

Severe nephropathies. Gastric and duodenal ulcer. Hemorrhagic diathesis. Do not administer in the last weeks of pregnancy and during lactation (see also section "Pregnancy and breastfeeding"). Do not administer to children under the age of 2 years. Avoid using the tablets in children under the age of 6 years.

Precautions for use What you need to know before taking Asacol

Before starting treatment with ASACOL, the patient must undergo the necessary clinical investigations to clarify the diagnosis and therapeutic indications.

In patients with impaired renal and hepatic function the product should be used with caution. Cases of renal failure, including minimal change nephropathy, and acute / chronic interstitial nephritis have been reported in association with mesalazine-containing preparations and mesalazine prodrugs. In patients with known renal dysfunction, the risk-benefit ratio of mesalazine treatment should be evaluated and caution should be exercised in these patients. A careful evaluation of renal function is recommended for all patients prior to initiation of therapy, and periodically during treatment, especially in patients with prior renal disease.

Interactions Which drugs or foods may change the effect of Asacol

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those without a prescription.

The simultaneous administration of Lactulose or other preparations which, by lowering the pH of the colon, can hinder the release of Mesalazine should be avoided.

Caution is recommended in the concomitant use of mesalazine and sulfonylureas which may be potentiated the hypoglycemic effect.Caution is advised in the concomitant use of mesalazine with coumarins, methotrexate, probenecid, sulfinpyrazone, spironolactone, furosemide and rifampicin as interactions cannot be excluded.

Caution is advised in concomitant use of mesalazine and agents known to be renal toxic, including non-steroidal anti-inflammatory drugs (NSAIDs) and azathioprine, as these drugs may increase the risk of adverse kidney reactions. In patients treated with azathioprine or 6-mercaptopurine, caution is recommended in concomitant use of mesalazine, as it may increase the risk of blood dyscrasias (see also sections "Special warnings" and "Undesirable effects").

Potentiation of undesirable effects of gastric corticosteroids is possible

Warnings It is important to know that:

Rare cases of severe blood dyscrasias have been reported following treatment with mesalazine. In the event that the patient develops haemorrhages of unclear etiology, hematomas, purpura, anemia, fever or laryngitis, haematological investigations should be conducted. If "blood dyscrasia" is suspected, treatment should be stopped. (see also sections "Interactions" and "Undesirable effects").

Rare mesalazine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported. Caution should be exercised when prescribing this drug to patients with conditions predisposing to myocarditis or pericarditis.

Mesalazine has been associated with an acute intolerance syndrome that may be difficult to distinguish from a relapse of inflammatory bowel disease. Although the exact frequency is not yet established, such cases occurred in 3% of patients in controlled clinical trials of mesalazine or sulfasalazine. Symptoms include cramps, acute abdominal pain and bloody diarrhea, sometimes fever, headache and erythema. In case of suspected acute intolerance syndrome, treatment should be stopped immediately.

There have been reports of elevated liver enzyme levels in patients treated with mesalazine-containing preparations.

Relapses of objective and subjective symptoms can occur both after drug withdrawal and during inadequate maintenance treatment.

The possible occurrence of hypersensitivity reactions entails the immediate interruption of treatment (see also section "Undesirable effects"). In patients with exceptionally slow gastric digestion or with pyloric stenosis, it may sometimes be possible to have a release of Mesalazine already in the stomach, with possible gastric irritation and a loss of efficacy of the drug.

In case of known intolerance to some sugars, contact your doctor before taking this medicine.

Pregnancy

There have been no adequate and well-controlled studies with mesalazine in pregnant women. Since it is known that mesalazine crosses the placental barrier, in case of confirmed or presumed pregnancy, administer only in case of real need and under strict medical supervision. However, its use should be avoided in the last weeks of pregnancy (see also section "Contraindications"). Ask your doctor or pharmacist for advice before taking any medicine.

Feeding time

Given the limited experience acquired in breastfeeding women treated with Mesalazine, its use should be avoided during breastfeeding (see also section "Contraindications"). Effects on ability to drive and use machines There is no evidence that ASACOL may impair the ability to drive or use machines.

Dosage and method of use How to use Asacol: Dosage

The dosage should be adapted to the individual patient based on the extent and severity of the disease. The indicative scheme is as follows:

Adults: 1-2 tablets of 400 mg, or 1 tablet of 800 mg, three times a day. The dosage can be increased up to 10 tablets of 400 mg or to 5 tablets of 800 mg per day in patients with severe forms, according to the judgment of the physician.

In case of first treatment, it is advisable to gradually increase the dosage for a few days before reaching the maximum dosage.

Children over 6 years: proportionally reduced doses in the opinion of the Doctor. There is only limited documentation on the effects in children (ages 6 - 18 years).

Children from 6 years of age:

Active phase of the disease: the posology must be determined individually, starting from 30-50 mg / kg / day in divided doses. Maximum dose: 75 mg / kg / day in divided doses. The total dose should not exceed 4 g / day (maximum dose in adults).
Maintenance treatment: the posology must be determined individually, starting from 15-30 mg / kg / day in divided doses. The total dose should not exceed 2 g / day (recommended adult dose).

It is generally recommended that children up to a body weight of 40 kg be given half the adult dose and children over 40 kg the normal adult dose.

Method of administration

The tablets should be swallowed whole, without breaking them or chewing them, preferably with a glass of water and between meals.

Duration of treatment

The duration of treatment for the active phases is on average 4-6 weeks and may vary, in the opinion of the doctor, according to the patient's condition and the evolution of the disease.

In long-term treatments to prevent relapses, the daily dosage and duration of treatment must be established by the doctor according to the patient's condition and the evolution of the disease.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist

Overdose What to do if you have taken too much Asacol

In case of ingestion of an excessive dose, resort to gastric lavage and venous infusion of electrolyte solutions. A specific antidote is not known.

In case of accidental intake of an excessive dose of the medicine, notify your doctor immediately or go to the nearest hospital.

Side Effects What are the side effects of Asacol

Like all medicines, this can cause side effects, although not everybody gets them.

Undesirable effects reported in general tolerability studies were generally mild and did not show a dose-dependent increase in incidence. Gastrointestinal disturbances (nausea, epigastralgia, diarrhea and abdominal pain) and headache have been reported.

The onset of hypersensitivity reactions (rash, itching) or episodes of acute intestinal intolerance with abdominal pain, bloody diarrhea, cramps, headache, fever and rash, requires discontinuation of treatment.

There are also sporadic reports of: leukopenia, neutropenia, thrombocytopenia, aplastic anemia, pancreatitis, hepatitis, interstitial nephritis, nephrotic syndrome and renal failure, pericarditis, myocarditis, eosinophilic pneumonia and interstitial pneumonia. The following table summarizes the event classes described.

Cardiac pathologies Very rare (≤1 / 10,000) Pericarditis, myocarditis Disorders of the blood and lymphatic system Very rare (≤1 / 10,000) Leukopenia, neutropenia, thrombocytopenia, aplastic anemia Nervous system disorders Common (≥1 / 100 to ≤1 / 10) Headache Skin and subcutaneous tissue disorders Common (≥1 / 100 to ≤1 / 10) Rash and other non-specific skin eruptions Uncommon (≥1 / 1,000 to ≤1 / 100) Itching Hepatobiliary disorders Very rare (≤1 / 10,000) Hepatitis Gastrointestinal disorders Common (≥1 / 100 to ≤1 / 10) Nausea, diarrhea Uncommon (≥1 / 1,000 to ≤1 / 100) Epigastralgia, bloody diarrhea, cramps and abdominal pain Very rare (≤1 / 10,000) Pancreatitis Renal and urinary disorders Very rare (≤1 / 10,000) Interstitial nephritis, nephrotic syndrome and renal failure Respiratory, thoracic and mediastinal disorders Very rare (≤1 / 10,000) Eosinophilic pneumonia, interstitial pneumonia General disorders and administration site conditions Very rare (≤1 / 10,000) Hyperpyrexia

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Expiry and Retention

Do not store above 30 ° C. Do not use the product if the package shows visible signs of deterioration.

Do not use the product beyond the expiration date indicated on the package.

The expiry date refers to the product being packaged. intact and correctly stored.

Keep this medicine out of the reach and sight of children

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

COMPOSITION

ASACOL 400 mg gastro-resistant tablets

Each tablet contains:

Active ingredient: Mesalazine (5-aminosalicylic acid, 5-ASA): 400 mg

Excipients: Mannitol, Povidone K30, Povidone K90, Sodium starch-glycolate type A, Magnesium stearate, Talc, Colloidal anhydrous silica, Copolymer type B of methacrylic acid, Triethyl citrate, Red iron oxide (E 172), Yellow iron oxide (E 172 ), Macrogol 6000.

ASACOL 800 mg gastro-resistant tablets

Each tablet contains:

Active ingredient: Mesalazine (5-aminosalicylic acid, 5-ASA): 800 mg

PHARMACEUTICAL FORM AND CONTENT

Gastro-resistant tablets.

30 gastro-resistant tablets of 400 mg, in blister packs *

60 gastro-resistant tablets of 400 mg, in blister packs

24 gastro-resistant tablets of 800 mg, in blister packs *

60 gastro-resistant tablets of 800 mg, in blister packs

96 gastro-resistant tablets of 800 mg, in blister packs *

* Non-commercial packaging

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Asacol can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

ASACOL

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

ASACOL 400 mg gastro-resistant tablets

Each tablet contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA): 400 mg.

ASACOL 800 mg gastro-resistant tablets

Each tablet contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA): 800 mg.

ASACOL 400 mg modified release capsules

Each capsule contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA): 400 mg.

ASACOL 500 mg suppositories

Each suppository contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA): 500 mg.

ASACOL 1 g suppositories

Each suppository contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA): 1 g.

ASACOL 2g / 50ml rectal suspension

Each 50 ml single-dose container contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA) 2 g.

ASACOL 4 g / 50 ml rectal suspension

Each 50 ml single-dose container contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA) 4 g.

ASACOL 4g / 100ml rectal suspension

Each 100 ml single-dose container contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA) 4 g

ASACOL 2 g granules for rectal suspension

Each sachet contains:

Active principle

Mesalazine (5-aminosaic acid, 5-ASA): 2 g.

ASACOL 2 g rectal foam

Each single-dose container contains:

Active principle

Mesalazine (5-aminosalicylic acid, 5-ASA) 2 g.

ASACOL 4 g rectal foam

Each single-dose container contains:

Active principle

Mesalazine (5-aminosaic acid, 5-ASA) 4 g.

ASACOL 1 g rectal foam

Each single dose of the multidose container contains:

Active principle

Mesalazine (5-aminosaic acid, 5-ASA): 1 g.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Gastro-resistant tablets, modified release capsules, suppositories, rectal suspension, granules for rectal suspension, rectal foam.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

GASTRORESISTANT TABLETS AND MODIFIED RELEASE CAPSULES

Ulcerative colitis and Crohn's disease.

SUPPOSITORIES

Ulcerative colitis in the localization at the rectal level.

RECTAL SUSPENSION AND GRANULES FOR RECTAL SUSPENSION

Ulcerative colitis in the rectosigmoid localization.

RECTAL FOAM

Ulcerative colitis localized to the distal parts of the intestine, from the transverse colon to the sigmoid and rectal ampulla.

ASACOL is indicated both in the treatment of the active phases of the disease and in the prevention of relapses.

In the severe active phase it is advisable to combine it with cortisone treatment.

04.2 Posology and method of administration

The dosage should be adapted to the individual patient based on the extent and severity of the disease.

The indicative scheme, which can be modified according to the prescriptions of the Doctor, is the following:

GASTRORESISTANT TABLETS

Adults: 1-2 tablets of 400 mg, or 1 tablet of 800 mg, three times a day. The dosage can be increased up to 10 tablets of 400 mg or up to 5 tablets of 800 mg per day in patients with severe forms, or according to the judgment of the doctor.

The tablets should be swallowed whole, without breaking them or chewing them, preferably with a glass of water and between meals.

Children over two years old: proportionally reduced doses in the opinion of the Doctor.

There is only limited documentation on the effects in children (ages 6 - 18 years).

Children from 6 years of age:

• Active phase of the disease: the posology must be determined individually, starting from 30-50 mg / kg / day in divided doses. Maximum dose: 75 mg / kg / day in divided doses. The total dose should not exceed 4 g / day (maximum dose in adults).

• Maintenance treatment: the posology must be determined individually, starting from 15-30 mg / kg / day in divided doses. The total dose should not exceed 2 g / day (recommended adult dose).

It is generally recommended that children up to a body weight of 40 kg can be given half the adult dose and children over 40 kg the normal adult dose.

MODIFIED RELEASE CAPSULES

Adults: 1-2 capsules of 400 mg, three times a day. The dosage can be increased up to 10 capsules per day in patients with severe forms.

The capsules should preferably be swallowed whole with a glass of water and away from meals, patients who, for various reasons, were unable to swallow the capsules whole, can open the capsule and take all the microgranules after having dispersed them in aqueous solution. In this case it is essential not to chew the microgranules themselves.

Children over two years old: proportionally reduced doses in the opinion of the Doctor.

There is only limited documentation on the effects in children (ages 6 - 18 years).

Children from 6 years of age:

• Maintenance treatment: the posology must be determined individually, starting from 15-30 mg / kg / day in divided doses. The total dose should not exceed 2 g / day (recommended adult dose).

It is generally recommended that children up to a body weight of 40 kg can be given half the adult dose and children over 40 kg the normal adult dose.

For oral forms: in case of first treatment, it is advisable to gradually increase the dosage for a few days before reaching the maximum dosage.

SUPPOSITORIES

Adults: on average 3 suppositories of 500 mg per day, divided into 2-3 doses, or 1 suppository of 1 g once a day, rectally.

To obtain a better therapeutic effect it is important that the suppository is held for at least 30 minutes, better if held for longer periods (for example for the whole night).

RECTAL SUSPENSION AND GRANULES FOR RECTAL SUSPENSION

Adults: on average 1 dose of 2 g of Mesalazine in 50 ml 1-2 times a day (morning and / or evening before bedtime), or 1 dose of 4 g in 50 ml or 4 g 100 ml, once a day (preferably in the evening before bedtime).

The ready rectal suspension must be shaken well before use to obtain a homogeneous suspension, with a slight pressure break the cap and insert the rectal cannula attached to the plastic container.

The granules for rectal suspension contained in a sachet must be poured into the plastic container; add water up to the mark, shake well to obtain a homogeneous suspension and screw the rectal cannula to the container.

To apply, lie down on the left side keeping the left leg straight and bending the right leg. Introduce the cannula completely into the anal orifice by gently pushing it; then press the container with gradual and constant pressure until the contents are completely ejected.

RECTAL FOAM (single-dose package)

Adults: on average 1 dose of 2 g, 1-2 times a day, in the morning and / or evening before going to bed, or 1 dose of 4 g, 1 time a day, in the evening before going to bed. Shake the container vigorously; insert the special rectal cannula in its seat, located in the container cap, until it is locked; tear off the seal collar all around the base of the container cap; lie down on the left side, keeping the left leg straight and bending the leg right; hold the container upside down, keeping the index finger over the container cap; completely insert the cannula into the anal orifice by gently pushing it; without removing the cannula, press the container cap 3-5 times, at intervals of a few seconds, until the dose is completely dispensed.

RECTAL FOAM (multidose package)

Adults: on average, two consecutive disbursements equal to 2 g of Mesalazine, 1-2 times a day, in the morning and / or evening before going to bed, or three-four consecutive disbursements equal to 3-4 g of Mesalazine, once a day, in the evening before bedtime. Shake the bottle vigorously; insert the appropriate rectal cannula in its seat, located under the cylinder cap, pushing the cannula all the way down; tear off the seal at the base of the cylinder cap; lie down on the left side, keeping the left leg straight and bending the right leg; hold the cylinder upside down by holding the index finger over the cylinder cap; insert the cannula into the anal orifice and gently push it all the way; without removing the cannula, press the cylinder cap all the way down and then release it completely, to deliver the first dose (equal to 1 g of Mesalazine); after a few seconds, repeat the operation to deliver the second dose, and so on, according to the recommended dosage, taking into account that each delivery corresponds to 1 g of Mesalazine.

For rectal suspensions and rectal foams: after introducing the preparation, turn a few times on both sides to facilitate a better distribution of the drug and remain lying down for at least 30 minutes. A better efficacy of the product is obtained by holding the drug for as long as possible or, better still, leaving it in place for the whole night, therefore it is preferable that at least one of the daily applications is carried out before going to bed.

For all rectal forms

Children over 2 years: proportionally reduced doses in the opinion of the Doctor. There is little experience and only limited documentation on the effects in children.

Duration of treatment scheduled for the active phases is on average 4-6 weeks and may vary according to the doctor's judgment, according to the patient's condition and the evolution of the disease. In long-term treatments, to prevent relapses, the daily dosage and duration of treatment they must be established by the doctor according to the patient's conditions and the evolution of the disease.

04.3 Contraindications

Hypersensitivity to the active substance, to closely related substances from a chemical point of view or to any of the excipients (in particular to salicylates and, for - ASACOL rectal suspension and ASACOL single-dose rectal foam, metabisulphites).

Severe nephropathies. Gastric and duodenal ulcer. Hemorrhagic diathesis. Do not administer in the last weeks of pregnancy and during lactation (see also section 4.6). Do not administer to children under 2 years of age. Avoid using tablets in children under 6 years of age.

04.4 Special warnings and appropriate precautions for use

Before starting treatment with ASACOL, the patient must undergo the necessary clinical investigations to clarify the diagnosis and therapeutic indications.

In patients with impaired renal and hepatic function the product should be used with caution.

Cases of renal failure, including minimal change nephropathy, and acute / chronic interstitial nephritis have been reported in association with mesalazine-containing preparations and mesalazine prodrugs. In patients with known renal dysfunction, the benefit-risk balance of mesalazine treatment should be evaluated and caution should be exercised in these patients. A careful evaluation of renal function is recommended for all patients prior to initiation of therapy, and periodically during treatment, especially in patients with prior renal disease.

Rare cases of severe blood dyscrasias have been reported following treatment with mesalazine. In the event that the patient develops haemorrhages of unclear etiology, hematomas, purpura, anemia, fever or laryngitis, haematological investigations should be conducted. If blood dyscrasia is suspected, treatment should be stopped. (see also sections 4.5 and 4.8).

There have been reports of elevated liver enzyme levels in patients treated with mesalazine-containing preparations.

Relapses of objective and subjective symptoms can occur both after drug withdrawal and during inadequate maintenance treatment.

In patients with exceptionally slow gastric digestion or with pyloric stenosis, after taking the modified-release tablets and capsules, mesalazine may be released already in the stomach, with possible gastric irritation and a loss of efficacy of the drug.

Any occurrence of hypersensitivity reactions leads to immediate discontinuation of treatment (see also section 4.8).

ASACOL rectal suspension and single-dose rectal foam contain metabisulphite. This substance can cause allergic reactions and severe asthmatic attacks in sensitive subjects and particularly in asthmatics (see also sections 4.3 and 4.8).

04.5 Interactions with other medicinal products and other forms of interaction

For oral forms: the simultaneous administration of Lactulose or other preparations which, by lowering the pH of the colon, can hinder the release of Mesalazine should be avoided.

Caution is recommended in the concomitant use of mesalazine and sulfonylureas which may be potentiated the hypoglycemic effect.

Caution is advised in the concomitant use of mesalazine with coumarins, methotrexate, probenecid, sulfinpyrazone, spironolactone, furosemide and rifampicin as interactions cannot be excluded.

In patients treated with azathioprine or 6-mercaptopurine, caution is recommended in concomitant use of mesalazine, as it may increase the risk of blood dyscrasias (see also sections 4.4 and 4.8).

Potentiation of undesirable effects of gastric corticosteroids is possible.

04.6 Pregnancy and lactation

Pregnancy

However, the use of the preparations should be avoided in the last weeks of pregnancy (see also section 4.3).

Feeding time

Given the limited experience acquired in breastfeeding women treated with mesalazine, the use of the preparations should be avoided during breastfeeding (see also section 4.3).

04.7 Effects on ability to drive and use machines

There is no evidence that ASACOL may impair the ability to drive or use machines.

04.8 Undesirable effects

Undesirable effects reported in general tolerability studies were generally mild and did not show a dose-dependent increase in incidence.

Gastrointestinal disturbances (nausea, epigastralgia, diarrhea and abdominal pain) and headache have been reported. The onset of hypersensitivity reactions (rash, itching) or episodes of acute intestinal intolerance with abdominal pain, bloody diarrhea, cramps, headache, fever and rash, requires discontinuation of treatment.

ASACOL rectal suspension and single-dose rectal foam contain metabisulphite.

This substance can cause allergic-type reactions and severe asthma attacks in sensitive individuals and particularly in asthmatics (see also sections 4.3 and 4.4).

The following table summarizes the event classes described.

(See also sections 4.4 Special warnings and precautions for use and 4.5 interactions with other medicinal products and other forms of interactions).

04.9 Overdose

As for modified release tablets and capsules, use gastric lavage and venous infusion of electrolyte solutions. A specific antidote is not known.

There are no known cases of overdose following rectal administration.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: aminosalicylic acid and analogues.

ATC code: A07E C02.

Mesalazine (5-aminosalicylic acid or 5-ASA) is a drug of proven usefulness in chronic intestinal inflammatory diseases, being endowed with a topical anti-inflammatory effect on the intestinal mucosal tracts affected by the lesions. Its presence in the intestinal lumen at sufficient concentrations is able to effectively inhibit the biosynthesis of derivatives of arachidonic acid metabolism, such as prostaglandin E2, thromboxane 132 and leukotrienes, whose levels are abnormally high in biopsy samples taken from the rectal mucosa. of patients with ulcerative colitis in the flare-up phase.

Mesalazine is the active fraction of salicylazosulfapyridine (SASP), a drug already used in these clinical forms.

ASACOL 400 mg gastro-resistant tablets and ASACOL 400 mg modified release capsules contain mesalazine in an amount equivalent to that theoretically available from the complete breakdown of the diazotized bond of 1 g of SASP respectively. Lacession of Mesalazine at the level of the terminal ileum and of the colon ensures an anti-inflammatory effect along this entire stretch.

ASACOL rectal suspension, rectal foam and suppositories are pharmaceutical forms that determine a prompt and efficient local anti-inflammatory effect on ulcerative lesions affecting the terminal tracts of the intestine.

05.2 Pharmacokinetic properties

The gastro-resistant tablets and modified-release capsules release Mesalazine in the terminal ileum and colon, thanks to the particular pharmaceutical preparation which has the characteristic of breaking up its own coating at a pH higher than 7. Radiological investigations show that the gastro-resistant tablets and the modified release capsules remain intact in the stomach and small intestine and disintegrate in the terminal ileum and right colon.

Absorption

The absorption of Mesalazine in the colon is modest. The substance is largely eliminated in the faeces and plasma levels are low. Following a single administration of ASACOL gastro-resistant tablets, in a dose corresponding to 2.4 g of Mesalazine, a plasma peak of 1.3 mcg / ml is obtained after 6 hours.

Distribution

Mesalazine has a relatively small volume of distribution of approximately 18 L, confirming that extravascular penetration of systemically available drug is minimal, as it is consistent with the absence of any significant secondary drug effects. Mesalazine binds to the 43% to plasma proteins when in vitro plasma concentrations are 2.5 mcg / ml.

Biotransformation

The absorbed amount is rapidly acetylated by the intestinal mucosa and liver to acetyl-5-aminosalicylic acid, it binds for the most part to plasma proteins and is eliminated in the urine.

Elimination

Mesalazine is eliminated primarily via the kidney in the urine. Renal clearance of aceti-5-aminosalicylic acid is 201 ml / min. Approximately 20% of the 1.6 g dose is found in the 24-hour urine, almost completely acetylated.

The rectal suspensions, rectal foams and suppositories of ASACOL release Mesalazine in the terminal part of the intestine. They have a very poor systemic absorption, equal to about 10% of the dose administered in subjects with intestinal inflammatory forms in the active phase.

05.3 Preclinical safety data

Pre-clinical data, based on conventional studies of tolerability, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity, did not reveal any particular risk for humans.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

GASTRORESISTANT TABLETS

Mannitol, povidone K30, povidone K90, sodium starch glycolate Type A, magnesium stearate, talc, colloidal anhydrous silica, copolymer type B of methacrylic acid, triethyl citrate, red iron oxide (E 172), yellow iron oxide (E 172), macrogol 6000.

MODIFIED RELEASE CAPSULES

hydroxypropyl cellulose, methacrylic acid copolymer (methacrylic acid-methyl methacrylate copolymer 1: 2), triethyl citrate, talc, anhydrous colloidal silica, gelatin, red iron oxide, yellow iron oxide, titanium dioxide.

SUPPOSITORIES

Solid semisynthetic glycerides (with vegetable lecithin).

RECTAL SUSPENSION

Colloidal silica, povidone, methylcellulose, sodium benzoate, potassium metabisulfite, phosphoric acid, water.

GRANULES FOR RECTAL SUSPENSION

Povidone, methylcellulose, colloidal silica.

RECTAL FOAM (Single-dose pack)

Xanthan gum, polysorbate 20, macrogol monostearate, sodium edetate, potassium metabisulfite, sodium benzoate, purified water, propane, isobutane, n-Butane.

RECTAL FOAM (Multidose package)

Propylene glycol, oxyethylenated caprylic / capric glycerides, polysorbate 20, emulsifying wax, citric acid monohydrate, sodium hydroxide, ascorbyl palmitate, ascorbic acid, methyl parahydroxybenzoate, propyl parahydroxybenzoate, purified water, isobutane, propane, n-Butane.

06.2 Incompatibility

They are not known.

06.3 Period of validity

2 years for gastro-resistant tablets, suppositories, rectal suspension, granules for rectal suspension, rectal foam; 3 years for unopened modified release capsules.

06.4 Special precautions for storage

For tablets: do not store above 30 ° C. For suppositories: store at temperatures not exceeding 30 ° C.

For the capsules: light sensitive product: keep inside the original package.

Do not use the product if the package shows visible signs of deterioration. Do not use after the expiration date indicated on the package.

06.5 Nature of the immediate packaging and contents of the package

GASTRORESISTANT TABLETS

Blister packs of PVC / aluminum coupled in a cardboard box together with the package leaflet.

30 gastro-resistant tablets of 400 mg

60 gastro-resistant tablets of 400 mg

24 gastro-resistant tablets of 800 mg

60 gastro-resistant tablets of 800 mg

96 gastro-resistant tablets of 800 mg

MODIFIED RELEASE CAPSULES

Blister packs of PVC / PVdC / aluminum coupled, inserted in a cardboard box, together with the package leaflet.

50 modified-release capsules of 400 mg

SUPPOSITORIES

Strip of shells with pre-formed pockets of rigid plastic material (PVC / PE), sealed by heat sealing, and inserted in a cardboard box together with the package leaflet.

10 suppositories of 500 mg

20 suppositories of 500 mg

28 suppositories of 1 g

RECTAL SUSPENSION

Soft polythene bottles, inserted in a cardboard box together with the rectal cannulas, in rigid polythene, and the package leaflet.

Rectal suspension 2 g / 50 ml - 7 single-dose containers 50 ml

Rectal suspension 4 g / 100 ml - 7 single-dose containers 100 ml

Rectal suspension 4 g / 50 ml - 7 single-dose containers 50 ml

GRANULES FOR RECTAL SUSPENSION

Heat-sealed sachets of coupled material (paper - aluminum - polythene) inserted in a cardboard box together with the package leaflet.

Granules for rectal suspension 2 g - 10 sachets

RECTAL FOAM (single-dose packs)

Single-dose aluminum cans with dispensing valves and attached rectal cannulas, in rigid polythene, inserted in a cardboard box together with the package leaflet.

2 g rectal foam - 7 single-dose containers 4 g rectal foam - 7 single-dose containers

RECTAL FOAM (multidose package)

Multidose cylinder in aluminum with dispensing valve and attached rectal cannulas, in rigid polythene, inserted in a cardboard box together with the package leaflet.

1 g rectal foam - 1 container of 14 doses

1 g rectal foam - 2 containers of 14 doses