CLETUS - PACKAGE LEAFLET - LEAFLETS

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Cletus - Package Leaflet

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

Active ingredients: Omeprazole

CLETUS 20 mg gastro-resistant hard capsules

Indications Why is Cletus used? What is it for?

CLETUS contains the active substance omeprazole. It belongs to a group of drugs called 'proton pump inhibitors', which work by reducing the amount of acid produced by the stomach. CLETUS is used to treat the following diseases:

In adults:

Gastro-oesophageal reflux disease "(GERD). This disease occurs when acid escapes from the stomach and passes into the esophagus (the tube that connects the throat to the stomach) causing pain, inflammation and heartburn.
Ulcers in the upper part of the intestine (duodenal ulcer) or stomach (gastric ulcer).
Ulcers infected with a bacterium called 'Helicobacter pylori.' If you suffer from this disease, your doctor may also prescribe antibiotics to treat the infection and allow the ulcer to heal.
Ulcers caused by medicines called NSAIDs (Non-Steroidal Anti-Inflammatory Drugs). CLETUS can also be used to prevent ulcers from forming if you are taking NSAIDs.
Excessive stomach acid caused by tissue growth in the pancreas (Zollinger-Ellison syndrome).

In children:

Children older than 1 year and with a body weight greater than or equal to 10 kg

Gastro-oesophageal reflux disease "(GERD). This disease occurs when acid escapes from the stomach and passes into the esophagus (the tube that connects the throat to the stomach) causing pain, inflammation and heartburn.
In children, symptoms of this disease also include stomach contents returning to the mouth (regurgitation), being sick (vomiting), and poor weight gain.

Children over 4 years of age and adolescents

Ulcers infected with a bacterium called 'Helicobacter pylori ". If the child suffers from this disease, the doctor may also prescribe antibiotics to treat the infection and allow the ulcer to heal.

Contraindications When Cletus should not be used

Do not take CLETUS

If you are allergic (Hypersensitive) to the active substance (omeprazole) or to any of the other ingredients of CLETUS.
If you are allergic to medicines containing other proton pump inhibitors (e.g. pantoprazole, lansoprazole, rabeprazole, esomeprazole).
If you are taking a medicine containing nelfinavir (used for HIV infections).

If you are not sure, talk to your doctor or pharmacist before taking CLETUS.

Precautions for use What you need to know before taking Cletus

Tell your doctor before taking CLETUS

CLETUS can hide the symptoms of other diseases. Therefore, if you experience any of the symptoms described below before taking CLETUS or while you are taking it, contact your doctor immediately:

Unmotivated weight loss and swallowing problems.
Stomach pain or indigestion.
Vomiting of food or blood.
Dark discoloration of the stool (presence of blood in the stool).
Severe or persistent diarrhea, because omeprazole has been associated with a slight increase in contagious diarrhea.
Severe liver problems.

Tell your doctor before taking CLETUS:

If you have ever had a skin reaction after treatment with a medicine similar to CLETUS that reduces stomach acid.

If you notice a skin rash, especially in areas exposed to sunlight, contact your doctor as soon as possible, as it may be necessary to stop taking CLETUS. Remember to also mention any other side effects such as joint pain.

If you have been taking CLETUS for a long time (more than 1 year) your doctor will prescribe regular checkups. Tell your doctor if you notice any new and unusual symptoms.

If you take a proton pump inhibitor such as CLETUS, especially for longer than one year, you may have a slightly increased risk of fracture of the hip, wrist or spine. If you have osteoporosis or are taking corticosteroids (which may increase the risk of osteoporosis) consult your doctor.

Interactions Which drugs or foods can modify the effect of Cletus

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. This is important because CLETUS can affect the way some medicines work and some medicines can affect the way CLETUS works.

Do not take CLETUS if you are taking a medicine containing nelfinavir (used to treat HIV infections).

Ketoconazole, itraconazole or voriconazole (used to treat infections caused by fungi)
Digoxin (used to treat heart problems)
Diazepam (used to treat anxiety, to relax muscles or for epilepsy).
Phenytoin (used for epilepsy). If you are taking phenytoin, your doctor will monitor you at the beginning and at the end of your treatment with CLETUS.
Medicines used to thin the blood, such as warfarin or other vitamin K blockers. Your doctor will monitor you at the beginning and at the end of your treatment with CLETUS.
Rifampicin (used to treat tuberculosis)
Atazanavir (used to treat HIV infection)
Tacrolimus (used in organ transplants)
St. John's wort (Hypericum perforatum) (used to treat mild depression)
Cilostazol (used to treat intermittent claudication)
Saquinavir (used to treat HIV infection)
Clopidogrel (used to prevent blood clots (thrombi)
Erlotinib (used for cancer treatment)
Methotrexate (a chemotherapy medicine used in high doses to treat cancer)
if you are taking methotrexate in high doses, your doctor may temporarily stop your treatment with CLETUS.
If your doctor has prescribed amoxicillin and clarithromycin antibiotics together with CLETUS for the treatment of ulcers caused by Helicobacter pylori infections, it is very important that you tell if you are taking any other medicines.

CLETUS with food and drink

The capsules can be taken with food or on an empty stomach.

Warnings It is important to know that:

Pregnancy and breastfeeding

Pregnancy

Ask your doctor or pharmacist for advice before taking any medicine. Before taking CLETUS, tell your doctor if you are pregnant or want to become pregnant. Your doctor will decide whether you can take CLETUS during this time.

Feeding time

Your doctor will decide whether you can take CLETUS if you are breastfeeding.

Driving and using machines

CLETUS is unlikely to affect your ability to drive or use tools or machines. Adverse drug reactions such as dizziness and visual disturbances may occur (see section 4). If you suffer from this, you should not drive or operate machinery.

Dose, Method and Time of Administration How to use Cletus: Posology

Always take CLETUS exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.

Your doctor will tell you how many capsules to take and for how long. This will depend on your condition and age.

The usual doses are given below.

ADULTS

To treat symptoms of GERD, such as heartburn and acid regurgitation:

If your doctor has told you that your esophagus is slightly damaged, the usual dose is 20 mg once a day for 4 to 8 weeks. Your doctor may increase the dose to 40 mg for another 8 weeks if the esophagus has not yet completely healed.
The usual dose once the esophagus has healed is 10 mg once a day.
If the esophagus is not damaged, the usual dose is 10 mg once a day.

For the treatment of ulcers in the upper part of the intestine (duodenal ulcer):

The usual dose is 20 mg once a day for 2 weeks. Your doctor may extend this dose for another 2 weeks if the ulcer has not yet healed.
If the ulcer does not fully heal, the dose can be increased to 40 mg once daily for 4 weeks.

For the treatment of stomach ulcers (gastric ulcer):

The usual dose is 20 mg once a day for 4 weeks. Your doctor may extend this dose for another 4 weeks if the ulcer has not yet healed.
If the ulcer does not fully heal, the dose can be increased to 40 mg once daily for 8 weeks.

To prevent duodenal and stomach ulcers from returning:

The usual dose is 10 mg or 20 mg once a day. Your doctor may increase the dose to 40 mg once a day.

For the treatment of duodenal and gastric ulcers caused by taking NSAIDs (Non-Steroidal Anti-Inflammatory Drugs):

The usual dose is 20 mg once a day for 4-8 weeks.

To prevent duodenal and stomach ulcers from forming if you are using NSAIDs:

The usual dose is 20 mg once a day.

For the treatment of ulcers caused by Helicobacter pylori infection and to prevent their reappearance:

The usual dose is 20 mg of CLETUS twice a day for one week.
Your doctor will tell you to also take two antibiotics including amoxicillin, clarithromycin and metronidazole.

To treat too much acid in the stomach caused by a growth of tissue in the pancreas (Zollinger-Ellison syndrome):

The usual dose is 60 mg per day.
Your doctor will adjust the dose according to your needs and will also decide how long you need to take the medicine for.

CHILDREN

To treat symptoms of GERD, such as heartburn and acid regurgitation:

CLETUS can be taken by children over 1 year of age and weighing more than 10 kg. The dose for children is based on the child's weight and the doctor will decide the correct dose.

For the treatment and prevention of the recurrence of ulcers caused by Helicobacter pylori infection:

CLETUS can be taken by children over 4 years of age. The dose for children is based on the child's weight and the doctor will decide the correct dose.
Your doctor will also prescribe two antibiotics called amoxicillin and clarithromycin for your child.

Taking this medicine

It is recommended to take the capsules in the morning.
The capsules can be taken with food or on an empty stomach.
The capsules should be swallowed whole with half a glass of water. The capsules should not be chewed or crushed, as they contain granules coated in such a way as to prevent the medicine from being broken down by stomach acid. It is important not to damage the granules.

What to do if you or the child have trouble swallowing the capsules

If you or the child have trouble swallowing the capsules:
- Open the capsules and swallow the contents directly with half a glass of water or pour the contents into a glass of water (non-fizzy), acidic fruit juice (e.g. apple, orange or pineapple) or apple puree.
- Always shake the contents before drinking (the mixture will not be clear), then drink the preparation immediately or within 30 minutes.
- To make sure that you have taken all of the medicine, rinse the glass very well with half a glass of water and drink the contents. The solid particles contain the medicine - do not chew or crush them.

If you forget to take CLETUS

If you forget to take a dose, take it as soon as you remember it.However, if it is almost time for your next dose, skip the missed dose. Do not take a double dose to make up for a forgotten dose.

Overdose What to do if you have taken too much Cletus

If you take more CLETUS than prescribed by your doctor, contact your doctor or pharmacist immediately.

Side Effects What are the side effects of Cletus

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

If you notice any of the following rare but serious side effects, stop taking CLETUS and contact your doctor immediately:

Sudden wheezing, swelling of the lips, tongue and throat or body, rash, fainting or difficulty in swallowing (severe allergic reaction).
Skin redness with blistering or peeling. Severe blistering may also appear with bleeding of the lips, eyes, mouth, nose and genitals. This could be "Stevens-Johnson syndrome" or "toxic epidermal necrolysis".
Yellow skin, dark urine and tiredness could be symptoms of liver problems.

Omeprazole is well tolerated and side effects that have occurred include:

Common side effects: affects up to 1 in 10 people

Headache.
Effects on the stomach or intestines: diarrhea, stomach pain, constipation, wind (flatulence).
Feeling sick (nausea) or being sick (vomiting).

Uncommon side effects: affects up to 1 in 100 people

Swelling of the feet and ankles.
Disturbed sleep (insomnia).
Dizziness, tingling, feeling sleepy.
Sensation of spinning (vertigo).
Changes in blood tests related to liver function.
Rash, rash with swelling of the skin (hives) and itchy skin.
General feeling of being unwell and lack of energy.
If you take a proton pump inhibitor such as CLETUS, especially for longer than one year, you may have a slightly increased risk of fracture of the hip, wrist or spine. If you have osteoporosis or are taking corticosteroids (which may increase the risk of osteoporosis) consult your doctor.

Rare side effects: affects up to 1 in 1000 people

Changes in the composition of the blood, such as a reduction in the number of white blood cells or platelets. This can cause weakness and easy bruising, or it can make infections more likely.
Allergic reactions, sometimes very serious, including swelling of the lips, tongue and throat, fever, wheezing.
Low levels of sodium in the blood. This can cause weakness, being sick (vomiting) and cramps.
Feeling agitated, confused or depressed.
Changes in taste.
Problems with your eyesight, such as blurred vision.
Sudden wheezing or shortness of breath (bronchospasm).
Dry mouth
Inflammation inside the mouth.
An infection called "thrush" which can affect the gut and is caused by a fungus.
Liver problems, including jaundice which can cause yellow skin, dark urine, and tiredness.
Hair loss (alopecia).
Skin rash on exposure to the sun.
Joint pain (arthralgia) or muscle pain (myalgia).
Severe kidney problems (interstitial nephritis).
Increased sweating.

Very rare side effects: affects up to 1 in 10,000 people

Changes in blood cell counts, including agranulocytosis (lack of white blood cells)
Aggression.
Seeing, feeling or hearing about unreal events (hallucinations).
Severe liver problems up to liver failure and inflammation of the brain.
Sudden onset of severe rash or blistering and peeling of the skin. These effects may be associated with high fever and joint pain (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)
Muscle weakness.
Chest enlargement in men.

Undesirable effects with frequency not known: frequency cannot be estimated from the available data.

Inflammation of the intestine (resulting in diarrhea).
If you take CLETUS for more than three months, your blood levels of magnesium may drop. Low magnesium levels can manifest themselves with fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate. If you have any of these symptoms, please consult your doctor immediately. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. Your doctor should decide whether to check your blood magnesium levels periodically.
Reduction in blood calcium levels (hypocalcaemia). The reduction in blood calcium levels can result from very low magnesium levels.
Erythema, possible joint pain.

In very rare cases, CLETUS can affect white blood cells leading to immune deficiency. If you develop an "infection with symptoms such as fever with a severe deterioration in general health or fever with symptoms of local infection such as pain in the neck, throat or mouth or difficulty urinating, you should see your doctor as soon as possible, in to rule out a lack of white blood cells (agranulocytosis) by carrying out a blood test It is important that in this case you tell your doctor what medicine you are taking.

Don't worry about the list of possible side effects. You may not get any.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at “www.agenziafarmaco.gov.it/it/responsabili.” By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

Expiry: see the expiry date indicated on the package
Do not use CLETUS after the expiry date which is stated on the pack after EXP. The expiry date refers to the last day of the month.
The date refers to the product in intact packaging, properly stored.
Do not store above 30 ° C.
Keep the blister in the original package or keep the bottle tightly closed to protect the medicine from moisture.
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.
Keep out of the sight and reach of children.

Deadline "> Other information

What CLETUS contains

The active ingredient is omeprazole.

CLETUS gastro-resistant hard capsules contain 20 mg of omeprazole.
Excipients are core: microcrystalline cellulose, low-substituted hydroxypropyl cellulose, mannitol, croscarmellose sodium, polysorbate 80, povidone K-30, arginine, sodium lauryl sulfate, glycine, light magnesium carbonate.
Coating: hypromellose, methacrylic acid-ethyl acrylate copolymer, triethyl citrate, sodium hydroxide, titanium dioxide, talc.
Capsule: gelatin, indigo carmine (E-132), titanium dioxide, water.

Description of what CLETUS looks like and contents of the pack

CLETUS 20 mg

Hard gastro-resistant capsules.

CLETUS is available in packs of 14 gastro-resistant 20 mg hard capsules.

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 Cletus 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 interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 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 RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

CLETUS 20 MG HARD GASTRORESISTANT CAPSULES

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

Each gastro-resistant hard capsule contains:

active principle: omeprazole 20 mg.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

Hard capsules containing gastro-resistant granules.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

CLETUS is available exclusively as a 20 mg gastro-resistant hard capsule formulation.

CLETUS capsules are indicated for:

Adults

• Treatment of duodenal ulcers

• Prevention of recurrence of duodenal ulcers

• Treatment of gastric ulcers

• Prevention of recurrence of gastric ulcers

• Eradication of Helicobacter pylori (H. pylori) in peptic ulcer, in association with appropriate antibiotic therapy

• Treatment of gastric and duodenal ulcers associated with the use of NSAIDs

• Prevention of gastric and duodenal ulcers associated with the use of NSAIDs in patients at risk

• Treatment of reflux esophagitis

• Long-term management of patients with healed reflux esophagitis

• Treatment of symptomatic gastroesophageal reflux disease

• Treatment of Zollinger-Ellison syndrome.

Pediatric use

Children over 1 year of age and with a body weight ≥ 10 kg

• Treatment of reflux esophagitis

• Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease

Children and adolescents over 4 years of age

• Treatment of duodenal ulcer caused by H. pylori, in association with antibiotic therapy

04.2 Posology and method of administration -

Dosage in adults

Treatment of duodenal ulcer

The recommended dose with active duodenal ulcer is CLETUS 20 mg once daily.

In most patients, ulcer healing is achieved within 2 weeks of starting treatment.

In the case of ulcers that have not completely healed during the first course of treatment, healing is usually achieved during prolonged treatment for another two weeks. In patients with poorly responsive duodenal ulcer CLETUS 40 mg once daily is recommended and healing is usually achieved within four weeks.

Prevention of relapse of duodenal ulcer

For the prevention of duodenal ulcer recurrence in negative patients H. pylori or when the eradication of H. pylori this is not possible, the recommended dose is CLETUS 20 mg once daily. In some patients a dose of 10 mg may be sufficient. In case of therapeutic failure, the dose can be increased to 40 mg.

Treatment of gastric ulcer

The recommended dose is CLETUS 20 mg once a day.

In most patients, healing is achieved within four weeks of starting treatment. In the case of ulcers that have not completely healed after the first course of treatment, healing is usually achieved during prolonged treatment for another four weeks. In patients with ulcers. gastric poorly responsive, once daily administration of CLETUS 40 mg is recommended, which generally results in healing within eight weeks.

Prevention of relapse in patients with gastric ulcer

For the prevention of relapse in patients with poorly responsive gastric ulcer, the recommended dose is CLETUS 20 mg once daily. If needed, the dose can be increased to CLETUS 40 mg once daily.

Eradication of H. pylori in peptic ulcer

For the "eradication of"H. pylori, Antibiotic selection must be based on the patient's individual drug tolerance and therapy must be undertaken according to local, regional, national resistance patterns and treatment guidelines.

• CLETUS 20 mg + clarithromycin 500 mg + amoxicillin 1,000 mg, each twice daily for one week, or

• CLETUS 20 mg + clarithromycin 250 mg (alternatively 500 mg) + metronidazole 400 mg (or 500 mg or tinidazole 500 mg), each twice daily for one week or

• CLETUS 40 mg once daily with amoxicillin 500 mg and metronidazole 400 mg (or 500 mg or tinidazole 500 mg), both three times a day for one week.

For each of the treatment regimens, should the patient still test positive for H. pylori therapy can be repeated.

Treatment of gastric and duodenal ulcers associated with the intake of NSAIDs

For the treatment of NSAID-associated gastric and duodenal ulcers, the recommended dose is CLETUS 20 mg once daily. In most patients, healing is achieved within four weeks of starting treatment. In patients not completely healed after the first course of treatment, healing is usually achieved by extending treatment for another four weeks.

Prevention of gastric and duodenal ulcers associated with the use of NSAIDs in patients at risk

For the prevention of NSAID-associated gastric or duodenal ulcers in patients at risk (age> 60, history of gastric and duodenal ulcers, history of upper gastrointestinal bleeding) the recommended dose is CLETUS 20 mg once daily.

Treatment of reflux esophagitis

The recommended dose is CLETUS 20 mg per day.

In patients with severe oesophagitis, CLETUS 40 mg once daily is recommended to achieve healing usually within eight weeks.

Long-term management of patients with healed reflux oesophagitis

For the long-term management of patients with healed reflux oesophagitis, the recommended dose is CLETUS 10 mg once daily. If necessary, the dose can be increased to CLETUS 20-40 mg once daily.

Treatment of symptomatic gastroesophageal reflux disease

The recommended dose is CLETUS 20 mg per day. Patients can respond adequately to the 10 mg daily dose, therefore individual dose adjustment should be considered.

If symptomatic control is not achieved after four weeks of treatment with CLETUS 20 mg daily, further investigation is advised.

Treatment of Zollinger-Ellison syndrome

In patients with Zollinger-Ellison syndrome, dosage should be individually adjusted and treatment continued for as long as clinically indicated. The recommended starting dose is CLETUS 60 mg per day. All patients with severe disease who responded poorly to other therapies maintained effective control and control was maintained in more than 90% of patients with doses of CLETUS between 20 mg and 120 mg / day. Daily dosages above 80 mg should be divided into two daily administrations.

Dosage in children

Children over 1 year of age and with a body weight ≥ 10 kg

Treatment of reflux esophagitis

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease

The recommended doses are as follows:

Age Weight Dosage ≥1 year of age 10-20 kg 10 mg once a day. The dose can be increased to 20 mg once daily if needed ≥2 years of age > 20 kg 20 mg once a day. The dose can be increased to 40 mg once daily if needed

Reflux esophagitis: The treatment period is 4-8 weeks.

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease: The treatment lasts 2-4 weeks. If symptomatic control is not achieved after 2-4 weeks, the patient should be further investigated.

Children and adolescents over 4 years of age

Treatment of duodenal ulcer caused by H. pylori

Official local, regional and national guidelines regarding bacterial resistance, duration of treatment (most commonly 7 days, but sometimes up to 14 days) and appropriate use of antibiotics should be considered when selecting the appropriate combination therapy.

The treatment must be carried out under the supervision of a specialist.

The recommended posology is as follows:

Weight Dosage 15-30 kg Combination with two antibiotics: CLETUS 10 mg, amoxicillin 25 mg / kg body weight and clarithromycin 7.5 mg / kg body weight, all administered simultaneously twice a day for one week. 31-40 kg Combination with two antibiotics: CLETUS 20 mg, amoxicillin 750 mg and clarithromycin 7.5 mg / kg body weight, are all administered twice daily for one week. > 40 kg Combination with two antibiotics: CLETUS 20 mg, amoxicillin 1 g and clarithromycin 500 mg, are all administered twice daily for one week.

Special populations

Impaired renal function

No dosage adjustment is required in patients with impaired renal function (see section 5.2).

Impaired liver function

In patients with impaired hepatic function, a daily dose of 10-20 mg may be sufficient (see section 5.2).

SENIOR CITIZENS(> 65 years)

Dosage adjustment is not necessary in elderly patients. (see section 5.2).

Method of administration

It is recommended to take CLETUS capsules in the morning, preferably on an empty stomach, swallowed whole with half a glass of water. The capsules should not be chewed or crushed.

For patients with swallowing difficulties and for children who can drink or swallow semi-solid foods

Patients can open the capsule and swallow the contents with half a glass of water, or mixed with slightly acidic liquids such as fruit juice or apple puree or still water. Patients should be advised that in such cases the dispersion should be swallowed immediately (or within 30 minutes) and that it should always be mixed just before drinking. Rinse the bottom with half a glass of water and drink the contents.

Alternatively, patients can dissolve the capsule in the mouth and swallow the contained granules with half a glass of water. The gastro-resistant granules should not be chewed.

04.3 Contraindications -

Hypersensitivity to omeprazole, benzimidazoline substitutes or to any of the excipients.

Omeprazole, like other proton pump inhibitors (PPIs), should not be administered concomitantly with nelfinavir (see section 4.5).

04.4 Special warnings and appropriate precautions for use -

In the presence of certain alarm symptoms (eg significant unintended weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when the presence of a gastric ulcer is suspected or confirmed, the malignant nature of the ulcer must be excluded as symptomatic response to therapy may delay a correct diagnosis.

Co-administration of atazanavir and proton pump inhibitors is not recommended (see section 4.5). If the combination of atazanavir and proton pump inhibitor is judged unavoidable, careful clinical monitoring (eg viral load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; the dose of omeprazole it must not exceed 20 mg.

Omeprazole, like all acid-suppressive medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into consideration in patients with low reserves or risk factors for reduced vitamin absorption. B12 in case of long-term therapies.

Omeprazole is a CYP2C19 inhibitor. Potential interaction with drugs metabolised by CYP2C19 should be considered at the initiation or end of treatment with omeprazole. An interaction between clopidogrel and omeprazole has been observed (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of clopidogrel and omeprazole should be discouraged (see section 4.5).

Interference with laboratory tests

An increased level of Chromogranin A (CgA) can interfere with diagnostic tests for neuroendocrine tumors. To avoid this interference, CLETUS treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). If the CgA and gastrin levels have not returned to the reference range after the initial measurement, measurements should be repeated 14 days after stopping the proton pump inhibitor treatment.

Hypomagnesemia

Proton pump inhibitors (PPIs) such as CLETUS have been shown to cause severe hypomagnesaemia in patients treated for at least three months and in many cases for one year. Serious symptoms of hypomagnesaemia include fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia. They can initially manifest insidiously and be neglected. Hypomagnesaemia in most patients improves after taking magnesium and discontinuing the proton pump inhibitor. Healthcare professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment. treatment in patients on therapy for a long time or on digoxin therapy or medicines that can cause hypomagnesaemia (e.g. diuretics). Severe hypomagnesaemia can produce hypocalcemia.

Fractures of the hip, wrist and spine

Proton pump inhibitors, especially when used in high doses and for prolonged periods (10% to 40% fracture. This increase may be partly due to other risk factors. Patients at risk of osteoporosis should receive treatment based on current clinical practice guidelines and must take an adequate amount of vitamin D and calcium.

Some children with chronic conditions may need long-term treatment although it is not recommended.

Treatment with proton pump inhibitors may cause a slightly increased risk of gastrointestinal infections from Salmonella And Campylobacter (see section 5.1).

As with all long-term treatments, especially if the duration of treatment is greater than 1 year, patients should be monitored regularly.

Subacute cutaneous lupus erythematosus (SCLE)

Proton pump inhibitors are associated with extremely infrequent cases of SCLE. In the presence of lesions, especially on the skin parts exposed to sunlight, and if accompanied by arthralgia, the patient should immediately consult a doctor and the healthcare professional should evaluate the opportunity to discontinue treatment with CLETUS. SCLE following treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

04.5 Interactions with other medicinal products and other forms of interaction -

Influence of omeprazole on the pharmacokinetics of other active substances

Active ingredients with pH-dependent absorption

Gastric pH-dependent absorption of active substances may be increased or decreased by decreased intragastric acidity during treatment with omeprazole.

Nelfinavir, atazanavir

Plasma levels of nelfinavir and atazanavir decrease when omeprazole is co-administered.

Concomitant administration of omeprazole and nelfinavir is contraindicated (see section 4.3). Co-administration of omeprazole (40 mg once daily) reduced the mean exposure of nelfinavir by approximately 40% and reduced the mean exposure of the pharmacologically active metabolite M8 by approximately 75-90%. The interaction may also involve inhibition of CYP2C19.

Concomitant administration of omeprazole and atazanavir is not recommended (see section 4.4). Co-administration of omeprazole (40 mg once daily) and atazanavir 300 mg / ritonavir 100 mg to healthy volunteers resulted in a 75% reduction in atazanavir exposure. The increase in atazanavir dose to 400 mg did not offset the impact of omeprazole on atazanavir exposure. Co-administration of omeprazole (20 mg once daily) and atazanavir 400 mg / ritonavir 100 mg to healthy volunteers resulted in an approximately 30% reduction in atazanavir exposure compared to atazanavir 300 mg / ritonavir 100 mg once. per day.

Digoxin

Concomitant treatment with omeprazole (20 mg / day) and digoxin in healthy subjects resulted in a 10% increase in the bioavailability of digoxin. Digoxin toxicity has rarely been reported. However, caution is advised in the use of high doses of omeprazole in elderly patients. Therapeutic monitoring of digoxin should therefore be increased.

Clopidogrel

Results from studies in healthy patients demonstrated a "pharmacokinetic (PK) / pharmacodynamic (PD) interaction between clopidogrel (loading dose 300 mg / maintenance dose 75 mg daily) and omeprazole (80 mg po daily), resulting in in a mean decrease of 46% in exposure to the active metabolite of clopidogrel and in a mean decrease of 16% in maximal inhibition (ADP induced) of platelet aggregation.

Diverging data from observational and clinical studies have been reported on the clinical implications of a PK / PD interaction of omeprazole in terms of major cardiovascular events. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged (see section 4.4).

Other active ingredients

The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and therefore clinical efficacy may be compromised. Concomitant use of posaconazole and erlotinib should be avoided.

Active substances metabolised by CYP2C19

Omeprazole is a moderate inhibitor of its main metabolising enzyme, CYP2C19. Therefore, the metabolism of concomitant active substances also metabolised by CYP2C19 may be decreased and systemic exposure to these substances increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin.

Cilostazol

Omeprazole, given at a dose of 40 mg to healthy volunteers in a cross-over study, increased the Cmax and AUC of cilostazol by 18% and 26%, respectively, and of one of its active metabolites by 29% and 69%, respectively. .

Phenytoin

Monitoring of phenytoin plasma concentration is recommended during the first two weeks after starting omeprazole treatment and, if a phenytoin dose adjustment is required, monitoring and further dose adjustment is recommended when ending treatment. with omeprazole.

Mechanism unknown

Saquinavir

Concomitant administration of omeprazole and saquinavir / ritonavir resulted in increased plasma levels of saquinavir up to approximately 70% with good tolerability in HIV-positive patients.

Tacrolimus

Concomitant administration of omeprazole has been reported to increase the serum levels of tacrolimus. Monitoring of tacrolimus concentrations and renal function (creatinine clearance) should be increased and, if necessary, the tacrolimus dosage adjusted.

Methotrexate

When given together with proton pump inhibitors, methotrexate levels have been reported to increase in some patients. When methotrexate is administered in high doses, a temporary withdrawal of omeprazole may need to be considered.

Influence of other active substances on the pharmacokinetics of omeprazole

CYP2C19 and / or CYP3A4 inhibitors

As omeprazole is metabolised by CYP2C19 and CYP3A4, the active substances inhibiting CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may increase the serum levels of omeprazole, decreasing its rate of metabolism. Co-administration of voriconazole results in more than doubled exposure to omeprazole. Since the administration of high doses of omeprazole was well tolerated, no dose adjustment of omeprazole is generally necessary. However, dose adjustment should be made. considered in patients with severe hepatic impairment and in the case of long-term treatment.

Inducers of CYP2C19 and / or CYP3A4

Active substances inducing CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort) may cause a decrease in the serum levels of omeprazole, increasing its metabolic rate.

04.6 Pregnancy and breastfeeding -

PREGNANCY

The results of three prospective epidemiological studies (more than 1000 exposed patient outcomes) indicate no adverse effects of omeprazole on pregnancy or fetal / newborn health. Omeprazole can be used during pregnancy.

FEEDING TIME

Omeprazole is excreted in breast milk but is unlikely to affect the infant when administered in therapeutic doses.

04.7 Effects on ability to drive and use machines -

CLETUS is unlikely to affect your ability to drive or use tools or machines.

Adverse drug reactions such as dizziness and visual disturbances may occur (see section 4.8). If they suffer from it, patients should not drive or operate machinery.

04.8 Undesirable effects -

The most common side effects (1-10% of patients) are headache, abdominal pain, constipation, diarrhea, flatulence, nausea / vomiting.

The following adverse reactions, identified or suspected, have been identified during clinical trials with omeprazole and post-marketing. In no case was a correlation with the administered drug dose established. Undesirable effects are classified according to frequency and Organ Classification System (SOC). Frequency categories are defined using the following convention: Very common (≥1 / 10), Common (≥1 / 100 to

SOC / frequency Side effects Disorders of the blood and lymphatic system Rare: Leukopenia, thrombocytopenia Very rare: Agranulocytosis, pancytopenia Disorders of the immune system Rare: Hypersensitivity reactions, eg. fever, angioedema and anaphylactic reaction / shock Metabolism and nutrition disorders Rare: Hyponatremia Not known: Hypomagnesaemia (see section 4.4 Special warnings and precautions for use), hypocalcaemia * Psychiatric disorders Uncommon: Insomnia Rare: Agitation, confusion, depression Very rare: Aggression, hallucinations Nervous system disorders Common: Headache Uncommon: Dizziness, paraesthesia, somnolence Rare: Changes in taste Eye disorders Rare: Blurred vision Ear and labyrinth disorders Uncommon: Dizziness Respiratory, thoracic and mediastinal disorders Rare: Bronchospasm Gastrointestinal disorders Common: Abdominal pain, constipation, diarrhea, flatulence, nausea / vomiting Rare: Dry mouth, stomatitis, gastrointestinal candidiasis Not known: Microscopic colitis Hepatobiliary disorders Uncommon: Elevation of liver enzyme values Rare: Hepatitis with or without jaundice Very rare: Hepatic failure, encephalopathy in patients with pre-existing liver disease Skin and subcutaneous tissue disorders Uncommon: Dermatitis, itching, rash, hives Rare: Alopecia, photosensitization Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN) Not known: subacute cutaneous lupus erythematosus (see section 4.4). Musculoskeletal and connective tissue disorders Uncommon Fracture of the hip, wrist or spine (see section 4.4 Special warnings and precautions for use) Rare: Arthralgia, myalgia Very rare: Muscle weakness Renal and urinary disorders Rare: Interstitial nephritis Diseases of the reproductive system and breast Very rare: Gynecomastia General disorders and administration site conditions Uncommon: Malaise, peripheral edema Rare: Increased sweating

* hypocalcemia can result from severe hypomagnesaemia.

Pediatric population

The safety of omeprazole was evaluated in a total of 310 children aged 0 to 16 years with acid-related disease. Limited long-term data are available in 46 children who received omeprazole maintenance therapy for up to 749 days in a clinical study in severe erosive esophagitis. The adverse event profile was generally the same as in adults. in both short-term and long-term treatment There are no long-term data regarding the effects of omeprazole treatment on puberty and growth.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address" www.agenziafarmaco.gov.it/it/responsabili ".

04.9 Overdose -

Information is available regarding overdose with omeprazole in humans. Doses up to 560 mg have been reported in the literature and there have been occasional reports of single oral doses up to 2400 mg of omeprazole (120 times the usually recommended clinical dose). nausea, vomiting, dizziness, abdominal pain, diarrhea and headache.In individual cases, apathy, depression and confusion were also observed.

The symptoms described were transient and no serious consequences were reported.

The rate of elimination did not change with increasing doses (first order kinetics). Treatment, if necessary, is symptomatic.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: acid pump inhibitor.

ATC code: A02BC01.

Mechanism of action

Omeprazole, a racemic mixture of two active enantiomers, reduces gastric acid secretion by a highly specialized mechanism of action. Omeprazole is a specific inhibitor of proton pump at the level of the gastric parietal cells.

It acts rapidly and promotes a reversible control of the inhibition of gastric acid secretion with a single daily administration.

Omeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the intracellular canaliculi within the parietal cell, where it inhibits the H +, K + -ATPase - proton pump. This action on the last stage of the gastric acid formation process is dose-dependent and causes a highly effective inhibition of acid secretion, both basal and stimulated, regardless of the stimulus used.

Pharmacodynamic effects

All observed pharmacodynamic effects are due to the activity of omeprazole on acid secretion.

Effects on gastric acid secretion

The oral administration of omeprazole once a day allows a rapid and effective inhibition of day and night gastric acid secretion, which reaches its maximum within the first 4 days of treatment.

In patients suffering from duodenal ulcer, the administration of 20 mg of omeprazole maintained an average reduction of 80% in intragastric acidity over 24 hours; 24 hours after the administration of omeprazole the peak of acid secretion, after stimulation with pentagastrin, is on average reduced by about 70%.

Oral administration of 20 mg of omeprazole maintains the intragastric pH at> 3 for a mean time of 17 hours out of 24 in patients with duodenal ulcer.

As a consequence of reduced acid secretion and intragastric acidity, omeprazole dose-dependently reduces / normalizes acid exposure of the esophagus in patients with gastroesophageal reflux disease.

Inhibition of acid secretion is related to the plasma concentration / time curve (AUC) of omeprazole and not to the actual plasma concentration at a given time.

No tachyphylaxis was observed during treatment with omeprazole.

Effects on Helicobacter pylori

Helicobacter pylori it is associated with peptic acid disease which includes duodenal ulcer disease and gastric ulcer disease. Helicobacter pylori it is considered the main culprit in the development of gastritis.

Helicobacter pylori together with gastric acid secretion they represent the most important factors for the development of peptic ulcer disease.

Helicobacter pylori it is the main factor in the development of atrophic gastritis which is associated with an increased risk of developing gastric tumors.

The eradication of Helicobacter pylori with omeprazole and antimicrobials it is associated with a high rate of scarring and long-term remission of peptic ulcers.

The dual therapies studied showed less efficacy than the triple therapies. However, they can be taken into account if known hypersensitivity precludes the use of a triple combination.

Other effects related to acid inhibition

During long-term treatment, an increase in the frequency of appearance of gastric glandular cysts has been observed, which represent the physiological consequence of the pronounced inhibition of acid secretion. These cystic formations are benign and reversible in nature.

The decrease in gastric acidity of any origin, including that due to proton pump inhibitors, increases the gastric bacterial load normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may cause a slightly increased risk of gastrointestinal infections Salmonella and Campylobacter.

During treatment with antisecretory medicinal products, serum gastrin increases in response to decreased acid secretion. Chromogranin A (CgA) also increases due to reduced gastric acidity. The increased level of CgA can interfere with diagnostic tests for neuroendocrine tumors. Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels, which may be falsely elevated following PPI treatment, to return within the reference range.

An increase in the number of ECL cells, possibly related to an increase in serum gastrin levels, has been observed in some patients (both children and adults) during long-term treatment with omeprazole.

Pediatric use

In an uncontrolled study with children (1 to 16 years of age) with severe reflux oesophagitis, omeprazole, at doses of 0.7 to 1.4 mg / kg, improved the degree of esophagitis in 90% of cases. and significantly reduced reflux symptoms. In a single-blind study, children aged 0-24 months with clinically diagnosed reflux oesophagitis were treated with 0.5, 1.0 or 1.5 mg omeprazole / kg. The frequency of vomiting / regurgitation episodes decreased by 50% after 8 weeks of treatment, regardless of dose.

Eradication of H. pylori in children

A double-blind, randomized clinical trial (Héliot study) established that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) is effective and safe in the treatment of H. pylori in children aged 4 and over with gastritis: eradication rate of "H. pylori: 74.2% (23/31 patients) with omeprazole + amoxicillin + clarithromycin versus 9.4% (3/32 patients) with amoxicillin + clarithromycin. However, no clinical benefit has been shown with regard to dyspeptic symptoms. This study does not support information for children under the age of 4.

05.2 "Pharmacokinetic properties -

Absorption

Omeprazole and omeprazole magnesium are sensitive to the acidic environment and are therefore administered orally in the form of gastro-resistant granules contained in capsules or tablets. The absorption of omeprazole is rapid, with maximum plasma levels visible approximately 1-2 hours after administration of the dose. . Absorption of omeprazole occurs in the small intestine and is usually completed within 3-6 hours. Concomitant food intake does not affect drug bioavailability. Systemic availability (bioavailability) after a single oral dose of omeprazole is approximately 40%. After repeated daily dosing the bioavailability increases to approximately 60%.

Distribution

The apparent volume of distribution in healthy subjects is approximately 0.3 L / kg body weight.

97% of omeprazole is bound to plasma proteins.

Metabolism

Omeprazole is completely metabolised by the cytochrome P450 (CYP) system. Most of the metabolism of omeprazole is dependent on the specific polymorphically expressed CYP2C19 isoform responsible for the formation of hydroxyomeprazole which is the major plasma metabolite. The remainder depends on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulfone. As a consequence of omeprazole's high affinity for CYP2C19, there is a potential for competitive inhibition and drug-drug metabolic interaction between omeprazole and other substrates of CYP2C19. . However, due to its low affinity for CYP3A4, omeprazole does not have the ability to inhibit the metabolism of other CYP3A4 substrates. Furthermore, omeprazole has no inhibitory effect on major CYP enzymes.

Approximately 3% of the Caucasian population and 15-20% of the Asian population have a functional deficiency of the CYP2C19 enzyme, thus being referred to as poor metabolisers. In these individuals, the metabolism of omeprazole is probably more catalysed by CYP3A4. After repeated dosing. of omeprazole 20 mg once daily, the mean AUC was 5 to 10 times higher in poor metabolisers than in subjects with a functional CYP2C19 enzyme (extensive metabolisers). Maximum plasma concentrations were 3 to 5 times higher. These results have no implications for the posology of omeprazole.

Excretion

The plasma elimination half-life of omeprazole is usually less than one hour after both single and repeated oral once-daily dosing. Omeprazole is completely cleared from plasma between doses, and there is therefore no tendency for accumulation during once daily administration. Approximately 80% of an oral dose of omeprazole is excreted in the urine as metabolites, the remainder in the faeces originating primarily from biliary secretion.

The AUC of omeprazole increases after repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. The dependence on time and dose is due to a decrease in first pass metabolism and systemic clearance. probably caused by an inhibition of the CYP2C19 enzyme by omeprazole and / or its metabolites (eg sulphone).

No effect of the metabolites on gastric acid secretion was observed.

Special populations

Impaired liver function

In patients with hepatic dysfunction, the metabolism of omeprazole is impaired, resulting in an increase in AUC. There was no tendency to accumulate when omeprazole was administered once daily.

Impaired renal function

The pharmacokinetics of omeprazole, including systemic bioavailability and rate of elimination, are not altered in patients with impaired renal function.

Senior citizens

The rate of metabolism of omeprazole is slightly reduced in elderly subjects (75-79 years of age).

Pediatric patients

During the treatment of children from 1 year of age at recommended doses, plasma concentrations comparable to those in adults were observed. In children less than 6 months of age, omeprazole clearance was reduced due to omeprazole's poor metabolic capacity.

05.3 Preclinical safety data -

Gastric ECL cell hyperplasia and carcinoids have been detected in trials in rats treated for life with omeprazole. These changes are the result of high hypergastrinemia secondary to acid inhibition and have been observed both following treatment with H2 antagonists, proton pump inhibitors and after partial fundus resection. These changes are therefore not attributable to a direct effect of any single active ingredient.

06.0 PHARMACEUTICAL INFORMATION -

06.1 Excipients -

Nucleus: microcrystalline cellulose, low-substituted hydroxypropyl cellulose, mannitol, croscarmellose sodium, polysorbate, povidone K-30, arginine, sodium lauryl sulfate, glycine, light magnesium carbonate.

Coating: hypromellose, methacrylic acid-ethyl acrylate copolymer, triethyl citrate, sodium hydroxide, titanium dioxide, talc.

Capsule: gelatin, indigo carmine (E-132), titanium dioxide, water.