Esomeprazole TilloMed

Package leaflet: Information for the patient

Esomeprazole Tillomed 40 mg powder for injectable/infusion solution

Esomeprazole
Generic medicine
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Esomeprazole Tillomed is and what it is used for
2. What you need to know before being administered Esomeprazole Tillomed
3. How Esomeprazole Tillomed is administered
4. Possible side effects
5. How to store Esomeprazole Tillomed
6. Contents of the pack and other information

1. What Esomeprazole Tillomed is and what it is used for

Esomeprazole Tillomed contains a medicine called esomeprazole. It belongs to a group of medicines known as "proton pump inhibitors", which work by reducing the amount of acid produced by the stomach.
Esomeprazole Tillomed is used for short-term treatment of certain conditions when the patient is unable to take oral therapy. It is used to treat the following indicated conditions:
Adults

• “Gastroesophageal reflux disease” (GERD). This condition occurs when stomach acid flows back into the oesophagus (the tube between the throat and stomach), causing pain, inflammation, and heartburn.
• Stomach ulcers caused by medicines called NSAIDs (non-steroidal anti-inflammatory drugs). Esomeprazole may also be used to prevent the development of stomach ulcers during treatment with NSAIDs.
• Prevention of rebleeding after endoscopic treatment for acute bleeding from gastric or duodenal ulcers.

Children and adolescents aged 1 to 18 years

• “Gastroesophageal reflux disease” (GERD). This condition occurs when stomach acid flows back into the oesophagus (the tube between the throat and stomach), causing pain, inflammation, and heartburn.

2. What you need to know before being given Esomeprazolo Tillomed

Esomeprazolo Tillomed must not be given to you if:

• you are allergic to esomeprazole or to any of the other ingredients of this medicine (listed in section 6).
• you have ever had a severe skin rash, skin peeling, skin rash with blisters and/or mouth ulcers after taking esomeprazole or other related medicines.
• you are allergic to other proton pump inhibitor medicines (e.g. pantoprazole, lansoprazole, rabeprazole, omeprazole).
• you are taking a medicine containing nelfinavir (used in the treatment of HIV infection).

Esomeprazolo Tillomed must not be given to you if any of the above apply. If you are unsure, consult your doctor or nurse before this medicine is administered.

Warnings and precautions

Talk to your doctor or pharmacist before being given Esomeprazolo Tillomed if:

• you have severe liver problems
• you have severe kidney problems
• you have ever had a skin reaction after treatment with a medicine similar to Esomeprazolo Tillomed that reduces stomach acidity
• you need to undergo a specific blood test (Chromogranin A).

Esomeprazole may mask symptoms of other diseases. Therefore, if any of the following
occur before or after administration of Esomeprazolo Tillomed, contact your doctor
immediately:

• you lose a lot of weight without an obvious reason and have difficulty swallowing
• you experience stomach pain or digestive problems
• you vomit food or blood
• your stools are black (blood in stools).

Use of a proton pump inhibitor such as esomeprazole may slightly increase the risk of fractures of the hip, wrist, or spine, especially if used for more than one year. If you suffer from osteoporosis or are taking corticosteroids (which may increase the risk of osteoporosis), inform your doctor. If you notice the appearance of a skin rash, especially in areas exposed to sunlight, contact your doctor as soon as possible, as treatment with esomeprazole may need to be discontinued. Remember to also report any other adverse effects such as joint pain.

Serious skin reactions have been reported during treatment with esomeprazole, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS). Stop taking esomeprazole and seek immediate medical advice if you notice any of the symptoms related to these serious skin reactions described in section 4.

If at any time during treatment (even after several weeks) you develop a skin rash or any of these skin symptoms, stop taking this medicine and contact your doctor immediately.

Other medicines and Esomeprazolo Tillomed

Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription. Esomeprazole may affect how some medicines work, and some medicines may affect the action of esomeprazole.

Esomeprazolo Tillomed must not be given to you if you are taking a medicine containing nelfinavir (used in the treatment of HIV infection).

Inform your doctor or nurse if you are taking any of the following medicines:

• atazanavir (used to treat HIV infection)
• clopidogrel (used to prevent blood clots)
• ketoconazole, itraconazole or voriconazole (used to treat fungal infections)
• erlotinib (used to treat cancer)
• citalopram, imipramine or clomipramine (used to treat depression)
• diazepam (used to treat anxiety, for muscle relaxation, or for epilepsy)
• phenytoin (used for epilepsy). If you are taking phenytoin, your doctor will need to monitor you when starting or stopping treatment with esomeprazole.
• medicines used to thin the blood, such as warfarin. Your doctor will need to monitor you when starting or stopping treatment with esomeprazole.
• cilostazol (used to treat intermittent claudication – leg pain when walking caused by poor blood circulation).
• cisapride (used for indigestion and heartburn)
• digoxin (used for heart problems)
• methotrexate (a medicine used in high-dose chemotherapy for cancer) – if you are taking a high dose of methotrexate, your doctor may temporarily discontinue your treatment with Esomeprazolo.
• tacrolimus (used in organ transplants)
• rifampicin (used to treat tuberculosis)
• St. John’s wort (Hypericum perforatum) (used to treat depression).

Pregnancy, breastfeeding and fertility

If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before this medicine is administered.

Pregnancy

Your doctor will decide whether you can take esomeprazole during this period.

Breastfeeding

It is not known whether esomeprazole passes into breast milk. Therefore, you must not receive esomeprazole if you are breastfeeding.

Driving and using machines

It is unlikely that esomeprazole will affect your ability to drive or use machines. However, side effects such as dizziness or blurred vision may rarely occur (see section 4). If affected, you must not drive or use machines.

3. How Esomeprazole Tillomed is administered

Esomeprazole may be administered to children and adolescents aged between 1 and 18 years, as well as to adults, including the elderly.
Instructions for use
Adults

• Esomeprazole Tillomed will be administered to you by a doctor, who will determine the dose necessary for you.
• The recommended dose is 20 mg or 40 mg administered once daily.
• If you have severe liver problems, the maximum dose is 20 mg per day (for gastroesophageal reflux disease).
• The medicine will be given as an injection or intravenous infusion. The procedure will last up to 30 minutes.
• The recommended dose for the prevention of re-bleeding from gastric or duodenal ulcers is 80 mg administered as an intravenous infusion over 30 minutes, followed by a continuous infusion of 8 mg/h for 3 days. If you have severe liver problems, a continuous infusion of 4 mg/h for 3 days may be sufficient.

Children and adolescents aged 1 to 18 years

• Esomeprazole Tillomed will be administered by a doctor, who will determine the necessary dose.
• For children aged between 1 and 11 years, the recommended dose is 10 mg or 20 mg once daily.
• For children aged between 12 and 18 years, the recommended dose is 20 mg or 40 mg once daily.
• The medicine will be administered as an injection or intravenous infusion. The administration will last up to 30 minutes.

If you are given more Esomeprazole Tillomed than you need
If you think you have been given an excessive amount of Esomeprazole Tillomed, inform your doctor immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice any of the following serious side effects, stop taking
Esomeprazole Tillomed and contact your doctor immediately:

• Sudden wheezing, swelling of the lips, tongue, throat or body, skin rash, fainting or difficulty swallowing (severe allergic reaction) (rare).
• Sudden onset of severe skin rashes or redness of the skin with blisters or peeling, which may occur even after several weeks of treatment. Severe blisters and bleeding of the lips, eyes, mouth, nose and genitals may also occur. Skin rashes may progress to severe widespread skin damage (peeling of the superficial epidermis and mucous membranes), which can be life-threatening. These may be signs of "erythema multiforme", "Stevens-Johnson syndrome", or "toxic epidermal necrolysis" (very rare).
• Widespread rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome), observed very rarely.
• Yellowing of the skin, dark urine and fatigue, which may be symptoms of liver problems (rare).

Other side effects include:
Common (may affect up to 1 in 10 people):

• Headache
• Stomach and/or intestinal problems: diarrhoea, stomach pain, constipation, flatulence
• Feeling unwell (nausea) or illness (vomiting)
• Reaction at the injection site
• Benign polyps in the stomach

Uncommon (may affect up to 1 in 100 people):

• Swelling of the feet and ankles
• Sleep disturbances (insomnia)
• Dizziness, tingling, tiredness
• Sensation of dizziness
• Visual disturbances such as blurred vision
• Dry mouth
• Changes in blood test values assessing liver function
• Skin rash, hives and itching
• Bone fracture of the hip, wrist or spine (when esomeprazole is used at high doses and for a long period of time)

Rare (may affect up to 1 in 1,000 people):

• Blood disorders, such as reduced number of white blood cells or platelets. This may cause weakness, bruising or increased susceptibility to infections.
• Low sodium levels in the blood. This may cause weakness, feeling unwell (vomiting) and muscle spasms.
• Restlessness, confusion, depression
• Taste disturbances
• Sudden sensation of breathlessness or shortness of breath (bronchospasm)
• Inflammation inside the mouth
• An infection called "candidiasis" affecting the intestine, caused by a fungus
• Liver problems, including jaundice, which may cause yellowing of the skin, dark urine and fatigue
• Hair loss (alopecia)
• Skin rash after exposure to sunlight
• Joint pain (arthralgia) or muscle pain (myalgia)
• General feeling of malaise and lack of energy
• Increased sweating

Very rare (may affect up to 1 in 10,000 people):

• Changes in blood cell counts including agranulocytosis (lack of white blood cells)
• Aggression
• Seeing, perceiving or hearing things that are not real (hallucinations)
• Severe liver problems leading to liver failure and brain inflammation (encephalitis)
• Muscle weakness
• Severe kidney problems
• Breast enlargement in men

Not known: frequency cannot be estimated from the available data

• If you take esomeprazole for more than three months, your blood magnesium levels may decrease. Low magnesium levels may cause fatigue, involuntary muscle contractions, confusion, cramps, dizziness or increased heart rate. If you experience any of these symptoms, consult your doctor immediately. Low magnesium levels may also lead to reduced levels of potassium or calcium in the blood. Your doctor may perform periodic blood tests to monitor your magnesium levels.
• Inflammation of the intestine (which may lead to diarrhoea).
• Skin rash, possibly associated with joint pain.

In very rare cases, esomeprazole may affect white blood cells and cause immunodeficiency. If you develop an infection with symptoms such as fever and a severe deterioration in your general health, or fever with signs of local infection such as pain in the neck, throat or mouth, or difficulty urinating, you must contact your doctor as soon as possible so that a lack of white blood cells (agranulocytosis) can be ruled out by a blood test. It is important that you inform your doctor about all medicines you are taking.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Esomeprazole Tillomed

Keep this medicine out of the sight and reach of children.
Your doctor or hospital pharmacist is responsible for the correct storage, use, and disposal of Esomeprazole Tillomed.
Do not use this medicine after the expiry date stated on the vial after "EXP.". The expiry date refers to the last day of that month.
Do not store above 25 °C.
Store in the original packaging to protect the medicine from light. However, vials may be kept under normal indoor lighting conditions outside the box for up to 24 hours.
Do not refrigerate.
Chemical and physical in-use stability has been demonstrated for 12 hours at a temperature of
30 °C.
From a microbiological standpoint, the product should be used immediately, unless the method of reconstitution excludes the risk of microbial contamination.
If not used immediately, the conditions and duration of in-use storage are the responsibility of the user.
Do not use the solution if its appearance has changed.

6. Package contents and other information

What Esomeprazolo Tillomed contains
The active substance is esomeprazole sodium. Each vial of powder for injectable/infusion solution contains 42.5 mg of esomeprazole sodium, equivalent to 40 mg of esomeprazole.
The other components are: disodium edetate and sodium hydroxide (for pH adjustment).
Each vial contains less than 1 mmol of sodium (23 mg), therefore it is essentially “sodium-free”.

Description of the appearance of Esomeprazolo Tillomed and contents of the pack
Esomeprazolo Tillomed 40 mg powder for injectable/infusion solution is presented as a white or almost white porous mass or powder. It is converted into a solution before administration.
Esomeprazolo Tillomed is contained in a 5 ml clear type I glass vial with a greyish-brown bromobutyl rubber stopper and a removable purple aluminium seal.
Esomeprazolo Tillomed is available in packs of 1, 10 and 50 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Tillomed Italia S.r.l.
Viale Richard 1, Torre A
20143, Milan
Italy

Manufacturer
Tillomed Malta Limited,
Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta

This medicinal product is authorised in the European Economic Area Member States under the following names:

| Country | Product Name | |--------|--------------| | Germany | Esomeprazol Tillomed 40 mg, powder for solution for injection/infusion | | Italy | Esomeprazolo Tillomed | | France | ESOMEPRAZOLE TILLOMED 40 mg, poudre pour solution injectable/pour perfusion | | Poland | Esomeprazole Zentiva | | Austria | Esomeprazol Tillomed 40 mg, powder for solution for injection/infusion | | Netherlands | Esomeprazol Tillomed 40 mg poeder voor oplossing voor injectie/infusie | | Ireland | Esomeprazole Tillomed 40 mg powder for solution for injection/infusion |

The following information is intended for healthcare professionals only.

Esomeprazole Tillomed 40 mg powder for injectable/infusion solution contains
40 mg of esomeprazole as the sodium salt. Each vial contains disodium edetate and
sodium hydroxide (sodium <1 mmol).
The vials are for single use only. If the entire reconstituted content of the vial is not required for a single dose, the unused solution must be discarded.
For further information on dosage recommendations and storage conditions, see sections 3 and 5, respectively.
Preparation and administration of the reconstituted solution
To reconstitute the solution, remove the coloured plastic cap from the top of the vial of Esomeprazole Tillomed 40 mg powder for injectable/infusion solution and pierce the stopper at the centre of the marked circle, keeping the needle in a vertical position to ensure proper penetration of the stopper.
The reconstituted injectable/infusion solution must be clear and colourless to very pale yellow. Before administration, it should be visually inspected for particulate matter and discoloration, and only a clear solution should be used.
Do not refrigerate.
Chemical and physical in-use stability has been demonstrated for 12 hours at a temperature of
30 °C.
From a microbiological standpoint, the product should be used immediately unless the reconstitution method excludes the risk of microbial contamination.
If not used immediately, the conditions and duration of in-use storage are the responsibility of the user.
Esomeprazole Tillomed 40 mg powder for injectable/infusion solution
Preparation of the injectable solution
40 mg injection
For the reconstituted esomeprazole solution at a concentration of 8 mg/ml: prepare the solution by adding 5 ml of 0.9% sodium chloride for intravenous use to the 40 mg esomeprazole vial.
The reconstituted injectable solution must be administered intravenously over at least 3 minutes.
For further information on dose administration, see section 4.2 of the SmPC.
Preparation of the infusion solution
40 mg infusion (400 µg/ml or 0.4 mg/ml)
Dissolve the contents of one 40 mg esomeprazole vial in 100 ml of 0.9% sodium chloride for intravenous use.
80 mg infusion (800 µg/ml or 0.8 mg/ml)
Dissolve the contents of two 40 mg esomeprazole vials in 100 ml of 0.9% sodium chloride for intravenous use.
For further information on dose administration, see section 4.2 of the SmPC.
Disposal
Any unused medicine and waste material arising from this medicine must be disposed of in accordance with local regulations.