MERREM

Package leaflet: Information for the user

Merrem 500 mg powder for solution for injection for intravenous use, 1000 mg powder for solution for injection for intravenous use

meropenem
Please read all of this leaflet carefully before you start using 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Merrem is and what it is used for

Merrem contains the active substance meropenem and belongs to a group of medicines called carbapenem antibiotics. It works by killing bacteria that can cause serious infections.
Merrem is used to treat the following conditions in adults and children aged three months and older:

• Lung infections (pneumonia)
• Lung and bronchial infections in patients with cystic fibrosis
• Complicated urinary tract infections
• Complicated abdominal infections
• Infections that may occur during or after childbirth
• Complicated skin and soft tissue infections
• Acute bacterial infections of the brain (meningitis)

Merrem may be used to treat febrile neutropenic patients with suspected bacterial infection.
Meropenem may be used to treat bacterial blood infections that could be associated with any of the above-mentioned types of infections.

2. What you need to know before using Merrem

Do not use Merrem if:

• you are allergic (hypersensitive) to meropenem or to any of the ingredients of this medicine (listed in section 6).
• you are allergic (hypersensitive) to other antibiotics such as penicillins, cephalosporins, or carbapenems; you may also be allergic to meropenem.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Merrem if:

• you have health problems, such as liver or kidney disease.
• you have previously experienced severe diarrhoea after taking other antibiotics.

You may develop a positive Coombs test, indicating the presence of antibodies that can destroy red blood cells. Your doctor will discuss this with you.
You may develop signs and symptoms of serious skin reactions (see section 4). If this occurs, speak immediately with your doctor or nurse so they can treat the symptoms.
If you notice unexplained muscle pain, tenderness or weakness and/or dark-coloured urine, inform your doctor immediately. This could be a sign of muscle breakdown (called rhabdomyolysis), which may lead to kidney problems.
Liver problems
Inform your doctor if you notice yellowing of the skin or eyes, itching of the skin, dark-coloured urine, or pale-coloured stools. These could be signs of a liver problem, which your doctor will need to investigate.
If you are unsure whether any of the above applies to you, consult your doctor or nurse before using Merrem.
Other medicines and Merrem
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
This is because Merrem may affect the way some medicines work, and some medicines may affect Merrem.
In particular, inform your doctor, pharmacist, or nurse if you are taking any of the following medicines:

• Probenecid (used to treat gout).
• Valproic acid/sodium valproate/valpromide (used to treat epilepsy). Merrem must not be used because it may reduce the effect of sodium valproate.
• Oral anticoagulant (used to treat or prevent blood clots).

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
It is preferable to avoid taking meropenem during pregnancy. Your doctor will decide whether you should use Merrem.
It is important that you inform your doctor if you are breastfeeding or intend to breastfeed before taking meropenem. Small amounts of the medicine may pass into breast milk. Therefore, your doctor will decide whether you should use Merrem while breastfeeding.
Driving and using machines
No studies have been conducted on the effect on the ability to drive or use machines. Merrem has been associated with headache, tingling or prickling sensation of the skin (paraesthesia). Any of these side effects may affect your ability to drive or use machines. Merrem may cause involuntary muscle movements leading to rapid and uncontrolled body movements (seizures). These are usually accompanied by loss of consciousness. Do not drive or operate machinery if you experience this side effect.
Merrem contains sodium
Merrem 500 mg: this medicine contains 45 mg of sodium (the main component of table salt or cooking salt) per 500 mg dose, equivalent to 2.25% of the maximum daily recommended sodium intake for an adult.
Merrem 1000 mg: this medicine contains 90 mg of sodium (the main component of table salt or cooking salt) per 1000 mg dose, equivalent to 4.5% of the maximum daily recommended sodium intake for an adult.
If you have a condition requiring sodium intake restriction, inform your doctor, pharmacist, or nurse.

3. How to use Merrem

Use this medicine exactly as instructed by your doctor, pharmacist,
or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.

Use in adults

• The dose depends on the type of infection you have, its location in the body, and its severity. Your doctor will decide the most appropriate dose for you.
• The usual dose for adults ranges from 500 mg (milligrams) to 2 g (grams). You will usually receive a dose every 8 hours. However, you may receive doses less frequently if your kidneys are not functioning properly.

Use in children and adolescents

• The dose for children aged over 3 months up to 11 years is determined based on the child's age and weight. The usual dose ranges from 10 mg to 40 mg of Merrem per kilogram (kg) of the child’s body weight. A dose is usually administered every 8 hours. Children weighing more than 50 kg will receive the same dose as adults.

How to use Merrem

• Merrem will be administered to you as an injection or infusion into a large vein.
• Normally, your doctor or nurse will administer Merrem to you.
• However, some patients, parents, or caregivers have been trained on how to administer Merrem at home. Instructions for administration are provided in this leaflet (in the section titled “Instructions for self-administration or administration to others of Merrem at home”). Always use Merrem exactly as directed by your doctor. Always consult your doctor if you have any doubts.
• Your injection must not be mixed or added to solutions containing other medicines.
• The injection may be given over approximately 5 minutes or over 15–30 minutes. Your doctor will instruct you on how to administer Merrem.
• Injections are usually given at the same time each day.

If you use more Merrem than you should
If you accidentally take more medicine than prescribed, inform your doctor immediately or go to the nearest hospital emergency department.

If you forget to use Merrem
If you miss an injection, take it as soon as possible. However, if it is almost time for the next dose, skip the missed dose.
Do not take a double dose (two injections at the same time) to make up for a forgotten dose.

If you stop using Merrem
Do not stop treatment with Merrem until your doctor tells you it is safe to do so.
If you have any questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Severe allergic reactions
If you experience any of the following signs or symptoms, seek immediate medical advice from your doctor or nurse.
You may need urgent medical treatment. Signs and symptoms may include sudden onset of:

• Severe rash, itching or hives.

• Swelling of the face, lips, tongue or other parts of the body.

• Shortness of breath, wheezing or difficulty breathing.

• Severe skin reactions including:

• Severe hypersensitivity reactions including fever, rash, changes in blood tests showing how your liver is functioning (increased liver enzyme levels), and an increase in a type of white blood cells (eosinophilia), as well as swollen lymph nodes. These may be signs of a multi-organ sensitivity disorder known as DRESS syndrome.

• Severe red, scaly skin rash, skin pustules, blisters or skin peeling, which may be associated with high fever and joint pain.

• Severe skin reactions that may appear as circular red patches, often with central blisters on the trunk, skin exfoliation, mouth, throat, nose, genital or eye ulcers, and which may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), or a more severe form (toxic epidermal necrolysis).

Damage to red blood cells (frequency not known)
Signs of such damage include:

• Unexpected shortness of breath.
• Red or brown discoloration of urine. If you notice any of the above signs, consult a doctor immediately.

Muscle breakdown

• Unexplained muscle pain, tenderness or weakness and/or dark-colored urine. If you notice these signs or symptoms, consult a doctor immediately.

Liver problems (uncommon)

• Yellowing of the skin and eyes (jaundice), itching, dark urine or pale stools. If you notice these signs or symptoms, consult a doctor immediately.

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

• Abdominal (stomach) pain.
• Feeling unwell (nausea).
• Malaise (vomiting).
• Diarrhea.
• Headache.
• Rash, itchy skin.
• Pain and inflammation.
• Increased number of platelets in the blood (detected by a blood test).
• Changes in blood tests, including those indicating liver function.

Uncommon (may affect up to 1 in 100 people)

• Blood disorders, including reduced platelet count (which may lead to easier bruising), increased number of certain white blood cells, reduced number of other white blood cells, and increased levels of a substance called 'bilirubin'. Your doctor will perform periodic blood tests.
• Changes in blood tests, including those indicating kidney function.
• Low potassium levels in the blood (which may cause weakness, muscle cramps, tingling sensations, and heart rhythm disturbances).
• Tingling sensation (pins and needles).
• Mouth or vaginal fungal infections (candidiasis).
• Intestinal inflammation with diarrhea.
• Pain in the veins at the injection site when Merrem is administered.
• Other blood abnormalities. Symptoms may include frequent infections, high body temperature and sore throat. Your doctor will perform periodic blood tests.

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

• Seizures.
• Acute disorientation and confusion (delirium).

Sudden chest pain, which may be a sign of a potentially severe allergic reaction known as Kounis syndrome, has been observed with other medicines of the same class. If this occurs, seek immediate medical advice from your doctor or nurse.

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

5. How to store Merrem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30°C.

Injection
After reconstitution:
Reconstituted solutions for intravenous injection must be used immediately.
The time interval between the start of reconstitution and the end of intravenous injection must not exceed:

• 3 hours if stored at temperatures up to 25°C;
• 12 hours if stored refrigerated (2°C–8°C).

Infusion
After reconstitution:
Reconstituted solutions for intravenous infusion must be used immediately.
The time interval between the start of reconstitution and the end of intravenous infusion must not exceed:

• 3 hours if stored at temperatures up to 25°C when Merrem is dissolved in sodium chloride;
• 24 hours if stored refrigerated at 2°C–8°C when Merrem is dissolved in sodium chloride;
• when Merrem is dissolved in dextrose, the solution must be used immediately.

From a microbiological point of view, unless the method of opening / reconstitution / dilution excludes the risk of microbiological contamination, the medicine should be used immediately.
If not used immediately, the times and conditions of storage during use are the responsibility of the user.
Do not freeze the reconstituted solution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the package and other information

What Merrem contains
The active substance is meropenem trihydrate, equivalent to 500 mg of anhydrous meropenem.
The active substance is meropenem trihydrate, equivalent to 1000 mg of anhydrous meropenem.
The other component is anhydrous sodium carbonate.
Description of the appearance of Merrem and contents of the pack

• Merrem is a powder ranging from white to pale yellow, for injectable solutions or infusion in vials. Packs containing 1 or 10 vials.

Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Manufacturer
Pfizer Service Company BV
10 Hoge Wei
1930 Zaventem
Belgium
This medicinal product is authorized in the Member States of the European Economic Area and in the
United Kingdom (Northern Ireland) under the following names:
Belgium: Meronem IV
Cyprus: MERONEM
Czech Republic: MERONEM
Finland: Meronem
France: MERONEM
Greece: Meronem
Italy: MERREM
Luxembourg: Meronem IV
Poland: Meronem
Sweden: Meronem
United Kingdom (Northern Ireland): Meronem IV
Medical notice/instructions
Antibiotics are used to treat infections caused by bacteria. They are not effective against infections caused by viruses.
Sometimes, a bacterial infection does not respond to a course of antibiotic treatment. One of the most common reasons for this is that the bacteria causing the infection are resistant to the antibiotic being taken. This means they can survive and even multiply despite the antibiotic.
Bacteria can become resistant to antibiotics for many reasons. Using antibiotics correctly can help reduce the likelihood of bacteria becoming resistant to them.
When a doctor prescribes a course of antibiotic treatment, it is intended solely for treating the current illness. Following the advice below will help prevent the development of bacterial resistance, which can stop antibiotics from working.

1. It is very important to take the correct dose of antibiotic, at the correct times and for the correct number of days. Read the instructions in the leaflet and, if you do not understand something, ask your doctor or pharmacist for clarification.
2. Do not take antibiotics unless they have been specifically prescribed for you, and use them only to treat the infection for which they were prescribed.
3. Do not take antibiotics that have been prescribed for other people, even if they have an infection similar to yours.
4. Do not give antibiotics prescribed for you to other people.
5. If you have leftover antibiotics after completing the course prescribed by your doctor, return them to a pharmacy for proper disposal.

The following information is intended exclusively for healthcare professionals or trained caregivers:
Instructions for self-administration or administration of Merrem to others at home
Some patients, parents, or caregivers have been trained to administer Merrem at home.
Caution – This medicine may be self-administered or administered to others at home only after receiving appropriate training from a doctor or nurse.
How to prepare this medicine

• The medicine must be mixed with another liquid (the solvent). Your doctor will tell you how much solvent to use.
• Use the medicine immediately after preparation. Do not freeze.
  1. Wash and dry your hands thoroughly. Prepare a clean work area.
  2. Remove the Merrem container (the vial) from its packaging. Check the vial and the expiration date. Ensure the vial is intact and shows no signs of damage.
  3. Remove the colored cap and clean the grey rubber stopper with alcohol. Allow the rubber stopper to dry.
  4. Insert a new sterile needle into a new sterile syringe, without touching the ends.
  5. Draw up the recommended amount of sterile "Water for Injections" and place it into the syringe. The amount of liquid required is indicated in the table below:

Note: If the prescribed dose of Merrem is greater than 1 g, you will need to use more than one vial of Merrem. You may then withdraw the liquid and transfer it into a syringe.

6. Insert the needle of the syringe into the center of the grey rubber stopper of the vial or vials of Merrem and inject the recommended amount of water for injections into the vial(s).
7. Remove the needle from the vial and shake the vial well for about 5 seconds, or until the powder is completely dissolved. Clean the grey rubber stopper again with a new alcohol-soaked swab and allow the rubber stopper to dry.
8. With the plunger fully inserted into the barrel of the syringe, reinsert the needle into the grey rubber stopper at the top. Hold both the syringe and the vial securely and turn the vial upside down.
9. Keeping the tip of the needle submerged in the liquid, pull back the plunger of the syringe to withdraw all the liquid from the vial into the syringe.
10. Remove the needle and syringe from the vial and dispose of the empty vial in a safe manner.
11. Hold the syringe upright with the needle tip pointing upwards. Tap the syringe gently to bring any air bubbles to the surface.
12. Remove any air from the syringe by gently pushing the plunger until all air is expelled.
13. If you are using Merrem at home, dispose of used needles and infusion lines properly. If your doctor decides to discontinue treatment, dispose of any unused Merrem appropriately.

How to administer the injection
This medicine may also be administered through a small cannula or venflon, or via a port-type catheter or central infusion line.

Administration of Merrem using a small cannula or venflon (cannula)

1. Remove the needle from the syringe and carefully dispose of the needle in a sharps container.
2. Wipe the tip of the small cannula or venflon with alcohol and allow it to dry. Open the cannula cap and attach it to the syringe.
3. Slowly push the syringe plunger to administer the antibiotic steadily over approximately 5 minutes.
4. Once the antibiotic has been administered and the syringe is empty, remove the syringe and flush the site as recommended by your doctor or nurse.
5. Replace the cap on the cannula and carefully dispose of the syringe in a sharps container.

Administration of Merrem using a port-type catheter or central infusion line

1. Remove the cap from the port or infusion line, clean the end of the line with alcohol, and allow it to dry.
2. Attach the syringe and gently push the plunger to administer the antibiotic steadily over approximately 5 minutes.
3. After administration of the antibiotic is complete, remove the syringe and flush the site as recommended by your doctor or nurse.
4. Attach a new sterile cap to the central infusion line and carefully dispose of the syringe in a sharps container.