Vaborem 1 g/1 g polvo para concentrado para solucion para perfusion

Prospecto: information for the patient

Vaborem 1g/1g powder for concentrate for solution for infusion

meropenem/vaborbactam

Read this prospect carefully before starting to use this medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

1.What is Vaborem and for what it is used

2.What you need to know before starting to receive Vaborem

3.How you will be administered Vaborem

4.Possible adverse effects

5.Storage of Vaborem

6.Contents of the package and additional information

What is Vaborem

Vaborem is an antibiotic that contains two active principles: meropenem and vaborbactam.

• Meropenem belongs to a group of antibiotics called «carbapenems». They can kill many types of bacteria by preventing them from building protective walls around their cells.
• Vaborbactam is a «beta-lactamase inhibitor». It blocks the action of an enzyme that allows some bacteria to resist the action of meropenem. This helps meropenem to kill some bacteria that it cannot kill on its own.

How Vaborem is used

Vaborem is used in adults to treat certain severe bacterial infections:

• of the bladder or kidneys (urinary tract infections)
• of the stomach and intestines (intra-abdominal infections)
• of the lungs (pneumonia)

It is also used to treat infections:

• of the blood associated with one of the infections mentioned above
• caused by bacteria that other antibiotics may not be able to kill

You should not receive Vaborem if

• you are allergic to meropenem, vaborbactam, or any of the other components of this medication (listed in section 6).
• you are allergic to other carbapenem antibiotics (the group to which meropenem belongs).
• you have ever had a severe allergic reaction to other antibiotics belonging to the beta-lactam group (including penicillins, cephalosporins, or monobactam antibiotics).

Warnings and precautions

Consult your doctor or nurse before starting to receive Vaborem if:

• you have ever had an allergic reaction to other antibiotics related to the beta-lactam group (including carbapenems, penicillins, cephalosporins, or monobactam antibiotics).
• you have ever had severe diarrhea during or after antibiotic treatment.
• you have ever had seizures.

If any of the above concerns you or if you are unsure, speak with your doctor or nurse before using Vaborem.

You may develop signs and symptoms of severe skin reactions (see section 4). If this happens, inform your doctor or nurse immediately so that they can treat the symptoms.

Speak with your doctor or nurse if you experience diarrhea during treatment.

This medication may affect the liver. Your doctor may take a blood sample to check how your liver is functioning while you are taking the medication.

New infection

Although Vaborem may combat certain bacteria, there is a possibility that you may develop a new infection caused by another microorganism during or after treatment. Your doctor will closely monitor you to detect any new infection and will give you another treatment if necessary.

Blood tests

If you are to undergo any blood tests, inform your doctor that you are taking Vaborem, as it may give an abnormal result with a test called the "Coombs test". The results of this test show the presence of antibodies that may destroy red blood cells or may be affected by your immune system's response to Vaborem.

Children or adolescents

Vaborem should not be used in children or adolescents under 18 years of age, as its safety in these age groups is unknown.

Other medications and Vaborem

Inform your doctor if you are using, have used recently, or may need to use any other medication.

It is especially important to inform your doctor if you are taking any of the following medications:

• medications used to treat epilepsy called valproic acid, sodium valproate, or valpromide, as Vaborem may reduce their effect
• a medication for gout called probenecid
• oral anticoagulants, such as warfarin (used to treat or prevent blood clots)
• oral contraceptives containing estradiols and/or progesterone, as Vaborem may reduce their effect.Women of childbearing age should be advised to use alternative effective contraceptive methods during Vaborem treatment and for a period of 28 days after treatment is discontinued.
• medications metabolized predominantly by CYP1A2 (e.g., theophylline), CYP3A4 (e.g., alprazolam, midazolam, tacrolimus, sirolimus, cyclosporine, simvastatin, omeprazole, nifedipine, quinidine, and ethinylestradiol) and/or transported by P-gp (e.g., dabigatran, digoxin) as Vaborem may reduce their effect.

If any of the above concerns you, inform your doctor before using Vaborem.

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, or intend to become pregnant, consult your doctor before receiving this medication.

As a precaution, you should not take this medication during pregnancy.

It is essential to inform your doctor if you are breastfeeding or intend to breastfeed before receiving Vaborem. Small amounts of this medication may pass into breast milk and affect the baby. Therefore, you should stop breastfeeding before starting Vaborem treatment.

Driving and operating machinery

Vaborem may make you feel dizzy, drowsy, and lethargic, may give you a headache or a tingling sensation, or, in rare cases, cause a seizure or convulsion. This may affect your ability to drive, use tools, or operate machinery.

Vaborem contains sodium

This medication contains 250mg of sodium (the main component of table salt/for cooking) in each vial. This is equivalent to 12.5% of the maximum daily sodium intake recommended for an adult.

The recommended dose is 2vials (a total of 2g of meropenem and 2gof vaborbactam), administered every 8 hours. Your doctor will decide how many days of treatment are needed, depending on the type of infection.

A doctor or nurse will administer Vaborem via infusion (drip) in a vein over 3 hours.

Patients with kidney problems

If you have kidney problems, your doctor may reduce the dose. Your doctor may want to do some blood tests to see how your kidneys are working.

If you are given too much Vaborem

A doctor or nurse will administer Vaborem, so it is unlikely that you will be given the wrong dose. If you think you have been given too much Vaborem, inform your doctor or nurse immediately.

If you miss a dose of Vaborem

If you think you have missed a dose, inform your doctor or nurse immediately.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

If you notice any of the following severe side effects, inform your doctor immediately as you may need urgent treatment:

• Severe allergic reactions that may include sudden swelling of the lips, face, throat, or tongue, difficulty swallowing or breathing, severe skin rash or other severe skin reactions, or a drop in blood pressure (which may cause dizziness or weakness). These reactions can be potentially fatal.
• Diarrhea that worsens over time or does not pass, or stools that contain blood or mucus. This can occur during treatment with Vaborem or after stopping it. It may be caused by bacteria called Clostridium difficile. If this happens, do not take medications that stop or reduce bowel movements.

Other side effects

If you notice any of the following side effects, inform your doctor or nurse:

Frequent:(may affect up to 1 in 10 people)

• Increased platelet count (a type of blood cell); appears in blood tests
• Decreased potassium or sugar levels; appears in blood tests
• Headache
• Low blood pressure
• Diarrhea
• Nausea or vomiting
• Swelling, redness, and/or pain around the needle through which the medicine is administered in a vein
• Fever
• Increased levels of certain liver enzymes called alanine aminotransferase or aspartate aminotransferase; appears in blood tests
• Increased levels of an enzyme called alkaline phosphatase that may be a sign that the liver, gallbladder, or bones are not functioning as well as they should; appears in blood tests
• Increased levels of an enzyme called lactate dehydrogenase that may be a sign of damage to some organs; appears in blood tests

Less frequent:(may affect up to 1 in 100 people)

• Swelling and irritation in the large intestine or colon; this may cause diarrhea, fever, and cramps and is due to another colon infection
• Fungal infections, including those of the vagina or mouth
• Decreased white blood cell count or some types of white blood cells called neutrophils and decreased platelet count; appears in blood tests
• Increased levels of a type of white blood cell called eosinophils; appears in blood tests
• Severe and sudden allergic reaction that requires urgent medical treatment and may include itching, skin color change, cramps, swelling, difficulty breathing, lightheadedness, and sudden drop in blood pressure
• Milder allergic reaction that may include redness, red bumps, skin peeling, itching, and general discomfort
• Reduced appetite
• Increased potassium or sugar levels; appears in blood tests
• Inability to fall asleep
• Seeing, hearing, or perceiving things that are not real
• Dizziness
• Trembling or agitation
• Itching or tingling sensation
• Feeling drowsy and lethargic
• Irritated, red, and swollen veins
• Pain in the veins
• Difficulty breathing
• Gas or feeling of fullness in the abdomen
• Stomach pain
• Itching skin
• Skin rash
• Skin rash with bumps that cause itching («hives»)
• Difficulty controlling the bladder
• Decreased kidney function
• Abnormal sensation in the chest
• At the site where Vaborem is administered in a vein, the following reactions may occur, alone or in combination: red skin (erythema); swollen, painful, and warm vein around the needle (phlebitis); a blood clot in the vein through which the needle was inserted into the skin (thrombosis at the infusion site)
• Pain
• Increased levels of a substance in the blood called creatine phosphokinase that is a sign of possible damage to certain tissues such as muscles and/or other organs; appears in blood tests
• Increased levels of a substance in the blood called bilirubin that is a sign of possible damage to red blood cells or that the liver is not functioning as well as it should; appears in blood tests
• Increased levels of certain substances in the blood called urea and creatinine that is a sign that the kidneys are not functioning as well as they should; appears in blood tests
• Reaction that occurs during or shortly after the administration of Vaborem that presents symptoms of general discomfort (feeling generally unwell) such as: decreased blood pressure, nausea, vomiting, cramps, fever, shortness of breath, rapid heartbeat, or difficulty breathing, headache

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

• Seizures (epileptic crises)

Frequency unknown:(cannot be estimated from available data)

• Very severe and severe decrease in white blood cell count; appears in blood tests
• Hemolytic anemia (a disease in which red blood cells are damaged and their number decreases), which may cause fatigue and yellowing of the skin and eyes
• Swelling of the tongue, face, lips, or throat
• Sudden appearance of a severe skin rash with large, itchy bumps or blisters or skin peeling, possibly with high fever, joint pain, abnormal liver function, kidney function, or lung function (these may be signs of more serious diseases called toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, generalized acute exanthematous pustulosis, or a disease known as drug reaction with eosinophilia and systemic symptoms (DRESS))
• Positive result in a test called the «Coombs test» that is used to identify hemolytic anemia (see above) or a reaction of your immune system to Vaborem
• Acute disorientation and confusion (delirium)

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through the national reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Composition of Vaborem

• The active principles are meropenem and vaborbactam. Each vial contains 1g of meropenem (in the form of meropenem trihydrate) and 1gvaborbactam.
• The other component is sodium carbonate

Appearance of the product and contents of the container

Vaborem is a white to light yellow powder for concentrate for solution for infusion supplied in a vial.

Vaborem is available in containers containing 6 vials.

Marketing Authorization Holder

Menarini International Operations Luxembourg S.A.

1, Avenue de la Gare

L-1611, Luxembourg

Luxembourg

Responsible for manufacturing

ACS Dobfar, S.p.A.

Nucleo Industriale S. Atto

(loc. S. Nicolo’ a Tordino)

64100 Teramo (TE)

Italy

For more information about this medicine, please contact the local representative of the

marketing authorization holder:

Last update of this leaflet:07/2023

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

Vaborem is intended for intravenous administration (i.v.), only after reconstitution and dilution.

Use aseptic techniques for the preparation and administration of the solution.

The number of vials used for a single dose will depend on the patient's creatinine clearance (ACr).

Reconstitution:

20ml of 9mg/ml (0.9%) sodium chloride (normal saline) injection solution from a 250ml infusion bag of 9mg/ml (0.9%) sodium chloride injection solution should be withdrawn and used to reconstitute each vial and the appropriate number of vials of meropenem/vaborbactam for the corresponding dose of Vaborem:

• Reconstitute 2vials for the 2g/2g dose of Vaborem
• Reconstitute 1vial for the 1g/1g and 0.5g/0.5g doses of Vaborem

After mixing carefully to dissolve, the reconstituted meropenem/vaborbactam solution will have an approximate concentration of 0.05g/ml of meropenem and an approximate concentration of 0.05g/ml of vaborbactam. The final volume is approximately 21.3ml. The reconstituted solution is not for direct injection. The reconstituted solution should be diluted before intravenous infusion.

Dilution:

To prepare the 2g/2g dose of Vaborem for intravenous infusion: immediately after reconstitution of two vials, the contents of each of the two reconstituted vials should be withdrawn and added to a 250ml infusion bag of 9mg/ml (0.9%) sodium chloride injection solution. The final concentration of the infusion of meropenem and vaborbactam will be approximately 8mg/ml each.

To prepare the 1g/1g dose of Vaborem for intravenous infusion: immediately after reconstitution of one vial, the contents of the reconstituted vial should be withdrawn and added to a 250ml infusion bag of 9mg/ml (0.9%) sodium chloride injection solution. The final concentration of the infusion of meropenem and vaborbactam will be approximately 4mg/ml each.

To prepare the 0.5g/0.5g dose of Vaborem for intravenous infusion: immediately after reconstitution of one vial, 10.5ml of the contents of the reconstituted vial should be withdrawn and added to a 250ml infusion bag of 9mg/ml (0.9%) sodium chloride injection solution. The final concentration of the infusion of meropenem and vaborbactam will be 2mg/ml each.

The solution should be visually inspected for particles after dilution. The color of the diluted solution is transparent to light yellow.

After dilution, the infusion should be administered within 4hours if stored at 25°C, or within 22hours if refrigerated at 2–8°C.

From a microbiological point of view, the medicinal product should be used immediately after reconstitution and dilution.

Vaborem is not chemically compatible with solutions containing glucose. This medicinal product should not be mixed with other products, except those mentioned in section 6.6 of the SmPC.