VABOREM 1 g/1 g POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you are given Vaborem

Vaborem must not be given to you if

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

Warnings and precautions

Tell your doctor or nurse before you are given Vaborem if:

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

If any of the above applies to you, or if you are not sure, tell your doctor or nurse before using Vaborem.

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

Tell your doctor or nurse if you get diarrhoea during treatment.

This medicine may affect your liver. Your doctor may take some blood from you to check how your liver is working while you are taking the medicine.

New infection

Although Vaborem can combat certain bacteria, there is a possibility that you may get a different 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 going to have any blood tests, tell your doctor that you are taking Vaborem, as you may get an abnormal result with a test called a ‘Coombs test’. The results of this test show the presence of antibodies that can destroy red blood cells or that may be affected by your immune system's response to Vaborem.

Children or adolescents

Vaborem must not be used in children or adolescents under 18 years of age, as it is not known if it is safe to use the medicine in these age groups.

Other medicines and Vaborem

Tell your doctor if you are taking, have recently taken or might take any other medicines.

It is especially important that you tell your doctor if you are taking any of the following medicines:

• medicines used to treat epilepsy called valproic acid, sodium valproate or valpromide as Vaborem may decrease their effect
• a medicine for gout called probenecid
• oral anticoagulants, such as warfarin (used to treat or prevent blood clots)
• hormonal oral contraceptives that contain oestrogen and/or progesterone, as Vaborem may decrease their effect. Women of childbearing age should be advised to use alternative effective contraceptive methods during treatment with Vaborem and for 28 days after stopping treatment.
• medicines that are mainly broken down by CYP1A2 (e.g. theophylline), CYP3A4 (e.g. alprazolam, midazolam, tacrolimus, sirolimus, cyclosporine, simvastatin, omeprazole, nifedipine, quinidine and ethinylestradiol) and/or CYP2C (e.g. warfarin, phenytoin) and/or transported by P-gp (e.g. dabigatran, digoxin) as Vaborem may decrease their effect.

If any of the above applies to you, tell your doctor before using Vaborem.

Pregnancy and breast-feeding

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

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

It is important that you tell your doctor if you are breast-feeding or planning to breast-feed before you are given Vaborem. Small amounts of this medicine may pass into breast milk and may affect your baby. Therefore, you should stop breast-feeding before you start treatment with Vaborem.

Driving and using machines

Vaborem may make you feel dizzy, drowsy or lethargic, may give you a headache or a tingling sensation (pins and needles) or, in rare cases, cause a fit or convulsions. This may affect your ability to drive, use tools or machines.

Vaborem contains sodium

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

3. How Vaborem will be given to you

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

A doctor or nurse will give you Vaborem by infusion (drip) into 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 take some blood from you to see how your kidneys are working.

If you are given too much Vaborem

A doctor or nurse will give you Vaborem, so it is unlikely that you will be given too much. If you think you have been given too much Vaborem, tell your doctor or nurse immediately.

If you miss a dose of Vaborem

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

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

4. Possible side effects

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

Serious side effects

If you notice any of the following side effects, tell your doctor immediately because you may need urgent medical treatment:

• Severe allergic reactions that can include sudden swelling of your lips, face, throat or tongue, difficulty swallowing or breathing, a severe skin rash or other severe skin reactions, or a drop in blood pressure (which can make you feel dizzy or weak). These reactions can be life-threatening.
• Diarrhoea that gets worse or does not go away, or stools that contain blood or mucus. This can happen during treatment with Vaborem or after stopping treatment. It can be due to bacteria called Clostridium difficile. If this happens, do not take medicines that stop or slow down bowel movements.

Other side effects

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

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

• Increased number of platelets (a type of blood cell); seen in blood tests
• Decreased amount of potassium or sugar; seen in blood tests
• Headache
• Low blood pressure
• Diarrhoea
• Feeling sick or being sick
• Swelling, redness and/or pain around the needle where the medicine is given into a vein
• Fever
• Increased amount of liver enzymes called alanine aminotransferase or aspartate aminotransferase; seen in blood tests
• Increased amount of an enzyme called alkaline phosphatase that can be a sign that your liver, gallbladder or bones are not working as well as they should; seen in blood tests
• Increased amount of an enzyme called lactate dehydrogenase that can be a sign of damage to some of your organs; seen in blood tests

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

• Swelling and irritation in the large intestine or colon; this can cause diarrhoea, fever and abdominal cramps and is due to another infection of the colon
• Fungal infections, including those of the vagina or mouth
• Decreased number of white blood cells or some types of white blood cells called neutrophils and a decrease in platelets; seen in blood tests
• Increased number of a type of white blood cell called eosinophils; seen in blood tests
• Severe allergic reaction that needs urgent medical treatment and can include itching, change in skin colour, abdominal cramps, swelling, difficulty breathing, rapid heart beats or low blood pressure
• Less severe allergic reaction that can include redness, rash, skin peeling, itching or general feeling of being unwell
• Decreased appetite
• Increased amount of potassium or sugar; seen in blood tests
• Difficulty sleeping
• Seeing, hearing or feeling things that are not there
• Feeling dizzy
• Shaking or trembling
• Feeling of tingling (pins and needles)
• Feeling drowsy or lethargic
• Irritated, red and swollen veins
• Pain in the veins
• Difficulty breathing
• Wind or feeling bloated in the abdomen
• Stomach pain
• Itching of the skin
• Rash
• Rash with blisters and itching (hives)
• Difficulty controlling your bladder
• Decreased kidney function
• Abnormal feeling in the chest
• In the area where Vaborem is given into a vein, the following reactions may occur, alone or in combination: red skin (erythema); swollen, painful and hot vein around the needle (phlebitis); a blood clot in the vein where the needle was inserted through the skin (thrombosis at the infusion site)
• Pain
• Increased amount 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; seen in blood tests
• Increased amount of a substance in the blood called bilirubin that is a sign of possible damage to red blood cells or that your liver is not working as well as it should; seen in blood tests
• Increased amount of some types of substances in the blood called urea and creatinine that is a sign that your kidneys are not working as well as they should; seen in blood tests
• Reaction that happens during or soon after the infusion of Vaborem with symptoms of general feeling of being unwell such as: low blood pressure, feeling sick, being sick, abdominal cramps, fever, flushing, rapid heart beats or difficulty breathing, headache

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

• Seizures (fits)

Frequency not known:(cannot be estimated from the available data)

• A very large and severe decrease in the number of white blood cells; seen in blood tests
• Haemolytic anaemia (a disease in which red blood cells are damaged and their number decreases), which can make you feel tired and make your skin and eyes turn yellow
• Swelling of the tongue, face, lips or throat
• Sudden appearance of a severe skin rash with blistering or peeling of the skin, possibly with high fever, pain in the joints, abnormal liver, kidney or lung function (these can be signs of more serious diseases called toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, acute generalized exanthematous pustulosis or a disease known as drug reaction with eosinophilia and systemic symptoms (DRESS))
• A positive result in a test called a ‘Coombs test’ used to identify haemolytic anaemia (see above) or a reaction of your immune system to Vaborem
• Acute confusion and disorientation (delirium)

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. Storage of Vaborem

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

Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to the last day of the month shown.

Do not store above 25°C.

6. Package Contents and Additional Information

Vaborem Composition

• The active ingredients are meropenem and vaborbactam. Each vial contains 1 g of meropenem (as meropenem trihydrate) and 1 g of vaborbactam.
• The other component is sodium carbonate

Product Appearance and Package Contents

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

Vaborem is available in packs containing 6 vials.

Marketing Authorization Holder

Menarini International Operations Luxembourg S.A.

1, Avenue de la Gare

L-1611, Luxembourg

Luxembourg

Manufacturer

ACS Dobfar, S.p.A.

Nucleo Industriale S. Atto

(loc. S. Nicolo’ a Tordino)

64100 Teramo (TE)

Italy

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:07/2023

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website http://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

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

Aseptic techniques must be used 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 (CrCl).

Reconstitution:

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

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

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

Dilution:

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

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

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

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

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

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

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