Vaborem

Package leaflet: Information for the patient

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

meropenem/vaborbactam
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 or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Vaborem is and what it is used for
2. What you need to know before you are given Vaborem
3. How Vaborem will be given to you
4. Possible side effects
5. How to store Vaborem
6. Contents of the pack and other information

1. What Vaborem is and what it is used for

What Vaborem is
Vaborem is an antibiotic medicine that contains two active substances: meropenem and vaborbactam.
Meropenem belongs to a class of antibiotics known as "carbapenems". It kills many types of bacteria by preventing them from building the protective walls around their cells.
Vaborbactam is a "beta-lactamase inhibitor". It blocks the action of an enzyme that enables certain bacteria to resist the effects of meropenem. This helps meropenem destroy some bacteria that it cannot kill on its own.

What Vaborem is used for
Vaborem is used in adults to treat certain serious 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 bloodstream infections associated with one of the above-mentioned infections
caused by bacteria that other antibiotics might not be able to kill.

2. What you need to know before receiving Vaborem

Do not receive Vaborem 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 class of antibiotics to which meropenem belongs).
you have ever had a severe allergic reaction to related antibiotics belonging to the beta-lactam class (such
as penicillins, cephalosporins, or monobactams).

Warnings and precautions
Talk to your doctor or nurse before receiving Vaborem if:
you have ever had an allergic reaction to other antibiotics belonging to the beta-lactam class (such as
carbapenems, penicillins, cephalosporins, or monobactams)
you have ever developed severe diarrhoea during or after antibiotic treatment
you have ever had seizures.

If any of the conditions listed above apply to you or if you have any doubts, consult your doctor or nurse before
using Vaborem.
You may develop signs and symptoms of serious skin reactions (see section 4). If this occurs, speak to your doctor or
nurse immediately so they can treat the symptoms.
Inform your doctor or nurse if you develop diarrhoea during treatment.
This medicine may affect the liver. Your doctor may prescribe blood tests to monitor your liver function during
treatment.

New infection
Although Vaborem can fight certain bacteria, there is a possibility that you may develop a different infection caused
by another organism during or after treatment. Your doctor will closely monitor you for any new infections and will
administer another treatment if necessary.

Blood tests
Inform your doctor that you are receiving Vaborem if you are scheduled for blood tests. This is because you may obtain
an abnormal result in the so-called “Coombs test”. The results of this test reveal the presence of antibodies that may
destroy red blood cells or may be influenced by the immune system’s response to Vaborem.

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

Other medicines and Vaborem
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
It is particularly important that you inform your doctor if you are taking any of the following medicines:
medicines used to treat epilepsy such as valproic acid, sodium valproate, or valpromide, because Vaborem may
reduce their effect
a medicine for gout called probenecid
oral anticoagulants such as warfarin (used to treat or prevent blood clots)
oral hormonal contraceptives containing estrogen and/or progesterone, because Vaborem may reduce their
effectiveness. Women of childbearing potential should be advised to use alternative and effective contraceptive
methods during treatment with Vaborem and for a period of 28 days after stopping treatment.
medicines metabolized mainly 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), because Vaborem may reduce their
effect.
Inform your doctor before using Vaborem if any of the above situations apply to you.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, or are planning to become pregnant, ask your doctor for advice before
receiving this medicine.
As a precautionary measure, this medicine should not be administered during pregnancy.
It is important that you inform your doctor if you are breastfeeding or intend to breastfeed before receiving Vaborem.
Small amounts of this medicine may pass into breast milk and may affect the infant. Therefore, you must stop
breastfeeding before receiving Vaborem.

Driving and using machines
Vaborem may cause dizziness, drowsiness, fatigue, headache, or a tingling sensation (“pins and needles”), or, in rare
cases, epileptic seizures or convulsions. These effects may impair your ability to drive or operate tools or machinery.

Vaborem contains sodium
This medicine contains 250 mg of sodium (the main component of table salt or cooking salt) per vial. This is equivalent
to 12.5% of the maximum daily recommended sodium intake for an adult.

3. How Vaborem will be administered to you

The recommended dose is 2 vials (a total of 2 g of meropenem and 2 g of vaborbactam), administered every 8 hours.
Your doctor will decide how many days the treatment will last, depending on the type of infection.
Vaborem will be administered to you by a doctor or nurse through an intravenous infusion over a period of 3 hours.

Patients with kidney problems
If you have kidney problems, your doctor may reduce your dose. Your doctor may also prescribe certain blood tests to assess how well your kidneys are functioning.

If you receive more Vaborem than you should
Since Vaborem is administered by a doctor or nurse, it is unlikely that you will receive an incorrect dose. However, if you think you have received 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 doubts about the use of this medicine, consult 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
Tell your doctor immediately if you notice any of the following serious side effects. You may need urgent medical treatment:
Severe allergic reactions which could include sudden swelling of the lips, face, throat or tongue, difficulty swallowing or breathing, or a severe skin rash or other serious skin reaction, or low blood pressure (which may cause you to faint or feel dizzy). These reactions can be life-threatening and potentially fatal.
Diarrhoea that continues to worsen or does not go away, or stools containing blood or mucus – this may occur during treatment with Vaborem or after stopping it. It may be caused by a bacterium called Clostridium difficile. In this case, do not take medicines that stop or slow down intestinal movements.
Other side effects
Tell your doctor or nurse if you notice any of the following side effects.
Common: (may affect up to 1 in 10 people)
Increase in the number of platelets (a type of blood cell) – detected in blood tests
Decrease in the amount of potassium or sugar – detected in blood tests
Headache
Low blood pressure
Diarrhoea
Feeling unwell (nausea) or sickness (vomiting)
Swelling, redness and/or pain at the site where the needle is inserted into the vein for administration of the medicine
Fever
Increased production of liver enzymes called alanine aminotransferase or aspartate aminotransferase – detected in blood tests
Increase in the level of an enzyme called alkaline phosphatase, which may indicate reduced function of the liver, gallbladder or bones – detected in blood tests
Increase in the level of an enzyme called lactate dehydrogenase, which may indicate damage to certain organs – detected in blood tests.
Uncommon: (may affect up to 1 in 100 people)
Swelling and inflammation of the large intestine or colon – may cause diarrhoea, fever and stomach cramps and are due to another colon infection
Fungal infections, including vaginal or oral infections
Decrease in the number of white blood cells or certain types of white blood cells called neutrophils, and decrease in platelets – detected in blood tests
Increase in a type of white blood cell called eosinophils in the blood – detected in blood tests
Sudden and severe allergic reaction requiring urgent medical treatment, which may include itching, change in skin colour, abdominal cramps, swelling, difficulty breathing, fainting and drop in blood pressure
Less severe allergic reaction which may include redness, red raised skin lesions, skin peeling, itching, feeling generally unwell
Loss of appetite
Increase in the amount of potassium or sugar – detected in blood tests
Difficulty sleeping
Seeing, hearing or sensing things that are not real
Feeling dizzy
Tremor or restlessness
Tingling sensation (pins and needles)
Drowsiness and weakness
Swelling, redness and irritation of the veins
Pain in the veins
Difficulty breathing
Swelling or feeling of fullness in the abdomen
Stomach ache
Itchy skin
Skin rash
Itchy rash with raised lesions (“hives”)
Difficulty controlling the bladder
Reduced kidney function
Unusual sensation in the chest
The following reactions may develop, either alone or in combination, at the site where Vaborem is administered intravenously: skin redness (erythema); warmth, tenderness and swelling of the vein around the needle (phlebitis); formation of a blood clot in the vein where the needle is inserted (infusion site thrombosis)
Pain
Increase in the level of a substance in the blood called creatine phosphokinase, which is a sign of possible damage to certain tissues such as muscles and/or other organs – detected in blood tests
Increase in the level of a substance in the blood called bilirubin, which is a sign of possible damage to red blood cells or reduced liver function – detected in blood tests
Increase in the level of certain substances in the blood called urea and creatinine, which is a sign of reduced kidney function – detected in blood tests
Onset of a reaction during or shortly after administration of Vaborem, presenting as a feeling of general discomfort, which may be accompanied by any of the following symptoms: drop in blood pressure, nausea, vomiting, abdominal cramps, fever, hot flushes, rapid heartbeat or difficulty breathing, headache.
Rare: (may affect up to 1 in 1,000 people)
Seizures (epileptic fits).
Not known: (frequency cannot be estimated from the available data)
Severe decrease in white blood cell count – detected in blood tests
Haemolytic anaemia (a condition in which red blood cells are damaged and decrease in number), which may cause tiredness and yellowing of the skin and eyes
Swelling of the tongue, face, lips or throat
Sudden onset of a severe skin rash with lesions resembling "target" or "bull's eye" spots, or formation of blisters or skin peeling, possibly accompanied by high fever, joint pain, and abnormalities in liver, kidney or lung function (may be signs of more serious medical conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, acute generalised exanthematous pustulosis, or a condition known as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome))
Positive result in a test known as the “Coombs test” used to detect the presence of haemolytic anaemia (see above) or immune system reaction to Vaborem.
Acute disorientation and confusion (delirium)
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Vaborem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of that month.
Do not store above 25 °C.

6. Package contents and other information

What Vaborem contains
The active substances 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.

Description of the appearance of Vaborem and contents of the pack
Vaborem is a white to pale yellow powder for concentrate for solution for infusion, supplied in a vial.
Vaborem is available in packs of 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)
64 100 Teramo (TE)
Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Menarini Benelux NV/SA UAB “BERLIN-CHEMIE MENARINI
Tél/Tel: + 32 (0)2 721 4545 BALTIC”
Tel: +370 52 691 947

България Luxembourg/Luxemburg
Берлин-Хеми/А. Менарини България EООД Menarini Benelux NV/SA
тел.: +359 24540950 Tél/Tel: + 32 (0)2 721 4545

Česká republika Magyarország
Berlin-Chemie/A.Menarini Ceska republika s.r.o. Berlin-Chemie/A. Menarini Kft.
Tel: +420 267 199 333 Tel.: +36 1799 732

Danmark Malta
Menarini International Operations Luxembourg Menarini International Operations Luxembourg
S.A. S.A.
Tlf: +352 264976 Tel: +352 264976

Deutschland Nederland
Berlin-Chemie AG Menarini Benelux NV/SA
Tel: +49 (0) 30 67070 Tel: +32 (0)2 721 4545

Eesti Norge
OÜ Berlin-Chemie Menarini Eesti Menarini International Operations Luxembourg
Tel: +372 667 5001 S.A.
Tlf: +352 264976

Ελλάδα Österreich
MENARINI HELLAS AE A. Menarini Pharma GmbH
Τηλ: +30 210 8316111-13 Tel: +43 1 879 95 85-0

España Polska
Laboratorios Menarini S.A. Berlin-Chemie/Menarini Polska Sp. z o.o.
Tel: +34-93 462 88 00 Tel.: +48 22 566 21 00

France Portugal
MENARINI France A. Menarini Portugal – Farmacêutica, S.A.
Tél: +33 (0)1 45 60 77 20 Tel: +351 210 935 500

Hrvatska România
Berlin-Chemie Menarini Hrvatska d.o.o. Berlin-Chemie A.Menarini S.R.L.
Tel: + 385 1 4821 361 Tel: +40 21 232 34 32

Ireland Slovenija
A. Menarini Pharmaceuticals Ireland Ltd Berlin-Chemie / A. Menarini Distribution
Tel: +353 1 284 6744 Ljubljana d.o.o.
Tel: +386 01 300 2160

Ísland Slovenská republika
Menarini International Operations Luxembourg Berlin-Chemie AG / A. Menarini Distribution
S.A. Slovakia s.r.o
Sími: +352 264976 Tel: +421 2 544 30 730

Italia Suomi/Finland
A. Menarini - Industrie Farmaceutiche Riunite - Berlin-Chemie/A.Menarini Suomi OY
s.r.l. Puh/Tel: +358 403 000 760
Tel: +39-055 56801

Κύπρος Sverige
MENARINI HELLAS AE Pharmaprim AB
Τηλ: +30 210 8316111-13 Tel: +46 8355933

Latvija United Kingdom (Northern Ireland)
SIA Berlin-Chemie/Menarini Baltic A. Menarini Farmaceutica Internazionale S.R.L.
Tel: +371 67103210 Tel: +44 (0)1628 856400

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu .

The following information is intended exclusively for healthcare professionals:

Vaborem is intended for intravenous (IV) administration only after reconstitution and dilution.
Standard 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:
For each vial, withdraw 20 mL of 9 mg/mL (0.9%) sodium chloride injectable solution (normal saline) from a 250 mL infusion bag of 9 mg/mL (0.9%) sodium chloride injectable solution, and reconstitute with the appropriate number of meropenem/vaborbactam vials according to the required Vaborem dosage:

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

Gently mix to dissolve. The reconstituted meropenem/vaborbactam solution will have an approximate concentration of 0.05 g/mL for meropenem and 0.05 g/mL for vaborbactam. The final volume is approximately 21.3 mL. The reconstituted solution must not be injected directly; it must be diluted prior to intravenous infusion.

Dilution:
To prepare Vaborem 2 g/2 g for administration by intravenous infusion: immediately after reconstituting two vials, withdraw the entire contents from each vial and transfer them into the 250 mL infusion bag containing 9 mg/mL (0.9%) sodium chloride injectable solution (normal saline). The final infusion solution will have a concentration of approximately 8 mg/mL for both meropenem and vaborbactam.

To prepare Vaborem 1 g/1 g for administration by intravenous infusion: immediately after reconstituting one vial, withdraw the entire reconstituted content and transfer it into the 250 mL infusion bag containing 9 mg/mL (0.9%) sodium chloride injectable solution (normal saline). The final infusion solution will have a concentration of approximately 4 mg/mL for both meropenem and vaborbactam.

To prepare Vaborem 0.5 g/0.5 g for administration by intravenous infusion: immediately after reconstituting one vial, withdraw 10.5 mL of the reconstituted solution and transfer it into the 250 mL infusion bag containing 9 mg/mL (0.9%) sodium chloride injectable solution (normal saline). The final infusion solution will have a concentration of approximately 2 mg/mL for both meropenem and vaborbactam.

The diluted solution should be inspected visually for particulate matter. The color of the diluted solution ranges from clear to pale yellow.

After dilution, the infusion must be completed within 4 hours if stored at 25 °C, or within 22 hours if refrigerated at 2–8 °C.
From a microbiological standpoint, the reconstituted and diluted medicinal product should be used immediately.

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