Emblaveo 1.5 g/0.5 g powder for concentrate for solution for infusion

Patient Information Leaflet

Introduction

Patient Information Leaflet

Emblaveo 1.5 g/0.5 g powder for concentrate for solution for infusion

aztreonam/avibactam

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

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

Leaflet Contents

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

1. What Emblaveo is and what it is used for

What Emblaveo is

Emblaveo is an antibiotic that contains two active substances: aztreonam and avibactam.

• Aztreonam belongs to a class of antibiotics known as "monobactams". It can kill certain types of bacteria (called gram-negative bacteria).
• Avibactam is a "beta-lactamase inhibitor" that helps aztreonam eliminate some bacteria that aztreonam cannot kill on its own.

What Emblaveo is used for

Emblaveo is used in adults to treat:

• complicated intra-abdominal infections (stomach and intestine) when the infection has spread into the abdominal cavity (space within the abdomen).
• hospital-acquired pneumonia (bacterial lung infection acquired during a hospital stay), including ventilator-associated pneumonia (pneumonia that develops in patients on a ventilator).
• complicated urinary tract infections (difficult to treat because they have spread to other parts of the body or the patient has other underlying conditions), including pyelonephritis (kidney infection).
• infections caused by gram-negative bacteria that other antibiotics cannot eliminate.

2. What you need to know before Emblaveo is administered to you

Do not administer Emblaveo if:

• you are allergic to aztreonam or avibactam, or to any of the other ingredients of this medicine (listed in section 6).
• you have ever had a severe allergic reaction (swelling of the face, hands, feet, lips, tongue, or throat; difficulty swallowing or breathing; or a severe skin reaction) to other antibiotics belonging to the penicillin, cephalosporin, or carbapenem groups.

Warnings and precautions

Talk to your doctor or nurse before starting treatment with Emblaveo if:

• you have ever had an allergic reaction (even if only a skin rash) to other antibiotics. Signs of an allergic reaction include itching, skin rash, or difficulty breathing.
• you have kidney problems or are taking medicines that affect kidney function, such as other antibiotics known as aminoglycosides (streptomycin, neomycin, gentamicin). If your kidney function is impaired, your doctor may give you a lower dose of Emblaveo and perform periodic blood tests during treatment to monitor your kidney function. In addition, you may have an increased risk of developing serious side effects affecting the nervous system, such as encephalopathy (a brain disorder that may be caused by diseases, injuries, medications, or chemicals), due to elevated blood levels of Emblaveo unless the dose is reduced. Symptoms of encephalopathy include confusion, seizures, and altered mental function (see section 3: If you use more Emblaveo than you should).
• you have liver problems. Your doctor may want to perform periodic blood tests during treatment to assess your liver function, as increases in liver enzymes have been observed during treatment with Emblaveo.
• you are taking medicines known as anticoagulants (medicines that prevent blood from clotting). Emblaveo may affect blood clotting. Your doctor will monitor your blood levels to determine whether your anticoagulant dose needs to be adjusted during treatment with Emblaveo.

Talk to your doctor if, after starting treatment with Emblaveo, you experience:

• severe, prolonged, or bloody diarrhea. This may be a sign of inflammation of the large intestine. It may be necessary to stop treatment with Emblaveo and start specific treatment for diarrhea (see section 4: Possible side effects).
• other infections. There is a small possibility that you may develop a different infection caused by another bacterium during or after treatment with Emblaveo.

Laboratory tests

Inform your doctor that you are taking Emblaveo if you are scheduled for any laboratory tests. This is because you may get an abnormal result in a test called the direct or indirect Coombs test. This test detects antibodies that attack your red blood cells.

Children and adolescents

Emblaveo must not be used in pediatric or adolescent patients under 18 years of age. This is because it is unknown whether the medicine is safe in this age group.

Other medicines and Emblaveo

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

Tell your doctor before using Emblaveo if you are taking any of the following medicines:

• A medicine for gout known as probenecid.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

This medicine may harm the unborn baby. It should only be used during pregnancy if considered necessary by your doctor and only if the benefit to the mother outweighs the risk to the unborn child.

This medicine may pass into breast milk. If you are breastfeeding, a decision must be made whether to discontinue breastfeeding or to discontinue treatment, taking into account the benefit of breastfeeding for the child and the benefit of treatment for the mother.

Driving and using machines

Emblaveo may cause side effects such as dizziness, which may affect your ability to drive or operate machinery. Do not drive or use tools or machines if you experience side effects such as dizziness (see section 4: Possible side effects).

Emblaveo contains sodium

This medicine contains approximately 44.6 mg of sodium (the main component of table/cooking salt) per vial. This corresponds to 2.2% of the recommended maximum daily intake of sodium for an adult.

3. How to use Emblaveo

A doctor or nurse will administer Emblaveo to you.

How much to use

Emblaveo is given as an intravenous infusion (a drip directly into a vein). The usual dose is one vial (containing 1.5 g of aztreonam and 0.5 g of avibactam) every 6 hours. The first dose is higher (2 g of aztreonam and 0.67 g of avibactam). The infusion lasts 3 hours. Treatment usually lasts between 5 and 14 days, depending on the type of infection you have and your response to treatment.

Patients with kidney problems

If you have kidney problems, your doctor may reduce your dose and increase the time interval between doses. This is because Emblaveo is eliminated from the body via the kidneys. If your kidney function is impaired, your blood levels of Emblaveo may be increased.

If you are given more Emblaveo than you should receive

A doctor or nurse will administer Emblaveo to you, so it is unlikely that you will receive more than the intended dose. However, if you experience side effects or think you have been given too much Emblaveo, inform your doctor or nurse immediately. You should tell your doctor if you experience confusion, changes in mental function, movement problems, or seizures.

If a dose of Emblaveo is missed

If you think a dose has not been administered, inform your doctor or nurse immediately.

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

4. Possible adverse effects

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

Serious adverse effects

Contact your doctor immediately if you experience any of the following serious adverse effects, as you may require urgent medical attention:

• Swelling of the face, lips, eyes, tongue and/or throat, hives, and difficulty swallowing or breathing. These may be signs of an allergic reaction or angioedema, which can be potentially life-threatening.
• Severe, persistent or bloody diarrhoea (which may be associated with stomach pain or fever). This may occur during or after antibiotic treatment and could be a sign of a serious intestinal inflammation. If this occurs, do not take medicines that stop or slow down bowel movements.
• Sudden onset of a severe skin rash, blisters or peeling of the skin, possibly accompanied by high fever or joint pain (these may be signs of more serious medical conditions such as toxic epidermal necrolysis, exfoliative dermatitis or erythema multiforme).

These serious adverse effects are uncommon (may affect up to 1 in 100 people).

Other adverse effects

Inform your doctor or nurse if you notice any of the following adverse effects:

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

• Decrease in red blood cell count, as shown in blood tests.
• Changes in the count of certain types of blood cells (called "platelets"), as seen in blood tests.
• Confusion.
• Dizziness.
• Diarrhoea.
• Nausea or vomiting.
• Stomach pain.
• Increase in certain liver enzymes in blood tests.
• Rash.
• Inflammation of a vein.
• Inflammation of a vein associated with a blood clot.
• Pain or swelling at the injection site.
• Fever.

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

• Increase in the count of certain types of white blood cells (called "eosinophils" and "leukocytes"), as reflected in blood tests.
• Difficulty falling or staying asleep.
• Encephalopathy (a condition affecting the brain causing mental disturbances and confusion).
• Headache.
• Decreased sensitivity to touch, pain and temperature in the mouth.
• Disturbance of taste sensation.
• Extra heartbeats.
• Bleeding.
• Decrease in blood pressure.
• Flushing of the face.
• Excessive contraction of the muscles in the airways causing difficulty breathing.
• Stomach bleeding.
• Mouth ulcers.
• Increased levels of certain substances in the blood (gamma-glutamyltransferase, alkaline phosphatase in blood, creatinine).
• Itching.
• Purple spots like bruises, small red spots.
• Excessive sweating.
• Chest pain.
• Weakness.

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

• Fungal infection of the vagina.
• Low levels of blood cells (pancytopenia).
• Marked decrease in a type of white blood cells (called "neutrophils") used to fight infections, as observed in blood tests.
• Prolonged time for a cut to stop bleeding.
• Spontaneous bruising.
• Abnormal result in a test called direct or indirect Coombs test. This test looks for antibodies that attack red blood cells.
• Seizures.
• Sensations such as numbness, tingling or prickling.
• Double vision.
• Sensation of spinning (vertigo).
• Ringing or buzzing in the ears (tinnitus).
• Difficulty breathing.
• Adventitious respiratory sounds (wheezing).
• Sneezing.
• Stuffy nose (nasal congestion).
• Bad breath.
• Inflammation of the liver.
• Yellowing of the skin and eyes (jaundice).
• Muscle pain.
• Breast tenderness.
• General feeling of being unwell.

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

• Superinfection (a new infection occurring after treatment for the current infection).

Sudden chest pain has been observed, which may be a sign of a potentially serious allergic reaction called Kounis syndrome, which has occurred with other medicines of the same class. If this occurs, speak to a doctor or nurse immediately.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Emblaveo

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the vial label and the carton after “EXP”. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C).

Keep in the original packaging to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Emblaveo

• The active substances are aztreonam and sodium avibactam. Each vial contains 1.5 g of aztreonam and sodium avibactam equivalent to 0.5 g of avibactam (see section 2: Emblaveo contains sodium).
• The other component is arginine.

Nature and contents of the container

Emblaveo is a white to slightly yellow powder for concentrate for solution for infusion, supplied in a glass vial closed with a rubber stopper and an aluminium seal with an easy-open cap.

It is available in packs of 10 vials.

Marketing Authorization Holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer

Pfizer Service Company BV
Hermeslaan 11
1932 Zaventem
Belgium

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the latest review of this leaflet: MM/YYYY. .

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu

This information is intended for healthcare professionals only:

Important: Consult the package leaflet or summary of product characteristics before prescribing.

This medicine must not be mixed with other medicinal products except with 0.9% sodium chloride injection solution, 5% glucose injection solution or lactated Ringer's solution, as described below.

The powder must be reconstituted with sterile water for injection and the resulting concentrate must be diluted immediately before use. The reconstituted solution is a clear, colourless to yellow solution free from visible particles.

Emblaveo (aztreonam/avibactam) is a combination product; each vial contains 1.5 g of aztreonam and 0.5 g of avibactam in a fixed 3:1 ratio.

Standard aseptic techniques must be used for the preparation and administration of the solution. Doses must be prepared in an intravenous infusion bag of appropriate size.

Parenteral medicinal products should be inspected visually for particulate matter prior to administration.

Each vial is for single use only.

The total time interval between the start of reconstitution and the completion of intravenous infusion preparation must not exceed 30 minutes.

Instructions for preparation of adult doses in an INFUSION BAG:

NOTE: The following procedure describes the steps to prepare an infusion solution with a final concentration of 1.5–40 mg/ml of aztreonam and 0.50–13.3 mg/ml of avibactam. All calculations must be completed before starting these steps.

1. Prepare the reconstituted solution (131.2 mg/ml aztreonam and 43.7 mg/ml avibactam):

2. Insert the needle through the vial closure and inject 10 ml of sterile water for injection.

3. Remove the needle and gently shake the vial to obtain a clear, colourless to yellow solution free from visible particles.

4. Prepare the final solution for infusion (the final concentration must be 1.5–40 mg/ml aztreonam and 0.50–13.3 mg/ml avibactam):

Infusion bag: for further dilution, transfer a correctly calculated volume of the reconstituted solution into an infusion bag containing one of the following: 0.9% sodium chloride injection solution, 5% glucose injection solution or lactated Ringer's solution.

Refer to Table 1 below:

Table 1. Preparation of Emblaveo for adult doses in an INFUSION BAG

From a microbiological standpoint, the medicine should be used immediately unless reconstitution and dilution have been carried out under controlled, validated aseptic conditions. If not used immediately, the in-use storage times and conditions prior to administration are the responsibility of the user and must not exceed those previously mentioned.

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.