RECARBRIO 500 mg/500 mg/250 mg POWDER FOR SOLUTION FOR INFUSION

2. What you need to know before you use Recarbrio

Do not use Recarbrio

• if you are allergic to imipenem, cilastatin, relebactam, or any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to carbapenem-type antibiotics
• if you have ever had a severe allergic reaction to penicillin-type or cephalosporin-type antibiotics.

You should not receive Recarbrio if any of the above applies to you. If you are not sure, consult your doctor or nurse before receiving Recarbrio.

Warnings and precautions

Talk to your doctor or nurse before starting Recarbrio if:

• you are allergic to any medicine - especially antibiotics
• you have ever had seizures (fits or convulsions)
• you have ever had confusion or muscle contractions with a medicine
• you are taking a medicine that contains valproic acid
• you have had diarrhea while receiving antibiotics in the past
• you have kidney problems - your doctor may reduce the dose

Tell your doctor immediately if you have an allergic reaction, seizures (fits or convulsions), diarrhea, or develop kidney problems while receiving Recarbrio (see section 3).

Children and adolescents

Recarbrio should not be used in children or adolescents under 18 years of age. This is because it is not known if the medicine is safe to use in these patients.

Other medicines and Recarbrio

Tell your doctor or nurse if you are using, have recently used, or might use any other medicines.

Tell your doctor about all the medicines you are taking, especially if you are taking:

• medicines that contain ganciclovir, used to treat some viral infections
• medicines that contain valproic acid or valproate semisodium, normally used to treat epilepsy, bipolar disorder, or migraine
• medicines to control blood clotting, such as warfarin

Pregnancy and breastfeeding

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

Driving and using machines

Recarbrio may make you feel dizzy, agitated, or cause seizures or fits. This could affect your ability to drive or use machines.

Recarbrio contains sodium

This medicine contains approximately 37.5 mg of sodium (a major component of cooking/table salt) in each vial. This is about 2% of the maximum recommended daily intake of sodium for an adult, and you should take this into account if you are on a low-sodium diet.

3. How to use Recarbrio

The recommended dose is one vial (which contains 500 mg of imipenem, 500 mg of cilastatin, and 250 mg of relebactam) every 6 hours. If you have kidney problems, your doctor may reduce the dose.

It is given by drip directly into a vein ("intravenous infusion"). The infusion will last 30 minutes.

The usual treatment cycle lasts from 5 to 14 days, depending on the type of infection you have and how you respond to treatment.

If you use more Recarbrio than you should

Recarbrio will be administered by a doctor or nurse, so it is unlikely that you will be given an incorrect dose. If you think you have been given too much Recarbrio, tell your doctor or nurse immediately.

If you forget to use Recarbrio

Tell your doctor or nurse immediately if you think you have missed a dose of Recarbrio.

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

Tell your doctor immediately if you notice any of the following serious side effects - the medicine should be stopped:

• allergic reactions - the signs may include hives, swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing
• severe skin reactions (e.g. intense rash, skin peeling, or blistering)

Other side effects

Common: (may affect more than 1 in 10 people)

• nausea, discomfort (vomiting), diarrhea
• blood test results that may show changes in the liver
• blood test results that may show an increase in the number of some types of blood cells called "eosinophils"
• blood test results that may show an increase in some white blood cells
• rash
• inflammation and pain caused by a blood clot in the vein

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

• hives
• itching of the skin
• seizures (fits) and nervous system problems such as tremor
• confusion
• seeing, hearing, or feeling something that is not there (hallucinations)
• dizziness, drowsiness
• low blood pressure
• blood test results that may show changes in the kidneys
• blood test results that may show a decrease in the number of red blood cells, white blood cells, and blood cells called platelets
• blood test results that may show an increase in the number of some blood cells called platelets
• abnormal function of the kidneys, liver, and blood detected in blood tests
• pain or redness or swelling at the injection site
• fever
• blood test results (called Coombs test) that show antibodies that can cause anemia by destroying red blood cells

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

• fungal infection (candidiasis)
• changes in taste
• brain disease, tingling sensation (tingling and numbness), localized tremor
• hearing loss
• discoloration of teeth and/or tongue
• inflammation of the colon with severe diarrhea (colitis)
• decrease in white blood cells, which can make it difficult for your body to fight infections
• inflammation of the liver
• liver failure
• kidney failure
• changes in the amount of urine, changes in the color of urine
• swelling of the skin
• painful rash with flu-like symptoms
• redness and peeling of the skin

Very rare: (may affect up to 1 in 10,000 people)

• inflammation of the stomach or intestine (gastroenteritis)
• anemia due to the destruction of red blood cells, leading to symptoms such as fatigue and pale skin
• headache
• worsening of a rare disease associated with muscle weakness (worsening of myasthenia gravis)
• spinning sensation (vertigo)
• ringing in the ears (tinnitus)
• irregular heartbeat, strong or rapid heartbeat
• discomfort in the chest, difficulty breathing, abnormally rapid and shallow breathing, pain in the upper back
• sore throat
• flushing, change in skin color, bluish discoloration of the face and lips, changes in skin texture, excessive sweating
• increased saliva production
• inflammation of the intestine with bloody diarrhea (hemorrhagic colitis)
• stomach pain
• heartburn
• red and swollen tongue, excessive growth of normal tongue bumps giving a hairy appearance
• severe loss of liver function due to inflammation (fulminant hepatitis)
• pain in various joints
• itching of the vulva in women
• weakness, lack of energy

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

• agitation
• abnormal movements
• jaundice (yellowing of the skin and eyes)
• blood test that shows an increase in a substance called lactate dehydrogenase (LDH), which can be a sign of tissue damage.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through 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 Recarbrio

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 is the last day of the month stated.

Store this medicine in the outer carton to protect it from light.

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

6. Container Contents and Additional Information

Composition of Recarbrio

• The active ingredients are imipenem, cilastatin, and relebactam. Each vial contains 500 mg of imipenem, 500 mg of cilastatin, and 250 mg of relebactam.
• The other components are sodium hydrogen carbonate.

Appearance of the Product and Container Contents

Recarbrio is a white to light yellow powder that is supplied for solution for infusion in glass vials. The pack size is 25 vials.

Marketing Authorization Holder and Manufacturer

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:{MM/YYYY}.

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 for healthcare professionals only:

Recarbrio is supplied as a dry powder in a single-dose vial that must be reconstituted and further diluted using aseptic techniques before intravenous infusion, as described below:

• To prepare the infusion solution, the contents of the vial should be transferred to 100 ml of a suitable infusion solution: sodium chloride 9 mg/ml (0.9%). In exceptional circumstances where sodium chloride 9 mg/ml (0.9%) cannot be used for clinical reasons, glucose 5% may be used instead.
• Withdraw 20 ml (2 x 10 ml) of diluent from the appropriate infusion bag and reconstitute the vial with 10 ml of the diluent. The reconstituted suspension should not be administered by direct intravenous infusion.
• After reconstitution, shake the vial well and transfer the resulting suspension to the remaining 80 ml of the infusion bag.
• Add the additional 10 ml of infusion diluent to the vial and shake well to ensure complete transfer of the vial contents; repeat the transfer of the resulting suspension to the infusion solution before administration. Shake the resulting mixture until it is clear.
• The reconstituted solutions of Recarbrio range from colorless to yellow. Variations in color within this range do not affect the potency of the product.
• In patients with renal impairment, a reduced dose of Recarbrio will be administered according to the patient's CrCl, as determined by the following table. Prepare 100 ml of infusion solution as described above. Select the volume (ml) of the final infusion solution necessary for the appropriate dose of Recarbrio as shown in the table below.

Parenteral medicinal products should be inspected visually for particulate matter and color change prior to administration, whenever the solution and container permit. Discard if color change or particulate matter is observed.

Preparation of Recarbrio Doses

The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Compatible Medicinal Products

The physical compatibility of Recarbrio with selected injectable medicinal products has been evaluated in two commonly used infusion solutions. The following medicinal products are compatible with the corresponding compatible diluent (i.e., dextrose 5% for injection or sodium chloride 0.9% for injection). Recarbrio should not be administered concomitantly with other medicinal products through the same intravenous line (or cannula), as compatibility data are not available. Refer to the Summary of Product Characteristics of the co-administered medicinal product(s) to confirm compatibility of concomitant administration. This medicinal product should not be mixed with other medicinal products except those mentioned below.

List of compatible injectable medicinal products for use with dextrose 5% or sodium chloride 0.9% for injection as diluents

• dexmedetomidine
• dopamine
• epinephrine
• fentanyl
• heparin
• midazolam
• norepinephrine
• phenylephrine

Intravenous Bags and Infusion Equipment Materials Compatibility

Recarbrio is compatible with the following intravenous bags and infusion equipment materials. No other infusion bag or equipment material should be used.

Infusion Bag Materials

Polyvinyl chloride (PVC) and polyolefin (polypropylene and polyethylene)

Intravenous Infusion Equipment Materials (with their tubes)

PVC + Di-(2-ethylhexyl)phthalate (DEHP) and PVC coated with polyethylene (PE)

Incompatible Medicinal Products

Recarbrio for solution for infusion is physically incompatible with propofol in dextrose 5% (also known as glucose) or sodium chloride 0.9%.

After Reconstitution and Dilution

The diluted solutions should be used immediately. The time interval between the start of reconstitution and the end of intravenous infusion should not exceed two hours.