IMIPENEM/CILASTATIN STERISCIENCE 500 mg/500 mg POWDER FOR SOLUTION FOR INFUSION

2. What you need to know before you are given Imipenem/Cilastatin Steriscience

You should not be given Imipenem/Cilastatin Steriscience

• if you are allergic to imipenem, cilastatin, or any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to any other carbapenem antibacterial medicine
• if you have a severe hypersensitivity (e.g., anaphylactic reaction, extensive skin rash) to any other type of beta-lactam antibacterial medicine (e.g., penicillins or cephalosporins).

Warnings and precautions

Talk to your doctor or nurse before you start using Imipenem/Cilastatin Steriscience.

Tell your doctor about any medical condition you have or have had, including:

• allergies to any other medicine, including antibiotics (sudden, potentially life-threatening allergic reactions that require immediate medical treatment)
• colitis or any other gastrointestinal disease
• any central nervous system disorder such as localized tremors or seizure (convulsions)
• liver, kidney, or urinary problems

Blood tests

You may have a positive test (Coombs test), which indicates the presence of antibodies that can destroy red blood cells. Your doctor will discuss this with you.

Children

Imipenem/Cilastatin Steriscience is not recommended for use in children under one year of age or in children with kidney problems.

Other medicines and Imipenem/Cilastatin Steriscience

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

Tell your doctor if you are taking:

• ganciclovir (used to treat some viral infections)
• valproic acid or sodium valproate (used to treat epilepsy, bipolar disorder, migraines, or schizophrenia)

• medicines used to prevent blood clotting, such as warfarin
• Probenecid (minimal increase in imipenem plasma half-life)

Your doctor will decide whether you should use Imipenem/Cilastatin Steriscience in combination with these medicines.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before receiving this medicine. Imipenem/Cilastatin Steriscience has not been studied in pregnant women. This medicine should not be used during pregnancy unless your doctor decides that the potential benefit justifies the potential risk to the developing baby.

Breastfeeding

Tell your doctor if you are breastfeeding or plan to breastfeed before receiving Imipenem/Cilastatin Steriscience. Small amounts of this medicine may be excreted in breast milk and affect your baby. Therefore, your doctor will decide whether you should use this medicine during breastfeeding.

Driving and using machines

There are some side effects associated with this medicine (such as seeing, hearing, or feeling things that are not there, dizziness, drowsiness, and a spinning sensation) that may affect some patients' ability to drive or operate machinery (see section 4).

Imipenem/Cilastatin Steriscience contains sodium

This medicine contains 36.1 mg/1.245 mmol of sodium per vial, equivalent to 9.23% of the maximum daily intake of 2 g of sodium recommended by the WHO for an adult, which should be taken into account if you are on a low-sodium diet.

3. How Imipenem/Cilastatin Steriscience is given

A doctor or other healthcare professional will prepare and administer Imipenem/Cilastatin. Your doctor will decide how much Imipenem/Cilastatin you need.

Adults and adolescents

The usual dose for adults and adolescents is 500 mg of imipenem/500 mg of cilastatin every 6 hours, or 1,000 mg of imipenem/1,000 mg of cilastatin every 6 or 8 hours. If you have kidney problems or weigh less than 70 kg, your doctor may reduce your dose.

Children

The usual dose for children one year of age or older is 15 mg/15 mg per kg per dose every 6 hours. This medicine is not recommended for use in children under one year of age or with kidney problems.

Method of administration

After reconstitution/dilution, Imipenem/Cilastatin Steriscience is administered intravenously (into a vein) over 20 to 30 minutes for doses of ≤500 mg/500 mg or over 40 to 60 minutes for doses of >500 mg/500 mg. The infusion rate may be reduced in patients who develop nausea during infusion.

If you receive more Imipenem/Cilastatin than you should

Symptoms of overdose may include seizures, confusion, tremors, nausea, vomiting, low blood pressure, and decreased heart rate. If you are concerned that you have received too much Imipenem/Cilastatin, consult your doctor or another healthcare professional immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If you miss a dose of Imipenem/Cilastatin Steriscience

If you are concerned that you have missed a dose, consult your doctor or another healthcare professional immediately.

Do not take a double dose to make up for missed doses.

If you stop treatment with Imipenem/Cilastatin Steriscience

Do not stop treatment with Imipenem/Cilastatin until your doctor tells you to.

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

4. Possible side effects

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

Serious side effects

The following side effects may occur rarely:

• Allergic reactions including rash, swelling of the face, lips, tongue, and/or throat (with difficulty breathing or swallowing), and/or low blood pressure. If these side effects occur while you are receiving or after receiving Imipenem/Cilastatin Steriscience, the administration of the medicine should be stopped immediately and your doctor should be informed immediately.
• Severe skin reactions (Stevens-Johnson syndrome and erythema multiforme)

Exfoliative dermatitis

Other side effects

Common (may affect up to 1 in 10 people)

• Nausea, vomiting, diarrhea. Nausea and vomiting are more frequent in patients with a reduced number of white blood cells
• Swelling and redness along a vein, extremely painful to the touch
• Rash
• Abnormal liver function detected in blood tests
• Increased white blood cell count

Uncommon (may affect up to 1 in 100 people)

• Local skin redness
• Pain and formation of a firm nodule at the injection site
• Itching of the skin
• Hives
• Fever
• Blood disorders that affect the cellular components of the blood and are usually detected in blood tests (symptoms may include fatigue, pale skin, and prolonged bruising after injury)
• Abnormal kidney, liver, and blood function detected in blood tests
• Tremors and uncontrolled muscle twitching
• Seizures (convulsions)
• Psychiatric disorders (such as mood changes and altered mental faculties)
• Seeing, hearing, or feeling things that are not there (hallucinations)
• Confusion
• Dizziness, drowsiness
• Low blood pressure

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

• Peeling of the skin (toxic epidermal necrolysis)
• Severe skin rash with skin and hair loss
• Fungal infection (candidiasis)
• Discoloration of teeth and/or tongue
• Inflammation of the colon with severe diarrhea
• Taste disorders
• Failure of the liver to perform its normal function
• Inflammation of the liver
• Failure of the kidney to perform its normal function
• Changes in urine quantity, changes in urine color
• Brain disease, tingling sensation (numbness), localized tremor
• Hearing loss

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

• Severe liver failure due to inflammation (fulminant hepatitis)
• Inflammation of the stomach or intestine (gastroenteritis)
• Inflammation of the intestine with bloody diarrhea (hemorrhagic colitis)
• Swelling and redness of the tongue, overgrowth of the normal projections of the tongue that give it a hairy appearance, heartburn, sore throat, increased saliva production
• Stomach pain
• Spinning sensation (vertigo), headache
• Ringing in the ears (tinnitus)
• Pain in several joints, weakness
• Irregular heartbeat, heartbeat is forceful or rapid
• Chest discomfort, difficulty breathing, abnormally rapid and shallow breathing, pain in the upper back
• Flushing, bluish discoloration of the face and lips, changes in skin texture, excessive sweating
• Vulvar itching in women
• Changes in blood cell counts
• Worsening of a rare disease associated with muscle weakness (worsening of myasthenia gravis)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Imipenem/Cilastatin Steriscience

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 vial and outer carton after EXP. The expiry date refers to the last day of the month shown.

Do not store above 25°C.

Shelf-life after reconstitution and dilution:

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

Do not refrigerate or freeze.

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. Contents of the pack and other information

Composition of Imipenem/Cilastatin Steriscience

• The active substances are imipenem and cilastatin.

Each vial contains imipenem monohydrate equivalent to 500 mg of imipenem and cilastatin sodium equivalent to 500 mg of cilastatin.

• The other ingredient is sodium hydrogencarbonate.

Appearance and pack size

Imipenem/Cilastatin Steriscience is a white or almost white powder for solution for infusion, which comes in a 20 ml Type I glass vial with a bromobutyl rubber stopper and an aluminum flip-off seal.

Pack sizes: 1 and 10 vials.

Not all pack sizes may be marketed.

Marketing authorization holder

Steriscience B.V.

Kranenburgweg 135-A

2583 ER The Hague

Netherlands

Manufacturer

Pharma Revolta s.r.o.

Rybné námestie 1

811 02 Bratislava

Slovakia

This medicine is authorized in the Member States of the European Economic Area under the following names:

This leaflet was approved in {June/2023}.

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): https://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

Each vial is for single use.

Reconstitution/dilution

The contents of each vial should be transferred to 100 ml of a suitable solution for infusion (see "Incompatibilities" below and "Shelf-life after reconstitution and dilution" in section 5 above): sodium chloride 9 mg/ml (0.9%) injection solution. In exceptional circumstances where a 9 mg/ml (0.9%) sodium chloride injection solution cannot be used for clinical reasons, 5% glucose may be used instead.

A suggested procedure is to add approximately 10 ml of the infusion solution to the vial.

Shake well and transfer the resulting mixture to the infusion solution container.

CAUTION: THE MIXTURE IS NOT FOR DIRECT INFUSION.

Repeat with another 10 ml of infusion solution to ensure complete transfer of the vial contents to the infusion solution. The resulting mixture should be shaken until a clear solution is obtained.

The concentration of the reconstituted solution using the above method is approximately 5 mg/ml of both imipenem and cilastatin.

The solution should only be used if it is clear and free of particles.

The infusion solution should be visually inspected before administration. The solid should be completely dissolved without visible particles. Only clear solutions without particles should be used.

Color variations, from colorless to yellow, do not affect the efficacy of the medicine.

This medicine should not be mixed with other medicines except those mentioned in the "Reconstitution/dilution" section above.

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

Incompatibilities

This medicine is chemically incompatible with lactate and should not be reconstituted with diluents containing lactate. However, it may be administered with an intravenous system through which a lactate solution is infused.