Imipenem + cilastatin noridem

Package leaflet: Information for the patient

Imipenem + Cilastatin Noridem, 500 mg+500 mg, powder for solution for infusion
Imipenemum + Cilastatinum
Please read carefully the entire leaflet before use, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms of illness are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Leaflet contents

1. What Imipenem + Cilastatin Noridem is and what it is used for
2. What you need to know before using Imipenem + Cilastatin Noridem
3. How to use Imipenem + Cilastatin Noridem
4. Possible side effects
5. How to store Imipenem + Cilastatin Noridem
6. Contents of the pack and other information

1. What Imipenem + Cilastatin Noridem is and what it is used for

Imipenem + Cilastatin Noridem belongs to a group of medicines called carbapenem antibiotics.
This medicine kills a wide range of bacteria (microorganisms) causing infections in various parts of the body in adults and children aged 1 year and older.
Treatment
Your doctor has prescribed Imipenem + Cilastatin Noridem because you have been diagnosed with at least one of the following infections:

• complicated intra-abdominal infections
• lung infection (pneumonia)
• infections acquired during or following childbirth
• complicated urinary tract infections
• complicated skin and soft tissue infections.

Imipenem + Cilastatin Noridem may be used to treat patients with low white blood cell counts who have fever likely caused by a bacterial infection.
Imipenem + Cilastatin Noridem may be used to treat bacterial blood infections, which may be associated with one of the types of infections listed above.

2. Important information before using Imipenem + Cilastatin Noridem

When not to use Imipenem + Cilastatin Noridem

• if the patient is allergic to imipenem, cilastatin, or any of the other ingredients of this medicine (listed in section 6),
• if the patient is allergic to other antibiotics such as penicillins, cephalosporins, or carbapenems.

Warnings and precautions
Before using Imipenem + Cilastatin Noridem, tell your doctor, pharmacist, or nurse about any medical conditions currently present or experienced in the past, including:

• allergies to any medicines, including antibiotics (sudden, life-threatening allergic reactions requiring immediate medical attention),
• colitis or any other gastrointestinal disease,
• kidney or urinary tract problems, including impaired kidney function (in patients with impaired kidney function, increased blood levels of Imipenem + Cilastatin Noridem have been observed. If the dose is not adjusted according to kidney function, adverse effects on the central nervous system may occur),
• any disorders of the central nervous system, such as localised tremors or seizures,
• liver problems.

The result of the test detecting antibodies in the blood that can destroy red blood cells (Coombs test) may be positive. Your doctor will discuss this issue with you.

Children
Imipenem + Cilastatin Noridem is not recommended for use in children under 1 year of age or in children with kidney disease.

Imipenem + Cilastatin Noridem and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

If the patient is taking ganciclovir, used to treat certain viral infections, inform your doctor.

Also inform your doctor if the patient is taking valproic acid or sodium valproate (medicines used for epilepsy, bipolar affective disorders, migraine, or schizophrenia) or any anticoagulant medicines such as warfarin.

Your doctor will decide whether the patient can receive Imipenem + Cilastatin Noridem together with these medicines.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she might be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine. Use of Imipenem + Cilastatin Noridem in pregnant women has not been studied. Imipenem + Cilastatin Noridem should not be used during pregnancy unless the doctor decides that the potential benefits outweigh the risks to the developing child.

If the patient is breastfeeding or intends to breastfeed, she should inform her doctor before starting Imipenem + Cilastatin Noridem. The medicine may pass into human milk in small amounts and may affect the breastfed child. Therefore, the doctor will decide whether Imipenem + Cilastatin Noridem can be used during breastfeeding.

Before taking any medicine, consult your doctor or pharmacist.

Driving and operating machinery
Some adverse effects associated with this medicine (such as hallucinations, i.e. seeing, feeling, or hearing things that are not real; dizziness, drowsiness, and balance disturbances) may affect the ability of some patients to drive or operate machinery (see section 4).

Imipenem + Cilastatin Noridem contains sodium
This medicinal product contains 37.6 mg (1.6 mmol) of sodium (the main component of table salt) in each 500 mg dose. This corresponds to 1.9% of the maximum recommended daily intake of sodium for adults.

3. How to use Imipenem + Cilastatin Noridem

Imipenem + Cilastatin Noridem will be prepared and administered to the patient by a doctor or another
healthcare professional. The doctor will decide how much Imipenem + Cilastatin Noridem should be
given to the patient.

Use in adults and adolescents
The recommended dose for adults and adolescents is 500 mg+500 mg every 6 hours or
1000 mg+1000 mg every 6 or 8 hours. In patients with kidney disease, the doctor may reduce the dose
of the medicine.

Use in children
The recommended dose for children aged one year or older is (15 mg+15 mg) or (25 mg+25 mg)/kg body weight every 6 hours. Imipenem + Cilastatin Noridem is not recommended for use in children under 1 year of age or in children with kidney disease.

Method of administration
Imipenem with cilastatin is administered intravenously; a dose ≤500 mg+500 mg is given over 20–30 minutes,
and a dose >500 mg+500 mg is given over 40–60 minutes. If nausea occurs, the infusion rate may be reduced.

Use of a higher than recommended dose of Imipenem + Cilastatin Noridem
Symptoms of overdose may include: seizures (epileptic fits), feeling disoriented, tremor, nausea, vomiting, low blood pressure, and slow heart rate. If there is any suspicion that too high a dose of Imipenem + Cilastatin Noridem has been administered, contact a doctor or another healthcare professional immediately.

Missed dose of Imipenem + Cilastatin Noridem
If there is concern that a dose of Imipenem + Cilastatin Noridem has been missed, contact a doctor or another healthcare professional immediately.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The frequency of the potential adverse effects listed below has been defined using the following convention:

• very common: affects more than 1 in 10 patients
• common: affects 1 to 10 in 100 patients
• uncommon: affects 1 to 10 in 1,000 patients
• rare: affects 1 to 10 in 10,000 patients
• very rare: affects fewer than 1 in 10,000 patients
• frequency not known: frequency cannot be estimated from the available data

During or after administration of Imipenem + Cilastatin Noridem, the following adverse effects have been reported rarely; however, if they occur, treatment must be discontinued immediately and a doctor should be contacted without delay.

• Hypersensitivity reactions, including rash, swelling of the face, lips, tongue, and (or) throat (causing breathing or swallowing difficulties) and (or) low blood pressure
• Skin peeling (toxic epidermal necrolysis)
• Severe skin reactions (Stevens-Johnson syndrome and erythema multiforme)
• Severe form of rash with skin peeling and hair loss (exfoliative dermatitis)

Other possible adverse effects:
Common (less than 1 in 10 people)

• Nausea, vomiting, diarrhoea. Nausea and vomiting appear to occur more frequently in patients with low white blood cell counts
• Swelling and redness along the vein, maximally tender to touch
• Rash
• Abnormal liver function detected in blood tests
• Increase in the number of certain types of white blood cells

Uncommon (less than 1 in 100 people)

• Local skin redness
• Pain and formation of a hard lump at the injection site
• Itching of the skin
• Urticaria (hives)
• Fever
• Blood disorders affecting blood cells, usually detected during blood analysis (symptoms may include fatigue, pale skin, and prolonged bruising after injury)
• Abnormal kidney, liver, and blood function detected in blood tests
• Tremor and uncontrolled muscle twitching
• Seizures (fits)
• Psychiatric disturbances (such as mood swings and impaired judgment)
• Hallucinations, i.e. seeing, hearing, or feeling things that are not real
• Feeling disoriented
• Dizziness, drowsiness
• Low blood pressure

Rare (less than 1 in 1,000 people)

• Fungal infection (candidiasis)
• Discoloration of teeth and (or) tongue
• Colitis (inflammation of the large intestine) with severe diarrhoea
• Taste disturbances
• Liver function disorders
• Hepatitis (liver inflammation)
• Kidney function disorders
• Changes in the amount of urine passed and changes in urine colour
• Brain function disturbances, sensation of tingling (numbness and pins and needles), local tremor
• Hearing loss

Very rare (less than 1 in 10,000 people)

• Severe liver dysfunction due to hepatitis (fulminant hepatitis)
• Gastritis or enteritis
• Inflammatory bowel disease with bloody diarrhoea (haemorrhagic colitis)
• Redness and swelling of the tongue, overgrowth of tongue papillae giving it a "hairy" appearance, heartburn, sore throat, increased salivation
• Stomach pain
• Sensation of spinning (disturbances in balance), headache
• Ringing in the ears (tinnitus)
• Joint pain, weakness
• Irregular heartbeat, rapid heartbeat, or strong palpitations
• Chest discomfort, difficulty breathing, abnormally fast or shallow breathing, pain in the upper spine
• Hot flushes with facial redness, bluish discoloration of the face and lips, changes in skin texture, excessive sweating
• Itching of the genital area in women
• Changes in blood cell counts
• Worsening of symptoms of a rare condition causing muscle weakness (exacerbation of myasthenia)

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

• Abnormal movements
• Restlessness

Reporting of adverse effects
If any adverse effects occur, including any possible adverse effects not listed in this leaflet, consult a doctor, pharmacist, or nurse. Adverse effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported directly to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store the medicine Imipenem + Cilastatin Noridem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and the outer cardboard
package following EXP. The expiry date refers to the last day of the specified month.
Do not store above 25°C.
Do not freeze the prepared solution.
Prepared solution:
The diluted solution should be used immediately. The time from the start of reconstitution to
the end of intravenous infusion should not exceed two hours.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. These measures will help protect the
environment.

6. Contents of the pack and other information

What Imipenem + Cilastatin Noridem contains

• The active substances are imipenem and cilastatin.
• Each vial contains imipenem monohydrate equivalent to 500 mg of anhydrous imipenem and sodium cilastatin equivalent to 500 mg of cilastatin.
• The other ingredient is sodium hydrogen carbonate.

What Imipenem + Cilastatin Noridem looks like and contents of the pack
Imipenem + Cilastatin Noridem is a white to slightly yellowish powder for solution for infusion, in a glass vial.
Pack sizes: 1, 10 or 25 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Noridem Enterprises Limited
Makariou & Evagorou 1
Mitsi Building 3, Office 115
1065 Nicosia, Cyprus
Tel.: +30 210 8161802, Fax: +30 2108161587

Manufacturer:
DEMO S.A. PHARMACEUTICAL INDUSTRY
21st Km National Road Athens–Lamia,
14568 Krioneri, Attiki, Greece

This medicinal product is authorised in the European Economic Area countries under the following names:
Germany: Imipenem/Cilastatin Noridem 500mg/500mg Pulver zur Herstellung einer Infusionslösung
Czech Republic: Imipenem/Cilastatin Noridem
Cyprus: Imipenem/Cilastatin Noridem 500 mg/500 mg κόνις για διάλυμα προς έγχυση
Denmark: Imipenem/Cilastatin Noridem
Finland: Imipenem/Cilastatin Noridem 500 mg/500 mg infuusiokuiva-aine, liuosta varten
France: IMIPENEM/CILASTATINE NORIDEM 500 mg/500 mg, poudre pour solution pour perfusion
Hungary: Imipenem/Cilastatin Noridem 500 mg/500 mg por oldatos infúzióhoz
Italy: Imipenem e cilastatina Noridem
Netherlands: Imipenem/Cilastatin Noridem 500 mg/500 mg poeder voor oplossing voor infusie
Norway: Imipenem/Cilastatin Noridem
Poland: Imipenem + Cilastatin Noridem
Romania: Imipenem/Cilastatin Noridem 500 mg/500 mg pulbere pentru soluţie perfuzabilă
Sweden: Imipenem/Cilastatin Noridem
Slovakia: Imipenem/Cilastatin Noridem 500 mg/500 mg prášok na infúzny roztok
Spain: Imipenem/Cilastatin a Noridem 500 mg/500 mg polvo para solución para perfusión EFG

The following information is intended solely for qualified medical personnel:

Each vial is for single use only.
Preparation of the solution
The contents of each vial should be transferred into 100 mL of an appropriate infusion solution (see sections
“ Pharmaceutical incompatibilities ” and “ After reconstitution ”): 0.9% sodium chloride solution. In
exceptional circumstances, if for clinical reasons 0.9% sodium chloride solution cannot be used, 5% glucose solution may be used instead.
According to the recommended procedure, approximately 10 mL of the appropriate infusion solution should be added to the vial.
The vial should be shaken vigorously, and the resulting mixture transferred into the container with the infusion solution.
NOTE: THE MIXTURE IS NOT INTENDED FOR DIRECT INFUSION.
The procedure should be repeated by adding another 10 mL of infusion solution to ensure that the entire contents of the vial have been transferred into the infusion solution. The resulting mixture should be shaken until it becomes clear.
The concentration of imipenem and cilastatin in the solution prepared according to the above procedure is approximately 5 mg/mL.
The ready-to-use infusion solution should be visually inspected before administration. Only clear, colorless solutions practically free from particulate matter should be administered.
Variations in color (from colorless to yellow) do not affect the potency of the medicinal product.
Pharmaceutical incompatibilities
This medicinal product shows chemical incompatibility with lactates and therefore should not be dissolved or diluted in solvents containing lactate. However, it may be administered through an infusion set through which a lactate-containing solution is being administered.
Do not mix this medicinal product with other medicinal products except those mentioned in the section “ Preparation of the solution ”.
After reconstitution
The diluted solution should be used immediately after preparation. The time from the beginning of dissolution to the end of intravenous infusion should not exceed two hours.
Any unused remnants of the medicinal product or waste material should be disposed of in accordance with local regulations.