IMIPENEM/CILASTATIN Aurovitas 500 mg/500 mg Powder for Solution for Infusion

2. What you need to know before you use Imipenem/Cilastatin Aurovitas

Do not use Imipenem/Cilastatin Aurovitas

• If you are allergic to imipenem, cilastatin, or any of the other components of this medicine (listed in section 6).
• If you are allergic to other antibiotics such as penicillins, cephalosporins, or carbapenems.

Warnings and precautions

Tell your doctor about any problems you have or have had, such as:

• Allergies to any medication, including antibiotics (unexpected allergic reactions that can be life-threatening require immediate medical treatment)
• Colitis or any other gastrointestinal disease
• Any disorder of the central nervous system, such as localized tremors or epileptic seizures
• Liver, kidney, or urine problems

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

Tell your doctor if you are taking valproic acid or sodium valproate (see Using Imipenem/Cilastatin Aurovitas with other medicinesbelow).

Children

Imipenem/cilastatin is not recommended for administration in children under one year of age or children with kidney problems.

Using Imipenem/Cilastatin Aurovitas with other medicines

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

Tell your doctor if you are taking ganciclovir, which is used to treat some viral infections.

Also, tell your doctor if you are taking valproic acid or sodium valproate (used to treat epilepsy, bipolar disorder, migraine, or schizophrenia) or any anticoagulant medication such as warfarin.

Your doctor will decide if you should use imipenem/cilastatin in combination with these medicines.

Pregnancy, breastfeeding, and fertility

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

Imipenem/cilastatin has not been studied in pregnant women. Imipenem/cilastatin should not be used during pregnancy unless your doctor decides that the potential benefit justifies the potential risk to the fetus.

Small amounts of this medicine may pass into breast milk and may affect the baby. Therefore, your doctor will decide if you should use imipenem/cilastatin during breastfeeding.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

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

Imipenem/Cilastatin Aurovitas contains sodium

Patients on low-sodium diets should note that this medicine contains 37.6 mg (1.6 mmol) of sodium per dose.

3. How to use Imipenem/Cilastatin Aurovitas

Imipenem/cilastatin will be prepared and administered by a doctor or other healthcare professional. Your doctor will decide how much imipenem/cilastatin you need.

Use in adults and adolescents

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

Use in children

The usual dose in children over one year of age is 15/15 or 25/25 mg/kg/dose every 6 hours. Imipenem/cilastatin is not recommended in children under one year of age and in children with kidney problems.

Method of administration

Imipenem/cilastatin is administered intravenously (into a vein) over 20-30 minutes for a dose of ≤500 mg/500 mg or 40-60 minutes for a dose of >500 mg/500 mg.

If you use more Imipenem/Cilastatin Aurovitas than you should

Overdose symptoms may include seizures, confusion, tremors, nausea, vomiting, low blood pressure, and slow heart rate. If you are concerned that you may have received too much imipenem/cilastatin, contact your doctor or other healthcare professional immediately.

If you forget to use Imipenem/Cilastatin Aurovitas

If you are concerned that you may have missed a dose, contact your doctor or other healthcare professional immediately.

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

If you stop using Imipenem/Cilastatin Aurovitas

Do not stop using imipenem/cilastatin until your doctor tells you to.

If you have any further questions about 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.

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

• Nausea, vomiting, diarrhea. Nausea and vomiting seem to occur more frequently in patients with a low white blood cell count
• Swelling and redness along a vein, extremely sensitive to touch
• Rash
• Liver function changes detected by blood tests
• Increased number of some white blood cells

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

• Local skin redness
• Localized pain and formation of a firm lump at the injection site
• Itching of the skin
• Hives
• Fever
• Blood disorders that affect cells and are usually detected by a blood test (symptoms may be fatigue, pale skin, and prolonged bruising after injuries)
• Kidney, liver, and blood changes detected by a blood test
• Tremors and uncontrolled muscle contractions
• Seizures
• Mental changes (such as mood changes and impairment of mental faculties)
• Seeing, hearing, or feeling something that is not there (hallucinations)
• Confusion
• Dizziness, drowsiness
• Low blood pressure (hypotension)

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

• Allergic reactions such as skin rash, swelling of the face, lips, tongue, and/or throat (with difficulty breathing or swallowing) and/or low blood pressure (hypotension). If these side effects occur while receiving or after receiving imipenem/cilastatin, the administration of the medicine should be discontinued, and you should contact your doctor immediately.
• Peeling of the skin (toxic epidermal necrolysis)
• Severe skin reactions (Stevens-Johnson syndrome and erythema multiforme)
• Severe skin rash with skin and hair loss (exfoliative dermatitis)
• Fungal infection (candidiasis)
• Discoloration of teeth and/or tongue
• Inflammation of the colon with severe diarrhea
• Changes in taste
• The liver cannot perform its normal function
• Inflammation of the liver
• The kidney cannot perform its normal function
• Changes in urine quantity, changes in urine color
• Brain disease, tingling sensation (pins and needles), localized tremor
• Hearing loss (hearing impairment)

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)
• Redness and swelling of the tongue, excessive growth of the normal projections of the tongue, giving it a hairy appearance, heartburn, sore throat, increased saliva production
• Stomach pain
• Sensation of spinning (vertigo), headache
• Ringing in the ears (tinnitus)
• Pain in several joints, weakness
• Irregular heartbeat, the heart beats strongly or rapidly
• Chest discomfort, difficulty breathing, abnormally rapid and shallow breathing, pain in the upper back
• Redness of the face (flushing), change in bluish discoloration of the face and lips, changes in skin texture, excessive sweating
• Itching of the vulva in women
• Changes in blood cell counts
• Worsening of a rare disease associated with muscle weakness (increased severity of myasthenia gravis)

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

• Abnormal movements
• Agitation

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 Surveillance System for Human Use: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Imipenem/Cilastatin Aurovitas

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 and on the vials after “EXP”. The expiry date is the last day of the month stated.

Imipenem/Cilastatin Aurovitas dry vials: no special storage conditions are required.

After reconstitution:

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.

Do not freeze the reconstituted solution.

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 Aurovitas

• The active substances are imipenem (as monohydrate) and cilastatin (as sodium salt).

Each vial of Imipenem/Cilastatin Aurovitas 500 mg/500 mg powder for solution for infusion contains 500 mg of imipenem (as 530 mg of imipenem monohydrate) and 500 mg of cilastatin (as 530 mg of cilastatin sodium salt).

• The other component is sodium hydrogencarbonate.

Appearance of the product and pack size

Imipenem/Cilastatin 500 mg is presented in 20 ml capacity type III colorless glass vials, closed with a 20 mm diameter bromobutyl rubber stopper and a flip-off cap.

Pack sizes:

1 x vial of 500 mg

10 x vial of 500 mg

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

ACS Dobfar S.p.A.

Nucleo Industriale S.Atto, S. Nicolò a Tordino

64100 Teramo

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Date of last revision of this leaflet: January 2018

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

This information is intended only for healthcare professionals:

Each vial is for single use.

Preparation of the intravenous solution

The following table is provided to facilitate the reconstitution of Imipenem/Cilastatin Aurovitas for intravenous infusion.

Reconstitution of Imipenem/Cilastatin Aurovitas 500 mg:

The contents of the vials should be dissolved and transferred to an appropriate infusion solution to achieve a volume of 100 ml.

A suggested procedure is to add approximately 10 ml of the infusion solution (see “Compatibility and stability”) to the vial. Shake well and transfer the resulting suspension to the infusion solution bottle.

CAUTION: THE SUSPENSION IS NOT FOR DIRECT INFUSION.

Repeat with an additional 10 ml of the infusion solution to ensure complete transfer of the vial contents to the infusion solution bottle. Make up to 100.0 with the same infusion solution. The resulting mixture should be shaken until a clear solution is obtained.

The concentration of the reconstituted solution, following the procedure described above, is approximately 5 mg/ml for both imipenem and cilastatin.

The reconstituted solution should be visually inspected for particles and/or color change before administration. Once reconstituted, the imipenem/cilastatin solution ranges from colorless to yellow. The color variation within this range does not affect the potency of the product.

Compatibility and stability

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

Imipenem/Cilastatin Aurovitas can be reconstituted in water for injection or in a 9 mg/ml (0.9%) sodium chloride infusion solution.

Do not freeze the reconstituted solution.

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