Package Leaflet: Information for the patient

Xantum 500 mg/500 mg Powder for Solution for Infusion

(imipenem with cilastatin)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor, pharmacist or nurse.

•    This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If you get any side effectstalk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1.    What Xantum is and what it is used for

2.    What you need to know before you use Xantum

3.    How to use Xantum

4.    Possible side effects

5.    How to store Xantum

6.    Contents of the pack and other information.

1. What Xantum is and what it is used for

Xantum belongs to a group of medicines called carbapenem antibiotics. It kills a wide range of bacteria (germs) that cause infections in various parts of the body in adults and children one year of age and above.

Treatment

Your doctor has prescribed Xantum because you have one (or more) of the following types of infection:

•    Complicated infections in the abdomen

•    Infection affecting the lungs (pneumonia)

•    Infections that you can catch during or after the delivery

•    Complicated urinary tract infections

•    Complicated skin and soft tissue infections

Xantum may be used in the management of patients with low white blood cell counts, who have fever that is suspected to be due to a bacterial infection.

Xantum may be used to treat bacterial infection of the blood which might be associated with a type of infection mentioned above.

2. What you need to know before you use Xantum

Do not use Xantum

-    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 other antibiotics such as penicillins, cephalosporins, or carbapenems. Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Xantum

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

-    allergies to any medicines including antibiotics (sudden life-threatening allergic reactions require immediate medical treatment)

-    colitis or any other gastrointestinal disease

-    kidney or urinary problems, including reduced kidney function (Xantum blood levels increase in patients with reduced kidney function. Central nervous system adverse reactions may occur if the dose is not adjusted to the kidney function)

-    any central nervous system disorders such as localized tremors or epileptic seizures

-    liver problems

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

Tell your doctor if you are taking medicines called valproic acid or sodium valproate (see Other medicines and Xantum below).

Children

Xantum is not recommended in children less than one year of age or children with kidney problems.

Other medicines and Xantum

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 blood thinners such as warfarin.

Your doctor will decide whether you should use Xantum in combination with these medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Xantum has not been studied in pregnant women. Xantum should not be used during pregnancy unless your doctor decides the potential benefit justifies the potential risk to the developing baby.

It is important that you tell your doctor if you are breast-feeding or if you intend to breastfeed before receiving Xantum. Small amounts of this medicine may pass into breast milk and it may affect the baby. Therefore, your doctor will decide whether you should use Xantum while breast-feeding.

Ask your doctor or pharmacist for advice before taking 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, sleepiness, and a spinning sensation) that may affect some patients' ability to drive or operate machinery (see section 4).

Xantum contains sodium

This medicinal product contains approximately 1.63 mmol (approximately 37.5 mg) of sodium per 500 mg dose which should be taken into consideration by patients on a controlled sodium diet.

3. How to use Xantum

Xantum will be prepared and given to you by a doctor or another health care professional. Your doctor will decide how much Xantum you need.

Use in adults and adolescents

The usual dose of Xantum 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 or weigh less than 70 kg, your doctor may lower your dose.

Use in children

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

Route and method of administration

Xantum is given 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. The rate of infusion may be slowed if you feel sick.

If you use more Xantum than you should

Symptoms of overdose may include seizures, confusion, tremors, nausea, vomiting, low blood pressure and slow heart rate. If you are concerned that you may have been given too much Xantum, contact your doctor or another healthcare professional immediately.

If you forget to use Xantum

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

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

4. Possible side effects

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

The frequency of possible side effects listed below is defined using the following convention:

•    very common: may affect more than 1 in 10 people

•    common: may affect up to 1 in 10 people

•    uncommon: may affect up to 1 to 100 people

•    rare: may affect up to 1 to 1,000 people

•    very rare: may affect up to 1 in 10,000 people

•    not known: frequency cannot be estimated from the available data

The following side-effects occur rarely, however if they do occur, while receiving or after receiving Xantum, the medicine must be stopped and your doctor contacted immediately.

-    Allergic reactions including rash, swelling of the face, lips, tongue, and/or throat (with difficulty in breathing or swallowing), and/or low blood pressure

-    Skin peeling (toxic epidermal necrolysis)

-    Severe skin reactions (Stevens-Johnson syndrome and erythema multiforme)

-    Severe skin rash with loss of skin and hair (exfoliative dermatitis)

Other possible side effects:

Common

•    Nausea, vomiting, diarrhoea. Nausea and vomiting appear to occur more frequently in patients with low number of white blood cells

•    Swelling and redness along a vein which is extremely tender when touched

•    Rash

•    Abnormal liver function detected by blood tests

•    Increase in some white blood cells

Uncommon

•    Local skin redness

•    Local pain and formation of a firm lump at the injection site

•    Skin itchiness

•    Hives

•    Fever

•    Blood disorders affecting the cell components of the blood and usually detected by blood tests (symptoms may be tiredness, paleness of skin, and prolonged bruising after injury)

•    Abnormal kidney, liver and blood function detected by blood tests

•    Tremors and uncontrolled twitching of muscles

•    Seizures (fits)

•    Psychic disturbances (such as mood swings and impaired judgment)

•    Seeing, hearing or feeling something that is not there (hallucinations)

•    Confusion

•    Dizziness, sleepiness

•    Low blood pressure

Rare

•    Fungal infection (candidiasis)

•    Staining of the teeth and/or tongue

•    Inflammation of the colon with severe diarrhoea

•    Disturbances in taste

•    Inability of the liver to perform normal function

• Inflammation of the liver

•    Inability of the kidney to perform normal function

•    Changes in the amount of urine, changes in urine colour

•    Disease of the brain, tingling sensation (pins and needles), localised tremor

•    Hearing loss

Very rare

•    Severe loss of liver function due to inflammation (fulminant hepatitis)

•    Inflammation of stomach or intestine (gastro-enteritis)

•    Inflammation of intestine with bloody diarrhoea (haemorrhagic colitis)

• Red swollen tongue, overgrowth of the normal projections on the tongue giving it a hairy appearance, heartburn, sore throat, increase in the production of saliva

•    Stomach pain

•    A spinning sensation (vertigo), headache

•    Ringing in the ears (tinnitus)

•    Pain in several joints, weakness

•    Irregular heartbeat, the heart beating forcefully or rapidly

•    Chest discomfort, difficulty breathing, abnormally fast and superficial breathing, pain in the upper spine

•    Flushing, bluish discoloration of the face and lips, skin texture changes, excessive sweating

•    Itching of the vulva in women

•    Changes in the amounts of blood cells

•    Worsening of a rare disease associated with muscle weakness (aggravation of myasthenia gravis)

Not known

•    Abnormal movements

•    Agitation

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This included any effects not listed in this leaflet. You can also report side effects directly via the Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can more information on the safety of this medicine.

5. How to store Santum

Keep this medicine out of the sight and reach of children.

Do not use Xantum after the expiry date stated on the container. The expiry date refers to the last day of that month.

Do not store above 25°C.

The container should be kept in the outer carton until immediately before use.

After reconstitution:

Diluted solutions should be used immediately.

Do not freeze the reconstituted solution.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information What Xantum contains

The active substances are imipenem and cilastatin. Each vial/monovial/infusion bottle contains imipenem monohydrate equivalent to 500 mg imipenem and cilastatin sodium equivalent to 500 mg cilastatin.

The other ingredient is sodium bicarbonate.

What Imipenem/Cilastatin looks like and contents of the pack

Xantum is a white to light yellow powder for solution for infusion.

Xantum 500 mg/500 mg Powder for Solution for Infusion is available as:

-    30 ml single vial and in package of 10 vials of 30 ml each

-    100 ml infusion bottles and in package of 10 bottles of 100 ml each

-    a monovial which has a built-in transfer needle to allow constitution of the product directly into an infusion bag

Not all pack types may be marketed in your country.

Marketing Authorisation Holder

Ranbaxy (UK) Limited 5th floor, Hyde Park, Hayes 3 11 Millington Road Hayes, UB3 4AZ United Kingdom

Manufacturer

Terapia S.A.

Str. Fabricii Nr. 124, Cluj-Napoca 400632

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87 2132JH Hoofddorp The Netherlands

This leaflet was last revised in July 2016.

Reconstitution

Preparation of intravenous solution

The following table is provided for convenience in reconstituting Imipenem/Cilastatin for intravenous infusion. 0.9 % Sodium Chloride is the recommended solvent.

Strength	Volume of solvent (0.9% Sodium Chloride) added (ml)	Approximate concentration of imipenem (mg/ml)
Imipenem/Cilastatin 500mg/500mg	100	5

Addition of Imipenem/Cilastatinin a Monovial to an infusion solution

1.    Check before use that there is no foreign material in the powder and that the seal between the cap and the vial is intact.

2.    Remove the cap by twisting and pulling until the seal breaks.

3.    The cannula is inserted into the addition port of the infusion bag. Push the cannula protector against the vial until you hear a click.

4.    Hold the vial upright and squeeze the infusion bag a few times so that 2/3 of the vial is filled with the solvent (0.9% Sodium Chloride). Shake the vial until the powder is completely dissolved.

5.    Invert the vial and transfer the content of the vial back into the infusion bag by squeezing the infusion bag.

Repeat steps 4 and 5 until the vial is completely empty.

6.    A part of the label of the vial may be detached and affixed to the infusion bag.

The bottle can be removed or can remain on the infusion bag.

Preparation of intravenous solution (30ml vial)

The following table is provided for convenience in reconstituting. 0.9 % Sodium Chloride is

the recommended solvent.

Imipenem/Cilastatin for intravenous infusion. Strength	Volume of solvent (0.9% Sodium Chloride) added (ml)	Approximate concentration of imipenem (mg/ml)
Imipenem/Cilastatin 500mg/500mg	100	5

The preparation of the Intravenous solution must be performed in appropriate conditions and environment.

Contents of the vials must be suspended and transferred to 100 ml of an appropriate infusion solution. A suggested procedure is:

1.    Check before use that there is no foreign material in the powder and that the seal between the cap and the vial is intact.

2.    Remove the cap by twisting and pulling until the seal breaks.

3.    Add approximately 10 ml from the appropriate infusion solution to the vial Shake well

4.    Transfer the resulting suspension to the infusion solution container

5.    Repeat the step 3 and 4.

CAUTION: THE SUSPENSION IS NOT FOR DIRECT INFUSION.

6.    The resulting mixture should be agitated until clear.

The reconstituted solution should be inspected visually for particulate matter and discoloration prior to administration. Variations of colour, from colourless to yellow, do not affect the potency of the product.

Incompatibility

This medicinal product is chemically incompatible with lactate and should not be reconstituted with solvent containing lactate. However, it can be administered into an IV tubing through which a lactate solution is being infused. This medicinal product must not be mixed with other medicinal products except those mentioned under Reconstitution.

After reconstitution

After reconsitution: The product should be used immediately.

Any unused solution and the vial should be adequately disposed of, in accordance with local requirements.