Package leaflet: Information for the user

Tacomylin 2 g/0.25 g, powder for solution for infusion

Tacomylin 4 g/0.5 g, powder for solution for infusion

piperacillin / tazobactam

Read all of this leaflet carefully before you start using 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 or pharmacist.

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

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

What is in this leaflet

1. What Tacomylin is and what it is used for

Piperacillin belongs to the group of medicines known as “broad-spectrum penicillin antibiotics”. It can kill many kinds of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects of piperacillin. This means that when piperacillin and tazobactam are given together, more types of bacteria are killed.

Tacomylin is used in adults and adolescents to treat bacterial infections, such as those affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin or blood. Tacomylin may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).

Tacomylin is used in children aged 2-12 years to treat infections of the abdomen such as appendicitis, peritonitis (infection of the fluid and lining of the abdominal organs), and gallbladder (biliary) infections. Tacomylin may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).

In certain serious infections, your doctor may consider using Tacomylin in combination with other antibiotics.

2. What you need to know before you are given Tacomylin

Do not use Tacomylin

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given Tacomylin:

• if you have allergies. If you have several allergies, make sure you tell your doctor or other healthcare professional before receiving this product.

• if you are suffering from diarrhoea before, or if you develop diarrhoea during or after your treatment. In this case, make sure you tell your doctor or other healthcare professional immediately. Do not take any medicine for the diarrhoea without first checking with your doctor.

• if you have low levels of potassium in your blood. Your doctor may want to check your kidneys before you take this medicine and may perform regular blood tests during treatment.

• if you have kidney or liver problems, or are receiving haemodialysis. Your doctor may want to check your kidneys before you take this medicine, and may perform regular blood tests during treatment.

• if you are taking certain medicines (called anticoagulants) to avoid an excess of blood clotting (see also Other medicines and Tacomylin in this leaflet) or any unexpected bleeding occurs during the treatment. In this case, you should inform your doctor or other healthcare professional immediately.

During treatment

• if you develop fits (convulsions) or if you think you developed a new or worsening infection, talk to your doctor or other healthcare professional.

Children

Piperacillin / tazobactam is not recommended for use in children below the age of 2 years due to insufficient data on safety and effectiveness.

Other medicines and Tacomylin

Tell your doctor, pharmacist or other healthcare professional if you are taking, have recently taken or might take any other medicines. Some medicines may interact with piperacillin and tazobactam.

These include:

• medicine for gout (probenecid). This can increase the time it takes for piperacillin and tazobactam to leave your body.

• medicines to thin your blood or to treat blood clots (e.g. heparin, warfarin or aspirin).

• medicines used to relax your muscles during surgery. Tell your doctor if you are going to have a general anaesthetic.

• methotrexate (medicine used to treat cancer, arthritis or psoriasis). Piperacillin and tazobactam can increase the time it takes for methotrexate to leave your body.

• medicines that reduce the level of potassium in your blood (e.g. tablets enhancing urination or some medicines for cancer).

• medicines containing the other antibiotics tobramycin or gentamycin. Tell your doctor if you have kidney problems.

Effect on laboratory tests

Tell the doctor or laboratory staff that you are taking Tacomylin if you have to provide a blood or urine sample.

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, pharmacist or other healthcare professional for advice before receiving this medicine. Your doctor will decide if Tacomylin is right for you.

Piperacillin and tazobactam can pass to a baby in the womb or through breast milk. If you are breast-feeding, your doctor will decide if Tacomylin is right for you.

Driving and using machines

The use of Tacomylin is not expected to affect the ability to drive or use machines.

Important information about some of the ingredients of Tacomylin

Tacomylin 2 g / 0.25 g contains 4.70 mmol (108 mg) of sodium per vial of powder for solution for infusion.

Tacomylin 4 g / 0.5 g contains 9.39 mmol (216 mg) of sodium per vial of powder for solution for infusion.

This should be taken into consideration if you are on a controlled-sodium diet.

3. How Tacomylin is given

Your doctor or other healthcare professional will give you this medicine through an infusion (a drip for 30 minutes) into one of your veins. The dose of medicine given to you depends on what you are being treated for, your age, and whether or not you have kidney problems.

Adults and adolescents aged 12 years or older

The recommended dose is 4 g / 0.5 g of piperacillin / tazobactam given every 6-8 hours, which is given into one of your veins (directly into the blood stream).

Children aged 2 to 12 years

The recommended dose for children with abdominal infections is 100 mg / 12.5 mg / kg of body weight of piperacillin / tazobactam given every 8 hours into one of your veins (directly into the blood stream). The recommended dose for children with low white blood cell counts is 80 mg / 10 mg / kg of body weight of piperacillin / tazobactam given every 6 hours into one of your veins (directly into the blood stream).

Your doctor will calculate the dose depending on your child’s weight but each individual dose will not exceed 4 g / 0.5 g of Tacomylin.

You will be given Tacomylin until the sign of infection has gone completely (5 to 14 days).

Patients with kidney problems

Your doctor may need to reduce the dose of Tacomylin or how often you are given it. Your doctor may also want to test your blood to make sure that your treatment is at the right dose, especially if you have to take this medicine for a long time.

If you receive more Tacomylinthan you should

As you will receive Tacomylin from a doctor or other healthcare professional, you are unlikely to be given the wrong dose. However, if you experience side effects, such as convulsions, or think you have been given too much, tell your doctor immediately.

If you miss a dose of Tacomylin

If you think you have not been given a dose of Tacomylin, tell your doctor or other healthcare professional immediately.

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

4. Possible side effects

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

If you notice any of the following side effects, stop taking this medicine and contact your doctor, or other healthcare professional, or go to the nearest hospital casualty department straight away:

Common: may affect up to 1 in 10 people

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

• serious skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis) appearing initially as reddish target-like spots or circular patches often with central blisters on the trunk. Additional signs include ulcers in the mouth, throat, nose, extremities, genitals and red and swollen eyes.

• severe or persistent diarrhoea accompanied by fever or weakness. This may be a sign of a certain form of infection of the colon (pseudomembranous colitis).

Not known: frequency cannot be estimated from the available data

• signs of serious allergic reactions, such as swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing, severe rash, itching or hives on the skin.

• yellowing of the eyes or skin. This may be a sign of inflammation of the liver (hepatitis).

• damage to blood cells (the signs include: being breathless when you do not expect it, red or brown urine, nosebleeds and bruising).

Other possible side effects:

Very common: may affect more than 1 in 10 people

Common: may affect up to 1 in 10 people

• yeast infection (candidiasis), such as thrush

• abnormal lab test (positive direct Coombs),

• decrease in blood protein

• headache, sleeplessness

• abdominal pain, vomiting, nausea, constipation, indigestion

• increase of liver enzymes in the blood

• skin rashes, itching

• Abnormal kidney blood tests

• fever, injection site reaction

• bruising or bleeding for longer than normal, particularly if you are taking anticoagulants such as warfarin.

Uncommon: may affect up to 1 in 100 people

• decrease of potassium in the blood (hypokalaemia), decrease of blood sugar (glucose),

• low blood pressure, inflammation of the veins (felt as tenderness or redness in the affected area), flushed red skin

• increase of a blood pigments breakdown product (bilirubin)

• nettle rash, skin reactions with redness and formation of skin lesions

• joint and muscle pain

• chills

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

bleeding of the nose (epistaxis)

Not known: frequency cannot be estimated from the available data

• small spot bruising (purpura),

• increase of a specific type of white blood cells (eosinophilia),

• increase of platelets (thrombocytosis)

• poor kidney functions and kidney problems (the signs include: passing little or no urine, pain in the back, cloudy urine or blood in the urine).

Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

Reporting of side effects

If you get 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 via 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. How to store Tacomylin

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 vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials: Do not store above 25°C.

For single use only. Discard any unused 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 Tacomylin contains

The active substances are piperacillin and tazobactam.

Each vial contains 2.085 g piperacillin (as sodium salt) and 0.268 g tazobactam (as sodium salt).

Each vial contains 4.17 g piperacillin (as sodium salt) and 0.536 g tazobactam (as sodium salt).

There are no other ingredients

What Tacomylin looks like and contents of the pack

Tacomylin is a white to off-white powder supplied in a vial.

Packs containing 1, 5, 10, 12 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

[To be completed nationally]

<This medicinal product is authorised in the Member States of the EEA under the following names:>

[To be completed nationally]

This leaflet was last revised in 2016-10-07.

Detailed information on this medicine is available on the website of {MS/Agency}

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The following information is intended for healthcare professionals only:

Instructions for use

Tacomylin will be given by intravenous infusion (a drip for 30 minutes).

Intravenous use

Each injection vial of Tacomylin needs to be reconstituted by adding 50 ml to 150 ml of one of the following solutions:

• Sterile water for injection⁽¹⁾

• 0,9% (9 mg/ml) sodium chloride solution for injection

• Glucose 5%

In a first step, add the volume of solution indicated in the table below to each injection vial:

Content of the vial	Volume of the solution to be added to the vial
2 g / 0.25 g (2 g piperacillin and 0.25 g tazobactam)	10 ml
4 g / 0.50 g (4 g piperacillin and 0.5 g tazobactam)	20 ml

⁽¹⁾ Maximum recommended volume of sterile water for injection per dose is 50 ml.

Shake strongly during 1 to 2 minutes. The reconstituted solutions may be further diluted to the desired volume (e.g. 50 ml to 150 ml) with the same solvents.

Shake strongly again until it is completely dissolved.

The reconstituted solutions should be withdrawn from the vial by syringe. When reconstituted as directed, the vial contents withdrawn by syringe will provide the labelled amount of piperacillin and tazobactam.

Incompatibilities

Whenever Tacomylin is used concurrently with another antibiotic (e.g. aminoglycosides), the substances must be administered separately. The mixing of beta-lactam antibiotics with aminoglycosides, in vitro, can result in substantial inactivation of the aminoglycoside.

Tacomylin should not be mixed with other substances in a syringe or infusion bottle since compatibility has not been established.

Because of chemical instability, Tacomylin should not be used with solutions containing sodium bicarbonate.

Lactated Ringer’s (Hartmann’s) solution is not compatible with Tacomylin.

Tacomylin should not be added to blood products or albumin hydrolysates.

Co-administration of Tacomylin with aminoglycosides

Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, Tacomylin and the aminoglycoside are recommended for separate administration. Tacomylin and the aminoglycoside should be reconstituted and diluted separately when concomitant therapy with aminoglycosides is indicated.

Tacomylin should be administered through an infusion set separately from any other drugs unless compatibility is proven.

Special precautions for storage

Before first opening:

Do not store above 25°C.

After reconstitution/dilution:

Chemical and physical in-use stability on the reconstituted/diluted solution has been demonstrated for 18 hours at 25°C and for 48 hours if stored under refrigeration (2 to 8°C).

From a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.