Limerik

PACKAGE LEAFLET: INFORMATION FOR THE USER

LIMERIK

2 g + 0,25 g/4 ml powder and solvent for injectable solution
4 g / 0,5 g powder for solution for infusion
Piperacillin / tazobactam
Read this leaflet carefully before using this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What LIMERIK is and what it is used for
2. Before you use LIMERIK
3. How to use LIMERIK
4. Possible side effects
5. How to store LIMERIK
6. Further information

1. WHAT LIMERIK IS AND WHAT IT IS USED FOR

Piperacillin belongs to a group of medicines known as "broad-spectrum penicillin antibiotics" and is capable of killing many types of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects of piperacillin. This means that when piperacillin and tazobactam are administered together, they can kill a wider range of bacterial types.
LIMERIK is used in adults and adolescents for the treatment of bacterial infections, such as those affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin, or blood. LIMERIK may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
LIMERIK is used in children aged between 2 and 12 years for the treatment of abdominal infections, such as appendicitis, peritonitis (infection of the fluid and lining of abdominal organs), and gallbladder (biliary) infections. LIMERIK may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
In certain severe infections, the doctor may consider using LIMERIK in combination with other antibiotics.

2. BEFORE USING LIMERIK

Do not use LIMERIK

• If you are allergic (hypersensitive) to piperacillin or tazobactam or to any of the excipients of LIMERIK.
• If you are allergic (hypersensitive) to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may also be allergic to LIMERIK.

Take special care with LIMERIK

• If you have allergies. If you have multiple allergies, inform your doctor or healthcare professional before receiving this medicine.
• If you have diarrhoea before treatment, or if you develop diarrhoea during or after treatment. In this case, you must inform your doctor or healthcare professional immediately. Do not take medicines for diarrhoea without first consulting your doctor.
• If you have low levels of potassium in your blood. Your doctor will need to check your kidney function before administering this medicine and may perform periodic blood tests during treatment.
• If you have kidney or liver problems or are undergoing haemodialysis. Your doctor will need to check your kidney function before administering this medicine and may perform periodic blood tests during treatment.
• If you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also section Use of LIMERIK with other medicines in this leaflet), or if unexpected bleeding occurs during treatment. In this case, you must inform your doctor or healthcare professional immediately.
• If you develop seizures during treatment. In this case, you must inform your doctor or healthcare professional.
• If you suspect you have developed a new infection or if your infection worsens. In this case, you must inform your doctor or healthcare professional.

Warnings and precautions
Haemophagocytic lymphohistiocytosis
Cases of a disease in which the immune system produces an abnormally high number of white blood cells called histiocytes and lymphocytes, resulting in inflammation (haemophagocytic lymphohistiocytosis), have been reported. This condition can be life-threatening if not diagnosed and treated early.
If you develop various symptoms such as fever, swollen lymph nodes, feeling weak, mental confusion, shortness of breath, bruising, or skin rash, contact your doctor immediately.
Children under 2 years of age
The use of piperacillin / tazobactam is not recommended in children under 2 years of age due to insufficient data on safety and efficacy.
Use with other medicines
Inform your doctor or healthcare professional if you are taking or have recently taken any other medicines, including those without a prescription. Some medicines may interact with piperacillin and tazobactam.
These include:

• Medicines for gout (probenecid). These may increase the time required for elimination of piperacillin and tazobactam from the body.

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

• Medicines used to relax muscles during surgery. Inform your doctor if you are undergoing general anaesthesia.

• Methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time required for elimination of methotrexate from the body.

• Medicines that may reduce potassium levels in the blood (e.g. tablets that increase urine production or certain cancer medicines).

• Medicines containing the antibiotics tobramycin or gentamicin. Inform your doctor if you have kidney problems.

Effect on laboratory tests
Inform your doctor or laboratory staff that you are taking LIMERIK if you are required to provide a blood or urine sample.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, or plan to become pregnant, inform your doctor or healthcare professional before receiving this medicine. Your doctor will decide whether LIMERIK is suitable for you.
Piperacillin and tazobactam may pass to the baby in the womb or through breast milk.
If you are breastfeeding, your doctor will decide whether LIMERIK is suitable for you.
Driving and using machines
LIMERIK is not expected to affect your ability to drive vehicles or operate machinery.
Important information about some of the excipients of LIMERIK
LIMERIK 2 g / 0.25 g contains 5.58 mmol (128 mg) of sodium.
LIMERIK 4 g / 0.5 g contains 11.16 mmol (256 mg) of sodium.
This should be taken into consideration if you are on a controlled sodium intake diet.

3. HOW TO USE LIMERIK

Limerik 2 g+0,25 g can be administered either by intramuscular injection or by slow intravenous injection (lasting at least 3–5 minutes) or by infusion (lasting 20–30 minutes).
The vial of solvent containing lidocaine, included in the Limerik 2 g+0,25 g pack, must be used only for intramuscular administration.
Limerik 4 g+0,5 g can only be administered by slow intravenous injection or by infusion.
The dose administered depends on the reason for treatment, age, and any possible kidney problems.

Adults and adolescents over 12 years of age
The usual dose is 2 g / 0,25 g of piperacillin / tazobactam every 12 hours by intramuscular injection.
For intravenous administration, the dosage ranges from a minimum of 2 g / 0,25 g to a maximum of 4 g / 0,5 g of piperacillin / tazobactam, given every 6, 8 or 12 hours.

Children aged 2 to 12 years
The usual dose for children with abdominal infections is 100 mg / 12.5 mg / kg body weight of piperacillin / tazobactam, administered intravenously every 8 hours (directly into the bloodstream).
The usual dose for children with low white blood cell counts is 80 mg / 10 mg / kg body weight of piperacillin / tazobactam, administered intravenously every 6 hours (directly into the bloodstream).
The doctor will calculate the dose based on the child's weight; in any case, the daily dose must not exceed 4 g / 0,5 g of LIMERIK.
LIMERIK will be administered until complete disappearance of signs of infection (5–14 days).

Patients with kidney problems
The doctor may need to reduce the dose of LIMERIK or the frequency of administration.
The doctor may also perform blood tests to ensure that the prescribed dose is appropriate, especially if you need to take this medicine for a prolonged period.

If you receive more LIMERIK than you should
If adverse effects such as seizures occur, or if you think you have been given an excessive dose, inform your doctor immediately.

If you miss a dose of LIMERIK
If you think a dose of LIMERIK has not been administered, inform your doctor or healthcare provider immediately.

If you have any doubts about using this product, consult your doctor or healthcare provider.

INSTRUCTIONS FOR RECONSTITUTION AND DILUTION

A. Intramuscular administration
Limerik 2 g+0,25 g must be reconstituted with the solvent vial supplied in the pack, containing 4 ml of 0.5% lidocaine solution.
The solvent vial containing lidocaine, supplied with the pack, must be used only for intramuscular administration.
Do not exceed a dose of 2 g+0,25 g of piperacillin/tazobactam per injection site.

For correct reconstitution, follow the procedure below:

1. Shake the vial containing the powder to loosen the powder from the bottom of the vial.
2. Remove the flip-off plastic cap from the vial to expose the central portion of the rubber stopper and keep the cap (Fig.1). Always avoid touching the central portion of the rubber stopper with your hands.

Fig.1
3) Using a syringe, withdraw the solvent containing lidocaine and inject it into the vial containing the powder.
4) Place the plastic cap back onto the rubber stopper to avoid touching the central portion with fingers. Shake vigorously until the powder is completely dissolved. With continuous shaking, reconstitution should occur within 10 minutes (Fig.2).

Fig. 2
5) Allow the resulting solution to stand until foam disappears and a clear solution is obtained. Ensure that no undissolved particles remain.
6) Remove the plastic cap and withdraw the solution using a 5 ml syringe for intramuscular administration.
After reconstitution, the solution must be administered immediately.
Unused solutions must be discarded.

B. Intravenous administration
To be performed exclusively by healthcare personnel.

Intravenous use
Reconstitute each vial with the volume of solvent indicated in the following table, using one of the compatible solvents for reconstitution. Shake with rotary motion until dissolved.
With continuous rotary agitation, reconstitution usually occurs within 5–10 minutes (for handling details, see below).

*Compatible solvents for reconstitution:

• 0.9% (9 mg/ml) sodium chloride injectable solution
• sterile water for injection
• 5% glucose

The recommended maximum volume of sterile water for injection for each dose is 50 ml.
The reconstituted solution must be withdrawn from the vial using a syringe. Once reconstituted
according to the instructions, the content of the vial withdrawn with the provided syringe will provide
the amount of piperacillin and tazobactam stated on the label.
Reconstituted solutions may be further diluted to the desired volume (e.g., from 50 ml to 150 ml) with
one of the following compatible solvents:

• 0.9% (9 mg/ml) sodium chloride injectable solution
• 5% glucose
• 6% dextran in 0.9% sodium chloride
• Ringer's lactate injectable solution
• Hartmann's solution
• Ringer's acetate
• Ringer's acetate/malate

Incompatibilities
When LIMERIK is used concomitantly with another antibiotic (e.g., aminoglycosides), the substances
must be administered separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may
cause substantial inactivation of the aminoglycoside.
However, compatibility of amikacin and gentamicin with LIMERIK has been determined in vitro in
certain diluents at specific concentrations (see section Co-administration of LIMERIK with
aminoglycosides).
LIMERIK must not be mixed with other substances in a syringe or infusion vial, as compatibility has
not been established.
Due to chemical instability, LIMERIK must not be used with solutions containing sodium
bicarbonate alone.
LIMERIK is compatible with Ringer's lactate solution for co-administration via a Y-site connector.
LIMERIK must not be added to blood products or hydrolysed albumins.

Co-administration of LIMERIK with aminoglycosides
Due to in vitro inactivation of aminoglycosides by beta-lactam antibiotics, it is recommended that
LIMERIK and the aminoglycoside be administered separately. When concomitant therapy with
aminoglycosides is indicated, LIMERIK and the aminoglycoside must be reconstituted and diluted
separately.
In circumstances where co-administration is recommended, LIMERIK is compatible for simultaneous
co-administration via infusion using a Y-site connector only with the following aminoglycosides, under
the following conditions:

* The aminoglycoside dose must be based on the patient's body weight, the severity of the infection (serious or potentially life-threatening), and renal function (creatinine clearance).
Compatibility of LIMERIK with other aminoglycosides has not been established. Only the concentrations and diluents for amikacin and gentamicin, using the LIMERIK dose reported in the previous table, have been demonstrated as compatible for co-administration by infusion via a Y-site connector. Simultaneous co-administration via a Y-site connector using conditions different from those described above may result in inactivation of the aminoglycoside by LIMERIK.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, LIMERIK may cause adverse reactions, although not everyone experiences them.
If any of the adverse reactions worsen, or if you notice any adverse reactions not listed in this leaflet, inform your doctor or healthcare professional.
Serious adverse reactions of LIMERIK include:

• severe skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) which initially present as reddish spots or circular rashes, often with central blisters, on the trunk. Further symptoms include ulcers in the mouth, throat, nose, extremities, genitals, and conjunctivitis (red and swollen eyes). The skin rash may progress to widespread blistering or skin peeling, which can potentially be life-threatening
• swelling of the face, lips, tongue, or other body parts
• shortness of breath, wheezing, or difficulty breathing
• severe rash, itching, or hives on the skin
• yellowing of the eyes or skin
• damage to blood cells (signs include: unexpected breathlessness, red or brown urine, nosebleeds, and appearance of bruises)
• severe or persistent diarrhoea accompanied by fever or weakness
• unexpected bleeding, especially in patients taking anticoagulants such as warfarin

If you experience any of the above reactions, consult your doctor immediately. For the frequency of these reactions, refer to the information below.
Possible adverse reactions are listed according to the following categories:

• common: affects 1 to 10 users in 100
• uncommon: affects 1 to 10 users in 1,000
• rare: affects 1 to 10 users in 10,000
• very rare: affects fewer than 1 user in 10,000

Common adverse reactions:

• diarrhoea, vomiting, nausea
• skin rash

Uncommon adverse reactions:

• oral thrush
• reduced (abnormal) number of white blood cells (leucopenia, neutropenia) and platelets (thrombocytopenia)
• allergic reaction
• headache, insomnia
• low blood pressure, inflammation of veins (felt as tenderness or redness in the affected area)
• jaundice (yellowing of the skin or whites of the eyes), inflammation of the mouth mucosa, constipation, indigestion, stomach discomfort
• increase in certain enzymes in the blood (increased alanine aminotransferase, increased aspartate aminotransferase)
• itching, urticaria
• increased muscle metabolism product in the blood (increased blood creatinine)
• fever, injection site reaction
• yeast infection (candida superinfection)

Rare adverse reactions:

• reduced (abnormal) number of red blood cells or blood pigment / haemoglobin, reduced (abnormal) red blood cells due to premature destruction (haemolytic anaemia), appearance of bruises with small spots (purpura), nosebleeds (epistaxis) and prolonged bleeding time, increased (abnormal) number of a specific type of white blood cells (eosinophilia)
• severe allergic reaction (anaphylactic/anaphylactoid reaction, including shock)
• flushed skin with hot flushes
• a certain form of colon infection (pseudomembranous colitis), abdominal pain
• liver inflammation (hepatitis), increased breakdown product of blood pigments (bilirubin), increased levels of certain blood enzymes (increased alkaline phosphatase in blood, increased gamma-glutamyl transferase)
• skin reactions with redness and skin lesions (exanthema, erythema multiforme), skin reactions with blister formation (bullous dermatitis)
• joint and muscle pain
• impaired kidney function and kidney problems
• chills / rigors

Very rare adverse reactions:

• severe reduction in granular white blood cells (agranulocytosis), severe reduction in red blood cells, white blood cells, and platelets (pancytopenia)
• prolonged blood clotting time (prolonged partial thromboplastin time, prolonged prothrombin time), abnormal laboratory test (positive direct Coombs test), increased platelet count (thrombocytosis)
• low potassium levels in the blood (hypokalaemia), low blood sugar (glucose), low levels of albumin protein in the blood, low total protein levels in the blood
• detachment of the upper layer of skin over the entire body (toxic epidermal necrolysis), severe widespread allergic reaction with skin rash and mucosal lesions and various skin eruptions (Stevens-Johnson syndrome)
• increased blood urea levels

Piperacillin therapy has been associated with a higher incidence of fever and rash in patients with cystic fibrosis.
Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at the website
www.agenziafarmaco.gov.it/it/responsabili. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE LIMERIK

Keep LIMERIK out of the sight and reach of children.
Do not use LIMERIK after the expiry date stated on the label and on the bottle after "Exp.". The expiry date refers to the last day of the month.
Intact vials: do not store above 25°C.
For single use only. Discard any unused solution.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. OTHER INFORMATION

What LIMERIK contains

• The active substances are piperacillin and tazobactam. Each vial contains 2 g of piperacillin (as the sodium salt) and 0.25 g of tazobactam (as the sodium salt). The solvent ampoule contains: lidocaine hydrochloride, water for injections. Each vial contains 4 g of piperacillin (as the sodium salt) and 0.5 g of tazobactam (as the sodium salt).

Description of the appearance of LIMERIK and contents of the pack

LIMERIK 2 g / 0.25 g is a white to off-white powder supplied in a vial.
Packs contain 1 vial of powder + 1 ampoule of solvent.
LIMERIK 4 g / 0.5 g is a white to off-white powder supplied in a vial.
Packs contain 1 vial.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
LABORATORIO FARMACEUTICO C.T. S.r.l. – Via Dante Alighieri, 71 - Sanremo (IM)
Manufacturer
LABORATORIO FARMACEUTICO C.T. S.r.l. – Via Dante Alighieri, 71 - Sanremo (IM)
MITIM S.r.l. – Via Cacciamali, 34-38 – Brescia (BS)
LPV