Taiper

PACKAGE LEAFLET: INFORMATION FOR THE USER

TAIPER

2g + 250mg/4ml powder and solvent for injectable solution
TAIPER
4g + 500mg powder for solution for infusion
PIPERACILLIN/TAZOBACTAM
Equivalent medicine
Read this leaflet carefully before using this medicine
because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. WHAT TAIPER IS AND WHAT IT IS USED FOR

Piperacillin belongs to a class of medicines known as "broad-spectrum penicillin antibiotics" and is capable of killing many types of bacteria. Tazobactam can prevent certain resistant bacteria from surviving the effects of piperacillin. This means that when piperacillin and tazobactam are administered together, they can kill a greater number of bacterial types.
TAIPER 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. TAIPER may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
TAIPER 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. TAIPER may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
In certain severe infections, the physician may consider using TAIPER in combination with other antibiotics.

2. What you should know before using TAIPER

Do not use TAIPER

• If you are allergic to piperacillin or tazobactam or to any of the excipients of this medicine (listed in section 6).
• If you are allergic to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, because you may also be allergic to TAIPER.
• If you are allergic to lidocaine (solvent for intramuscular use).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using TAIPER:

• If you have allergies. If you have multiple allergies, inform your doctor or healthcare provider before receiving this medicine.
• If you already have diarrhoea, or if you develop diarrhoea during or after treatment. In this case, you must inform your doctor or healthcare provider immediately. Do not take anti-diarrhoeal medicines without first consulting your doctor.
• If you have low levels of potassium in the blood. 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 another antibiotic called vancomycin. Taking TAIPER and vancomycin together may increase the risk of kidney damage (see also section “Other medicines and TAIPER” in this leaflet).
• 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 Other medicines and TAIPER), or if unexpected bleeding occurs during treatment. In this case, you must inform your doctor or healthcare provider immediately.
• If you develop seizures during treatment. In this case, you must inform your doctor or healthcare provider.
• If you suspect you have developed a new infection or if your infection has worsened. In this case, you must inform your doctor or healthcare provider immediately.

Haemophagocytic lymphohistiocytosis
Cases of a condition in which the immune system produces higher than normal levels of white blood cells called histiocytes and lymphocytes, leading to inflammation (haemophagocytic lymphohistiocytosis), have been reported. This condition can be life-threatening if not diagnosed and treated early.
If you develop several symptoms such as fever, swollen lymph nodes, feeling weak, mental confusion, shortness of breath, bruising, or skin rash, contact your doctor immediately.

Children
The use of piperacillin/tazobactam is not recommended in children under 2 years of age due to insufficient data on safety and efficacy.

Other medicines and TAIPER
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
Some medicines may interact with piperacillin and tazobactam.
These include:

• Medicines for gout (probenecid). This 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 to undergo 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 other antibiotics tobramycin, gentamicin, or vancomycin. Taking TAIPER together with vancomycin may cause acute kidney damage, even if you do not have kidney problems.

Effect on laboratory test results
Inform your doctor or laboratory staff that you are taking TAIPER if you are required to provide a blood or urine sample.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or healthcare provider before taking this medicine. Your doctor will decide whether TAIPER is suitable for you.
Piperacillin and tazobactam may pass to the baby through the womb or breast milk. If you are breastfeeding, your doctor will decide whether TAIPER is suitable for you.

Driving and using machines
TAIPER is not expected to affect the ability to drive or use machinery.

TAIPER contains sodium
TAIPER 2g + 250mg/4ml powder and solvent for injectable solution
This medicine contains 108 mg of sodium (a main component of table salt) per vial.
This corresponds to 5.4% of the maximum recommended daily dietary intake for an adult.
TAIPER 4g + 500mg powder for infusion solution
This medicine contains 216 mg of sodium (a main component of table salt) per vial.
This corresponds to 10.8% of the maximum recommended daily dietary intake for an adult.

3. HOW TO USE TAIPER

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
TAIPER 2g + 250mg can be administered both by intramuscular route and by slow intravenous injection
(duration of at least 3-5 minutes) or by infusion (duration 20-30 min).
The vial of solvent containing lidocaine, included in the TAIPER 2g + 250mg package, should be used only for
intramuscular administration.
TAIPER 4g + 500mg can only be administered by slow intravenous injection or by infusion. Your doctor or
another healthcare professional will administer this medicine to you as an infusion (a 30-minute intravenous
drip) into a vein.
Dosage
The dose of medicine administered depends on the condition being treated, age, and any possible kidney problems.
Adults and adolescents over 12 years of age
The usual dose for adults and adolescents aged 12 years and older with normal kidney function is 2g/250mg of
piperacillin and tazobactam every 12 hours by intramuscular injection; when administered intravenously (directly
into the bloodstream), the usual dose is 4g/500mg of piperacillin/tazobactam every 6-8 hours.
Children from 2 to 12 years of age
The usual dose for children with abdominal infections is 100mg/12.5mg/kg body weight of
piperacillin/tazobactam, every 8 hours, administered intravenously (directly into the bloodstream).
The usual dose for children with low white blood cell count is 80mg/10mg/kg body weight of
piperacillin/tazobactam, every 6 hours, administered intravenously (directly into the bloodstream).
The doctor will calculate the dose based on the child's body weight; in any case, no single dose will exceed
4g/500mg of TAIPER.
TAIPER will be administered to you until complete disappearance of signs of infection (5-14 days).
Patients with kidney problems
It may be necessary for your doctor to reduce the dose of TAIPER or the frequency of administration. Your
doctor may also perform blood tests to ensure that the prescribed dose is appropriate, especially if you are
to receive this medicine for a prolonged period.
If you take more TAIPER than you should
Intramuscular use
If you think you have used an excessive dose of the medicine or if you experience adverse effects such as
seizures, inform your doctor immediately.
Intravenous use
Since TAIPER will be administered by a doctor or healthcare professional, it is unlikely that you will receive an
incorrect dose. However, if you experience adverse effects such as seizures, or if you think you have been given
an excessive dose of the medicine, inform your doctor immediately.
If you miss a dose of TAIPER
If you miss a dose of TAIPER or think that a dose has not been administered, inform your doctor or healthcare professional immediately.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, TAIPER may cause adverse reactions, although not everyone experiences them.
Contact a doctor immediately if you experience any of the following potentially serious adverse reactions with TAIPER:
Serious adverse reactions of TAIPER include:

• severe skin reactions (Stevens-Johnson syndrome, bullous dermatitis, exfoliative dermatitis, toxic epidermal necrolysis), which initially appear as reddish target-shaped spots or circular patches, often with central blisters on the trunk. Other signs include mouth, throat, nose, extremities, genital ulcers, and conjunctivitis (red, swollen eyes). The rash may progress to widespread blisters or extensive skin peeling and may be potentially fatal;

• a severe, potentially life-threatening allergic condition (drug reaction with eosinophilia and systemic symptoms) that may affect the skin and, particularly, internal organs such as the kidneys and liver;

• a skin condition (generalized exanthematous pustulosis) accompanied by fever, characterized by numerous small fluid-filled blisters appearing within large areas of swollen, reddened skin;

• swelling of the face, lips, tongue, or other parts of the body;

• shortness of breath, wheezing, or difficulty breathing;

• severe skin rash or hives, itching, or skin eruptions;

• yellowing of the eyes or skin;

• blood cell damage, signs of which include: unexplained shortness of breath, red or brown urine, nosebleeds and pinpoint bruising, severe decrease in white blood cells;

• severe or persistent diarrhoea associated with fever or weakness.

If any of the following adverse reactions worsen, or if you notice any adverse reactions not listed in this leaflet, inform your doctor or healthcare professional.
Very common adverse reactions (may affect more than 1 in 10 people):

• diarrhoea.

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

• fungal infection;
• reduced platelet count, reduced red blood cells or blood pigment/hemoglobin, abnormal laboratory test results (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time);
• reduced protein levels in the blood; headache, insomnia;
• abdominal pain, vomiting, nausea, constipation, stomach discomfort;
• increased liver enzymes in the blood;
• skin rash, itching;
• abnormal blood tests for kidney function;
• fever, injection site reaction.

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

• decreased white blood cell count (leucopenia), prolonged blood clotting time (prolonged prothrombin time);
• low potassium levels in the blood, low blood sugar;
• seizures, reported in patients receiving high doses or with kidney problems;
• low blood pressure, vein inflammation (felt as tenderness or redness in the affected area), skin redness;
• increased levels in blood of a pigment produced during breakdown (bilirubin);
• skin reactions with redness, skin lesions, hives;
• joint and muscle pain;
• chills.

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

• severe decrease in white blood cells (agranulocytosis), nosebleeds;
• severe colon infection, inflammation of the mucous membranes lining the mouth;
• detachment of the upper layer of skin over the entire body (toxic epidermal necrolysis).

Not known (frequency cannot be estimated from available data):

• severe reduction in red blood cells, white blood cells, and platelets (pancytopenia), reduced white blood cells (neutropenia), reduced red blood cells due to premature breakdown or destruction, appearance of bruises with small spots, prolonged bleeding time, increased platelet count, increased levels of a specific type of white blood cells (eosinophilia);
• allergic reaction and severe allergic reaction;
• liver inflammation, yellowish discoloration of the skin or whites of the eyes;
• severe, widespread allergic reaction affecting the entire body with skin and mucosal rash, blisters, and various skin eruptions (Stevens-Johnson syndrome), severe allergic reaction involving the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters appearing within large areas of swollen, reddened skin accompanied by fever (generalized acute exanthematous pustulosis), skin reactions with blisters (bullous dermatitis);
• impaired kidney function and kidney problems;
• a form of lung disease in which eosinophils (a type of white blood cell) appear in increased numbers in the lungs;
• acute disorientation and confusion (delirium).

Treatment with piperacillin has been associated with a higher incidence of fever and rash in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin/tazobactam, may lead to manifestations of encephalopathy and seizures.
Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE TAIPER

Keep this medicine out of the sight and reach of children.
Do not use TAIPER after the expiry date stated on the carton and vial after "Exp.".
The expiry date refers to the last day of that month.
Intact vials: do not store above 25°C.
For single use only. Discard any unused solution.
Do not dispose of any medicine via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer used. This will help protect
the environment.

6. OTHER INFORMATION

What TAIPER contains
TAIPER 2g + 250mg/4ml powder and solvent for injectable solution for intramuscular use

• Active substances: each vial of powder contains piperacillin (as sodium salt) equivalent to 2g and tazobactam (as sodium salt) equivalent to 250mg.
• Excipients: the solvent vial contains lidocaine hydrochloride, water for injectable preparations.

TAIPER 4g + 500mg powder for infusion solution

• Active substances: each vial of powder contains piperacillin (as sodium salt) equivalent to 4g and tazobactam (as sodium salt) equivalent to 500mg.

Description of the appearance of TAIPER and contents of the pack
TAIPER 2g + 250mg is a white to off-white powder supplied in a vial with 1 solvent ampoule containing 20 mg/4 ml of lidocaine hydrochloride.
TAIPER 4g + 500mg is a white to off-white powder supplied in a vial.

Marketing Authorization Holder and Manufacturer
Errekappa Euroterapici S.p.A.
Via Ciro Menotti, 1a
20190 Milano
Italy

Manufacturer
MITIM S.r.l.
Via Cacciamali, 34
25125 Brescia (BS)
Italy

This patient information leaflet was last approved: January 2022

The following information is intended exclusively for healthcare professionals.

RECONSTITUTION AND DILUTION INSTRUCTIONS
A. Intramuscular administration
TAIPER 2 g + 250 mg must be reconstituted with the vial of solvent supplied in the package, containing 4 ml of 0.5% lidocaine solution.
The solvent vial containing lidocaine supplied in the package must be used only for
intramuscular administration.
Do not exceed a dose of 2 g + 250 mg of piperacillin/tazobactam per injection site.
For correct reconstitution, follow the procedure below:

1. Shake the vial containing the lyophilisate to be reconstituted to detach 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 hands.

Fig. 1
3) Using a syringe, withdraw the solvent containing lidocaine and transfer it into the vial containing the lyophilisate.
4) Place the plastic cap back onto the rubber stopper to prevent touching the central portion with fingers. Shake vigorously until the powder is completely dissolved. Under continuous agitation, reconstitution should be completed 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.
Any unused solutions must be discarded.

The following information is intended exclusively for physicians or healthcare professionals

B. Intravenous use
Instructions for use
TAIPER must be administered by intravenous infusion (a 30-minute infusion).
This must be performed only by healthcare personnel.

Intravenous administration
Reconstitute each vial with the volume of diluent indicated in the table below, using one of the compatible diluents for reconstitution. Gently swirl until dissolution is complete. When continuously swirled, reconstitution usually occurs within 5–10 minutes (for details on handling, see below).

| Volume of diluent* to add to vial | Vial contents | |--- | ---| | 10 ml | TAIPER 2g + 250 mg (2g piperacillin and 250mg tazobactam) | | 20 ml | TAIPER 4g + 500 mg (4g piperacillin and 500mg tazobactam) |

*Compatible diluents for reconstitution:

• Water for injections
• Sodium chloride solution (0.9%)
• Sodium chloride solution with benzyl alcohol
• Sodium chloride solution with parabens
• 5% Dextrose solution

The reconstituted solution should be withdrawn using a syringe. Once reconstituted according to instructions, the vial contents withdrawn with a syringe will provide the amount of piperacillin and tazobactam stated on the label.

The reconstituted solutions may be further diluted to the desired volume (e.g., from 50 ml to 150 ml) with one of the following compatible diluents:

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

Incompatibilities
When TAIPER is used concomitantly with another antibiotic (e.g., aminoglycosides), the substances must be administered separately. Mixing beta-lactam antibiotics with an aminoglycoside in vitro may result in substantial inactivation of the aminoglycoside. However, compatibility of amikacin and gentamicin with TAIPER has been established in vitro under certain conditions and in specific diluents at defined concentrations (see section Co-administration of TAIPER with aminoglycosides).

TAIPER must not be mixed with other substances in the same syringe or infusion vial, as compatibility has not been established.

Due to chemical instability, TAIPER must not be used in solutions containing sodium bicarbonate alone.

TAIPER is compatible with lactated Ringer's solution and for co-administration via a Y-site infusion line.

TAIPER must not be added to blood products or hydrolyzed albumins.

Co-administration of TAIPER with aminoglycosides
Due to in vitro inactivation of aminoglycosides by beta-lactam antibiotics, it is recommended that TAIPER and aminoglycosides be administered separately. When concomitant therapy with an aminoglycoside is indicated, TAIPER and the aminoglycoside must be reconstituted and diluted separately.

In circumstances where co-administration is recommended, TAIPER is compatible for simultaneous co-infusion via a Y-site infusion line 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).
The compatibility of TAIPER with other aminoglycosides has not been established. Only the concentrations and diluents for amikacin and gentamicin, together with the TAIPER dose specified in the preceding table, have been shown to be 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 TAIPER.