Piperacillin and tazobactam Mylan Generics

PACKAGE LEAFLET: INFORMATION FOR THE USER

Piperacillin and Tazobactam Mylan Generics 2 g + 0.25 g / 4 ml powder and solvent for injectable solution

for intramuscular use
Piperacillin and Tazobactam Mylan Generics 4 g / 0.5 g powder for solution for infusion
Piperacillin/tazobactam
Generic Medicine
Please 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, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Piperacillin and Tazobactam Mylan Generics is and what it is used for
2. What you need to know before using Piperacillin and Tazobactam Mylan Generics
3. How to use Piperacillin and Tazobactam Mylan Generics
4. Possible side effects
5. How to store Piperacillin and Tazobactam Mylan Generics
6. Package contents and other information

1. What Piperacillin and Tazobactam Mylan Generics 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 certain 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.
Piperacillin and Tazobactam Mylan Generics 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. Piperacillin and Tazobactam Mylan Generics may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin and Tazobactam Mylan Generics 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. Piperacillin and Tazobactam Mylan Generics 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 Piperacillin and Tazobactam Mylan Generics in combination with other antibiotics.

2. What you should know before using Piperacillin and Tazobactam Mylan Generics

Do not use Piperacillin and Tazobactam Mylan Generics

• If you are allergic to piperacillin or tazobactam or to any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may also be allergic to Piperacillin and Tazobactam Mylan Generics.
• If you are allergic to lidocaine (the solvent for intramuscular use only of Piperacillin and Tazobactam Mylan Generics 2 g + 0.25 g/4 ml powder and solvent for injectable solution for intramuscular use).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Piperacillin and Tazobactam Mylan Generics.

• If you suffer from allergies. If you have multiple allergies, inform your doctor or healthcare provider before using this medicine.
• If you have had diarrhoea previously, or if you develop diarrhoea during or after treatment. In this case, you must inform your doctor or healthcare provider immediately. Do not take medicines for diarrhoea without first consulting your doctor.
• If you have low levels of potassium in the blood. Your doctor may wish to check your kidney function before administering this medicine and may perform regular blood tests during treatment.
• If you have kidney or liver problems or are undergoing haemodialysis. Your doctor may wish to check your kidney function before administering this medicine and may perform regular blood tests during treatment.
• If you are taking another antibiotic called vancomycin. Taking Piperacillin and Tazobactam Mylan Generics together with vancomycin may increase the risk of kidney damage (see also section “Other medicines and Piperacillin and Tazobactam Mylan Generics” in this leaflet).
• If you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also section “Other medicines and Piperacillin and Tazobactam Mylan Generics”), 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 immediately.
• 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 an abnormally high number 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 various 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 Piperacillin and Tazobactam Mylan Generics
Inform your doctor or healthcare provider if you are taking, have recently taken, or might take any other medicines, including those without a prescription. Some medicines may interact with piperacillin and tazobactam.
These include:

• Medicines for gout (probenecid), which 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 due 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., diuretic tablets or certain anticancer medicines);
• Medicines containing other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Taking Piperacillin and Tazobactam Mylan Generics and vancomycin at the same time may increase the risk of 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 Piperacillin and Tazobactam Mylan Generics if you are required to provide a blood or urine sample.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or healthcare provider before using this medicine.
Your doctor will decide whether Piperacillin and Tazobactam Mylan Generics is appropriate for you.
Piperacillin and tazobactam may pass to the unborn baby through the womb or through breast milk.
If you are breastfeeding, your doctor will decide whether Piperacillin and Tazobactam Mylan Generics is suitable for you.

Driving and using machines
Piperacillin and Tazobactam Mylan Generics is not expected to affect your ability to drive or use machines.

Piperacillin and Tazobactam Mylan Generics contains sodium
Piperacillin and Tazobactam Mylan Generics 2 g/0.25 g contains 4.70 mmol (108 mg) of sodium (the main component of table salt) per vial, while Piperacillin and Tazobactam Mylan Generics 4 g/0.5 g contains 9.39 mmol (216 mg) of sodium per vial. This corresponds to 5.4% and 10.8%, respectively, of the maximum daily dietary intake recommended for an adult.

3. How to use Piperacillin and Tazobactam Mylan Generics

Piperacillin and Tazobactam Mylan Generics 2 g/0.25 g may be administered either intramuscularly or by slow intravenous injection (lasting at least 3–5 minutes) or by infusion (an intravenous drip over at least 30 minutes) only by a doctor or healthcare professional. The vial of solvent containing lidocaine supplied with the Piperacillin and Tazobactam Mylan Generics 2 g/0.25 g pack must be used only for intramuscular administration.
Piperacillin and Tazobactam Mylan Generics 4 g/0.5 g may only be administered by slow intravenous injection or by infusion. Your doctor or healthcare professional will administer this medicine to you via an infusion (an intravenous drip over 30 minutes) into a vein.
The dose of medicine you will receive depends on the reason for treatment, your age, and whether you have any 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 2 g/0.25 g of piperacillin/tazobactam every 12 hours administered intramuscularly. For intravenous administration, the dosage ranges from a minimum of 2 g/0.25 g up to a maximum of 4 g/0.5 g of piperacillin/tazobactam, given every 6, 8, or 12 hours.
When Piperacillin and Tazobactam Mylan Generics is used as empirical monotherapy for suspected infections in febrile adult patients with neutropenia, the recommended dosage is 4 g/0.5 g of Piperacillin and Tazobactam Mylan Generics every 6–8 hours, administered intravenously.

Children from 2 to 12 years of age
The usual dose for children with abdominal infections is 100 mg/12.5 mg/kg body weight of piperacillin/tazobactam, administered every 8 hours intravenously (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 every 6 hours intravenously (directly into the bloodstream).
The doctor will calculate the dose based on the child's body weight; however, no single dose should exceed 4 g/0.5 g of Piperacillin and Tazobactam Mylan Generics.
Piperacillin and Tazobactam Mylan Generics will be administered until all signs of infection have completely disappeared (5–14 days).

Patients with kidney problems
The doctor may need to reduce the dose of Piperacillin and Tazobactam Mylan Generics or the frequency of administration. The doctor may also order blood tests to monitor the appropriateness of the treatment dose, especially if you need to take this medicine for a prolonged period.

If you use more Piperacillin and Tazobactam Mylan Generics than you should
Since Piperacillin and Tazobactam Mylan Generics 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 an excessive dose has been administered, inform your doctor immediately.

If you forget to use Piperacillin and Tazobactam Mylan Generics
If you think a dose of Piperacillin and Tazobactam Mylan Generics has not been administered, inform your doctor or healthcare professional immediately.
If you have any doubts about how to use this product, consult your doctor or healthcare professional.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Contact a doctor immediately if you experience any of the following potentially serious side effects (frequency indicated in brackets):

• severe skin rashes (Stevens-Johnson syndrome, bullous dermatitis (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)), which initially present as red, target-shaped spots or circular patches, often with central blisters, usually on the trunk. Other signs include mouth, throat, nose, extremities, or genital ulcers, and conjunctivitis (red, swollen eyes). The rash may progress to widespread blistering or extensive skin peeling and may be potentially life-threatening;
• severe, potentially fatal 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 acute exanthematous pustulosis) accompanied by fever, characterized by numerous small fluid-filled blisters appearing within large areas of swollen, red skin;
• swelling of the face, lips, tongue, or other body parts (not known);
• shortness of breath, wheezing, or breathing difficulties (not known);
• severe skin rash or hives (uncommon), itching or skin rash (common);
• yellowing of the eyes or skin (not known);
• blood cell damage, with signs including: unexplained breathlessness, red or brown urine (not known), nosebleeds (rare), pinpoint bruising (not known), severe decrease in white blood cells (rare);
• severe or persistent diarrhoea accompanied by fever or weakness (rare).

If any of the following side effects worsen, or if you notice any side effect not listed in this leaflet, inform your doctor or another healthcare professional.

Very common side effects (may affect more than 1 in 10 people):

• diarrhoea.

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

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

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

• decreased white blood cell count (leukopenia), prolonged blood clotting time (prothrombin time);
• low blood potassium levels (hypokalaemia), low blood sugar (hypoglycaemia);
• seizures;
• low blood pressure (hypotension), vein inflammation perceived as tenderness or redness in the affected area (thrombophlebitis, phlebitis), flushed skin with hot flushes;
• increased levels in blood of a pigment produced during breakdown (bilirubin);
• skin reactions with redness (erythema multiforme), development of skin lesions (maculopapular rash), urticaria;
• joint and muscle pain (arthralgia, myalgia);
• chills.

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

• severe reduction in white blood cells (agranulocytosis), nosebleeds (epistaxis);
• severe intestinal infection (pseudomembranous colitis), inflammation of the mucous membranes lining the mouth (stomatitis);
• widespread skin detachment (toxic epidermal necrolysis).

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

• reduction in all blood cells (pancytopenia), red blood cells (haemolytic anaemia), white blood cells (neutropenia), appearance of small bruised spots (purpura), prolonged bleeding time;
• increase in a specific type of white blood cells (eosinophilia);
• increased platelet count (thrombocytosis);
• allergic reaction (including severe);
• delirium;
• liver inflammation (hepatitis), yellowing of the skin and eyes (jaundice);
• severe, widespread allergic reaction affecting the whole body with skin rash and blisters (Stevens-Johnson syndrome), severe allergic reaction involving both the skin and other organs such as the kidneys and liver (DRESS), widespread pustules accompanied by fever (AGEP), severe skin inflammations (exfoliative dermatitis, bullous dermatitis);
• kidney failure, kidney inflammation (tubulointerstitial nephritis);
• a form of lung disease characterized by increased eosinophils (a type of white blood cell) in the lungs (eosinophilic pneumonia);
• acute disorientation and confusion (delirium).

Treatment with piperacillin has been associated with a higher incidence of fever and skin rashes in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin/tazobactam, may lead to manifestations of encephalopathy and seizures.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Piperacillin and Tazobactam Mylan Generics

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

6. Package contents and other information

What Piperacillina e Tazobactam Mylan Generics contains
The active substances are piperacillin and tazobactam.
Piperacillina e Tazobactam Mylan Generics 2 g+0.25 g/4 ml powder and solvent for injectable
solution for intramuscular use
Each vial contains 2 g of piperacillin (as sodium salt) and 0.25 g of tazobactam (as sodium salt).
The solvent vial contains: hydrochloride lidocaine, water for injectable preparations.
Piperacillina e Tazobactam Mylan Generics 4 g/0.5 g powder for infusion solution
Each vial contains 4 g of piperacillin (as sodium salt) and 0.5 g of tazobactam (as sodium salt).

Description of the appearance of Piperacillina e Tazobactam Mylan Generics and pack contents
Piperacillina e Tazobactam Mylan Generics 2 g+0.25 g/4 ml powder and solvent for injectable
solution for intramuscular use
Powder and solvent for injectable solution for intramuscular use (the solvent vial, containing
hydrochloride lidocaine, is for exclusive intramuscular use only).
Carton pack containing 1 vial of 2 g/0.25 g powder of piperacillin and tazobactam and 1 solvent vial containing 20 mg/4 ml hydrochloride lidocaine.
Piperacillina e Tazobactam Mylan Generics 4 g/0.5 g powder for infusion solution
Powder for infusion solution.
Carton pack containing 1 or 10 vials of 4 g/0.5 g powder of piperacillin and tazobactam.

Marketing Authorization Holder
Mylan S.p.A., via Vittor Pisani 20, 20124 Milano
Manufacturer
Laboratorio Farmaceutico C.T. S.r.l., via Dante Alighieri 71, 18038 Sanremo (IM)
Mitim S.r.l., via Cacciamali 34-38, 25125 Brescia (BS)

The following information is intended exclusively for physicians or healthcare professionals:
Instructions for use
Intramuscular administration
Piperacillina e Tazobactam Mylan Generics 2 g/0.25 g must be reconstituted with the solvent vial supplied in the package, containing 4 ml of 0.5% lidocaine solution.
The solvent vial containing lidocaine supplied in the package must only be used 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 lyophilized powder 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 aside (Fig. 1).
3. Always avoid touching the central portion of the rubber stopper with hands.

Fig. 1
4) Using a syringe, withdraw the solvent containing lidocaine and inject it into the vial containing the lyophilized powder.
5) 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. Under continuous agitation, reconstitution should be complete within 10 minutes (Fig. 2).

Fig. 2
6) Allow the resulting solution to stand until foam disappears and a clear solution is obtained. Ensure that no undissolved particles remain.
7) 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.

Intravenous use
To be performed exclusively by healthcare personnel.
Each vial of Piperacillina e Tazobactam Mylan Generics must be reconstituted by adding 50 ml of one of the following solutions:

• Sterile water for injection
• 0.9% Sodium chloride injection solution (mg/ml)
• Sodium chloride solution with benzyl alcohol
• Sodium chloride solution with parabens
• 5% Dextrose

Initially, add to each injection vial the volume of solution indicated in the following table:

Shake the medicinal product vigorously for 1-2 minutes to detach the powder from the bottom of the vial, then add the same solution up to a final volume of 50 ml.
Shake the medicinal product again vigorously until complete dissolution. Under constant agitation, reconstitution should be achieved within 10 minutes.
Allow the resulting solution to stand until foam disappears and a clear solution is obtained. Ensure that no undissolved particles remain before withdrawing with a suitable syringe.
If reconstitution has been performed as indicated, the solution withdrawn will contain 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 diluents:

• Sodium chloride solution (physiological saline)
• 5% glucose solution
• 6% Dextran in sodium chloride solution

Incompatibilities
When Piperacillin and Tazobactam Mylan Generics is used concomitantly with another antibiotic (e.g., aminoglycosides), the substances must be administered separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may result in substantial inactivation of the aminoglycoside.
In case of intramuscular administration, piperacillin/tazobactam and aminoglycosides must be reconstituted and administered separately at different injection sites.
Piperacillin and Tazobactam Mylan Generics must not be mixed with other substances in the same syringe or infusion vial, as compatibility has not been established.
Piperacillin and Tazobactam Mylan Generics must be administered through a separate infusion set from all other drugs unless compatibility has been demonstrated.
Due to chemical instability, Piperacillin and Tazobactam Mylan Generics must not be used with solutions containing sodium bicarbonate alone.
Lactated Ringer's solution is not compatible with Piperacillin and Tazobactam Mylan Generics.
Piperacillin and Tazobactam Mylan Generics must not be added to blood derivatives or hydrolysed albumins.

Co-administration of Piperacillin and Tazobactam Mylan Generics with aminoglycosides
Due to in vitro inactivation of aminoglycosides by beta-lactam antibiotics, it is recommended that Piperacillin and Tazobactam Mylan Generics and aminoglycosides be administered separately. When concomitant therapy with aminoglycosides is indicated, Piperacillin and Tazobactam Mylan Generics and the aminoglycoside must be reconstituted and diluted separately.
Piperacillin and Tazobactam Mylan Generics must be administered through a separate infusion set from aminoglycosides.

Unused solutions must be discarded.