TAZOPENIL 2 G/0.25 G/4 ML Proszek i rozpuszczalnik do roztworu do wstrzykiwań

Treść ulotki

1. TAZOPENIL 4 g/0.5 g powder for solution for infusion
   1. WHAT IS TAZOPENIL AND WHAT IT IS USED FOR
   2. WHAT YOU NEED TO KNOW BEFORE USING TAZOPENIL
   3. HOW TO USE TAZOPENIL
   4. POSSIBLE SIDE EFFECTS
   5. HOW TO STORE TAZOPENIL
   6. CONTENUTO DELLA CONFEZIONE E ALTRE INFORMAZIONI

TAZOPENIL 2 g/0.25 g/4 ml powder and solvent for injectable solution for intramuscular use

TAZOPENIL 4 g/0.5 g powder for solution for infusion

Piperacillin / tazobactam
Equivalent medicinal product
Read this leaflet carefully before using this medicine as 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. WHAT IS TAZOPENIL AND WHAT IT IS USED FOR

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

2. WHAT YOU NEED TO KNOW BEFORE USING TAZOPENIL

DO NOT USE TAZOPENIL

• If you are allergic to piperacillin, tazobactam, lidocaine or 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, because you may be allergic to TAZOPENIL;

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

• if you have allergies. If you have several allergies, tell your doctor, pharmacist or nurse before taking this medicine;
• if you suffer from diarrhoea before or if you develop diarrhoea during or after treatment. In this case you should immediately inform your doctor, pharmacist or nurse. Do not take medicines for diarrhoea without first consulting your doctor;
• if you have low levels of potassium in your blood. Your doctor may decide to check your kidney function before giving you this medicine and may prescribe you to undergo periodic blood tests during treatment;
• if you have kidney or liver problems or if you are undergoing haemodialysis. Your doctor may decide to check your kidney function before giving you this medicine and may prescribe you to undergo periodic blood tests during treatment;
• if you are taking another antibiotic called vancomycin. Taking Tazopenil and vancomycin at the same time may increase the risk of kidney damage (see also section “other
• if you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also section “Other medicines and Tazopenil ”), or if unexpected bleeding occurs during treatment. In this case you should immediately inform your doctor, pharmacist or nurse;
• if you develop convulsions during treatment. In this case you should immediately inform your doctor, pharmacist or nurse;
• if you think you have developed a new infection or if the infection has worsened. In this case you should inform your doctor, pharmacist or nurse.

Hemophagocytic lymphohistiocytosis
Cases of a disease in which the immune system produces a higher amount than normal of white blood cells called histiocytes and lymphocytes have been reported, resulting in inflammation
(hemophagocytic lymphohistiocytosis). This condition can be life-threatening if not diagnosed and
treated early.
If you develop several symptoms such as fever, swollen lymph nodes, feeling of weakness, feeling of
mental disorientation, shortness of breath, bruising or rash, contact your doctor immediately.
If you notice pain, tenderness or muscle weakness and/or dark-colored urine, immediately inform your
doctor who will interrupt the treatment, as these symptoms may be a sign of muscle degeneration
(rhabdomyolysis) which can lead to kidney problems.

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

Other medicines and Tazopenil
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or may
take or must take any other medicine, including those available without a prescription.
Some medicines may interact with piperacillin and tazobactam. These include:

• medicine for gout (probenecid). It may increase the time it takes to eliminate piperacillin and tazobactam from the body;
• medicines to make the blood more fluid or to treat blood clots (e.g. heparin, warfarin or aspirin);
• medicines used to relax muscles during surgery. Tell your doctor if you need to undergo general anesthesia;
• methotrexate (medicine used to treat tumors, arthritis or psoriasis). Piperacillin and tazobactam may increase the time it takes to eliminate methotrexate from the body;
• medicines that may reduce the level of potassium in the blood (e.g. tablets that increase urine production or some cancer medicines);
• medicines containing other antibiotics such as tobramycin, gentamicin or vancomycin. Tell your doctor if you have kidney problems. Taking Tazopenil and vancomycin at the same time may cause acute kidney damage even if you do not have any kidney problems.

Effect on laboratory tests
Tell your doctor or laboratory personnel that you are taking TAZOPENIL if you need to provide a
blood or urine sample.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy or are breastfeeding with
breast milk, ask your doctor, pharmacist or nurse for advice before using this medicine.
The doctor will decide if TAZOPENIL is suitable for you.
Piperacillin and tazobactam can pass to the baby in the womb or pass through breast milk.
If you are breastfeeding, your doctor will decide if TAZOPENIL is suitable for you.

Driving and operating machinery
It is not expected that the use of TAZOPENIL will impair the ability to drive vehicles and operate machinery.

TAZOPENIL contains sodium
TAZOPENIL 2 g/0.25 g/4 ml contains 108 mg of sodium.
This is equivalent to 5.4% of the maximum recommended daily intake with the diet of an adult.
TAZOPENIL 4 g/0.5 g contains 216 mg of sodium.
This is equivalent to 10.8% of the maximum recommended daily intake with the diet of an adult.
To be taken into consideration in people with reduced kidney function or who are following a low-sodium
diet.

3. HOW TO USE TAZOPENIL

Use this medicine following exactly the instructions of the doctor, pharmacist or
nurse. If you have any doubts, ask your doctor or pharmacist or nurse.
TAZOPENIL 2 g/0.25 g can be administered both intramuscularly and by slow intravenous injection
(duration at least 3-5 minutes) or by infusion (an intravenous drip for 30 minutes) into a vein.
The vial of solvent with lidocaine, included in the package of TAZOPENIL 2 g/0.25 g/4 ml, must be used
exclusively for intramuscular administration.
TAZOPENIL 4 g/0.5 g can only be administered by slow intravenous injection or by infusion (an
intravenous drip for 30 minutes) into a vein.
The doctor or another healthcare professional will administer this medicine to you by infusion (an intravenous
drip of 30 minutes) into a vein.
Dosage
The dose of medicine that will be administered to you depends on the condition for which you are being treated, your age
and the possible presence of kidney problems.

Adults and adolescents over 12 years of age
TAZOPENIL 2 g/0.25 g/4 ml powder and solvent for injectable solution for intramuscular use
The usual dosage for adults and adolescents aged 12 years and over with normal kidney function is 2 g/0.25 g of
piperacillin and tazobactam every 12 hours to 2 g/0.25 g every 6 hours to be administered by
intramuscular injection.

TAZOPENIL 4 g/0.5 g powder for solution for infusion
The usual dose is 4 g/0.5 g of piperacillin/tazobactam, administered every 6-8 hours into a vein
(directly into the bloodstream).

Children aged between 2 and 12 years
The usual dose for children with abdominal infections is 100 mg/12.5 mg/kg of body weight of
piperacillin/tazobactam, administered every 8 hours into a vein (directly into the bloodstream).
The usual dose for children with a low number of white blood cells is 80 mg/10 mg/kg of 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; but each individual dose will not
exceed 4 g/ 0.5 g of TAZOPENIL.
TAZOPENIL must be used until the complete disappearance of the signs of infection (from 5 to 14 days). The
duration of treatment must be established following the doctor's instructions. If you have any doubts about the use
of this medicine, contact your doctor.

For instructions for use and correct reconstitution, see the paragraph “The following information
is intended exclusively for doctors or healthcare professionals” at the end.
Patients with kidney problems
It may be necessary for the doctor to reduce the dose of TAZOPENIL or the frequency of administration. The
doctor may also perform blood tests to ensure that the prescribed dose for treatment is
correct, especially if you have to take this medicine for a prolonged period.

If you use more TAZOPENIL than you should
If you think you have used or have been given an excessive dose of medicine or if side effects appear, such as
convulsions, inform your doctor immediately.

If you forget to use TAZOPENIL
If you think you have not been given or have forgotten a dose of TAZOPENIL, inform
immediately your doctor, pharmacist or nurse.
If you have any doubts about the use of this medicine, contact your doctor or nurse.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Seek immediate medical attentionif you experience any of these potentially serious side effects of Tazopenil:
The serious side effects of Tazopenil are:

• severe skin rashes (Stevens-Johnson syndrome, blistering dermatitis and toxic epidermal necrolysis) which initially appear as reddish spots or as circular blisters often with central blisters on the trunk. Further symptoms include the presence of ulcers in the mouth, throat, nose, extremities, genitals and conjunctivitis (red and swollen eyes). The rash may increase with widespread blisters or skin peeling which may potentially be life-threatening; severe skin inflammation that causes peeling over large areas of the body (exfoliative dermatitis)
• severe allergic condition potentially fatal (drug reaction with eosinophilia and systemic symptoms) that can involve the skin and, especially, other subcutaneous organs, such as the kidney and liver;
• a skin condition (acute generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small pustules filled with liquid contained within large areas of swollen and reddened skin;
• swelling of the face, lips, tongue or other parts of the body;
• shortness of breath, wheezing or difficulty breathing;
• sudden chest pain that may occur with an allergic reaction known as Kounis syndrome;
• severe skin rash, itching or hives;
• yellowing of the eyes or skin;
• damage to blood cells (signs include: unexpected shortness of breath, urine that is red or brown, nosebleeds, pinpoint bruising, severe decrease in the number of white blood cells;
• severe or persistent diarrhea accompanied by fever or weakness;
• pain, tenderness or muscle weakness and/or dark urine (rhabdomyolysis, frequency not known)

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

• diarrhea

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

• yeast infection;
• reduction of platelets, reduction of red blood cells or blood pigment/hemoglobin, abnormal laboratory test (positive direct Coombs test), prolonged bleeding time (prolonged activated partial thromboplastin time);
• reduction of albumin protein in the blood, reduction of total proteins in the blood;
• headache, insomnia;
• abdominal pain, vomiting, nausea, indigestion, stomach discomfort;
• increase of some enzymes in the blood (alkaline phosphatase, increased alanine aminotransferase, increased aspartate aminotransferase);
• skin rash, itching;
• abnormalities in blood tests of kidney function (increased creatinine in the blood);
• fever, reaction at the injection site.

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

• reduction of white blood cells (leukopenia), prolongation of blood coagulation time (prolonged prothrombin time);
• reduction of potassium in the blood (hypokalaemia), reduction of sugar in the blood (glucose);
• seizures, reported in patients taking high doses or with kidney problems;
• low blood pressure, inflammation of the veins (felt as tenderness or redness of the affected area)
• flushed skin with hot flushes;
• increase of the degradation product of blood pigments (bilirubin);
• skin reactions with redness, formation of lesions on the skin (rash, erythema multiforme)
• urticaria;
• pain in the joints and muscles;
• chills.

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

• severe reduction of granular white blood cells (agranulocytosis), nosebleeds;
• serious infection of the colon
• inflammation of the mucous membranes of the mouth;
• detachment of the upper layer of the skin all over the body (toxic epidermal necrolysis)

Frequency not known (frequency cannot be estimated based on available data):

• severe reduction of red blood cells, white blood cells and platelets (pancytopenia), reduction of white blood cells (neutropenia), reduction of red blood cells due to premature degradation (hemolytic anemia), appearance of bruises with small spots (purpura), prolongation of bleeding time;
• increase of platelets, increase of a specific type of white blood cells (eosinophilia);
• severe allergic reaction;
• jaundice (yellowing of the skin or whites of the eyes);
• severe allergic reaction spreading throughout the body with rash on the skin and mucous membranes and various skin eruptions (Stevens-Johnson syndrome), severe allergic reaction involving the skin and other subcutaneous organs such as the kidney and liver (drug reaction with eosinophilia and systemic symptoms), numerous small pustules filled with liquid contained within large areas of swollen and reddened skin accompanied by fever (acute generalized exanthematous pustulosis);
• skin reactions with blisters (blistering dermatitis);
• poor kidney function and kidney problems;
• accumulation of eosinophils, a type of white blood cells, in the lungs (eosinophilic pneumonia);
• acute disorientation and confusion (delirium).

Therapy 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, can lead to manifestations of signs of altered brain function (encephalopathy) and seizures.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can contribute to providing more information on the safety of this medicine.

5. HOW TO STORE TAZOPENIL

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 package and vial after
“Exp.”. The expiry date refers to the last day of that month.
Intact vials: do not store at temperatures above 25°C.
For single use only.
Reconstituted solution: after reconstitution, the solution must be administered immediately.
Discard any unused solution.
Do not dispose of any medicine in wastewater or household waste.
Ask your pharmacist how to dispose of medicines you no longer use. This will help protect
the environment.

6. CONTENUTO DELLA CONFEZIONE E ALTRE INFORMAZIONI

Cosa contieneTAZOPENIL

• I principi attivi sono piperacillina (come sale sodico) e tazobactam (come sale sodico).

TAZOPENIL 2 g/0,25 g/4 ml polvere e solvente per soluzione iniettabile per uso intramuscolare
Ogni flaconcino contiene 2 g di piperacillina (come sale sodico) e 0,25 g di tazobactam (come sale sodico).
La fiala solvente contiene: lidocaina cloridrato, acqua per preparazioni iniettabili

TAZOPENIL 4 g/0,5 g polvere per soluzione per infusione
Ogni flaconcino contiene 4 g di piperacillina (come sale sodico) e 0,5 g di tazobactam (come sale sodico).

Descrizione dell’aspetto di TAZOPENIL e contenuto della confezione
TAZOPENIL 2 g/0,25 g è una polvere di colore da bianco a biancastro, fornita in un flaconcino.
La confezione contiene 1 flaconcino di polvere e 1 fiala di solvente da 20 mg/ml di lidocaina cloridrato.

(la fiala di solvente contenente lidocaina cloridrato è per esclusivo uso intramuscolare).
TAZOPENIL 4 g/0,5 g è una polvere di colore da bianco a biancastro fornita in un flaconcino.
La confezione contiene 1 flaconcino oppure 10 flaconcini.
È possibile che non tutte le confezioni siano commercializzate.

Titolare dell’autorizzazione all’immissione in commercio
Aesculapius Farmaceutici S.r.l.-Via Cefalonia, 70 - 25124 Brescia

Produttore
Mitim S.r.l. – Via Cacciamali 34-36-38 – 25125 Brescia

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Le informazioni seguenti sono destinate esclusivamente ai medici o agli operatori sanitari.
Istruzioni per l’uso

• A. Uso intramuscolare

TAZOPENIL 2 g / 0,25 g deve essere ricostituito con la fiala di solvente acclusa alla confezione, contenente
4 ml di una soluzione di lidocaina allo 0,5 %.

La fiala di solvente con lidocaina, acclusa alla confezione, deve essere impiegata solo per la
somministrazione intramuscolare.
Non superare la dose di 2 g / 0, 25 g di piperacillina/tazobactam per sito iniettivo.

Per una corretta ricostituzione osservare la seguente procedura

• 1. Agitare il flaconcino in modo da ottenere il distacco della polvere dal fondo del flaconcino.
• 2. Rimuovere il cappuccio di plastica con apertura rovesciabile dal flaconcino per scoprire la porzione centrale del tappo di gomma e conservarlo (Fig. 1). Evitare sempre di toccare con la mano la porzione centrale del tappo di gomma.

• 3. Con una siringa prelevare il solvente contenuto nella fiala e introdurlo nel flaconcino contenente la polvere.
• 4. Adagiare il cappuccio di plastica sul tappo di gomma per evitare di toccare con le dita la porzione centrale del tappo. Agitare vigorosamente fino a completa dissoluzione della polvere. Sotto agitazione costante, la ricostituzione dovrebbe avvenire entro 10 minuti (Fig. 2).
• 5. Lasciare riposare la soluzione ottenuta fino a scomparsa della schiuma e all'ottenimento di una soluzione limpida. Assicurarsi che non vi siano particelle residue indisciolte.

• 6. Rimuovere il cappuccio di plastica e prelevare la soluzione con una siringa da 5 ml per somministrazione intramuscolare.
• 7. Iniettare la soluzione ricostituita in profondità in un muscolo

Dopo la ricostituzione la soluzione deve essere somministrata immediatamente
Le soluzioni non utilizzate vanno eliminate

• B. Uso endovenoso

Ricostituire ciascun flaconcino con il volume di solvente riportato nella seguente tabella, utilizzando per la
ricostituzione uno dei solventi compatibili.
Agitare con movimento rotatorio fino alla dissoluzione. Con una rotazione costante la ricostituzione
generalmente richiede dai 5 ai 10 minuti (per maggiori informazioni sulla manipolazione, vedere di seguito).

*Solventi compatibili per la ricostituzione:

• Acqua sterile per preparazioni iniettabili
• Soluzione iniettabile di sodio cloruro allo 0,9% (9 mg/ml)
• Glucosio 5%

Agitare il flaconcino contenente la polvere da ricostituire in modo da ottenere il distacco della polvere dal
fondo del flaconcino.
Con una siringa prelevare un idoneo solvente e introdurlo nel flaconcino contenente la polvere.
Agitare vigorosamente fino a completa dissoluzione della polvere. Sotto agitazione costante, la ricostituzione
dovrebbe avvenire entro 10 minuti.
Lasciare riposare la soluzione ottenuta fino a scomparsa della schiuma e all'ottenimento di una soluzione
limpida. Assicurarsi che non vi siano particelle residue indisciolte prima di prelevarla con idonea siringa.
La soluzione ricostituita deve essere prelevata dal flaconcino con una siringa. Una volta ricostituito secondo
le istruzioni, i l contenuto del flaconcino prelevato con la siringa fornirà la quantità di piperacillina e
tazobactam indicata in etichetta.
Le soluzioni ricostituite possono essere ulteriormente diluite al volume desiderato (ad es. da 50 a 150 ml)
con uno dei seguenti solventi compatibili:

• Acqua sterile per preparazioni iniettabili
• Soluzione iniettabile di sodio cloruro allo 0,9% (9 mg/ml)
• glucosio al 5%
• Destrano 6% in sodio cloruro allo 0,9% (9 mg/ml) Il volume massimo raccomandato di acqua sterile per preparazioni iniettabili per ogni dose è 50 ml

Incompatibilità
Quando TAZOPENIL viene utilizzato in concomitanza con un altro antibiotico (per es. aminoglicosidi), le
sostanze devono essere somministrate separatamente. La miscelazione di antibiotici beta-lattamici con
aminoglicosidi in vitropuò provocare un’ inattivazione sostanziale dell'aminoglicoside.
In caso di somministrazione per via intramuscolare la piperacillina/tazobactam e gli aminoglicosidi devono
essere ricostituiti e somministrati separatamente in diversi siti iniettivi.
TAZOPENIL non deve essere miscelato con altre sostanze nella stessa siringa o flacone per infusione poiché
la compatibilità non è stata stabilita.
A causa dell’instabilità chimica, TAZOPENIL non deve essere usato con soluzioni contenenti solo
bicarbonato di sodio.
TAZOPENIL non deve essere aggiunto a emoderivati o idrolisati di albumina.

Sovradosaggio
Sono stati segnalati casi di sovradosaggio con piperacillina e tazobactam.
La maggioranza degli eventi di cui si ha esperienza, comprese nausea, vomito e diarrea sono stati riportati
con i dosaggi soliti raccomandati. I pazienti possono sperimentare eccitabilità neuromuscolare o convulsioni
se sono somministrate per via endovenosa dosi più elevate di quelle raccomandate (in modo particolare in
presenza di insufficienza renale).
II trattamento deve essere di supporto e sintomatico secondo il quadro clinico del paziente. Eccessive
concentrazioni sieriche della piperacillina o del tazobactam potrebbero essere ridotte con l'emodialisi.

Co-somministrazione di Tazopenil con aminoglicosidi
A causa dell’inattivazione in vitrodell’aminoglicoside da parte degli antibiotici beta-lattamici, si
raccomanda di somministrare Tazopenil e l’aminoglicoside separatamente. Quando è indicata una terapia
concomitante con aminoglicosidi, Tazopenil e l’aminoglicoside devono essere ricostituiti e diluiti
separatamente.