ZENGAC 1000 mg Порошок Для Инъекционного Раствора

Содержание инструкции

1. ZENGAC 1 g Powder for concentrate for intravenous solution and for oral use
   1. What is Zengac and what is it used for
   2. What you need to know before using Zengac
   3. How to use Zengac
   4. Possible side effects
   5. How to store Zengac
   6. Contents of the pack and other information

ZENGAC 500 mg Powder for concentrate for intravenous solution and for oral use

ZENGAC 1 g Powder for concentrate for intravenous solution and for oral use

Vancomycin
Equivalent medicinal product
Read this leaflet carefully before taking 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 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 any not listed in this leaflet, tell your doctor, hospital pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What is Zengac and what is it used for

Zengac is an antibiotic that belongs to a group of antibiotics called “glycopeptides”. Zengac works
by eliminating some bacteria that cause infections.
Zengac powder is transformed into a solution for intravenous infusion or an oral solution.
Zengac is used in all age groups by infusion for the treatment of the following serious infections:

• skin and underlying tissue infections.
• bone and joint infections.
• lung infection called “pneumonia”.
• infection of the inner lining of the heart (endocarditis) and to prevent endocarditis in patients at risk when undergoing major surgical procedures.
• infection of the central nervous system.
• blood infection related to the aforementioned infections.

Zengac is used in adults and children for the treatment of infections of the mucous membrane of the small and
large intestine with damage to the mucosa (pseudomembranous colitis), caused by the bacterium Clostridium difficile.

2. What you need to know before using Zengac

Do not use Zengac

• if you are allergic to vancomycin or any of the other ingredients of this medicine (listed in section 6);

Warnings and precautions
Talk to your doctor, hospital pharmacist or nurse before using Zengac if:

• you have previously had an allergic reaction to the medicine teicoplanin, as this could mean you are also allergic to Zengac.
• you suffer from a hearing disorder, especially if you are elderly (you may need hearing tests during treatment).
• you have kidney disease (you will need blood and kidney tests during treatment).
• you are receiving Zengac by intravenous infusion for the treatment of diarrhea associated with Clostridium difficileinfection rather than orally .

Talk to your doctor, hospital pharmacist or nurse during treatment with Zengac if:

• you have received Zengac for a long period (you may need blood tests for liver and kidney function during treatment).
• you develop any skin reaction during treatment.
• you develop severe or prolonged diarrhea during or after using Zengac, contact your doctor immediately. This could be a sign of inflammation of the intestine (pseudomembranous colitis) which can occur following antibiotic treatment.

Children
Zengac will be used with particular caution in premature infants and newborns, as their kidneys are not
fully developed and may accumulate Zengac in the blood. This age group needs blood tests to monitor Zengac
levels in the blood.
The simultaneous administration of Zengac and anesthetic agents has been associated with skin flushing
(erythema) and allergic reactions in children. Similarly, concomitant use with other medicines such as
aminoglycoside antibiotics, non-steroidal anti-inflammatory agents (NSAIDs, e.g. ibuprofen) or amphotericin B
(medicine for fungal infections) may increase the risk of kidney damage and therefore more frequent blood and
kidney tests may be necessary.

Other medicines and Zengac
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.
Talk to your doctor before using Zengac if you are taking any of the following medicines:

• Anesthetic agents
• Medicines for the treatment of fungal infections (amphotericin B)
• Medicines for the treatment of cancer (cisplatin)
• Medicines for the treatment of infections caused by bacteria (polymyxin B, colistin, bacitracin, aminoglycosides)
• Medicines used to relieve the symptoms of inflammation (NSAIDs, non-steroidal anti-inflammatory drugs)

Pregnancy, breastfeeding and fertility
If you are pregnant or suspect you may be pregnant, or if you are breastfeeding, ask your doctor or hospital
pharmacist for advice before using this medicine. If you are pregnant or breastfeeding, ZENGAC should only be administered
in cases of absolute necessity. Your doctor may decide to stop breastfeeding.

Driving and using machines
No adverse effects on the ability to drive and operate machinery are known.

3. How to use Zengac

Zengac will be administered to you by medical personnel while you are in hospital. The doctor will decide how much of
this medicine you need to receive each day and how long the treatment will last.

Dosage
The dose administered will depend on:

• your age,
• your weight,
• the infection you have,
• the condition of your kidney function,
• your hearing ability,
• other medicines you are taking.

Intravenous administration
Adults and adolescents (from 12 years of age)
The dose will be calculated based on your body weight. The usual intravenous infusion dose is 15-20 mg per
kg of body weight. It is generally administered every 8 - 12 hours. In some cases, the doctor may
decide to administer an initial dose of up to 30 mg for each kg of body weight. The maximum daily
dose should not exceed 2 g.

Use in children

Children from one month up to less than 12 years of age
The dose will be calculated based on your body weight. The usual intravenous infusion dose is 10- 15 mg
per kg of body weight. It is generally administered every 6 hours.

Premature infants and newborns (from 0 to 27 days)
The dosage will be calculated based on post-menstrual age [time elapsed from the first day of the last menstrual
cycle and birth (gestational age) plus the time elapsed after birth (postnatal age)].
Elderly patients, pregnant women and patients with kidney disease, including those on dialysis,
may need a different dose.

Oral administration
For adults and adolescents (from 12 to 18 years)
The recommended dose is 125 mg every 6 hours. In some cases, the doctor may decide to give you a
higher daily dose, up to 500 mg every 6 hours. The maximum daily dose should not exceed 2 g.
If you have previously suffered from other episodes (mucosal infection), you may need a different
dose and a different duration of therapy.

Use in children

Newborns, infants and children under 12 years of age
The recommended dose is 10 mg per kg of body weight. It is generally administered every 6
hours. The maximum daily dose should not exceed 2 g.

Method of administration
Intravenous infusion means that the medicine flows from a bottle or infusion bag through a tube
into one of your blood vessels and into your body. The doctor or nurse will always administer Zengac into
your bloodstream and not into your muscle.
Zengac will be administered into the vein for at least 60 minutes.
If administered for the treatment of gastric disorders (so-called pseudomembranous colitis), the
medicine must be administered as an oral solution (you will take the medicine by mouth).

Duration of treatment
The duration of treatment depends on the infection you have and may last for several weeks.
The duration of therapy may be different for each patient based on the individual response to treatment.
During treatment, you may need to undergo blood tests, you may be asked to provide
urine samples and also have hearing tests to check for signs of possible side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Zengac may cause allergic reactions, although severe allergic reactions (anaphylactic shock) are
rare. Tell your doctor immediately if you experience sudden wheezing, difficulty
breathing, redness of the upper body, rash or itching.
The absorption of Zengac from the gastrointestinal tract is negligible. However, if you have an inflammatory
disease of the digestive tract, especially if you also have kidney disease, side effects may appear
that occur when Zengac is administered by intravenous infusion.

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

• Reduction in blood pressure
• Shortness of breath, noisy breathing (a sharp sound caused by obstruction of airflow in the upper airways)
• Rash and inflammation of the inside of the mouth, itching, itchy rash, hives
• Kidney problems that can be detected mainly in blood tests
• Redness of the upper body and face, inflammation of a vein

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

• Temporary or permanent hearing loss

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

• Decrease in white blood cells, red blood cells and platelets (blood cells responsible for coagulation) Increase in some white blood cells in the blood.
• Loss of balance, ringing in the ears, dizziness
• Inflammation of blood vessels
• Nausea (feeling of disgust)
• Inflammation of the kidneys and kidney failure
• Chest and back muscle pain
• Fever, chills

Very rare side effects (may affect up to 1 in 10,000 people):

• Sudden onset of severe allergic reaction with blistering or peeling of the skin. This may be associated with high fever and joint pain
• Cardiac arrest
• Inflammation of the intestine causing abdominal pain and diarrhea, which may contain blood.

Frequency not known (the frequency cannot be estimated from the available data):

• Vomiting, diarrhea
• Confusion, dizziness, loss of energy, swelling, fluid retention, decreased urine
• Rash with swelling or pain behind the ears, neck, groin, under the chin and armpits (swollen lymph nodes), abnormal liver and blood function tests
• Rash with blisters and fever.

Reporting of side effects
If you get any side effects, talk to your
doctor or pharmacist at the hospital or nurse. You can also report side effects
directly through the national reporting system at
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 Zengac

Keep this medicine out of the sight and reach of children.
Do not store at a temperature above 25°C.
Do not use this medicine after the expiry date which is stated on the pack after “Expiry”. The expiry date refers to the last day of that month.
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. Contents of the pack and other information

What contains ZENGAC 500 mg
The active ingredient is vancomycin. Each vial contains 500 mg of vancomycin (hydrochloride) equivalent to

• 500,000 IU of vancomycin.

What contains ZENGAC 1 g
The active ingredient is vancomycin. Each vial contains 1000 mg of vancomycin (hydrochloride) equivalent
to 1,000,000 IU of vancomycin.

Description of the appearance of ZENGAC and contents of the pack
ZENGAC 500 mg Powderfor concentrate for solution for infusionintravenous and for oral use
Pack containing 10 vials of powder of 500 mg.

ZENGAC 1g Powderfor concentrate for solution for infusionintravenous and for oral use
Pack containing 1 vial of powder of 1 g.

Marketing Authorisation Holder
Fisiopharma srl – Industrial Area – 84020 Palomonte (SA) Italy

Manufacturer
Fisiopharma srl – Industrial Area – 84020 Palomonte (SA) Italy

Other sources of information
Advice/medical information
Antibiotics are used to treat bacterial infections. They are ineffective against viral infections.
If your doctor has prescribed antibiotics, these are precisely for your current illness.
Despite antibiotics, some bacteria can survive or grow. This phenomenon is called
resistance: some antibiotic treatments become ineffective. The abuse of antibiotics increases resistance.
It can also help bacteria become resistant and therefore delay cure or decrease antibiotic efficacy
if you do not respect the appropriate:

• dosage
• schedule
• duration of treatment

Consequently, to maintain the effectiveness of this medicine:

• 1- Use antibiotics only when prescribed,
• 2- Strictly follow the instructions,
• 3- Do not reuse an antibiotic without a prescription, even if you want to treat a similar illness.

The following information is intended exclusively for doctors or healthcare professionals
Posology and method of administration
Posology
Where appropriate, vancomycin should be administered in combination with other antibacterial agents.
Intravenous administration
The initial dose should be based on total body weight. Subsequent dose adjustments should
be based on serum concentrations to achieve the established therapeutic concentrations. Renal function must be
taken into consideration for subsequent doses and for the administration interval.

Patients aged 12 years or older
The recommended dose is 15-20 mg/kg of body weight every 8-12 h (should not exceed 2 g per dose).
In severely ill patients, an initial dose of 25-30 mg/kg of body weight may be used to
facilitate the possibility of rapidly achieving the established minimum serum concentration.

Infants and children from one month to 12 years of age:
The recommended dose is 10 -15 mg/kg of body weight every 6 hours (see section 4.4).
Full-term newborns (from birth to 27 days of age) and premature newborns (from birth to the expected
date of birth plus 27 days)
To establish the dosage regimen for newborns, the opinion of a doctor experienced in the care
of newborns should be sought.
A possible way to dose vancomycin in newborns is illustrated in the following table (see section

• 4.4):

PMA: post-menstrual age [time elapsed from the first day of the last menstrual cycle and birth (gestational age) plus the time elapsed after birth (postnatal age)].
Prophylactic perioperative treatment of bacterial endocarditis in all age groups
The recommended dose is an initial dose of 15 mg/kg before induction of anesthesia. Depending on the duration
of the surgery, a second dose of vancomycin may be required.

Duration of treatment
The suggested duration of treatment is shown in the table below. In any case, the duration of treatment
should be adjusted according to the type and severity of the infection and the individual clinical response.

* Continue until further debridement is no longer necessary, the patient has clinically improved and
the patient has been fever-free for 48 - 72 hours.
** In the case of prosthetic joint infections, longer periods of oral suppressive treatment with the indicated antibiotics should be considered.
*** The duration and need for combination therapy is based on the type of valve and organism.
Special populations

Elderly
Lower maintenance doses may be necessary due to age-related reduction in renal function

Renal impairment
In pediatric and adult patients with renal impairment, consideration should be given to an initial dose followed by minimum serum levels of vancomycin, rather than a scheduled dosage regimen, particularly in patients with severe renal impairment or those undergoing renal replacement therapy (RRT), due to the many variable factors that can affect vancomycin levels in such patients.
In patients with mild or moderate renal insufficiency, the initial dose should not be reduced. In patients
with severe renal insufficiency, it is preferable to prolong the administration interval rather than
administer lower daily doses.
Particular consideration should be given to the concomitant administration of medicines that may
reduce the clearance of vancomycin and/or potentiate its adverse effects (see section 4.4).
Vancomycin is poorly dialyzed by intermittent hemodialysis. However, the use of high-flux membranes and continuous renal replacement therapy (CRRT) increases the clearance of vancomycin and
generally requires a replacement dose (usually after the hemodialysis session in the case of intermittent hemodialysis).

Adults
Dose adjustments in adult patients may be based on estimated glomerular filtration rate
(eGFR) using the following formula:
Men: [Weight (kg) x 140 - age (years)]/ 72 x serum creatinine (mg/dl)
Women: 0.85 x value calculated with the previous formula.
The usual initial dose for adult patients is 15 - 20 mg/kg which can be administered every 24 hours in
patients with creatinine clearance between 20 and 49 ml/min. In patients with severe renal impairment

(creatinine clearance less than 20 ml/min) or those undergoing renal replacement therapy, the appropriate timing and amount of subsequent doses largely depends on the mode of RRT and must be based
on serum vancomycin minimum levels and residual renal function (see section 4.4). Depending on
the clinical situation, it may be considered to delay the next dose to await the results of vancomycin levels.
In severely ill patients with renal insufficiency, the initial loading dose (25 - 30 mg/kg) should not
be reduced.

Paediatric population
Dose adjustments in paediatric patients aged 1 year or older may be based
on estimated glomerular filtration rate (eGFR) using the revised Schwartz formula:
eGFR (mL/min/1.73m ) = (height in cm x 0.413)/serum creatinine (mg/dl)
eGFR (mL/min/1.73m ) = (height in cm x 36.2/serum creatinine (µmol/L)
For neonates and infants under 1 year of age, the opinion of an expert should be sought, as
the Schwartz formula is not relevant for them.
The guiding dosage recommendations for the paediatric population are shown in the table
below which follows the same principles as adult patients.

* The appropriate timing and amount of subsequent doses largely depends on
the mode of RRT and must be based on serum vancomycin levels obtained before
dosing and residual renal function. Depending on the clinical situation, it may be
considered to delay the next dose to await the results of
vancomycin levels.

Hepatic impairment
No dosage adjustment is necessary in patients with hepatic insufficiency.

Pregnancy
Significantly increased doses may be required to achieve therapeutic serum concentrations
in pregnant women (see section 4.6).

Obese patients
In obese patients, the initial dose should be adjusted individually based on total body weight as
in non-obese patients.

Oral administration

Patients aged 12 years or older
Treatment of Clostridium difficileinfection (CDI)
The recommended dose of vancomycin is 125 mg every 6 hours for 10 days for the first episode of non-severe CDI. This dose may be increased to 500 mg every 6 hours for 10 days in cases of severe illness or with
complications. The maximum daily dose should not exceed 2 g.
In patients with multiple recurrences, treating the current episode of CDI with vancomycin 125 mg four times a day for 10 days, followed by a gradual dose reduction to 125 mg per day or a stepped regimen, i.e., 125-500 mg/day every 2-3 days for at least
3 weeks, may be considered.

Neonates, infants and children under 12 years of age
The recommended dose of vancomycin is 10 mg/kg orally every 6 hours for 10 days. The maximum
daily dose should not exceed 2 g.
The duration of treatment with vancomycin may need to be adjusted based on the clinical course of individual
patients. When possible, the antibiotic suspected of causing the CDI should be discontinued. Adequate fluid and electrolyte replacement must be ensured.
Monitoring of vancomycin serum concentrations
The frequency of Therapeutic Drug Monitoring (TDM) should be individualized based on the
clinical situation and response to treatment, ranging from daily sampling that may be
required in some hemodynamically unstable patients, to at least once a week in stable patients
showing a response to treatment. In patients with normal renal function, vancomycin serum
concentration should be monitored on the second day of treatment just before the
next dose.
In patients undergoing intermittent dialysis, vancomycin levels should generally be obtained before
the start of the hemodialysis session.
Monitoring of vancomycin serum concentrations should be performed after oral administration
in patients with inflammatory bowel disease (see section 4.4).
The target minimum therapeutic levels of vancomycin blood levels should normally be 10-20 mg/L, based
on the site of infection and the pathogen's sensitivity. Minimum values of 15-20 mg/l are generally
recommended by clinical laboratories to better cover pathogens classified as susceptible with MIC ≥1 mg/L
(see sections 4.4 and 5.1).
Model-based methods can be useful for predicting individual dose requirements to achieve an
adequate AUC. The modeling approach can be used both in calculating the personalized initial dose
and for dose adjustments based on TDM results (see section 5.1).
Route of administration
Intravenous administration
Vancomycin for intravenous use is generally administered as an intermittent infusion and the
dosage recommendations presented in this paragraph for the intravenous route correspond to this
type of administration.
Vancomycin will be administered only as a slow intravenous infusion lasting at least one hour or at
a maximum rate of 10 mg/min (whichever is longer) that is sufficiently diluted (at least
100 ml for 500 mg or at least 200 ml for 1000 mg) (see section 4.4).
Patients whose fluid intake needs to be limited may also receive a 500 mg/50
ml or 1000 mg/100 ml solution, although the risk of infusion-related adverse effects may be increased
with these higher concentrations.
For information on solution preparation, see section 6.6.
Continuous vancomycin infusion may be considered, e.g., in patients with unstable vancomycin
clearance.
Oral administration
The contents of one vial (500 mg) can be diluted in approximately 50 ml of water and administered to the patient
orally or via a nasogastric tube.

Overdosage
Supportive care, such as maintaining glomerular filtration, is recommended. Vancomycin is
poorly removed by dialysis.
Increased vancomycin clearance has been achieved through hemofiltration and hemoperfusion
with polysulfonic acid resins.
In the treatment of overdose, consider the possibility of overdose due to multiple drugs, to
drug interactions or to unusual pharmacokinetics in the patient.

Special precautions for disposal and handling
Vancomycin solution has a low pH and may cause physical instability of other compounds. Before
administration, parenterally administered drugs should be inspected for particulate matter and/or color changes whenever the solution and container permit.

Solution preparation
At the time of use, add 10 ml of sterile water for injection to the 500 mg vial of drug or
20 ml of sterile water for injection to the 1 g vial; this yields a solution of 50 mg/ml
Further dilution is necessary. Read the following instructions:

• 1. Intermittent intravenous administration (preferred route). Solutions obtained as described above (containing 500 mg and 1 g of vancomycin) are added to 100 ml and 200 ml of physiological saline or 5% dextrose solution, respectively. The intravenous infusion is performed in at least 60 minutes (see Adverse Effects) and repeated at 6-hour intervals. Reconstituted vancomycin further diluted with 5% dextrose solution or 0.9% sodium chloride solution can be stored in the refrigerator for 14 days without significant loss of potency.

Compatibility with other intravenously administered liquids
Solutions, further diluted with the following infusion liquids, can be stored in
refrigerator for 96 hours:

• 5% dextrose solution and 0.9% NaCl solution
• Ringer's Lactate solution
• Ringer's Lactate solution and 5% dextrose solution
• Normosol-M solution with 5% dextrose
• Isolyte-E solution
• Ringer's acetate solution
• 2. Continuous infusion administration (to be used only when the intermittent route is not possible): add the contents of the solution vials, prepared as described above, to the amount of physiological saline or 5% dextrose solution necessary to allow slow intravenous infusion by drip for 24 hours.

Oral administration
The contents of one vial (500 mg) can be diluted in approximately 50 ml of water and administered orally
via a nasogastric tube.