BRAMICIL 100 mg / 2 Ml Injectable Solution

Зміст інструкції

1. BRAMICIL 100 mg/2 ml injectable solution, 150 mg/2 ml injectable solution
   1. What is BRAMICIL and what is it used for
   2. What you need to know before using BRAMICIL
   3. How to use BRAMICIL
   4. Possible side effects
   5. How to store BRAMICIL
   6. Contents of the pack and other information
   7. Reduction of the dose to be administered every 8 hours

BRAMICIL 100 mg/2 ml injectable solution, 150 mg/2 ml injectable solution

Tobramycin
Generic medicine

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 or nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What is BRAMICIL and what is it used for

BRAMICIL contains the active ingredient tobramycin which belongs to the class of aminoglycoside antibiotics.
This medicine is used for the treatment of severe bacterial infections, such as:

• severe blood infections (septicemia);
• lung infections;
• severe infections of the nervous system (meningitis);
• abdominal infections (including peritonitis);
• infections of the bones, skin and skin appendages (nails, sebaceous glands);
• complicated or recurrent urinary tract infections;
• infections from E. coliand Staphylococcus, as a second-choice medicine.

2. What you need to know before using BRAMICIL

Do not use BRAMICIL

• if you are allergic to tobramycin, to other similar medicines (aminoglycoside antibiotics) or to any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant and during breastfeeding.

Warnings and precautions
Consult your doctor or nurse before using this medicine.
Pay particular attention to the use of this medicine and avoid high dosages for long
periods, especially if you suffer from serious kidney problems (renal insufficiency) as the use
of BRAMICIL is associated with kidney and hearing toxicity. If these conditions occur, stop treatment immediately. Furthermore, decreased reflexes (numbness), tingling, muscle contractions and
convulsions may occur.
During therapy, you must monitor kidney function, and periodically perform
blood and urine tests. In particular, the parameters to be monitored include levels of
nitrogen and creatinine in the blood (azotemia and creatininemia), the presence of protein in
urine (proteinuria) and the degree of elimination (clearance) of creatinine.
Avoid the simultaneous use with other medicines potentially harmful to the kidneys and
hearing.
During therapy, regularly check the levels of the medicine in the blood, to avoid cases
of accumulation. Levels above 12 micrograms/ml for prolonged periods should be avoided.
Baseline serum levels that tend to increase exceeding 2 micrograms/ml may
be indicative of tissue accumulation.
In people with extensive burns, it is appropriate to monitor the levels of BRAMICIL in the blood to
calculate the necessary dosage.
The use of BRAMICIL in people undergoing anesthesia with medicines that cause a
neuromuscular block such as succinylcholine, tubocurarine, decamethonium or massive doses of
citrate blood, can cause serious respiratory problems (apnea).
‐ If you or your family members have a mitochondrial mutation disease (condition caused
by variants in the genome of mitochondria, the parts of cells that contribute to producing
energy) or hearing loss due to the intake of antibiotic medicines, certain mitochondrial mutations
may increase the risk of hearing loss with this product.

Children
BRAMICIL must be administered with caution in premature children and newborns
because of its toxicity to the kidneys.

Other medicines and BRAMICIL
Tell your doctor or nurse if you are taking, have recently taken or might take
any other medicine.
Avoid using BRAMICIL together with the following medicines:

• medicines used for infections, such as cephalosporins, amikacin, streptomycin, neomycin, kanamycin, gentamicin and paromomycin, cefaloridine, viomycin, polymyxin B, colistin and vancomycin;
• a medicine called cisplatin, used for antitumor therapy;
• medicines used to facilitate the elimination of fluids (diuretics) such as furosemide and ethacrinic acid.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or if you
are breastfeeding, ask your doctor or nurse for advice before using
this medicine.
Do not use this medicine if you are pregnant as it may cause serious harm to the
fetus (e.g. deafness). Serious harm to the mother, fetus and newborns has occurred
following treatment with other aminoglycosides.

Driving and using machines
BRAMICIL does not impair the ability to drive vehicles and use machinery.

BRAMICIL contains sodium metabisulfite and sodium
This medicine contains sodium metabisulfite which rarely may cause serious reactions of
hypersensitivity and bronchospasm.
This medicine contains less than 23 mg (1 mmol) of sodium per vial, i.e. it is practically
‘sodium-free’.

3. How to use BRAMICIL

Use this medicine following exactly the instructions of the doctor or
nurse. If you have any doubts, consult your doctor or nurse.
This medicine can be administered into the muscle (intramuscularly) or directly
into the vein (intravenously).
The dosage will be appropriately adjusted by the doctor based on the severity of the
infection, body weight and medicine levels in the blood. The usual duration of treatment is
7-10 days.

Intramuscular administration
The recommended dose is 1 mg per kilogram (kg) of body weight every 8 hours, for 7-10
days.
Higher dosages (up to 5 mg/kg per day) may be required in cases of very
severe infections. This dosage should be reduced to 3 mg per kg of body weight per day as
soon as possible.

Intravenous administration
This medicine will be administered directly into the vein (intravenously), only
when it is not possible to administer it into the muscle (intramuscularly).
The recommended dose is equal to that used intramuscularly, without
exceeding the limit of 1 mg of BRAMICIL per ml.
The duration of intravenous administration is 1-2 hours.
Possibly this medicine should not be administered in association with other
medicines.

Use in children
The recommended dose ranges from 6 to 7.5 mg per kilogram (kg) of body weight per day, divided
into 3-4 doses administered at regular intervals.
The maximum recommended dose in newborns and premature babies is 4 mg per kilogram of
body weight (kg) per day, divided into 2 doses every 12 hours.

Use in people with kidney problems (renal insufficiency)
The recommended initial dose is 1 mg per kilogram (kg) of body weight. The doctor
will subsequently decide how to adjust the dose based on the results of specific values from
your blood tests (creatinine clearance, creatinine levels).

If you use more BRAMICIL than you should
This medicine will be administered by specialized medical personnel, so an
overdose is unlikely.
However, in case of prolonged treatment with a dosage higher than that
recommended or in people with reduced kidney function, dehydrated people, elderly people or
people receiving other medicines toxic to the hearing simultaneously, the following symptoms may
occur:

• hearing toxicity that can manifest with a feeling of faintness, dizziness, development of annoying noises in the ear (tinnitus), hearing loss;
• problems with the nervous system and muscles (neuromuscular block), respiratory block or difficulty breathing (respiratory paralysis, respiratory failure), especially if you suffer from a serious disease of the nervous system called Parkinson's disease or a disease that causes muscle weakness (myasthenia gravis);

Keep in mind that if you accidentally ingest BRAMICIL, it is unlikely that you will have
an intoxication because these types of medicines (aminoglycosides) are poorly
absorbed by the intestine.
However, if you think you have been given an excessive dose of BRAMICIL, inform
your doctor or another healthcare professional immediately.
If you have any doubts about the use of this medicine, contact your doctor or
nurse immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur, particularly in people treated for
long periods and with high doses:

• dizziness;
• unpleasant noises generated in the ear (tinnitus, acouphena), irreversible hearing loss;
• increased nitrogen (total and urea nitrogen) and creatinine in the blood;
• decreased amount of urine produced (oliguria);
• presence of protein in the urine (proteinuria, cylindruria);
• serious respiratory problems (secondary or prolonged apnea) in anesthetized patients;
• decrease in red blood cells, white blood cells and platelets (anemia, granulocytopenia, thrombocytopenia);
• fever;
• skin rash, itching, urticaria;
• nausea, vomiting, diarrhea;
• headache, drowsiness (lethargy), mental confusion and disorientation;
• pain at the injection site;
• increased serum transaminases (SGOT, SGPT) and lactic dehydrogenase;
• decreased calcium, magnesium, sodium and potassium in the blood;
• decrease in white blood cells (leukopenia, leukocytosis and eosinophilia).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet,
tell your doctor or pharmacist. 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 BRAMICIL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is reported on the packaging after
“Exp. date:”.
The expiry date refers to the last day of that month and to the product in
intact packaging, correctly stored.
Do not store above 25°C.
Do not dispose of any medicine in the 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 BRAMICIL contains
BRAMICIL 100 mg/2 ml
Each vial contains:

• active ingredient: tobramycin sulfate equivalent to Tobramycin 100 mg
• other components: phenol, sodium metabisulfite, disodium edetate, water for injection

BRAMICIL 150 mg/2 ml
Each vial contains:

• active ingredient: tobramycin sulfate equivalent to Tobramycin 150 mg
• other components: phenol, sodium metabisulfite, disodium edetate, water for injection

Description of the appearance of BRAMICIL and contents of the pack
Each pack of BRAMICIL 100 mg/2 ml contains 10 vials of 2 ml injectable solution.
Each pack of BRAMICIL 150 mg/2 ml contains 10 vials of 2 ml injectable solution.

Marketing Authorisation Holder and Manufacturer
FISIOPHARMA s.r.l. Nucleo Industriale 84020 PALOMONTE (SA)

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The following information is intended exclusively for doctors or healthcare professionals
BRAMICIL 100 mg/2 ml injectable solution
BRAMICIL 150 mg/2 ml injectable solution
Tobramycin
Generic medicine

Dosage and administration
Administration in patients with renal insufficiency
It is recommended to carefully monitor serum levels of BRAMICIL. If this is not
possible, it is advisable to administer a loading dose of 1 mg/kg as a precaution and
administer subsequent doses based on creatinine clearance or creatinine levels,
as the half-life of BRAMICIL is correlated with these values. It is recommended to use one of
the following methods:

1. Reduction of the dose to be administered every 8 hours

If the values of creatinine clearance (Ccr) or those of creatinine in the blood are known, the
amount of
BRAMICIL to be administered can be established as reported in the following
table:

MAINTENANCE DOSES IN PATIENTS WITH ALTERED RENAL FUNCTION (*)

(*) For infections that threaten the patient's life, doses 50% higher than those recommended may be administered, to be reduced as soon as the first
improvement is noticed.
(**) If used to assess the degree of renal insufficiency, serum creatinine concentrations should reflect a constant rate of azotemia.
(***) When dialysis is not performed.
Alternatively, the dose to be administered can be calculated in a more
approximate manner by dividing the weight-based dose by the creatinine values.

• 2. Normal dose to be administered at prolonged intervals.If the values of creatinine clearance are not known and the patient's condition is stable, the dosage is determined based on the patient's weight, while the frequency of administration in hours is calculated by multiplying by 6 the value of creatinine in the blood.

Overdosage
Signs and Symptoms
The severity of the signs and symptoms resulting from Tobramycin overdose depends on the dose
administered, the patient's renal function, hydration status, age, and
concurrent administration or not of other drugs with similar toxicity. Toxicity can occur in patients treated for more than 10 days with a dosage greater than 5
mg/kg per day or 7.5 mg/kg per day in children or patients with reduced
renal function, if the dosage has not been appropriately corrected, in dehydrated patients, or in patients receiving ototoxic drugs concurrently.
Elderly patients with altered renal function and undergoing concomitant treatment with other
nephrotoxic drugs or with reduced blood volume are at greater risk of developing
renal damage (acute tubular necrosis).
Auditory and vestibular toxicity have been associated with aminoglycoside overdose.
These patients may experience a feeling of faintness, tinnitus (perception of
ringing noises), vertigo, and a loss of hearing for high tones as a progression of ototoxicity. Signs and symptoms of ototoxicity may not
occur even for a long period of time after the drug has been discontinued.
Neuromuscular blockade, respiratory paralysis, and respiratory failure may
occur following the administration of aminoglycosides, more commonly in patients
with myasthenia gravis or Parkinson's disease. Respiratory paralysis may occur
even in patients anesthetized with agents that cause neuromuscular blockade.
Toxicity is unlikely in the case of ingestion of Tobramycin, as
aminoglycosides are poorly absorbed from the intact gastrointestinal tract.

Treatment
In the treatment of Tobramycin overdose, it is necessary to consider the possibility of
multiple overdoses, interaction with other drugs, and unusual kinetics in the patient
in question.
In the event of tobramycin overdose, the initial intervention must focus on the
respiratory system to ensure ventilation and oxygenation.
If neuromuscular blockade occurs, this can be treated by administering calcium salts; mechanical ventilation may also be necessary.
If respiratory paralysis occurs, prompt resuscitation measures must be taken.
Patients with normal renal function who have received tobramycin in overdose
should be adequately hydrated to maintain a urine clearance of 3-5 ml/kg/h.
Fluid balance, creatinine clearance, and plasma tobramycin levels should be
carefully monitored until serum tobramycin levels fall below
2 mcg/ml. Patients with an elimination half-life greater than 2 hours or whose
renal function is impaired may require more aggressive treatment. Hemodialysis
may be beneficial in such patients.

Incompatibilities
Tobramycin is compatible with most commonly used intravenous fluids,
but is not compatible with heparin solutions and may interact chemically with
beta-lactam compounds, depending on the concentration and pH of both Tobramycin
and the beta-lactam compounds. Aminoglycosides are in fact inactivated in vitro by various
penicillins and cephalosporins, through an interaction with the beta-lactam ring; inactivation
depends on temperature, concentration, and duration of contact. Tobramycin
has been found to be the most sensitive to inactivation.
Given their potential for incompatibility in general, aminoglycosides should not
be mixed with other agents in the same syringe or in infusion solutions and should not
be administered through the same intravenous line. When aminoglycosides are administered concurrently with a beta-lactam, administration
should occur at different sites.

Tobramycin is incompatible with infusion solutions containing alcohol, with sargramostimand with clindamycin phosphate when diluted with glucose injectable solution. Tobramycin is physically incompatible with carbenicillin.
Instructions for use.
Route of administration
For intravenous administration in adults, the dose of BRAMICIL should be diluted in 50-100 ml
of physiological solution or 5% glucose solution and infused over a period of 60 minutes.
In children, proportionally lower doses of diluent are used.
BRAMICIL should not be mixed with other drugs, but administered separately.

Please consult the Summary of Product Characteristics for more detailed
prescribing information.