Tobramycin b. braun

Package leaflet: Information for the user

Tobramycin B. Braun, 1 mg/ml, solution for infusion
Tobramycin B. Braun, 3 mg/ml, solution for infusion
tobramycin
Please read carefully all the information in this leaflet before receiving this medicine, as it contains important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please consult your doctor or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse. See section 4.

Leaflet contents

1. What Tobramycin B. Braun solution for infusion is and what it is used for
2. Important information before using Tobramycin B. Braun
3. How to use Tobramycin B. Braun
4. Possible side effects
5. How to store Tobramycin B. Braun
6. Contents of the pack and other information

1. What Tobramycin B. Braun is and what it is used for
Tobramycin B. Braun belongs to a group of medicines called antibiotics, meaning it is used to treat severe bacterial infections that can be killed by the active substance – tobramycin. Tobramycin may be given to treat the following conditions:

• Hospital-acquired lung and lower respiratory tract infections;
• Lung and lower respiratory tract infections in patients with cystic fibrosis;
• Complicated and recurrent kidney, urinary tract and bladder infections;
• Intra-abdominal infections;
• Skin and soft tissue infections, including severe burns.
  If necessary, therapy may also include other antibiotics.

2. Important information before using Tobramycin B. Braun

When not to use Tobramycin B. Braun

• If you are allergic to tobramycin, other aminoglycosides, or any of the other ingredients of this medicine (listed in section 6).
• If you have myasthenia gravis.

Warnings and precautions
Before starting treatment with Tobramycin B. Braun 1 mg/ml or 3 mg/ml, discuss this with your doctor or pharmacist.
Exercise special caution if:

• You have kidney disease;
• You have hearing problems or any inner ear abnormalities;
• You have Parkinson's disease;
• You or members of your family have a disease associated with mitochondrial mutation (a disorder caused by variants in mitochondrial genomes – parts of cells involved in energy production) or antibiotic-induced hearing loss; certain mitochondrial mutations may increase the risk of hearing loss after using this medicine.

If you have any of the above conditions, inform your doctor.
Tobramycin may have harmful effects on the kidneys and auditory nerve, so you will be closely monitored for any symptoms indicating such damage during treatment.
Monitoring of kidney function, hearing, and balance is particularly important if you already have, or may develop, impaired kidney function, or if kidney function deteriorates during treatment.

Avoid using tobramycin together with fast-acting diuretics (medicines that increase urine production) or other medicines that may also damage the kidneys and auditory nerve.
Monitoring will include:

• Kidney function, especially if you are elderly or have impaired kidney function;
• Hearing;
• Blood levels of tobramycin, as frequently as possible.

If symptoms indicating reduced kidney function occur or if kidney function worsens, daily doses will be reduced and/or the dosing interval will be extended. If kidney dysfunction becomes severe, treatment will be discontinued. Treatment with tobramycin will also be stopped if damage to the auditory nerve occurs, manifesting as tinnitus (ringing in the ears) or hearing loss.
If you develop severe diarrhoea, inform your doctor immediately.
If muscle function blockade occurs, it may be treated with calcium salts.
Fluid and electrolyte levels will be monitored during treatment.
If you have extensive burn wounds, blood levels of tobramycin will be monitored particularly closely.
If you undergo surgical procedures involving wound irrigation with solutions containing tobramycin or other aminoglycosides, this will be taken into account when determining the tobramycin dose.
Exercise special caution if you are elderly.

Children
Tobramycin will be administered with special caution in premature and full-term newborns.

Tobramycin B. Braun and other medicines
Inform your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Pay attention to the following medicines:

Medicines causing muscle relaxation, ether, citrated stored blood:
These may increase the risk of nerve or muscle function blockade. Such combinations will be avoided whenever possible.

Anaesthesia with methoxyflurane
Inform your anaesthesiologist before undergoing anaesthesia with methoxyflurane (an anaesthetic gas) that you are taking or have taken aminoglycosides. Methoxyflurane should be avoided whenever possible due to increased risk of kidney damage.

Other medicines that may also damage the kidneys and auditory nerve
The harmful effects of tobramycin on the kidneys and auditory nerve may be enhanced by:

• Other agents used to treat infections, such as amphotericin B, polymyxin B, colistin, cephalothin, aminoglycosides;
• Cisplatin (an anticancer medicine – in this case, kidney damage may occur even three to four weeks after administration of these medicines);
• Cyclosporine, tacrolimus (immunosuppressive agents that suppress unwanted immune reactions);
• Fast-acting diuretics: furosemide or ethacrynic acid.
  Concomitant administration of these medicines with tobramycin, or after tobramycin use, should be avoided whenever possible.

Other antibiotics
Combination therapy with appropriate antibiotics (e.g. beta-lactams) may significantly enhance therapeutic effect. However, the action of tobramycin may be reduced by penicillin-like antibiotics if you have severe kidney dysfunction.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.

Pregnancy
Your doctor will prescribe this medicine only if absolutely necessary during pregnancy.

Breastfeeding
Although tobramycin is generally not absorbed from the intestines of breastfed infants, your doctor will carefully consider whether to discontinue breastfeeding or tobramycin treatment.

Driving and operating machinery
Caution is advised when driving and operating machinery due to possible adverse effects such as dizziness.

Tobramycin B. Braun contains sodium
Tobramycin B. Braun, 1 mg/ml
This medicine contains 283 mg of sodium (main component of table salt) in each 80 ml vial. This corresponds to 14.2% of the maximum recommended daily dietary sodium intake for adults.

Tobramycin B. Braun, 3 mg/ml
This medicine contains 283 mg of sodium (main component of table salt) in each 80 ml vial. This corresponds to 14.2% of the maximum recommended daily dietary sodium intake for adults.
This medicine contains 425 mg of sodium (main component of table salt) in each 120 ml vial. This corresponds to 21.3% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Tobramycin B. Braun

Tobramycin B. Braun is administered by intravenous infusion (IV infusion) as a slow intravenous drip.
The recommended time for infusion of the contents of one vial is 30 minutes, but may be extended up to 60 minutes.
The appropriate dose will be determined by the physician.
The following are the usual recommended doses.

Dosing in patients with normal renal function
Adults and adolescents
Severe infections
3 mg of tobramycin per kg of body weight (b.w.) per day as a single dose or 1 mg/kg b.w. divided into equal doses administered every 8 hours.
Life-threatening infections
Up to 5 mg of tobramycin per kg b.w. per day as a single dose or 1.66 mg/kg b.w. in equal divided doses administered every 8 hours (or 1.25 mg/kg b.w. every 6 hours). As soon as the patient's clinical condition improves, the dose should be reduced.
Cystic fibrosis
Up to 8–10 mg of tobramycin per kg b.w. per day in divided equal doses.

Newborns and children older than 1 week of age:
6 to 7.5 mg of tobramycin per kg b.w. per day as a single dose or 2 to 2.5 mg per kg b.w. every 8 hours, or
1.5 to 1.9 mg per kg b.w. every 6 hours.

The dose and vial size the patient receives depend on the patient's body weight. The physician or nurse will ensure that the volume administered does not exceed the recommended dose. It is essential that the patient receives the correct dose.

Daily dose of tobramycin may be given as a single dose.
However, this does not apply to patients with impaired immunity, renal failure, hearing loss or symptoms indicating hearing impairment, ascites, extensive burns (over 20% of body surface area), or pregnant women. Patients with normal renal function may receive 5 mg/kg b.w. as a single daily dose.

Dosing in patients with impaired renal function
If the patient has impaired renal function, serum tobramycin levels and renal function will be carefully and frequently monitored to allow appropriate dose adjustment. The physician knows how to calculate and adjust the doses to be administered.
If the patient is undergoing hemodialysis or peritoneal dialysis, the dose will be carefully adjusted based on serum tobramycin concentrations.

Patients with significant overweight
In these patients, the dose is calculated based on estimated ideal body weight plus 40% of excess body weight.

Duration of treatment
Treatment with tobramycin usually lasts 7–10 days. Longer treatment may be necessary in cases of severe or complicated infections. Renal function, hearing, and vestibular function will be monitored.

Administration of a higher than recommended dose of Tobramycin B. Braun
Overdose may lead to kidney damage, ototoxicity (hearing nerve damage), or neuromuscular blockade (paralysis). In such cases, tobramycin infusion should be discontinued. In patients with normal renal function, the physician will monitor adequate urine output. Tobramycin elimination can be enhanced by dialysis. Neuromuscular blockade can be treated by administering calcium salts. If respiratory paralysis occurs, respiratory support may be necessary.
In the event of an acute allergic reaction, emergency measures should be initiated.

If you have any further questions about the use of this medicine, consult your physician.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
In this leaflet, the frequency of occurrence of adverse effects is defined as follows:
Very common: occurs in more than 1 in 10 treated patients;
Common: occurs in 1 to 10 in 100 treated patients;
Uncommon: occurs in 1 to 10 in 1,000 treated patients;
Rare: occurs in 1 to 10 in 10,000 treated patients;
Very rare: occurs in less than 1 in 10,000 treated patients;
Frequency not known: frequency cannot be estimated based on available data.
Tobramycin can harm the auditory nerve and kidneys. Kidney function disorders have been observed
uncommonly in patients treated with tobramycin. These disorders usually resolve after discontinuation
of the medicine. In most cases, harmful effects are associated with excessively high doses or prolonged
treatment, pre-existing kidney abnormalities, or are related to other substances which also have harmful
effects on the kidneys. The occurrence of harmful effects is more likely in elderly individuals and in
patients with fluid deficiency. Adverse effects can largely be avoided by strictly observing precautions
and careful dosing according to instructions.
The following adverse effects, which may occur only rarely, can be severe and require immediate
treatment:

• Severe acute allergic (hypersensitivity) reactions with shock,
• Hearing impairment which may progress to deafness,
• Acute kidney failure.

Adverse effects that may be caused by treatment are listed below according to frequency of occurrence.
Common adverse effects

• Increased number of a certain type of white blood cells (eosinophilia).
• Inner ear damage in patients with impaired kidney function, manifesting as dizziness, balance disturbances, tinnitus (ringing or buzzing in the ear), and hearing loss.
• Thrombophlebitis and phlebitis.
• Elevated levels of bilirubin and certain liver enzymes (aspartate aminotransferase, alanine aminotransferase).
• Kidney damage in patients with impaired kidney function.
• Pain and local reactions at the injection site.

Uncommon adverse effects

• Low overall number of white blood cells (leukopenia).
• Headache.
• Inner ear damage in patients with normal kidney function (same symptoms as above).
• Nausea, vomiting.
• Elevated levels of bilirubin and activity of certain liver enzymes (alkaline phosphatase, lactate dehydrogenase).
• Allergic skin rash, itching.
• Kidney damage in patients with normal kidney function.

Rare adverse effects

• Low number of red blood cells, certain type of white blood cells (granulocytes), and platelets; increased overall number of white blood cells (leukocytosis).
• Hypersensitivity reactions (rash, itching, urticaria).
• Mental confusion, disorientation.
• Diarrhea.
• Skin redness.
• Fever, apathy.
• Low blood levels of calcium, magnesium, sodium, and potassium.

Very rare adverse effects

• Severe acute allergic (hypersensitivity) reaction up to shock.
• Severe allergic reaction affecting the skin and mucous membranes, with blister formation and skin redness (erythema multiforme), which in very severe cases may affect internal organs and take the form of a life-threatening reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Acute kidney failure.

Adverse effects with unknown frequency

• Inflammation of the large intestine (usually may be caused by other antibiotics), infection with bacteria resistant to tobramycin.
• Numbness, tingling of the skin, muscle twitching, convulsions, drowsiness.
• Neuromuscular blockade.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Tobramycin B. Braun
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and outer packaging. The expiry date refers to the last day of the stated month.
The abbreviation "EXP" means the expiry date.
Only clear solutions without particles should be used.
No special storage instructions apply.
The medicine is for single use only.
Any unused solution should be discarded.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines properly. This will help protect the environment.

6. Contents of the package and other information

What Tobramycin B. Braun contains

• The active substance is tobramycin. 1 ml of Tobramycin B. Braun 1 mg/ml solution for infusion contains 1 mg of tobramycin. One polyethylene bottle with a capacity of 80 ml contains 80 mg of tobramycin. 1 ml of Tobramycin B. Braun 3 mg/ml solution for infusion contains 3 mg of tobramycin. One polyethylene bottle with a capacity of 80 ml contains 240 mg of tobramycin. One polyethylene bottle with a capacity of 120 ml contains 360 mg of tobramycin.
• Other ingredients are:
  Tobramycin B. Braun, 1 mg/ml:
  Sodium chloride
  Water for injections
  Sulfuric acid (for pH adjustment)

Tobramycin B. Braun, 3 mg/ml:
Sodium chloride
Water for injections
Hydrochloric acid (for pH adjustment)

What Tobramycin B. Braun looks like and contents of the pack
Tobramycin B. Braun is a solution for infusion, meaning it is administered as an intravenous infusion through a thin tube or cannula placed into a vein.
It is a clear, colourless solution.
Tobramycin B. Braun 1 mg/ml solution for infusion is supplied in 80 ml polyethylene bottles.
It is available in packs of 10 or 20 bottles.
Tobramycin B. Braun 3 mg/ml solution for infusion is supplied in 80 ml or 120 ml polyethylene bottles.
It is available in packs of 10 or 20 bottles.

Marketing Authorisation Holder
B. Braun Melsungen AG
Carl-Braun-Strasse 1
34212 Melsungen
Germany

Manufacturer
B. Braun Medical S.A.
Carretera de Terrassa, 121
08191 Rubí (Barcelona)
Spain

This medicinal product is authorised in the European Economic Area (EEA) under the following names:
Austria: Tobramycin B. Braun 1 mg/ml Infusionslösung
Tobramycin B. Braun 3 mg/ml Infusionslösung
Germany: Tobramycin B. Braun 1 mg/ml Infusionslösung
Tobramycin B. Braun 3 mg/ml Infusionslösung
Finland: Tobramycin B. Braun 1 mg/ml infuusioneste, liuos
Tobramycin B. Braun 3 mg/ml infuusioneste, liuos
Italy: Tobramicina B. Braun 1 mg/ml soluzione per infusione
Tobramicina B. Braun 3 mg/ml soluzione per infusione
Luxembourg: Tobramycin B. Braun 1 mg/ml Infusionslösung
Tobramycin B. Braun 3 mg/ml Infusionslösung
Norway: Tobramycin B. Braun 1 mg/ml Infusjonsvæske, oppløsning
Tobramycin B. Braun 3 mg/ml Infusjonsvæske, oppløsning
Poland: Tobramycin B. Braun, 1 mg/ml, solution for infusion
Tobramycin B. Braun, 3 mg/ml, solution for infusion

Information intended exclusively for healthcare professionals:

Tobramycin B. Braun is a ready-to-use solution.
Aminoglycosides must never be mixed in the same infusion solution with beta-lactam antibiotics (e.g. penicillins, cephalosporins), as this may result in physico-chemical inactivation of the combined drug. If tobramycin is administered together with penicillin or a cephalosporin, both substances must be given separately. The recommended dose must be used for each medicinal product.
Tobramycin is incompatible with heparin.
For intravenous use only.
For single use only.
Any unused solution must be discarded.
Only clear solutions without particles are suitable for use.
From a microbiological point of view, the product should be used immediately. If not used immediately, the user is responsible for storage conditions and duration prior to use. Under proper conditions, storage should not exceed 24 hours at 2–8°C.
The solution must be administered using sterile equipment and aseptic technique. Equipment should be prepared together with the solution to avoid introduction of air into the system.
For detailed dosing information, see section 4.2 of the Summary of Product Characteristics (SmPC).