Amikacin b.braun

Package leaflet: Information for the patient

Amikacin B. Braun, 2.5 mg/ml, solution for infusion
Amikacin B. Braun, 5 mg/ml, solution for infusion
Amikacin B. Braun, 10 mg/ml, solution for infusion
Amikacinum
Please read this leaflet carefully before using the 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 questions, consult your doctor or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Amikacin B. Braun is and what it is used for

Amikacin B. Braun belongs to a group of medicines called antibiotics. It is used to treat severe bacterial infections caused by organisms sensitive to the active substance – amikacin.
Amikacin belongs to a group of substances known as aminoglycosides.
You may be given amikacin to treat the following conditions:

• lung and lower respiratory tract infections occurring during hospital treatment, including severe pneumonia;
• intra-abdominal infections, including peritonitis;
• complicated and recurrent kidney, urinary tract and bladder infections;
• skin and soft tissue infections, including severe burns;
• bacterial endocarditis;
• postoperative abdominal infections.

Amikacin B. Braun may also be used to treat patients who have inflammatory conditions of internal organs associated with any of the above-mentioned infections or in whom such an association is suspected.

2. Important information before using Amikacin B. Braun

When not to use Amikacin B. Braun

• If the patient is allergic (hypersensitive) to amikacin, to other similar substances (other aminoglycosides), or to any of the other components of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Amikacin B. Braun, discuss this with your doctor.
Special caution is required when using Amikacin B. Braun if the patient:

• has impaired kidney function,
• has hearing disorders,
• has neuromuscular disorders, such as myasthenia gravis (a specific type of muscle weakness),
• has Parkinson's disease,
• if the patient or members of their family have a disease associated with mitochondrial mutation (a genetic disorder) or hearing loss caused by antibiotic use, it is recommended to inform the doctor or pharmacist before taking an aminoglycoside; certain mitochondrial mutations may increase the risk of hearing loss after administration of this medicine. Before administering Amikacin B. Braun, the doctor may recommend genetic testing,
• has previously been treated with another antibiotic similar to amikacin. In each of these situations, the doctor will exercise special caution.

If any of the following factors apply to the patient, there is an increased risk of harmful effects of the medicine on hearing or nerves:

• impaired kidney function,
• advanced age (≥60 years),
• dehydration,
• receiving high doses of this medicine,
• treatment lasting longer than 5–7 days, even in patients who have already been cured.

The first signs of harmful effects on hearing or nerves, occurring after administration of this medicine, may include:

• difficulty hearing high-pitched sounds (hearing loss affecting high frequencies),
• dizziness,
• tingling or numbness of the skin, muscle twitching, convulsions.

After administration of the medicine, respiratory arrest (paralysis of respiratory muscles) and suppression of nerve and related muscle function (neuromuscular blockade) may occur.
In such a case, the doctor will initiate appropriate treatment.
Elderly patients
In elderly patients, the doctor will pay special attention to kidney function. The doctor may perform several tests to ensure there is no harmful effect on the kidneys, as the risk of kidney dysfunction is higher in elderly patients.
Children
Caution is also required when using this medicine in premature infants or full-term newborns due to immature kidney function.
During treatment with this medicine, the patient will be closely monitored, with particular attention to hearing and kidney function.
The following will be monitored in the patient:

• kidney function, especially in patients with kidney failure or symptoms of kidney dysfunction occurring during treatment,
• hearing,
• blood concentration of amikacin (if necessary).

If kidney failure symptoms appear or worsen, the doctor will reduce the daily dose and (or) extend the intervals between doses. In case of severe kidney failure, amikacin administration will be discontinued.
Treatment with amikacin should also be stopped if tinnitus or hearing loss occurs.
If during surgery the patient's wounds are irrigated with solutions containing amikacin or a similar antibiotic, this will be taken into account when calculating the amikacin dose.
Amikacin B. Braun and other medicines
Inform your doctor or pharmacist about all medicines currently used or recently used, as well as any medicines you plan to take.
The harmful effects of amikacin on the kidneys and auditory nerve may be intensified by:

• other antibiotics similar to amikacin (e.g., kanamycin, paromomycin),
• other agents used to treat infections, such as bacitracin, amphotericin B, cephalosporins, vancomycin, polymyxins (polymyxin B, colistin), viomycin,
• anticancer drugs: carboplatin (at high doses), cisplatin, oxaliplatin (especially if the patient previously had impaired kidney function),
• immunosuppressive agents: cyclosporine, tacrolimus,
• fast-acting diuretics: furosemide or ethacrynic acid (which may lead to hearing damage, as fluid deficiency in the body leads to high amikacin concentration),
• methoxyflurane used for anesthesia: the anesthesiologist should be informed that the patient has received or is receiving amikacin or a similar antibiotic before using methoxyflurane (anesthetic gas), and this gas should be avoided if possible due to increased risk of severe kidney or nerve damage.

If it is necessary to use amikacin together with the above-mentioned substances, frequent and thorough monitoring of hearing and kidney function will be performed. If amikacin is used together with fast-acting diuretics, fluid balance will be monitored.
Concurrent use of amikacin and muscle relaxants or other substances acting on muscles and nerves
The doctor will observe the patient particularly carefully if the patient is receiving amikacin together with muscle relaxants (such as succinylcholine, decamethonium, atracurium, rocuronium, vecuronium), large volumes of blood with an anticoagulant (citrate), or anesthetic agents: respiratory arrest (paralysis of respiratory muscles) may occur.
If the patient is being treated with amikacin, inform the anesthesiologist before surgery due to the risk of significant intensification of neuromuscular blockade. If aminoglycosides cause neuromuscular blockade, it may be reversed using calcium salts.
Indomethacin
In newborns receiving amikacin and indomethacin (an anti-inflammatory and pain-relieving medicine) simultaneously, the blood concentration of amikacin will be closely monitored. Indomethacin may increase the blood concentration of amikacin.
Bisphosphonates
Concurrent use with bisphosphonates (used in the treatment of osteoporosis and similar conditions) is associated with a high risk of decreased blood calcium levels (hypocalcemia).
Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
Pregnancy
If the patient is pregnant, she will receive this medicine only if absolutely necessary.
Breastfeeding
Although it is unlikely that amikacin will be absorbed from the infant's intestine during breastfeeding, the doctor will carefully consider whether to discontinue breastfeeding or amikacin treatment.
Fertility
Animal studies have not shown any effect on fertility.
Driving and operating machinery
No studies have been conducted on the effect of the medicine on the ability to drive vehicles or operate machinery. If the patient receives the medicine in an outpatient setting, caution is advised when driving vehicles or operating machinery due to possible adverse effects such as dizziness and balance disturbances.
Important information about certain components of Amikacin B. Braun
This medicine contains 354 mg of sodium in the form of salt (the main component of table salt) per 100 ml of solution, corresponding to 17.7% of the recommended maximum daily sodium intake for adults.

3. How to use Amikacin B. Braun

Amikacin B. Braun is administered by intravenous infusion (into a vein). The contents of one vial are given over 30–60 minutes.
Duration of treatment
Amikacin is usually administered for 7–10 days; longer treatment is reserved only for severe or complicated infections. Treatment effects are typically observed within 24 to 48 hours; otherwise, a change of therapy may be necessary. In such cases, the physician will assess the patient's condition and consider modifying the treatment.
The appropriate dose for each patient is determined by the physician. The usual recommended doses are provided below.
Dosing in patients with normal kidney function

• Adults and adolescents over 12 years of age (body weight above 33 kg): The usual dose is 15 mg of amikacin per kg of body weight (b.w.) every 24 hours, given as a single dose or divided into two equal doses of 7.5 mg/kg b.w. every 12 hours. Up to 1.5 grams per day may be administered for a short period if such high doses are absolutely necessary and if close and continuous monitoring of the patient is possible.
• Infants, young children, and children: A single daily dose of amikacin ranging from 15 to 20 mg/kg b.w., or a dose of 7.5 mg/kg b.w. administered every 12 hours.
• Dosing in newborns: Initial dose is 10 mg of amikacin per kg b.w., followed 12 hours later by 7.5 mg of amikacin per kg b.w. Treatment should continue with 7.5 mg of amikacin per kg b.w. every 12 hours.
• Dosing in premature infants: 7.5 mg of amikacin per kg b.w. every 12 hours.

However, this does not apply to patients with impaired immunity, kidney dysfunction, cystic fibrosis, ascites, endocarditis, extensive burns (affecting more than 20% of skin surface), elderly patients, or pregnant women.
During treatment, blood levels of amikacin will be carefully monitored and the dose adjusted accordingly.
Dosing in patients with impaired kidney function
In patients with kidney dysfunction, blood levels of amikacin and kidney function will be monitored periodically to allow appropriate dose adjustment.
The physician knows how to calculate the correct dose to administer to the patient.
Dosing in patients undergoing hemodialysis or peritoneal dialysis
In these patients, amikacin dosage may need to be modified. The physician will ensure that the appropriate dose has been established for the individual patient.
Elderly patients
To achieve therapeutic plasma concentrations, lower doses of amikacin may be required in elderly patients compared to younger individuals. Whenever possible, kidney function should be assessed and the dose adjusted accordingly if necessary.
Patients with significant overweight
In these patients, the dose is calculated based on ideal body weight plus 40% of excess weight. The dose may later be adjusted according to measured blood levels of amikacin. The physician will not administer a dose exceeding 1.5 g of amikacin per day.
Patients with ascites
Higher doses should be administered to achieve adequate drug levels in the blood.
Overdose of Amikacin B. Braun
Overdose may cause kidney damage, damage to the auditory nerves, or muscle paralysis. In such cases, amikacin infusion will be discontinued, and procedures to remove the drug from the blood (e.g. dialysis, hemofiltration) may be initiated. In newborns, exchange transfusion may be considered, but specialist advice should be sought before implementing this approach.
If neuromuscular blockade with respiratory arrest occurs, the physician will initiate all necessary supportive treatments. Calcium salts (e.g. as calcium gluconate or calcium lactobionate in a 10–20% solution) may be administered to reverse muscle paralysis. Mechanical ventilation may be required in case of respiratory failure.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, Amikacin B. Braun may cause adverse reactions, although not everyone will
experience them.
Amikacin (and all other similar substances) may have toxic effects on the auditory nerve and kidneys,
and may block neuromuscular transmission. Such effects are most commonly observed in patients:

• with impaired kidney function,
• receiving other medications that also have harmful effects on the auditory nerve and kidneys, and
• receiving excessive doses or undergoing prolonged treatment.

Adverse reactions that may be caused by treatment are listed below according to their absolute
frequency of occurrence.
The adverse symptoms described below may be severe and may require immediate treatment.
Very rare (may occur in not more than 1 in 10,000 patients):

• respiratory depression (paralysis of respiratory muscles).

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

• allergic reactions, up to anaphylactic shock,
• deafness (irreversible),
• acute kidney failure, kidney damage,
• paralysis.

Other adverse reactions
Uncommon (may occur in not more than 1 in 100 patients):

• superinfection or colonization by resistant microorganisms,
• dizziness, loss of balance,
• nausea, vomiting,
• damage to certain parts of the kidneys (renal tubules),
• rash.

Rare (may occur in up to 1 in 1,000 patients):

• anaemia, increased number of certain types of white blood cells (eosinophilia),
• itching, urticaria,
• low magnesium levels in blood,
• headache, numbness, tremors, loss of balance,
• low blood pressure,
• joint pain, uncontrolled muscle movements,
• reduced urine output, presence of albumin, white and (or) red blood cells in urine,
• increased levels of creatinine and (or) other nitrogenous compounds in blood (oliguria, azotemia),
• drug fever,
• blindness or other vision disturbances*,
• tinnitus (ringing in the ears), mild hearing loss (hearing impairment).

* This medicine is not intended for ocular use. Cases of blindness and retinal infarction have been reported following intraocular injection of this medicine.
Frequency not known (frequency cannot be determined from available data):

• presence of cells in urine,
• respiratory arrest, bronchospasm.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C,
02-222 Warsaw,
tel.: (22) 4921 301,
fax: (22) 4921 309,
website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Amikacin B. Braun

Keep this medicine out of the sight and reach of children.
Do not use Amikacin B. Braun after the expiry date stated on the vial and outer packaging. The expiry date refers to the last day of the stated month.
There are no special storage requirements for this medicinal product.
The infusion solution should be used immediately.
For single use only.
Any unused portion of the product must be discarded.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the package and other information

What Amikacin B. Braun contains

• The active substance is amikacin.

1 ml of Amikacin B. Braun 2.5 mg/ml solution for infusion contains 2.5 mg of amikacin as
amikacin sulfate.
1 vial of 100 ml contains 250 mg of amikacin.
1 ml of Amikacin B. Braun 5 mg/ml solution for infusion contains 5 mg of amikacin as
amikacin sulfate.
1 vial of 100 ml contains 500 mg of amikacin.
1 ml of Amikacin B. Braun 10 mg/ml solution for infusion contains 10 mg of amikacin as
amikacin sulfate.
1 vial of 100 ml contains 1000 mg of amikacin.

• Other ingredients: sodium chloride, sodium hydroxide (for pH adjustment), water for injections.

What Amikacin B. Braun looks like and contents of the pack
Amikacin B. Braun is a clear, colourless solution for infusion.
It is available in 100 ml polyethylene vials.
It is supplied in packs containing 10 or 20 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
B. Braun Melsungen AG
Carl-Braun-Strasse 1
34212 Melsungen
Germany
Tel: +49-5661-71-0
Fax: +49-5661-71-4567

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

This medicinal product is authorised in the European Economic Area countries under the
following names:
Austria Amikacin B. Braun 2.5 mg/ml Infusionslösung
Amikacin B. Braun 5 mg/ml Infusionslösung
Belgium Amikacine B. Braun 5 mg/ml
Solution pour perfusion, Oplossing voor infusie, Infusionslösung
Amikacine B. Braun 10 mg/ml
Solution pour perfusion, Oplossing voor infusie, Infusionslösung
Bulgaria Amikacin B. Braun 5 mg/ml infusion solution
Amikacin B. Braun 10 mg/ml infusion solution
Czech Republic Amikacin B. Braun 5 mg/ml
Amikacin B. Braun 10 mg/ml
Germany Amikacin B. Braun 2.5 mg/ml Infusionslösung
Amikacin B. Braun 5 mg/ml Infusionslösung
Amikacin B. Braun 10 mg/ml Infusionslösung
Estonia Amikacin B. Braun 5 mg/ml
Amikacin B. Braun 10 mg/ml
Greece Amikacin B. Braun 5 mg/ml solution for infusion
France AMIKACINE B. Braun 2.5 mg/ml, solution for infusion
AMIKACINE B. Braun 5 mg/ml, solution for infusion
AMIKACINE B. Braun 10 mg/ml, solution for infusion
Hungary Amikacin B. Braun 5 mg/ml oldatos infúzió
Italy Amikacina B. Braun 5 mg/ml solution for infusion
Amikacina B. Braun 10 mg/ml solution for infusion
Luxembourg Amikacin B. Braun 2.5 mg/ml Infusionslösung
Amikacin B. Braun 5 mg/ml Infusionslösung
Amikacin B. Braun 10 mg/ml Infusionslösung
Latvia Amikacin B. Braun 5 mg/ml solution for infusion
Amikacin B. Braun 10 mg/ml solution for infusion
Poland Amikacin B. Braun, 2.5 mg/ml, solution for infusion
Amikacin B. Braun, 5 mg/ml, solution for infusion
Amikacin B. Braun, 10 mg/ml, solution for infusion
Slovakia Amikacin B. Braun 5 mg/ml
Amikacin B. Braun 10 mg/ml

Information intended exclusively for healthcare professionals:

Neurotoxicity and ototoxicity
In patients treated with aminoglycoside antibiotics, toxic effects on the nervous system may occur, manifesting as vestibular nerve toxicity as well as bilateral toxicity to the auditory nerve. The risk of ototoxicity associated with aminoglycosides is higher in patients with impaired renal function and in patients receiving the drug for longer than 5–7 days, even in patients who have already been cured.
The first sign is high-frequency hearing loss, which can only be detected by audiometric testing. Severe dizziness may occur, which may indicate damage to the vestibular nerve. Other symptoms of neurotoxic effects may include skin tingling and prickling sensations, muscle cramps, and convulsions.
Increased risk of ototoxicity occurs in patients with mitochondrial DNA mutations (especially nucleotide substitution at position 1555 A to G in the 12S rRNA gene), even when serum aminoglycoside concentrations during treatment remain within the recommended range. In these patients, alternative treatment methods should be considered.
In patients with a history of significant mutations or aminoglycoside-induced deafness, alternative treatment methods or genetic testing should be considered prior to administration.
In patients developing cochleovestibular nerve damage during treatment, there may be no warning symptoms of toxic effects on the eighth cranial nerve; however, after completion of treatment, complete or partial bilateral deafness or disabling dizziness may occur.
Aminoglycoside-induced ototoxicity is usually irreversible.

Toxic effects on neuromuscular transmission
During treatment with aminoglycosides, regardless of the route of administration, neuromuscular blockade leading to respiratory muscle paralysis should be considered, especially in patients concurrently receiving other medicinal products that block neuromuscular transmission. In the event of neuromuscular blockade, calcium salts may reverse respiratory muscle paralysis; however, mechanical ventilation may be necessary. Neuromuscular blockade and muscle paralysis have been demonstrated in laboratory animals administered high doses of amikacin.

Effect on laboratory test results
Serum creatinine concentrations may be falsely elevated when cephalosporins are administered concomitantly.
Mutual inactivation of amikacin and beta-lactam antibiotics may also occur in samples (e.g., serum, cerebrospinal fluid) collected for aminoglycoside concentration measurement, leading to inaccurate results. Therefore, samples should be analyzed immediately after collection, stored refrigerated after collection, or the beta-lactam antibiotic should be inactivated by adding beta-lactamase. Inactivation of the aminoglycoside antibiotic is clinically significant only in patients with severe renal impairment.

Patient monitoring
Renal function and the eighth cranial nerve should be closely monitored, especially in patients with diagnosed or suspected renal impairment at the start of treatment, and in patients with initially normal renal function who develop signs of renal impairment during treatment. Whenever possible, serum amikacin concentrations should be monitored to ensure adequate levels and to avoid toxic concentrations. Urinalysis should be performed to detect decreased specific gravity, increased protein excretion, and presence of cells or casts. Blood urea nitrogen, serum creatinine concentration, or creatinine clearance should be determined periodically. Audiograms should be performed serially in patients of appropriate age and particularly in high-risk patients. If symptoms of ototoxicity (peripheral or central dizziness, tinnitus or acute sounds in the ears, hearing loss) or nephrotoxicity occur, treatment must be discontinued or the dosage regimen modified.

Pharmaceutical incompatibilities
Amikacin B. Braun, 2.5 mg/ml, 5 mg/ml, and 10 mg/ml, infusion solution, are ready-to-use products. They must not be mixed with any other medicinal product and should be administered separately according to the recommended dose and route of administration.
Under no circumstances should aminoglycosides be mixed in the same infusion solution with beta-lactam antibiotics (e.g., penicillins, cephalosporins), as this may result in physicochemical inactivation of one or both drugs.
Chemical incompatibilities are known with amphotericin, chlorothiazides, erythromycin, heparin, nitrofurantoin, novobiocin, phenytoin, sulfadiazine, thiopental, chlortetracycline, vitamin B, and vitamin C. Amikacin must not be mixed with these medicinal products.
Inactivation occurring when aminoglycosides are mixed with beta-lactam antibiotics may persist even when samples are collected for serum antibiotic concentration measurement, leading to significant underestimation and dosing errors, and consequently to the risk of toxicity. Such samples must be analyzed promptly and placed on ice or beta-lactamase should be added.

Shelf life
Before opening
3 years
After first opening of the container
From a microbiological standpoint, the product should be used immediately. If not used immediately, the user is responsible for the storage duration and conditions prior to use. It is generally recommended not to store beyond 24 hours at a temperature of 2°C to 8°C.

Dosage
Accurate administration of Amikacin B. Braun 2.5 mg/ml, 5 mg/ml, and 10 mg/ml infusion solution is possible only when using an infusion pump.
This pharmaceutical form is ready for use; the solution must not be diluted before administration and is intended for single use only.
To avoid overdosing, especially in children, the most appropriate available strength should be selected.

Infusion solution volume in patients with normal renal function

Patients with impaired renal function (creatinine clearance <60 ml/min)
Warning. Once-daily administration of amikacin is not recommended in patients with impaired renal function (creatinine clearance <60 ml/min).
Due to expected accumulation of amikacin in patients with impaired renal function and creatinine clearance <60 ml/min, dose reduction or prolonged intervals between doses are recommended. The loading dose in this patient group is 7.5 mg/kg body weight. The interval between doses is calculated by multiplying the serum creatinine concentration by 9.
For example, if the serum creatinine concentration is 2 mg/100 ml, the recommended single dose for the patient (7.5 mg/kg body weight) should be administered every 2 × 9 = 18 hours.
In patients with chronic renal failure and known creatinine clearance, the maintenance dose administered every 12 hours is calculated using the formula:
creatinine clearance [ml/min]
× amikacin dose 7.5 mg/kg body weight.
creatinine clearance [ml/min]
The values in the table below may be used as a guideline.

For complete information about this medicinal product, please refer to the
product characteristics.