Amikacin B. Braun

Patient Information Leaflet: Information for the Patient

Amikacina B. Braun 2.5 mg/ml solution for infusion, 5 mg/ml solution for infusion, 10 mg/ml solution for infusion

Amikacin
Please 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 pharmacist.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml is and what it is used for;
2. What you need to know before being given Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml;
3. How to use Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml;
4. Possible side effects;
5. How to store Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml;
6. Contents of the pack and other information.

1. What Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml is and what it is used for

Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml belongs to a group of medicines called antibiotics. It is used to treat severe infections caused by bacteria that can be killed by the active substance amikacin. Amikacin belongs to a group of substances called aminoglycosides. You may be given amikacin to treat the following conditions:

• Infections of the lungs and lower respiratory tract occurring during hospital treatment, including severe pneumonia.
• Intra-abdominal infections, including inflammation of the peritoneum.
• Complicated and recurrent infections of the kidneys, urinary tract, and bladder.
• Skin and soft tissue infections, including severe burns.
• Bacterial inflammation of the inner lining of the heart.
• Infections following abdominal surgery.
• Amikacina 2.5 mg/ml, 5 mg/ml, 10 mg/ml may also be used to treat patients with systemic inflammatory response syndrome associated with any of the listed infections, or where such an association is suspected.

2. What you should know before being given Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml

Do not take Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml

• if you are allergic (hypersensitive) to amikacin, to other similar substances (other aminoglycosides), or to any of the other ingredients of this medicine;

Warnings and precautions
Talk to your doctor before taking Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml.
Special caution must be exercised with Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml if:

• you have impaired kidney function,
• you have hearing impairment,
• you have neurological or muscular disorders, such as a specific type of muscle weakness called myasthenia gravis,
• you have Parkinson's disease,
• you have previously been treated with another antibiotic similar to amikacin. In all these cases, your doctor must pay particular attention.

If you have any of the following conditions, you may be at higher risk of developing harmful effects on your hearing or nerves:

• impaired kidney function,
• advanced age (≥ 60 years),
• dehydration,
• administration of high doses of this medicine,
• prolonged therapy beyond 5–7 days, even in healthy patients.

The first signs of harmful effects on your hearing or nerves after taking this medicine may include:

• difficulty hearing high-pitched sounds (high-frequency hearing loss),
• dizziness,
• numbness, skin tingling, muscle spasms, seizures.

After administration of this medicine, breathing (respiratory paralysis) and neuromuscular functions (neuromuscular blockade) may be suppressed. Your doctor will take appropriate countermeasures.
Elderly patients
If you are an elderly patient, your doctor will pay particular attention to your kidney function and may perform several tests to ensure your kidneys are not impaired, as elderly patients are more likely to have impaired kidney function.
Paediatric population
Caution is also required when administering this medicine to newborns or premature infants due to immature kidney function.
During treatment with this medicine, your doctor will closely monitor you, paying particular attention to your hearing ability and kidney function.
Monitoring will include:

• kidney function, especially if you have kidney failure or signs indicating its onset during treatment;
• hearing and blood levels of amikacin, if necessary.

If signs of kidney damage appear or if kidney damage worsens, your doctor will reduce the daily doses and/or extend the intervals between doses. If kidney damage becomes severe, amikacin will be discontinued.
Treatment with amikacin must also be stopped if you experience tinnitus (ringing in the ears) or hearing loss.
If during surgery wound irrigation procedures are performed using solutions containing amikacin or a similar antibiotic, this must be taken into account when determining the amikacin dosage.
Other medicines and Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
The harmful effects of amikacin on the kidneys and auditory nerve may be enhanced by:

• other antibiotics similar to amikacin (e.g. kanamycin, paromomycin);
• other substances 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 in case of pre-existing kidney impairment);
• immunosuppressive agents: cyclosporine, tacrolimus;
• rapidly acting diuretics that increase urine flow: furosemide or ethacrynic acid (may damage hearing because dehydration leads to higher amikacin concentrations);
• anaesthesia with methoxyflurane: the anaesthetist must know if you have taken or are taking amikacin or a similar antibiotic before administering methoxyflurane (an anaesthetic gas), and should avoid using this agent whenever possible, due to an increased risk of severe kidney and nerve damage.

When amikacin must be combined with such substances, monitoring of hearing and kidney function must be very frequent and rigorous. If amikacin is used together with rapidly acting diuretics, fluid balance must be closely monitored.
Concomitant treatment with amikacin and muscle relaxants or other substances affecting muscles and nerves
Your doctor will pay particular attention if you receive amikacin together with muscle relaxants (such as succinylcholine, decamethonium, atracurium, rocuronium, vecuronium), large amounts of citrated blood (to prevent coagulation), or anaesthetics: respiratory paralysis (respiratory blockade) may occur.
During surgery, the anaesthetist must be informed about ongoing amikacin treatment due to the risk of enhanced neuromuscular blockade.
If the aminoglycoside causes neuromuscular blockade, it may be reversed with calcium salts.
Indomethacin
In newborns receiving amikacin and indomethacin (a medicine for inflammation and pain) concomitantly, blood levels of amikacin must be closely monitored. Indomethacin may increase amikacin blood levels.
Bisphosphonates
Combination therapy with bisphosphonates (used to treat osteoporosis and similar conditions) carries a high risk of lowering blood calcium levels (hypocalcaemia).
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Pregnancy
You will receive this medicine only if absolutely necessary.
Breastfeeding
Although it is unlikely that amikacin is absorbed through the infant's intestine when breastfeeding, your doctor will carefully evaluate whether to discontinue breastfeeding or amikacin treatment.
Fertility
Animal studies have shown no effect on fertility.
Driving and using machines
No studies on the ability to drive or use machines have been conducted. In case of administration to outpatients, caution is advised when driving or operating machinery, considering possible adverse effects such as dizziness and vertigo.
Important information about some excipients of Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml
This medicine contains 354 mg (or 15 mmol) of sodium per 100 ml in the form of common salt; this should be taken into account in patients on a low-sodium diet.

3. How Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml is administered

Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml is administered by direct intravenous infusion (intravenous infusion). The contents of one vial should be infused over a period of 30–60 minutes.
Your doctor will determine the correct dose for you. The usual doses are as follows:
Dosage in patients with normal renal function

• Adults and adolescents over 12 years of age (body weight over 33 kg): The usual dose is 15 mg of amikacin per kg of body weight (BW) per 24 hours, divided into two equal doses: 7.5 mg per kg of BW every 12 hours. A maximum of 1.5 grams per kg of BW per day may be administered for a short period if absolutely necessary; in such cases, strict and continuous monitoring must be performed during treatment. The total amount of amikacin received throughout the entire course of treatment must not exceed 15 grams.
• Infants, toddlers, and children: A single daily dose of 15–20 mg/kg of amikacin or a dose of 7.5 mg/kg every 12 hours.
• Dosage for neonates: The initial dose is 10 mg of amikacin per kg of body weight, followed 12 hours later by 7.5 mg of amikacin per kg of body weight. Treatment continues with 7.5 mg of amikacin per kg of body weight every 12 hours.
• Dosage for premature infants: 7.5 mg of amikacin per kg of body weight every 12 hours.

However, this does not apply to patients with weakened immune systems, renal insufficiency, cystic fibrosis, presence of fluid in the abdomen, inflammation of the inner lining of the heart (endocarditis), extensive burns (more than 20 percent of body surface area), elderly patients, or during pregnancy.
Duration of treatment
Amikacin treatment is usually administered for 7–10 days, and only in cases of severe or complicated infections for a longer period. The therapeutic effect is usually evident within 24–48 hours; otherwise, it may be necessary to switch to another medication. In such cases, your doctor will evaluate your condition and reconsider the treatment.
Careful monitoring of amikacin blood levels is required, and the dosage should be carefully adjusted throughout the therapy.
Dosage in patients with impaired renal function
If your renal function is impaired, amikacin blood levels and kidney function must be carefully and frequently monitored so that the amikacin dose can be adjusted as needed. Your doctor knows how to calculate the doses you should receive.
In patients undergoing hemodialysis or peritoneal dialysis, a modified dose of amikacin may be required. In such cases, your doctor will determine the correct dose for you.
Elderly patients.
In elderly patients, lower doses of amikacin than in younger patients may be required to achieve therapeutic plasma concentrations. Whenever possible, renal function should be assessed and, if necessary, the dose administered should be adjusted accordingly.
Severely overweight patients
In these patients, dosing is calculated based on ideal body weight, adding 40% of the excess weight. Subsequently, dosage adjustments may be made based on amikacin blood levels. Your doctor will not administer more than 1.5 g of amikacin per day.
The usual duration of treatment ranges between 7 and 10 days.
Patients with presence of fluid in the abdomen
Higher doses are required to achieve adequate blood levels.
If you are given more Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml than you should
Overdose can damage the kidneys and auditory nerves or cause muscular function block (paralysis). In such cases, amikacin infusion must be discontinued, and procedures to remove the drug from the blood (dialysis, hemofiltration) may be initiated. In neonates, blood exchange may be considered; however, expert consultation must be obtained before implementing this measure.
In case of muscular and neurological block accompanied by respiratory arrest, your doctor will administer the necessary treatment. To counteract the paralyzing effect, calcium salts may be used (e.g., 10–20% gluconate or lactobionate solution). Mechanical ventilation may be required in cases of respiratory paralysis.
If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml can cause side effects, although not everyone experiences them.
Amikacin and all other similar substances may have toxic effects on the auditory nerve, kidneys, and may cause neuromuscular blockade. These effects are more frequently observed in patients

• with kidney problems,
• treated with other medicines that also have harmful effects on the auditory nerve and kidneys,
• receiving too high a dose or prolonged treatment.

The adverse reactions that may be caused by treatment are listed below according to their absolute frequency.
The following adverse reactions can be serious and require immediate treatment:
Very rare (may affect up to 1 in 10,000 people)

• respiratory paralysis (respiratory arrest)

Not known (frequency cannot be estimated from available data)

• allergic reactions up to and including shock;
• deafness (irreversible);
• acute renal failure, kidney damage;
• paralysis.

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

• Further infection or condition caused by resistant microorganisms.
• Dizziness, vertigo.
• Nausea, vomiting.
• Damage to certain parts of the kidney (renal tubules).
• Rash.

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

• Anaemia, increased count of a certain type of white blood cells (eosinophils).
• Itching, urticaria.
• Low magnesium levels in the blood.
• Headache, numbness, tremors, loss of balance.
• Low blood pressure.
• Joint pain, involuntary muscle movements.
• Reduced urine output, presence of albumin, white and/or red blood cells in urine.
• Increased levels of creatinine and/or nitrogen-containing compounds in the blood (oliguria, azotemia).
• Drug-related fever.
• Blindness or other vision problems*
• Ringing in the ears (tinnitus), mild hearing loss (hypacusis).

*This medicine is not intended for use in the eye. Blindness and retinal infarction have been reported following injection of this medicine into the eye.
Not known (frequency cannot be estimated from available data):

• cells in the urine.
• respiratory arrest, breathing difficulties (bronchospasm).

Reporting of suspected adverse reactions
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml

Keep this medicine out of the sight and reach of children.
Do not use Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml after the expiry date stated on the
vial and outer carton. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
The infusion solution must be used immediately.
Single-use.
Discard any unused solution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Other information

What Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml contains
The active substance is:
amikacin.
1 ml of Amikacina 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 Amikacina 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 Amikacina 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 components are:
• sodium chloride, sodium hydroxide (for pH adjustment), water for injections.

Description of the appearance of Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml and contents of the
pack
Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml is a clear, colourless aqueous solution for
infusion.
It is supplied in 100 ml polyethylene vials.
It is available in packs of 10 and 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

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 2.5 mg/ml Solution pour perfusion,
Oplossing voor infusie, Infusionslösung;
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 Амикацин Б. Браун 2.5 mg/ml инфузионен разтвор
Амикацин Б. Браун 5 mg/ml инфузионен разтвор
Амикацин Б. Браун 10 mg/ml инфузионен разтвор
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 2.5 mg/ml διάλυμα για έγχυση
Amikacin B. Braun 5 mg/ml διάλυμα για έγχυση
Amikacin B. Braun 10 mg/ml διάλυμα για έγχυση
France AMIKACINE B. Braun 2.5 mg/ml, solution pour perfusion;
AMIKACINE B. Braun 5 mg/ml, solution pour perfusion;
AMIKACINE B. Braun 10 mg/ml, solution pour perfusion
Hungary Amikacin B. Braun 5 mg/ml oldatos infúzió;
Amikacin B. Braun 10 mg/ml oldatos infúzió
Italy Amikacina B. Braun 2.5 mg/ml soluzione per infusione
Amikacina B. Braun 5 mg/ml soluzione per infusione
Amikacina B. Braun 10 mg/ml soluzione per infusione
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 šķīdums infūzijām;

The following information is intended exclusively for physicians or healthcare professionals:
Additional warnings:
Neuro/ototoxicity
During treatment, patients who develop cochlear or vestibular damage may not experience symptoms indicating the development of eighth nerve toxicity and may present with irreversible, partial or complete bilateral deafness, or disabling vertigo after discontinuation of the drug.
Toxic effects on the eighth cranial nerve may result in hearing loss, loss of balance, or both. Amikacin primarily affects auditory function. Cochlear damage includes high-frequency hearing loss and usually occurs before clinical hearing loss can be detected by audiometric testing.
Aminoglycoside-induced ototoxicity is generally irreversible.

Neuromuscular toxicity
The possibility of respiratory paralysis should be considered if aminoglycosides are administered by any route, especially in patients receiving concomitant medications that induce neuromuscular blockade. If neuromuscular blockade occurs, calcium salts may reverse respiratory paralysis; however, mechanical respiratory support might be necessary. Neuromuscular blockade and muscular paralysis have been demonstrated in laboratory animals receiving high doses of amikacin.

Interference with laboratory tests
Serum creatinine assays may yield falsely elevated values when cephalosporins are administered concomitantly.
Mutual inactivation between amikacin and beta-lactam antibiotics may continue in samples (e.g., serum, cerebrospinal fluid, etc.) collected for aminoglycoside measurement, thus leading to erroneous results. Therefore, samples must be analyzed immediately after collection or refrigerated, or the beta-lactam antibiotic must be inactivated by adding beta-lactamase. Aminoglycoside inactivation is clinically significant only in patients with severely impaired renal function.

Patient monitoring
Renal function and eighth cranial nerve function should be monitored as closely as possible in patients with known or suspected renal impairment at the start of therapy, as well as in those whose renal function is initially normal but who develop signs of renal dysfunction during treatment. Whenever possible, serum concentrations of amikacin should be monitored to ensure adequate levels and to avoid potentially toxic levels. Urine should be examined for decreased specific gravity, increased protein excretion, and presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained whenever possible in patients old enough to undergo testing, particularly in high-risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, ear noise, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.

Incompatibilities
Amikacina B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml are ready-to-use formulations and must not be mixed with any other medicinal product, but administered separately according to the recommended dose and route of administration.
Under no circumstances should aminoglycosides be mixed in an infusion solution with beta-lactam antibiotics (e.g., penicillins, cephalosporins), due to the risk of causing physical-chemical inactivation of the associated antibiotic.
Chemical incompatibilities are known with amphotericin, chlorothiazides, erythromycin, heparin, nitrofurantoin, novobiocin, phenytoin, sulfadiazine, thiopental, chlortetracycline, vitamin B, and vitamin C. Amikacin must not be pre-mixed with these medicinal products.
Inactivation caused by mixing aminoglycosides and beta-lactams may persist even in blood samples drawn to measure serum antibiotic levels, leading to significant underestimation and resulting in dosing errors and risk of toxicity. Samples must be processed promptly and placed on ice or beta-lactamase added.

Shelf life
Before opening:
3 years.
In-use shelf life (after opening):
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, which normally should not exceed 24 hours at a temperature of 2–8°C.

Dosage
Infusion volumes in patients with normal renal function:

When administering Amikacin B. Braun 2.5 mg/ml, 5 mg/ml, 10 mg/ml infusion solution using an infusion pump, dosing accuracy is improved.
This formulation is for single use only, is ready for use, and must not be diluted prior to administration.
To avoid overdose, especially in children, the most appropriate concentration among those available should be selected.

Patients with impaired renal function ( creatinine clearance < 50 ml/min)
Note: Once-daily administration of amikacin is not recommended in patients with impaired renal function ( creatinine clearance < 50 ml/min).

In cases of impaired renal function with glomerular filtration rate below 70 ml/min, it is advisable to reduce doses or extend dosing intervals, as accumulation of amikacin is likely. In patients with impaired renal function, the loading dose of amikacin is 7.5 mg/kg of body weight. The dosing interval for individual patients should be calculated as 9 times the serum creatinine level. For example, if the creatinine concentration is 2 mg/100 ml, the recommended individual dose (7.5 mg/kg of body weight) should be administered every 2 x 9 = 18 hours.

For patients with chronic renal failure and known creatinine clearance, the maintenance dose administered at 12-hour intervals is calculated using the formula:
(patient’s creatinine clearance in ml/min ÷ normal value of creatinine clearance in ml/min) x amikacin 7.5 mg/kg of body weight.

The values in the following table may be used as a guide:

| Creatinine clearance [ml/min] | Amikacin dose every 12 hours for a 70 kg patient [mg] | Daily amikacin dose [mg/kg body weight/day] |
|-------------------------------|--------------------------------------------------------|---------------------------------------------|
| 70 – 80 | 266 – 280 | 7.6 – 8 |
| 60 – 69 | 224 – 266 | 6.4 – 7.6 |
| 50 – 59 | 186 – 224 | 5.4 – 6.4 |
| 40 – 49 | 147 – 186 | 4.2 – 5.4 |
| 30 – 39 | 112 – 147 | 3.2 – 4.2 |
| 20 – 29 | 77 – 112 | 2.1 – 3.1 |
| 15 – 19 | 56 – 77 | 1.6 – 2.0 |

For complete information on this medicinal product, refer to the Summary of Product Characteristics.