Amikacin kabi

Patient Information Leaflet

Amikacin Kabi, 5 mg/mL, solution for infusion
Amikacinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist or nurse.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Leaflet Contents

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

1. What Amikacin Kabi is and what it is used for

Amikacin Kabi contains the active substance amikacin. It belongs to a group of medicines called antibiotics. These are used to treat serious bacterial infections caused by bacteria sensitive to amikacin. Amikacin belongs to a group of substances called aminoglycosides. You may be given amikacin to treat the following conditions:

• Lung and lower respiratory tract infections occurring during hospital treatment, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP);
• Complicated infections of the kidneys, urinary tract and bladder;
• Complicated intra-abdominal infections, including peritonitis;
• Skin and soft tissue infections, including severe burns;
• Bacterial endocarditis (infection of the inner lining of the heart chambers and valves) – only in combination therapy with other antibiotics.

Amikacin Kabi may also be used to treat patients who have systemic inflammatory response associated with any of the above-mentioned infections, or in whom such an association is suspected.

2. Important information before using Amikacin Kabi

When not to use Amikacin Kabi:

• if the patient is allergic to amikacin or to any of the other ingredients of this medicine (listed in section 6);
• if the patient is allergic to similar substances (other aminoglycoside antibiotics).

Warnings and precautions
Before starting treatment with Amikacin Kabi, discuss this with your doctor, pharmacist, or
nurse.
Inform your doctor if the patient:

• has impaired kidney function;
• has hearing disorders;
• has neuromuscular disorders, such as a specific type of muscle weakness called myasthenia gravis;
• suffers from Parkinson's disease;
• has previously been treated with another antibiotic similar to amikacin. In each of these situations, the doctor will exercise special caution.

If the patient or members of their family have a disease associated with mitochondrial mutation
(genetic disorder) or hearing loss caused by aminoglycoside antibiotics, it is recommended to
inform the doctor or pharmacist before using aminoglycoside antibiotics;
certain mitochondrial mutations may increase the risk of hearing loss after administration of this medicine.
Before administering Amikacin Kabi, the doctor may recommend genetic testing.
The doctor will also exercise special caution if the patient is 60 years of age or older or if the patient is dehydrated (has a water deficit in the body).
During treatment, the doctor will monitor the patient's condition, including:

• kidney function, especially if the patient is 60 years of age or older or has impaired kidney function;
• hearing;
• blood levels of amikacin, if necessary.

If kidney function disorders occur or worsen, the daily doses should be reduced and/or the intervals between doses extended. If severe kidney function impairment occurs, amikacin administration will be discontinued.
Treatment with amikacin should also be discontinued if tinnitus or hearing loss occurs.
To avoid the risk of kidney damage, auditory nerve damage, and muscle function impairment, Amikacin Kabi should not be used for longer than 10 days unless deemed necessary by the doctor.
During treatment, adequate fluid intake should be ensured for the patient.
If the patient received wound irrigation with solutions containing amikacin or a similar antibiotic during surgery, this should be taken into account when calculating the amikacin dose.

Children
Caution should be exercised when administering this medicine to premature infants and newborns due to immature kidney function in these patients.

Amikacin Kabi and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
The harmful effects of Amikacin Kabi on the kidneys and auditory nerve may be intensified by the following medicines:

• other antibiotics similar to amikacin;
• other agents used to treat infections, such as bacitracin, amphotericin B, antibiotics from the penicillin or cephalosporin groups, vancomycin, kanamycin, paromomycin, polymyxin B, colistin;
• anticancer agents: carboplatin (in high doses), cisplatin, oxaliplatin (particularly if the patient previously had impaired kidney function);
• immunosuppressive agents: cyclosporine, tacrolimus;
• potent diuretics: furosemide or ethacrynic acid (may lead to irreversible hearing damage);
• bisphosphonates (used in the treatment of osteoporosis and similar diseases);
• thiamine (vitamin B_), as its effectiveness may be reduced;
• indomethacin (an anti-inflammatory medicine used to reduce fever, pain, and joint swelling and stiffness). This may lead to increased levels of Amikacin Kabi in newborns.

Concomitant administration of the above-mentioned medicines with Amikacin Kabi should be avoided if possible.
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 potent diuretics, fluid balance will be monitored.

Special caution is also required during:

• Anaesthesia with methoxyflurane
  Before starting anaesthesia with methoxyflurane (an anaesthetic gas), the anaesthesiologist should check whether the patient has received or is receiving amikacin or a similar antibiotic. This combination should be avoided due to the increased risk of severe kidney and nerve damage.

• Concomitant use of amikacin with muscle relaxants (e.g. d-tubocurarine), other curare-like agents, botulinum toxins, or anaesthetic gases such as halothane
  If the patient is being treated with amikacin, inform the anaesthesiologist before surgery due to the risk of significant intensification of neuromuscular blockade. If aminoglycosides cause neuromuscular blockade, it may be reversed with calcium salts. In newborns receiving both Amikacin Kabi and indomethacin (an anti-inflammatory and analgesic medicine), blood levels of amikacin will be closely monitored. Indomethacin may increase blood levels of amikacin.

• Use with other antibiotics
  Combination therapy with appropriate antibiotics may significantly enhance the therapeutic effect.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
The patient will receive this medicine during pregnancy only if, in the doctor's opinion, it is absolutely necessary.

Breastfeeding
Although it is unlikely that amikacin is absorbed from the infant's intestine when breastfeeding, the doctor will carefully consider whether to discontinue breastfeeding or amikacin treatment.

Driving and using machines
No studies on the effect of amikacin on the ability to drive vehicles and operate machinery have been conducted. If the patient receives amikacin in an outpatient setting, caution should be exercised when driving vehicles and operating machinery due to possible adverse effects such as centrally or labyrinthine-induced dizziness.

Amikacin Kabi contains sodium
This medicine contains 177 mg of sodium (main component of table salt) in 50 mL. This corresponds to 8.85% of the maximum recommended daily sodium intake in the adult diet.
This medicine contains 354 mg of sodium (main component of table salt) in 100 mL. This corresponds to 17.7% of the maximum recommended daily sodium intake in the adult diet.
This medicine contains 708 mg of sodium (main component of table salt) in 200 mL. This corresponds to 35.4% of the maximum recommended daily sodium intake in the adult diet.

3. How to use Amikacin Kabi

Amikacin Kabi is administered by intravenous infusion (into a vein). The infusion time may last between 30 and 60 minutes.
The dose appropriate for each patient is determined by the physician. The usual doses are given below.
Patients with normal kidney function
Adults and adolescents aged 12 years and older (body weight above 33 kg)
The usual dose is 15 mg of amikacin per kg of body weight (b.w.) every 24 hours, given either as a single dose or divided into two equal doses: 7.5 mg per kg b.w. every 12 hours.
The maximum dose a patient may receive is up to 1.5 grams per day for a short period, if it is absolutely necessary to administer such high doses (e.g. life-threatening infections and/or infections caused by certain bacteria such as Pseudomonas, Acinetobacter, or Enterobacteriales) and if close and continuous monitoring of the patient during treatment is possible.
The total amount of amikacin a patient may receive throughout the entire treatment will not exceed 15 g.
Infants, young children and children (aged 4 weeks to 11 years)
A single daily dose of amikacin ranging from 0.15 to 0.20 mg/kg b.w., or a dose of 7.5 mg/kg b.w. administered every 12 hours.
Newborns (aged 0 to 27 days)
The 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.
Premature infants
7.5 mg of amikacin per kg b.w. every 12 hours.
Special patient groups
Single daily dosing is not recommended in patients with weakened immune systems, kidney impairment, cystic fibrosis, ascites, endocarditis, extensive burns (affecting more than 20% of the skin), or in pregnant women.
Patients with impaired kidney function
If a patient has impaired kidney function, blood levels of amikacin and kidney function will be monitored regularly to allow appropriate dose adjustment. The physician knows how to calculate the required dose.
Patients undergoing haemodialysis or peritoneal dialysis
Patients in this group receive half the normal dose at the end of dialysis.
Elderly patients
In elderly patients, kidney function may be reduced. Kidney function should be assessed whenever possible, and the dose adjusted accordingly if necessary.
Patients with obesity
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 serum amikacin concentrations. The maximum dose is 1.5 g of amikacin per day. The duration of treatment is usually 7–10 days.
Patients with ascites
Higher doses are required to achieve adequate drug levels in the blood.
Duration of treatment
The duration of treatment is usually 7–10 days. It may be extended only in cases of severe or complicated infections. Clinical response to treatment usually occurs within 24–48 hours; otherwise, a change in therapy may be necessary.
Serum amikacin levels will be closely monitored in all patients, particularly elderly patients, newborns, obese patients, and patients with impaired kidney function or cystic fibrosis, and the dose will be carefully adjusted during treatment.
If you receive more Amikacin Kabi than you should
If you think you have received more than the recommended dose, you should contact your doctor or nurse immediately.
Overdose may cause kidney damage, damage to the auditory nerves, or muscle paralysis. In such cases, amikacin infusion will be stopped.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
In patients treated with amikacin, toxic effects on the auditory nerve and kidneys have been observed. These adverse reactions can be prevented by strictly adhering to contraindications and careful dose determination by the physician, in accordance with recommendations. The physician will monitor signs of adverse reactions.

If any of the following serious adverse reactions occur, contact a doctor immediately:

Very rare (may occur in not more than 1 in 10,000 patients):

• swelling of the face, lips or tongue, skin rash, difficulty breathing – these may be symptoms of an allergic reaction;
• ringing in the ears or hearing loss (deafness);
• respiratory muscle paralysis;
• kidney function disorders, including reduced urine output (acute kidney failure).

Other adverse reactions:

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

• dizziness, loss of balance;
• involuntary eye movements (nystagmus);
• additional infection or colonization (by yeast-like fungi, resistant fungal cells called Candida);
• tinnitus, sensation of pressure in the ears, hearing disturbances;
• nausea;
• damage to specific parts of the kidneys, kidney function disorders.

Rare (may occur in not more than 1 in 1,000 patients):

• abnormally low counts of white or red blood cells or platelets, increased number of certain white blood cells (eosinophilia);
• allergic reactions, skin rash, itching, urticaria;
• low blood magnesium levels;
• headache, migraine, numbness, tremors;
• blindness or other vision disturbances;
• low blood pressure;
• respiratory depression;
• vomiting;
• joint pain;
• drug-induced fever;
• increased activity of certain liver enzymes in the blood.

Very rare (may occur in not more than 1 in 10,000 patients):

• muscular blockade;
• acute kidney failure.

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

• allergic reactions to antibiotics similar to amikacin (aminoglycosides);
• apnoea (temporary cessation of breathing), breathing difficulties caused by airway constriction.

Reporting of adverse reactions

If any adverse reactions occur in patients, including any possible adverse reactions not listed in this leaflet, inform a doctor, pharmacist or nurse. Adverse reactions can also be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 reactions may 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 Kabi

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and carton. The expiry date refers to the last day of the specified month.
No special storage conditions are required for this medicine.
Shelf-life after first opening/dilution:
Chemical and physical stability of the medicine has been demonstrated for 24 hours at 25°C and from 2°C to 8°C.
From a microbiological standpoint, the medicine should be used immediately. If the medicine is not used immediately, the responsibility for the storage duration and conditions prior to use lies with the user, and this period should usually not exceed 24 hours at a temperature of 2°C to 8°C, unless the opening/dilution was carried out under controlled and validated aseptic conditions.
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 pack and other information

What Amikacin Kabi contains

• The active substance is amikacin.

Each mL of infusion solution contains 5 mg of amikacin (as amikacin sulfate).
One 50 mL vial contains 250 mg of amikacin.
One 100 mL vial contains 500 mg of amikacin.
One 200 mL vial contains 1000 mg of amikacin.

• The other components are: sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injections.

What Amikacin Kabi looks like and contents of the pack
Amikacin Kabi is an infusion solution administered intravenously by drip through a small tube or cannula inserted into a vein.
It is a clear, colourless, aqueous solution.
Amikacin Kabi is supplied in a KabiPac bottle made of LDPE, closed with a PP or PE/PP cap and rubber discs allowing needle insertion, packed in a cardboard box.
Pack sizes: 10 x 50 mL, 10 x 100 mL and 10 x 200 mL of infusion solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Manufacturer
Fresenius Kabi Polska Sp. z o.o.
ul. Sienkiewicza 25
99-300 Kutno
For further information about this medicinal product, please contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Tel.: +48 22 345 67 89
This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Information intended exclusively for medical professionals:

Incompatibilities
Amikacin Kabi is a ready-to-use medicinal product and must not be mixed with any other medicines
(except those listed below). It 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 either drug.
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 mixing aminoglycosides and beta-lactam antibiotics may also persist
when serum samples are collected for antibiotic concentration measurements, potentially leading to
substantial underestimation, incorrect dosing, and consequently, risk of toxicity. Such samples should be
promptly analyzed, placed on ice, or beta-lactamase should be added.
Special precautions for disposal of unused portions
For single use only.
Any unused portion of the medicinal product must be discarded.
Dilution must be performed under aseptic conditions. Prior to administration, the solution should be
inspected visually for particulate matter and discoloration. Only clear, particle-free solutions should be used.
Amikacin Kabi is compatible with the following infusion solutions:

• Ringer's solution;
• Ringer's lactate solution;
• Sodium chloride 9 mg/mL (0.9%) solution for injection;
• Glucose 50 mg/mL (5%) solution for injection;
• Glucose 100 mg/mL (10%) solution for injection.

Storage instructions
See section 5: "How to store Amikacin Kabi".
Route of administration
See section 3: "How to use Amikacin Kabi".
Dosage
See section 3: "How to use Amikacin Kabi".
Amikacin Kabi must be administered exclusively by intravenous infusion, with infusion duration of 30 to
60 minutes.
Infusion volumes for patients with normal renal function:

The dosing accuracy of Amikacin Kabi is greater when an infusion pump is used.
Instructions for dilution
Before administration of Amikacin Kabi to children and adolescents, dilution is recommended.
To obtain amikacin at a concentration of 2.5 mg/mL, the appropriate volume (in mL) of
Amikacin Kabi 5 mg/mL should be mixed with an equal volume of one of the infusion solutions listed above.
The solution should be administered as an infusion lasting 30 to 60 minutes. Infants should receive the infusion over 1 to 2 hours.
Volumes of diluted infusion solution containing 2.5 mg/mL of amikacin:

Treatment of overdose
In case of overdose or occurrence of toxic symptoms, infusion of amikacin should be discontinued; forced diuresis may be applied to accelerate amikacin elimination from the blood. Peritoneal dialysis and hemodialysis may contribute to the elimination of amikacin accumulating in the blood. Hemodialysis is more effective than peritoneal dialysis in removing amikacin from the blood.
In neonates, exchange transfusion may be considered; however, specialist advice must be sought before applying this measure.
To counteract the muscle-relaxing effect, administration of calcium salts is indicated. If respiratory paralysis occurs, mechanical ventilation may be necessary.