AMIKACIN 250 mg /Ml Solution

Contents of the leaflet

1. Leaflet accompanying the packaging: patient information
2. Amikacin Adamed, 250 mg/mL, solution for injection
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Amikacin Adamed and what is it used for
4. Important information before using Amikacin Adamed
   1. When not to use Amikacin Adamed:
   2. Warnings and precautions
   3. The first symptoms of harmful effects on hearing or nerves after administration of this medicine may be:
   4. If the patient experiences such symptoms, they should immediately inform their doctor.
   5. Children
   6. Amikacin Adamed and other medicines
   7. In particular, inform your doctor if you are taking any of the following medicines:
   8. Pregnancy and breastfeeding
   9. Driving and using machines
   10. Amikacin Adamed contains sodium metabisulfite
   11. Amikacin Adamed contains sodium
5. How to use Amikacin Adamed
   1. Using a higher dose of Amikacin Adamed than recommended
   2. Missing a dose of Amikacin Adamed
6. Possible side effects
   1. In case of severe side effects, such as:
   2. Amikacin Adamed and additional treatment.
   3. Other possible side effects
   4. Reporting side effects
7. How to store Amikacin Adamed
8. Contents of the packaging and other information
   1. What Amikacin Adamed contains
   2. What Amikacin Adamed looks like and contents of the packaging
   3. Marketing authorization holder
   4. Manufacturer
   5. Date of last revision of the leaflet:
   6. Information intended for healthcare professionals only
   7. Dosage
   8. Preterm infants
   9. Newborns
   10. Infants from 4 weeks of age and children up to 12 years
   11. Adults and adolescents over 12 years
   12. Patients with impaired kidney function
   13. Impaired kidney function
   14. Method of administration
   15. Recommendations for intravenous administration
   16. Instructions for preparing the medicine for use
   17. Preparing solutions for intravenous infusions

Leaflet accompanying the packaging: patient information

Amikacin Adamed, 250 mg/mL, solution for injection

Amikacin

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Amikacin Adamed and what is it used for
• 2. Important information before using Amikacin Adamed
• 3. How to use Amikacin Adamed
• 4. Possible side effects
• 5. How to store Amikacin Adamed
• 6. Contents of the packaging and other information

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

The active substance of Amikacin Adamed is amikacin, an aminoglycoside antibiotic that acts bactericidally on susceptible bacteria.
Amikacin Adamed is intended for short-term treatment of severe infections caused by bacteria susceptible to amikacin, such as:

• respiratory tract infections,
• bone and joint infections,
• skin and soft tissue infections,
• intra-abdominal infections, including peritonitis,
• burn and postoperative wound infections (also in vascular surgery),
• severe, complicated and recurrent urinary tract infections (in uncomplicated infections, amikacin is used only when the causative bacteria are resistant to other antibiotics),
• septicemia, usually in combination with a beta-lactam antibiotic,
• infections of the central nervous system.

2. Important information before using Amikacin Adamed

When not to use Amikacin Adamed:

Warnings and precautions

Before starting treatment with Amikacin Adamed, discuss with your doctor:

Before starting and during treatment with Amikacin Adamed, the doctor will closely monitor the patient, paying particular attention to their hearing and kidney function.
The following will be monitored in the patient:

• kidney function, especially in patients with kidney failure or signs of kidney failure that have occurred during treatment, as well as in elderly patients,
• hearing,
• amikacin concentration in the blood (if necessary).

If the patient has any of the following factors, there is a higher risk of harmful effects on hearing or nerves:

• impaired kidney function,
• advanced age (≥65 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 symptoms of harmful effects on hearing or nerves after administration of this medicine may be:

• difficulty hearing high-pitched sounds (hearing loss affecting high frequencies),
• dizziness,
• a feeling of numbness and tingling of the skin, muscle cramps, seizures.

If the patient experiences such symptoms, they should immediately inform their doctor.

If the patient experiences or worsens symptoms of kidney failure, the doctor will reduce the daily dose and (or) prolong the intervals between individual doses. If severe kidney failure occurs, the administration of amikacin will be discontinued.
Treatment with amikacin should also be discontinued if tinnitus or hearing loss occurs.
During treatment, the patient should drink plenty of fluids; it may be necessary to administer supplementary fluids by infusion to prevent the accumulation of amikacin in the kidneys and damage to the renal tubules.
In patients with reduced urine excretion and improper dosing of the antibiotic, it may accumulate in the body and cause side effects. If this occurs, the doctor may use hemodialysis, peritoneal dialysis, or continuous arteriovenous hemofiltration. In newborns and infants, exchange transfusion may be necessary.

Like other antibiotics, amikacin can lead to excessive growth of non-susceptible microorganisms, in which case appropriate treatment will be initiated.
After intravitreal injection of amikacin (into the eye), cases of macular infarction have been reported, sometimes leading to permanent vision loss.

Children

Aminoglycosides should be used with caution in premature infants and newborns due to their immature kidney function.

Amikacin Adamed 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.
Amikacin Adamed may affect the action of other medicines. Other medicines may also affect the action of Amikacin Adamed.

In particular, inform your doctor if you are taking any of the following medicines:

• medicines that can damage the kidneys, hearing, or nervous system, such as: cisplatin, platinum compounds - medicines used in cancer treatment, cyclosporine, tacrolimus - medicines that suppress the immune system, medicines used to treat infections, such as: bacitracin, cephaloridine, amphotericin B, paromomycin, viomycin, polymyxin B, colistin, vancomycin, and aminoglycoside antibiotics (e.g. streptomycin, gentamicin, tobramycin, neomycina);
• beta-lactam antibiotics (penicillins) in patients with severe kidney failure may weaken the action of Amikacin Adamed;
• muscle relaxants or anesthetics such as ether, halothane, tubocurarine, succinylcholine, decamethonium, atracurium, rocuronium, vecuronium, or transfusing large amounts of blood with citrate as an anticoagulant may cause neuromuscular blockade and respiratory muscle paralysis;
• rapidly acting diuretics, especially when administered intravenously, such as mannitol, ethacrynic acid, furosemide, may cause hearing damage, and even irreversible deafness - it is recommended to avoid concurrent use of these medicines;
• indomethacin - an anti-inflammatory medicine may increase the concentration of amikacin in the blood of newborns;
• bisphosphonates - medicines used to treat osteoporosis and similar diseases, used concurrently with Amikacin Adamed may lead to decreased calcium levels in the blood;
• thiamine (vitamin B1) - may be broken down as a result of the reaction with sodium metabisulfite contained in the Amikacin Adamed solution.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Pregnancy
Using Amikacin Adamed during pregnancy is only justified when, in the doctor's opinion, it is absolutely necessary for the mother.
Amikacin crosses the placenta into fetal circulation and amniotic fluid and may cause fetal damage.
Breastfeeding
Amikacin Adamed should be avoided in breastfeeding women. If amikacin is essential for the mother, the doctor will decide whether to discontinue breastfeeding or stop treatment.

Driving and using machines

The effect of amikacin on the ability to drive and use machines has not been determined. However, if the patient experiences side effects such as dizziness and balance disorders, they should not drive or operate machinery.

Amikacin Adamed contains sodium metabisulfite

The medicine may rarely cause severe hypersensitivity reactions and bronchospasm.

Amikacin Adamed contains sodium

The medicine contains 1.98 mmol (45 mg) of sodium (the main component of table salt) in the maximum daily dose of the medicine (1.5 g). This corresponds to 2.25% of the maximum recommended daily sodium intake in the diet for adults.

3. How to use Amikacin Adamed

This medicine should always be used as directed by your doctor. If you have any doubts, consult your doctor.
Amikacin Adamed is administered by intramuscular injection or intravenous infusion (in a drip).
The dosage and method of administration suitable for the patient are determined by the doctor, depending on the patient's body weight, age, and kidney function, as well as the type and severity of the infection.
After administration of the recommended dose, in the case of uncomplicated infections and susceptible bacterial strains, the body's response to treatment should occur within 24 to 48 hours.
If there is no response to treatment within three to five days, the doctor will consider discontinuing the use of this medicine and using alternative treatment after re-determining the susceptibility of the microorganisms to the antibiotic.
Detailed dosing and administration instructions are provided at the end of the leaflet, in the section "Information intended for healthcare professionals only".

Using a higher dose of Amikacin Adamed than recommended

If you think you have received too much Amikacin Adamed, inform your doctor. The doctor will decide on the administration of calcium (e.g. in the form of gluconate or lactobionate in a 10-20% solution) to prevent neuromuscular blockade, the use of hemodialysis, peritoneal dialysis, or continuous arteriovenous hemofiltration. In newborns and infants, exchange transfusion may be necessary.

Missing a dose of Amikacin Adamed

If you think you have missed a dose of Amikacin Adamed, inform your doctor as soon as possible.
In case of any further doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur during treatment with Amikacin Adamed.

In case of severe side effects, such as:

• tinnitus, hearing impairment,
• decreased urine output,
• breathing difficulties,
• skin disorders, rash,

you should immediately inform your doctor, as it may be necessary to discontinue the use of the medicine and use additional treatment.

Amikacin Adamed and additional treatment.

Other possible side effects

Uncommon side effects(may occur in less than 1 in 100 people):

• bacterial or fungal infections that are not susceptible to the medicine,
• nausea, vomiting,
• rash.

Rare side effects(may occur in less than 1 in 1,000 people):

• anemia, increased white blood cell count in the blood (eosinophilia),
• decreased magnesium levels in the blood,
• tingling or numbness, tremors, headaches, balance disorders,
• vision loss (after injection into the eye),
• tinnitus, hearing loss,
• low blood pressure,
• itching, hives,
• muscle cramps, joint pain,
• decreased urine output (oliguria),
• in blood tests: increased levels of nitrogen, urea,
• in urine tests: presence of protein, white or red blood cells,
• fever.

Side effects with unknown frequency(frequency cannot be determined from available data):

• allergic reactions, including severe allergic reactions,
• muscle paralysis,
• hearing loss,
• apnea, bronchospasm,
• acute kidney failure, toxic kidney damage,
• in urine tests: presence of cells.

Reporting side effects

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

5. How to store Amikacin Adamed

There are no special storage instructions for the medicine.
The diluted solution can be stored for 24 hours at a temperature of 2°C to 8°C.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "EXP".
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Amikacin Adamed contains

• The active substance of the medicine is amikacin. One mL of the solution contains 250 mg of amikacin in the form of amikacin sulfate. One vial (2 mL of solution for injection) contains 500 mg of amikacin in the form of amikacin sulfate.
• The other ingredients are: sodium citrate, sodium metabisulfite (E 223), sulfuric acid, water for injections. See section 2: "Amikacin Adamed contains sodium".

What Amikacin Adamed looks like and contents of the packaging

Amikacin Adamed is a clear, colorless or light yellow, aqueous solution for injection.
The packaging is a 4 mL clear glass type I vial, sealed with a bromobutyl rubber stopper with an aluminum seal and a plastic flip-off cap, in a cardboard box.
Pack size: 1 vial containing 2 mL of solution in a cardboard box.

Marketing authorization holder

Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Poland

Manufacturer

Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Poland
ANFARM HELLAS S.A
53-57 Perikleous str., Gerakas
15344, Attiki,
Greece
To obtain more detailed information about this medicine, please contact the marketing authorization holder:
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Poland
phone: +48 22 732 77 00

Date of last revision of the leaflet:

_________________________________________________________________________________

Information intended for healthcare professionals only

Dosage

Before calculating the correct dose, determine the patient's body weight.
Monitor kidney function by measuring serum creatinine or calculating endogenous creatinine clearance. The value of blood urea nitrogen (BUN) is less reliable in this case. Repeat kidney function assessments periodically during treatment.
If possible, measure the amikacin concentration in the serum to ensure the correct dose and avoid excessive levels. It is recommended to measure both the maximum and minimum concentrations in the serum during treatment, i.e., 30-90 minutes after injection and just before the next dose.
Avoid peak concentrations (30-90 minutes after injection) above 35 μg/mL and minimum concentrations (just before the next dose) above 10 μg/mL. Adjust the dosage accordingly. In patients with normal kidney function, the product can be administered once a day; the maximum serum concentration in this case may exceed 35 μg/mL.
Treatment usually lasts 7 to 10 days. The total daily dose of amikacin for all routes of administration should not exceed 15 to 20 mg/kg body weight/day. In severe and complicated infections, when treatment lasts longer than 10 days, the use of amikacin sulfate injections should be re-evaluated; if the decision is made to continue treatment, monitor kidney function, hearing, and balance, as well as serum amikacin concentrations. The safety of using amikacin for more than 14 days has not been confirmed.
After administration of the recommended dose, in the case of uncomplicated infections caused by susceptible microorganisms, the body's response to treatment should occur within 24 to 48 hours.
If there is no clear clinical response within 3 to 5 days, treatment should be discontinued and the susceptibility of the microorganisms to the antibiotic should be re-determined. Lack of response to treatment may be due to resistance of the microorganism or the presence of infection foci requiring surgical drainage.

Preterm infants

The recommended dose for preterm infants is 7.5 mg/kg every 12 hours (see sections 4.4 and 5.2).

Newborns

The recommended initial loading dose is 10 mg/kg, then 7.5 mg/kg every 12 hours (see sections 4.4 and 5.2).

Infants from 4 weeks of age and children up to 12 years

The recommended dose for children with normal kidney function is 15 to 20 mg/kg/day, administered once a day or 7.5 mg/kg every 12 hours.
In the treatment of endocarditis and in patients with neutropenia and fever, the product should be administered twice a day, due to the lack of sufficient data confirming the effectiveness of once-daily administration.

Adults and adolescents over 12 years

The recommended dose for adults and adolescents with normal kidney function (creatinine clearance ≥50 mL/min) is 15 mg/kg/day and can be administered in a single daily dose or in two equal divided doses of 7.5 mg/kg every 12 hours. Do not exceed the total daily dose of 1.5 g.
In the treatment of endocarditis and in patients with neutropenia and fever, the product should be administered twice a day, due to the lack of sufficient data confirming the effectiveness of once-daily administration.

Patients with impaired kidney function

Amikacin is excreted by the kidneys. If possible, determine kidney function and adjust the dosage as described in the section on dosing in patients with impaired kidney function.
Infections that are life-threatening and (or) caused by Pseudomonas
The dose in adults can be increased to 500 mg every 8 hours, but should not exceed 1.5 g/day and should not be administered for more than 10 days. Do not exceed the maximum total dose for adults, which is 15 g.
Urinary tract infections (other than those caused by Pseudomonas)
Administer 7.5 mg/kg/day in two divided doses (equivalent to 250 mg twice a day in adults). Since the activity of amikacin increases with pH, alkalizing agents can be administered concurrently.

Impaired kidney function

In patients with impaired kidney function, when creatinine clearance is less than 50 mL/min, it is not recommended to administer the recommended total daily dose of amikacin in a single dose, as the patient will be exposed to high minimum concentrations for a long time. See the dosing instructions for patients with impaired kidney function below.
The product can be administered to patients with impaired kidney function, usually two or three times a day, and the dose should be adjusted if possible by monitoring the amikacin concentration in the serum using appropriate measurement methods. In patients with impaired kidney function, the dose can be adjusted by either administering the usual dose less frequently or administering a reduced dose without changing the dosing interval.
Both methods are based on creatinine clearance or serum creatinine values, as these values correlate with the half-lives of aminoglycosides in patients with reduced kidney function. When using these dosing schedules, closely monitor the patient's clinical condition and laboratory parameters, and modify the dosing schedule as needed, taking into account any dialysis being performed.

Method of administration

Amikacin sulfate can be administered intramuscularly or intravenously.
In the treatment of most infections, intramuscular administration is recommended; however, in life-threatening infections and in patients for whom intramuscular administration is not possible, the product can be administered intravenously, either as a short injection lasting 2 to 3 minutes (bolus) or as an infusion (0.25% over 30 minutes).

Recommendations for intravenous administration

In adults, the product should be administered after appropriate dilution, in a slow infusion lasting 30 to 60 minutes.
In children, the volume of the diluent used depends on the dose of amikacin tolerated by the patient. The solution is usually administered in an infusion lasting 30 to 60 minutes. Infants should receive an infusion over 1 to 2 hours.
Amikacin should not be mixed with other medicines, but should be administered separately, according to the recommended dose and route of administration.
In the case of administration with another antibiotic, the medicines should be injected at different sites or administered in separate infusions.

Instructions for preparing the medicine for use

Before intramuscular administration, there is no need to dilute the medicine.

Preparing solutions for intravenous infusions

Intravenous infusions are prepared by diluting the contents of the vial in one of the commonly used infusion solutions, to achieve an antibiotic concentration in the range of 2.5 to 5 mg/mL, e.g., 500 mg of amikacin can be diluted in 100 or 200 mL of one of the following solutions:
0.9% sodium chloride solution,
5% glucose solution.
In newborns, infants, and children, use infusions with smaller volumes, adjusted to the patient's body weight.
Prepared infusion solutions, without a preservative, can be stored at a temperature of 2°C to 8°C for no longer than 24 hours.