Biodacina

Leaflet accompanying the packaging: patient information

BIODACYNA, 125 mg/ml, solution for injection and infusion

BIODACYNA, 250 mg/ml, solution for injection and infusion

Amikacin

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should 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 tell their doctor or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Biodacyna and what is it used for

The active substance of Biodacyna is amikacin, an aminoglycoside antibiotic with a bactericidal effect.
The medicine is intended for short-term treatment of severe infections caused by bacteria sensitive to amikacin (including those resistant to other aminoglycoside antibiotics), such as:

• respiratory tract infections,
• bone and joint infections,
• skin and soft tissue infections,
• intra-abdominal infections, including peritonitis,
• burn and post-operative 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),
• sepsis, most often in combination with a beta-lactam antibiotic,
• infections of the central nervous system.

2. Important information before using Biodacyna

When not to use Biodacyna:

• if the patient is allergic to amikacin or any of the other ingredients of this medicine (listed in section 6);
• if the patient has myasthenia gravis (muscle weakness);
• if the patient is allergic to any aminoglycoside antibiotic (e.g. streptomycin, gentamicin, tobramycin, neomycin) or has experienced severe side effects after using these antibiotics in the past - cross-sensitivity to drugs in this group may occur.

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reakcje niepożądane po tych antybiotykach - może występować nadwrażliwość krzyżowa na
leki tej grupy.

Warnings and precautions

Before starting treatment with Biodacyna, the patient should discuss it with their doctor or nurse.

• Biodacyna should be used strictly according to the doctor's instructions, who will monitor the patient's condition. Improper use of Biodacyna may cause severe kidney and/or hearing disorders, and even hearing loss. Nephrotoxic or ototoxic effects are more likely to occur in patients with pre-existing kidney function disorders and in patients treated with high doses of the medicine for longer than recommended.
• Before starting Biodacyna, the doctor will recommend testing kidney function and hearing. Kidney function and hearing tests will also be performed regularly during treatment. If treatment is to last seven days or longer, in patients with kidney function disorders or 10 days in other patients, the doctor will recommend an audiogram before starting treatment and during therapy.
• If the patient or their family members have a mitochondrial mutation-related disease (genetic disease) or hearing loss caused by the use of antibiotic drugs, they should inform their doctor or pharmacist before taking an aminoglycoside; some mitochondrial mutations may increase the risk of hearing loss after using this medicine. Before administering Biodacyna, the doctor may recommend genetic testing.
• 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, the antibiotic may accumulate in the body and cause side effects. If this occurs, the doctor may use hemodialysis or peritoneal dialysis.
• If the patient's urine output decreases, blood tests show an increase in nitrogen levels, or hearing is impaired, treatment with Biodacyna should be discontinued immediately. If the patient experiences tinnitus, dizziness, high-frequency hearing loss, they should inform their doctor immediately, as these may be the first symptoms of toxic effects of the medicine.
• If the patient has been treated with any aminoglycoside antibiotic in the past, they should inform their doctor before starting treatment, especially if they experienced toxicity symptoms related to the use of such an antibiotic (kidney or hearing damage).
• Particular caution should be exercised in patients with Parkinson's disease or those receiving muscle relaxants, anesthetics, or large amounts of blood preserved with citrates as an anticoagulant. In sensitive patients, respiratory disorders (neuromuscular blockade with respiratory muscle paralysis) may occur.
• After intravitreal administration (injection into the eye) of amikacin, retinal detachment has been reported, sometimes leading to permanent vision loss.
• As with the use of other antibiotics, there is a risk of superinfection with non-sensitive bacteria.

Children

Aminoglycosides should be used with caution in premature infants and newborns due to the immaturity of their kidneys, which prolongs the half-life of drugs in this group in the serum.

Biodacyna and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
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• Using medicines that can damage the kidneys, hearing, or nervous system, such as bacitracin, cisplatin, amphotericin B, cyclosporine, tacrolimus, cefaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, and aminoglycoside antibiotics (e.g. streptomycin, gentamicin, tobramycin, neomycin) together with Biodacyna (or shortly before or after its use) may increase the risk of side effects.
• Using beta-lactam antibiotics (penicillins) in patients with severe kidney failure may reduce the effectiveness of Biodacyna.
• Using Biodacyna together with muscle relaxants or anesthetics (such as ether, halothane, tubocurarine, succinylcholine, decamethonium, atracurium, rocuronium, vecuronium) or in patients who have received large amounts of blood preserved with citrate as an anticoagulant may cause neuromuscular blockade and respiratory muscle paralysis.
• Using Biodacyna together with potent diuretics, such as mannitol, ethacrynic acid, furosemide, may cause hearing damage, even permanent deafness - concurrent use of these medicines should be avoided.
• Indomethacin may increase amikacin levels in the serum of newborns.
• There is an increased risk of hypocalcemia when aminoglycosides are administered concurrently with bisphosphonates.
• There is an increased risk of toxic kidney damage and possible toxic hearing damage when aminoglycosides are administered concurrently with platinum compounds.
• Concomitantly administered thiamine (vitamin B1) may be degraded as a result of a reaction with sodium metabisulfite contained in the Biodacyna solution.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.
Pregnancy
Use of Biodacyna during pregnancy is only justified when it is absolutely necessary for the mother and the use of a safer alternative medicine is not possible or is contraindicated.
Amikacin quickly crosses the placenta into the fetal circulation and amniotic fluid and may cause fetal damage.
Breastfeeding
Biodacyna 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, but the symptoms of the disease and the patient's condition may make it impossible to perform these activities.

Biodacyna contains sodium metabisulfite (E 223)

The medicine may rarely cause severe hypersensitivity reactions and bronchospasm.

Biodacyna contains sodium

Biodacyna, 125 mg/ml, contains 3.73 mg (0.16 mmol) of sodium (the main component of common salt) per 1 ml. This corresponds to 0.19% of the maximum recommended daily intake of sodium in the diet for adults.
The maximum daily dose of this medicine (1.5 g amikacin, i.e. 12 ml solution) contains 44.76 mg (1.95 mmol) of sodium (the main component of common salt). This corresponds to 2.24% of the maximum recommended daily intake of sodium in the diet for adults.
1 mmol (23 mg) of sodium is present in 6 ml of Biodacyna, 125 mg/ml.
Biodacyna, 250 mg/ml, contains 7.49 mg (0.32 mmol) of sodium (the main component of common salt) per 1 ml. This corresponds to 0.38% of the maximum recommended daily intake of sodium in the diet for adults.
The maximum daily dose of this medicine (1.5 g amikacin, i.e. 6 ml solution) contains 44.94 mg (1.95 mmol) of sodium (the main component of common salt). This corresponds to 2.25% of the maximum recommended daily intake of sodium in the diet for adults.
1 mmol (23 mg) of sodium is present in 3 ml of Biodacyna, 250 mg/ml.
The medicine may be diluted - see "Instructions for preparing the medicine for use".
The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared dilution of the medicine. To obtain accurate information about the sodium content in the solution used for dilution, refer to the product characteristics of the diluent used.

3. How to use Biodacyna

This medicine should always be used in accordance with the doctor's instructions. If you have any doubts, consult your doctor.
Biodacyna is administered by intramuscular injection or intravenous infusion (in a drip).
Dosage and method of administration are determined by the doctor based on the patient's body weight.
After administration of the recommended dose, in the case of uncomplicated infections and sensitive 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 alternative treatment.
Detailed dosage and administration instructions, as well as preparation instructions for administration, are provided at the end of the leaflet, in the section "Information intended for healthcare professionals only".

Using a higher dose of Biodacyna than recommended

If the patient suspects that they have received too high a dose of Biodacyna, they should inform their 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 Biodacyna

If the patient suspects that a dose of Biodacyna has been missed, they should inform their doctor as soon as possible.
If you have any further doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

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

If you experience symptoms such as:

• tinnitus, hearing loss,
• decreased urine output,
• breathing difficulties,
• skin problems, rash,

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you should immediately inform your doctor,as it may be necessary to discontinue Biodacyna and administer 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 sensitive 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,
• balance disorders,
• headache,
• sensory disturbances,
• tremor,
• vision loss (after injection into the eye),
• tinnitus,
• temporary or permanent hearing loss,
• hypotension,
• itching, urticaria,
• muscle tremors, joint pain,
• decreased urine output (oliguria),
• blood tests: increased levels of nitrogen, urea, and creatinine,
• urine tests: presence of protein, white or red blood cells,
• fever.

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

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

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should inform your doctor or nurse. Side effects can be reported directly to the Department of Drug Adverse Reaction Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 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 Biodacyna

Store at a temperature not exceeding 25°C. Protect from light.
The diluted solution can be stored for 24 hours at a temperature between 2°C and 8°C.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the month stated.
The inscription on the packaging after the abbreviation EXP means the expiry date, and after the abbreviation Lot means the batch number.
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 Biodacyna contains

• The active substance of Biodacyna is amikacin. 1 ml of solution contains 125 mg or 250 mg of amikacin (in the form of amikacin disulfate).
• The other ingredients are: sodium citrate, sodium metabisulfite (E 223), sulfuric acid, water for injections.

What Biodacyna looks like and what the packaging contains

Biodacyna is a colorless or light yellow aqueous solution.
The single-dose packaging contains 1 ampoule.

Marketing authorization holder and manufacturer

Polpharma S.A.
Pelplińska 19, 83-200 Starogard Gdański
Phone: +48 22 364 61 01
Date of last revision of the leaflet:April 2023
_________________________________________________________________________________

Information intended for healthcare professionals only

Dosage and administration

The doctor will recommend testing kidney function by measuring serum creatinine levels or calculating endogenous creatinine clearance. The value of blood urea nitrogen (BUN) is less reliable in this case.
Repeated assessment of kidney function should be performed periodically during treatment.
If possible, serum amikacin levels should be measured to achieve the appropriate level, not exceeding the maximum values.
It is recommended to measure both the maximum and minimum serum concentrations (just before the next dose) at regular intervals during treatment.

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The maximum concentration (30-90 minutes after injection) should not exceed 35 µg/ml, and the minimum concentration (just before the next dose) should not exceed 10 µg/ml. The dosage should be adjusted accordingly.
In patients with normal kidney function, the medicine 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 is 15 to 20 mg/kg body weight/day and should not be exceeded.
Lack of response to treatment may be due to resistance of the microorganism or the presence of infection foci requiring surgical drainage.
In severe and complicated infections, when treatment lasts longer than 10 days, the use of amikacin disulfate in injections should be reassessed; if the decision is made to continue treatment, kidney function, hearing, and balance should be monitored, as well as serum amikacin levels.
The safety of using amikacin for longer than 14 days has not been established.

Preterm infants

The recommended dose for preterm infants is 7.5 mg/kg every 12 hours.

Newborns

The recommended initial loading dose is 10 mg/kg, then 7.5 mg/kg every 12 hours.

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 body weight/day, administered once a day or 7.5 mg/kg every 12 hours.
During treatment for endocarditis and in patients with neutropenia and fever, the medicine should be administered twice a day, due to the lack of available data confirming the effectiveness of once-daily administration.

Adults and children over 12 years

The recommended dose for adults and adolescents with normal kidney function (creatinine clearance >50 ml/min) is 15 mg/kg body weight/day and can be administered in a single daily dose or in two equal divided doses of 7.5 mg/kg, administered every 12 hours. The total daily dose should not exceed 1.5 g.
During treatment for endocarditis and in patients with neutropenia and fever, the medicine 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, kidney function should be assessed and the dosage adjusted as described in the section on dosing in patients with impaired kidney function.
Life-threatening infections and/or Pseudomonas infections
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 longer than 10 days.
The maximum total dose for adults should not exceed 15 g.

Urinary tract infections (other than Pseudomonas infections)

The dose is 7.5 mg/kg body weight/day, administered in two equal divided doses (corresponding 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 levels for a long time.
Refer to the information on adjusting the dosage in patients with impaired kidney function below.
In patients with impaired kidney function, who normally receive amikacin two or three times a day, serum amikacin levels should be monitored using appropriate measurement methods, if possible.
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 intervals between doses. Both methods are based on creatinine clearance values or serum creatinine levels, as these values correlate with the half-lives of aminoglycosides in patients with reduced kidney function.
When using these dosing schedules, the patient's clinical condition and laboratory parameters should be closely monitored, and the dosing schedule modified if necessary, taking into account any dialysis performed.

Reduced doses administered at usual intervals

If creatinine clearance is not known and the patient's condition is stable, the intervals (in hours) between usual single doses (i.e. the dose usually recommended for a patient with normal kidney function, 7.5 mg/kg every 12 hours) can be calculated by multiplying the patient's serum creatinine level (in mg/100 ml) by nine; i.e. if the serum creatinine level is 2 mg/100 ml, the recommended single dose (7.5 mg/kg) should be administered every 18 hours.

Intervals between amikacin doses of 7.5 mg/kg

depending on serum creatinine levels.

2 2.5 3 3.5 4 4.5 5 5.5 6

Interval between doses
(i.m. administration)
[hours]

13.5 18 22.5 27 31.5 36 40.5 45 49.5 54

Reduced doses administered at usual intervals
If kidney function is impaired and it is indicated to administer amikacin disulfate in injections at usual intervals, the dose should be reduced.
In these patients, serum amikacin levels should be measured to ensure precise administration and avoid excessive serum amikacin levels.
If measuring amikacin in the serum is not possible and the patient's condition is stable, the most readily available parameters to determine the degree of kidney function impairment for dosing purposes are serum creatinine levels and creatinine clearance.
Treatment should be started with a usual dose of 7.5 mg/kg as a loading dose. This is the same as the dose usually recommended for a patient with normal kidney function, as described above.
To determine the maintenance dose administered every 12 hours, the loading dose should be reduced proportionally to the reduction in the patient's creatinine clearance:
maintenance dose administered every 12 hours =
= (observed creatinine clearance of the patient [ml/min] × calculated loading dose [mg])
normal creatinine clearance [ml/min]
An alternative, approximate method of determining reduced doses administered every 12 hours (for patients with known steady-state serum creatinine levels) is to divide the usual dose by the patient's serum creatinine level.

Instructions for intravenous administration

Adults should be administered the medicine after appropriate dilution, in a slow infusion lasting from 30 to 60 minutes.
The volume of the diluent used in children depends on the dose of amikacin tolerated by the patient.
The solution is usually administered over 30 to 60 minutes. Infants should receive the infusion over 1 to 2 hours.
Amikacin should not be mixed with other medicines but administered separately, according to the recommended dose and route of administration.

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 ampoule 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,
5% glucose solution with 0.9% sodium chloride solution (2:1),
5% glucose solution with 0.2% sodium chloride solution,
Ringer's solution with lactates.
In newborns, infants, and children, infusions with smaller volumes should be used, adapted to the patient's body weight.
Prepared infusion solutions without a preservative can be stored at a temperature between 2°C and 8°C for no longer than 24 hours.

Instructions for use

Read the instructions carefully before use.
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