Biodacyna

Package leaflet: Information for the patient

BIODACYNA, 125 mg/ml, solution for injection and infusion
BIODACYNA, 250 mg/ml, solution for injection and 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, please consult your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse. See section 4.

Leaflet contents

1. What Biodacyna is and what it is 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 pack and other information

1. What Biodacyna is and what it is used for

The active substance in Biodacyna is amikacin, an aminoglycoside antibiotic with bactericidal action.
Biodacyna 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,
• infections of burn wounds and postoperative wounds (including in vascular surgery),
• severe, complicated and recurrent urinary tract infections (in uncomplicated infections, amikacin should be used only if the causative bacteria are resistant to other antibiotics),
• sepsis, usually in combination with a β-lactam antibiotic,
• central nervous system infections.

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 suffers from myasthenia gravis (muscle weakness);
• if the patient is allergic to any aminoglycoside antibiotic (e.g. streptomycin, gentamicin, tobramycin, neomycin) or has previously experienced severe adverse reactions to these antibiotics – cross-sensitivity to drugs of this group may occur.

Warnings and precautions

Before starting treatment with Biodacyna, discuss this with your doctor or nurse.

• Biodacyna must be used strictly according to the doctor's instructions, who will monitor the patient's condition. Improper use of Biodacyna may cause severe urinary system disorders and/or hearing and balance disturbances, even leading to hearing loss. Kidney damage, hearing impairment, or nerve paralysis are more likely in patients with pre-existing kidney function disorders and in patients treated with high doses of the drug for longer than recommended.
• Before starting administration of Biodacyna, the doctor will recommend kidney function and hearing tests. Kidney function and hearing will be monitored regularly during treatment. If treatment lasts seven days or longer in patients with impaired kidney function, or 10 days or longer in other patients, the doctor will order an audiogram before starting treatment and during therapy.
• If the patient or family members 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 drug. Before administering Biodacyna, the doctor may recommend genetic testing.
• During treatment, the patient should drink plenty of fluids; intravenous fluid replacement may be necessary to prevent accumulation of amikacin in the kidneys and damage to renal tubules. In patients with reduced urine output and inappropriate antibiotic dosing, the drug may accumulate in the body and cause adverse effects. If this occurs, the doctor may perform hemodialysis or peritoneal dialysis.
• If the patient's urine output decreases, blood tests show increased nitrogen levels, or if hearing damage occurs, treatment with Biodacyna must be stopped immediately. If the patient experiences tinnitus, dizziness, or loss of hearing high-frequency sounds, they should immediately inform the doctor, as these may be the first signs of drug toxicity.
• If the patient has previously been treated with any aminoglycoside antibiotic, this should be reported to the doctor before starting treatment, especially if symptoms of toxicity related to such antibiotics (kidney or hearing damage) occurred at that time.
• Particular caution is required in patients with Parkinson's disease or those receiving concomitant muscle relaxants, anesthetics, or large amounts of citrated blood. In sensitive patients, respiratory disturbances (neuromuscular blockade with paralysis of respiratory muscles) may occur.
• Following intravitreal injection (injection into the eye), amikacin has been associated with macular infarction, sometimes leading to permanent vision loss.
• As with other antibiotics, there is a risk of overgrowth of resistant microorganisms.

Children

Aminoglycosides should be used with caution in premature infants and newborns due to immature kidney function in these patients, which leads to prolonged half-life of these drugs in serum.

Biodacyna and other medicines

Inform your doctor about all medicines currently taken or recently taken, as well as any medicines planned for future use.

• Concomitant use of drugs that may damage the kidneys, hearing, or nervous system, such as: bacitracin, cisplatin, amphotericin B, cyclosporine, tacrolimus, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, and aminoglycoside antibiotics (e.g. streptomycin, gentamicin, tobramycin, neomycin) together with Biodacyna (or within a short time before or after its use) increases the risk of severe adverse effects.
• Use of beta-lactam antibiotics (penicillins) in patients with severe renal impairment may reduce the effectiveness of Biodacyna.
• Concomitant use of Biodacyna 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 containing citrate as an anticoagulant may cause neuromuscular blockade and paralysis of respiratory muscles.
• Concomitant use of Biodacyna with potent diuretics such as mannitol, ethacrynic acid, or furosemide may cause hearing damage and even irreversible deafness – simultaneous use of these drugs should be avoided.
• Indomethacin may increase amikacin plasma concentrations in newborns.
• There is an increased risk of hypocalcemia when aminoglycosides are administered concurrently with bisphosphonates.
• There is an increased risk of nephrotoxicity and ototoxicity when aminoglycosides are administered concurrently with platinum compounds.
• Concurrently administered thiamine (vitamin B_) may degrade due to a reaction with sodium metabisulfite contained in the Biodacyna solution.

Pregnancy and breastfeeding

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

Pregnancy

Biodacyna should be used during pregnancy only if absolutely necessary for the mother, and when the use of a safer alternative drug is impossible or contraindicated.

Amikacin rapidly crosses the placenta into fetal circulation and amniotic fluid and may cause fetal harm.

Breastfeeding

Use of this medicine in breastfeeding women should be avoided. In case of absolute necessity for the mother to receive amikacin, the doctor will decide whether to discontinue breastfeeding or stop treatment.

Driving and operating machinery

The effect of amikacin on the ability to drive vehicles and operate machinery has not been specifically established; however, disease symptoms and the patient's condition may impair the ability to perform these activities.

Biodacyna contains sodium metabisulfite (E 223)

This 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 (main component of table salt) per 1 ml. This corresponds to 0.19% of the maximum recommended daily dietary sodium intake 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 (main component of table salt). This corresponds to 2.24% of the maximum recommended daily dietary sodium intake 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 (main component of table salt) per 1 ml. This corresponds to 0.38% of the maximum recommended daily dietary sodium intake 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 (main component of table salt). This corresponds to 2.25% of the maximum recommended daily dietary sodium intake 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 preparation of the medicine for use".
The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared diluted solution. For accurate information on the sodium content in the solution used to dilute the medicine, refer to the summary of product characteristics of the diluent used.

3. How to use Biodacyna

This medicine should always be used according to the doctor's instructions. If in doubt, consult your
doctor.
Biodacyna is administered by intramuscular injection or intravenous infusion (via drip).
The dosage and method of administration are determined by the doctor depending on the patient's body weight.
After administration of the recommended dose, in uncomplicated infections and with susceptible 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 therapy.
Detailed dosage instructions, as well as administration and preparation of the medicine, are provided at the end of this leaflet under the section “Information intended exclusively for healthcare professionals”.
Use of a higher than recommended dose of Biodacyna
If the patient suspects that an excessive dose of Biodacyna has been administered, the doctor should be informed immediately. The doctor will decide whether to administer calcium (e.g., as gluconate or lactobionate in a 10–20% solution) to prevent neuromuscular blockade, and whether to initiate hemodialysis, peritoneal dialysis, or continuous arteriovenous hemofiltration. In neonates and infants, exchange transfusion may be necessary.
Missed dose of Biodacyna
If the patient suspects that a dose of Biodacyna has been missed, inform the doctor as soon as possible.
If there are any further doubts regarding the use of this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions may occur during treatment with Biodacyna.
If any of the following symptoms occur:

• tinnitus, hearing impairment,
• reduced volume of urine output,
• breathing difficulties,
• skin disorders, rash,

a doctor should be informed immediately, as it may be necessary to discontinue treatment with
Biodacyna and initiate additional therapy.
Other possible adverse reactions
Uncommon adverse reactions (may occur in fewer than 1 in 100 people):

• bacterial or candidal infections resistant to the drug,
• nausea, vomiting,
• rash.

Rare adverse reactions (may occur in fewer than 1 in 1,000 people):

• anaemia,
• increased blood levels of a certain type of white blood cells (eosinophilia),
• decreased magnesium levels in blood,
• loss of balance,
• headaches,
• sensory disturbances,
• tremor,
• vision loss (after intraocular injection),
• tinnitus,
• transient or permanent hearing loss,
• hypotension,
• itching, urticaria,
• muscle twitching, joint pain,
• reduced volume of urine output (oliguria),
• blood tests: increased levels of nitrogen, urea and creatinine,
• urine tests: presence of protein, white or red blood cells,
• fever.

Adverse reactions with unknown frequency (cannot be estimated from available data):

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

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the 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 can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide 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 may be stored for 24 hours at a temperature between 2°C and 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.
The expiry date refers to the last day of the stated month. The marking on the packaging following the abbreviation EXP indicates the expiry date, and following the abbreviation Lot indicates the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Contents of the packaging and other information

What Biodacyna contains

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

What Biodacyna looks like and contents of the pack
Biodacyna is a colourless or slightly yellow aqueous solution.
The unit pack contains 1 ampoule.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01

Information intended exclusively for healthcare professionals

Dosage and administration
The physician should monitor renal function by measuring serum creatinine concentration or calculating endogenous creatinine clearance. Serum blood urea nitrogen (BUN) levels are less reliable in this context. Renal function should be reassessed periodically during treatment.

Serum amikacin concentrations should be measured whenever possible to ensure appropriate levels and to avoid exceeding maximum recommended values. It is recommended to periodically monitor both peak and trough serum concentrations during therapy, with the trough level measured immediately before the next dose. Peak serum concentrations (measured 30–90 minutes after injection) should not exceed 35 µg/ml, and trough concentrations (measured just before the next dose) should not exceed 10 µg/ml. Dosage should be adjusted accordingly. In patients with normal renal function, the drug may be administered once daily; in such cases, peak serum concentrations may exceed 35 µg/ml.

Treatment typically lasts 7 to 10 days. The total allowable 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 microbial resistance or the presence of infection foci requiring surgical drainage.

In severe and complicated infections where treatment duration exceeds 10 days, the continued use of amikacin sulfate by injection should be re-evaluated. If continuation of therapy is decided, renal function, hearing, vestibular function, and serum amikacin concentrations should be monitored.

The safety of amikacin use for longer than 14 days has not been established.

Preterm neonates
The recommended dose for preterm neonates is 7.5 mg/kg body weight every 12 hours.

Newborns
The recommended initial loading dose is 10 mg/kg body weight, followed by 7.5 mg/kg body weight every 12 hours.

Infants from 4 weeks of age and children up to 12 years
The recommended intramuscular or intravenous dose (slow infusion) in children with normal renal function is 15 to 20 mg/kg body weight/day, administered either once daily or as 7.5 mg/kg body weight every 12 hours.

In the treatment of endocarditis and in febrile neutropenic patients, the drug should be administered twice daily due to lack of sufficient data supporting once-daily efficacy.

Adults and children over 12 years of age
The recommended intramuscular or intravenous dose for adults and adolescents with normal renal function (creatinine clearance >50 ml/min) is 15 mg/kg body weight/day, which may be given as a single daily dose or divided into two equal doses of 7.5 mg/kg body weight administered every 12 hours. The total daily dose should not exceed 1.5 g.

In the treatment of endocarditis and in febrile neutropenic patients, the drug should be administered twice daily due to insufficient data confirming the efficacy of once-daily administration.

Elderly patients
Amikacin is eliminated via the kidneys. Renal function should be assessed whenever possible, and dosage adjusted as described in the section on dosage in patients with renal impairment.

Life-threatening infections and (or) infections caused by Pseudomonas
The dose in adults may be increased to 500 mg every eight 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, 15 g, should not be exceeded.

Urinary tract infections (other than those caused by Pseudomonas )
Administer 7.5 mg/kg body weight/day in two divided doses (equivalent to 250 mg twice daily in adults). Since amikacin activity increases with pH, alkalinizing agents may be administered concomitantly.

Renal impairment
In patients with impaired renal function (creatinine clearance <50 ml/min), administration of the recommended total daily dose as a single dose is not advised, as this may result in prolonged exposure to high trough concentrations. Refer to the information below on dosage adjustment in patients with renal impairment.

In patients with renal impairment receiving amikacin two or three times daily, serum amikacin concentrations should be monitored using appropriate assay methods whenever possible.

In patients with renal impairment, dosage may be adjusted either by administering the usual dose at longer intervals or by administering reduced doses at usual intervals. Both methods are based on creatinine clearance or serum creatinine concentration, as these correlate with aminoglycoside half-life in patients with reduced renal function.

When using these dosing regimens, patients should be closely monitored clinically and laboratory parameters should be checked. The regimen should be modified as necessary, taking into account any dialysis being performed.

Usual doses administered less frequently
If creatinine clearance is unknown and the patient's condition is stable, the interval (in hours) between usual single doses (i.e., doses equivalent to 7.5 mg/kg body weight twice daily in patients with normal renal function) can be calculated by multiplying the patient's serum creatinine concentration (in mg/100 ml) by nine. For example, if serum creatinine concentration is 2 mg/100 ml, the recommended single dose (7.5 mg/kg body weight) should be administered every 18 hours.

Interval between doses of amikacin 7.5 mg/kg body weight according to serum creatinine concentration:

| Serum creatinine [mg/100 ml] | 1.5 | 2 | 2.5 | 3 | 3.5 | 4 | 4.5 | 5 | 5.5 | 6 | |------------------------------|--------|------|--------|------|--------|------|--------|------|--------|------| | Dose interval [hours] (i.m. administration) | 13.5 | 18 | 22.5 | 27 | 31.5 | 36 | 40.5 | 45 | 49.5 | 54 |

Reduced doses administered at usual intervals
If renal function is impaired and amikacin sulfate by injection is indicated, the dose should be reduced when administered at usual intervals.

In these patients, serum amikacin concentrations should be measured to ensure precise dosing and to avoid excessive serum concentrations.

If serum amikacin monitoring is not possible and the patient's condition is stable, the most readily available parameters for assessing the degree of renal impairment and guiding dosage are serum creatinine concentration and creatinine clearance.

Treatment should be initiated with a standard loading dose of 7.5 mg/kg body weight, equivalent to the dose recommended for patients with normal renal 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 every 12 hours =
= (patient's observed creatinine clearance [ml/min] × calculated loading dose [mg]) / normal creatinine clearance [ml/min]

An alternative empirical method for determining reduced doses administered every 12 hours (for patients with known steady-state serum creatinine concentrations) is to divide the standard dose by the patient's serum creatinine concentration.

Due to the possibility of significant changes in renal function during treatment, serum creatinine concentration should be frequently monitored and the dosing regimen modified as necessary.

Recommendations for intravenous administration
In adults, the drug should be administered after appropriate dilution as a slow infusion lasting 30 to 60 minutes.

In children, the volume of diluent used depends on the amikacin dose 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 drugs but should be administered separately, according to the recommended dose and route.

Instructions for preparation of the medicinal product for use
No dilution is necessary prior to intramuscular administration.

Preparation of intravenous infusion solutions
Intravenous infusions are prepared by diluting the contents of the vial in one of the commonly used infusion fluids to achieve an antibiotic concentration of 2.5 to 5 mg/ml. For example, 500 mg of amikacin may be diluted in 100 or 200 ml of one of the following solutions:

• 0.9% sodium chloride solution,
• 5% glucose solution,
• 5% glucose with 0.9% sodium chloride solution (2:1),
• 5% glucose with 0.2% sodium chloride solution,
• Ringer's lactate solution.

In newborns, infants, and children, smaller infusion volumes adjusted to the patient's body weight should be used.

Prepared infusion solutions, which do not contain a preservative, may be stored at 2°C to 8°C for no longer than 24 hours.