Gentamicin bialmed

Patient Information Leaflet

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Gentamicin Bialmed (Gentamicină EIPICO), 40 mg/ml, solution for injection/infusion
Gentamicinum
Gentamicin Bialmed and Gentamicină EIPICO are different brand names for the same medicine.
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

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

1. What Gentamicin Bialmed is and what it is used for

Gentamicin Bialmed is an antibiotic belonging to the aminoglycoside group. It destroys bacteria that cause serious infections in the body.
When Gentamicin Bialmed is used
Gentamicin Bialmed is used to treat severe infections caused by aerobic Gram-negative bacteria sensitive to its action. These include:

• septicaemia and other severe systemic infections,
• intra-abdominal infections: peritonitis, abscesses, biliary tract infections (usually administered in combination with metronidazole or clindamycin),
• urinary tract infections,
• respiratory tract infections,
• secondary infections of burns and traumatic or postoperative wounds,
• severe infections in newborns.

2. Important information before using Gentamicin Bialmed

When not to use Gentamicin Bialmed

• if the patient is allergic to gentamicin, other aminoglycoside antibiotics, or any of the other ingredients of this medicine (listed in section 6),
• if the patient suffers from a disease called myasthenia gravis (muscle weakness).

Warnings and precautions
If the patient suffers from any chronic disease, has metabolic disorders, hypersensitivity
(allergy) to other medicines, or is taking other medicines, he/she should inform the doctor before starting
treatment with Gentamicin Bialmed.
The patient should also inform the doctor if:

• he/she has hearing or balance disorders, Parkinson's disease, or has previously suffered from any kidney disease,
• he/she has low blood calcium levels (hypocalcemia),
• hearing disturbances, dizziness, or ringing in the ears occur after starting treatment,
• severe diarrhoea occurs.

If the patient develops severe or prolonged diarrhoea associated with gentamicin treatment, he/she should
immediately consult a doctor, who will determine whether it is pseudomembranous colitis – a potentially life-threatening complication that may sometimes occur as a result of antibiotic use.
Appropriate treatment may be necessary. If diarrhoea occurs during gentamicin treatment, do not take any drugs that inhibit intestinal motility (peristalsis).
During treatment with Gentamicin Bialmed, symptoms of hearing disturbances may occur, especially in
children, elderly patients, patients with impaired kidney function, patients who previously experienced such disorders, patients treated with other ototoxic drugs, dehydrated patients, or patients treated with higher doses of gentamicin for a prolonged period.
The doctor will closely monitor the patient's condition during treatment to prevent hearing damage.
The doctor may perform tests to assess hearing, balance, kidney function, and blood gentamicin levels.
Gentamicin may cause kidney function disorders. This is more likely when high doses of gentamicin are used, in elderly patients, in women, in patients with impaired kidney function, in dehydrated patients, in patients with nephrotic syndrome, in patients with diabetic nephropathy, and in patients treated with other nephrotoxic drugs.
Gentamicin Bialmed with other medicines
Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to use.
The simultaneous use of Gentamicin Bialmed and other medicines increases the risk of adverse reactions. Inform your doctor if you are taking any of the following medicines:

• diuretics (especially ethacrynic acid and furosemide),
• succinylcholine, tubocurarine, botulinum toxin (muscle relaxants),
• certain antibiotics (amikacin, tobramycin, vancomycin, cephaloridine, viomycin, polymyxin B, netromycin, neomycin, clindamycin, piperacillin, and streptomycin),
• oral anticoagulants,
• amphotericin B (used for fungal infections),
• cyclosporine (an immunosuppressive medicine),
• methoxyflurane (used for general anaesthesia during surgery),
• foscarnet (used for viral infections),
• cisplatin (used in the treatment of certain tumours),
• bisphosphonates (used in the treatment of osteoporosis),
• neostigmine, pyridostigmine (used in the treatment of muscle weakness),
• indomethacin (used in inflammatory conditions),
• intravenous contrast agents.

Indomethacin may additionally increase gentamicin plasma levels in newborns.
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 a doctor or pharmacist before using this medicine.
Pregnancy
Aminoglycoside antibiotics cross the placental barrier and may damage the hearing and balance organs of the foetus. If a woman is pregnant, the doctor may prescribe Gentamicin Bialmed only in life-threatening situations, when no other safer antibiotic is available.
Breastfeeding
Gentamicin passes into human milk; therefore, breastfeeding is not recommended during treatment with Gentamicin Bialmed.
Driving and using machines
Gentamicin Bialmed may cause balance disturbances, nausea, and dizziness. These symptoms may also occur after completion of treatment. During treatment, do not drive or operate machinery. If such disturbances occur, consult a doctor.
Gentamicin Bialmed contains methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216).
This medicine may cause allergic reactions (delayed-type reactions possible) and exceptionally bronchospasm.
Gentamicin Bialmed contains sodium metabisulfite (E 223).
This medicine may rarely cause severe hypersensitivity reactions and bronchospasm.
Gentamicin Bialmed contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning the medicine is considered "sodium-free".

3. How to use Gentamicin Bialmed

Dosage
This medicine should always be used exactly as prescribed by the doctor. If in doubt, consult the doctor or pharmacist.
The doctor will determine the dose, frequency of administration, and duration of treatment depending on the disease, the patient's tolerance to the medicine, response to treatment, and any adverse effects.
Dosage in patients with normal kidney function
Children, adolescents, and adults: 3 to 6 mg/kg body weight per day, administered as a single dose (recommended) or divided into two doses given every 12 hours.
Infants from 2 months of age: 4.5 to 7.5 mg/kg body weight per day, administered as a single dose (recommended) or divided into two doses given every 12 hours.
Newborns: 4 to 7 mg/kg body weight per day. Due to the longer half-life of the drug in newborns, the daily dose should be administered as a single dose.
Dosage in patients with renal impairment
The initial dose is the same as in patients with normal kidney function. During continued treatment, the doctor may increase the intervals between doses or reduce the dose according to kidney function. Detailed recommendations are provided at the end of this leaflet, in the section intended for healthcare professionals.
Method of administration
Gentamicin Bialmed is administered intramuscularly or intravenously. The dose is the same in both cases. Detailed recommendations are provided at the end of this leaflet, in the section intended for healthcare professionals.
Overdose of Gentamicin Bialmed
Excessively high doses or rapid administration of this medicine may lead to breathing difficulties, nausea, dizziness, vomiting, tinnitus, ringing in the ears, sensation of pressure in the ears, and leg muscle spasms.
If such symptoms occur or if an overdose is suspected, inform the doctor immediately.
Missed dose of Gentamicin Bialmed
The frequency of injections is determined by the doctor. If an injection has not been administered for any reason, inform the doctor.
Discontinuation of Gentamicin Bialmed treatment
Premature discontinuation of treatment may result in worsening of disease symptoms.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.
If any of the following adverse effects occur, inform your doctor immediately.
Effects occurring not very common (in 1 to 10 out of 100 patients):

• Ringing, buzzing, or a feeling of pressure in the ears (ear blockage), nausea, vomiting, and dizziness

These may be the first signs of hearing and balance organ damage. Hearing and balance disturbances, although rare, are usually irreversible and may worsen even after treatment has ended. The occurrence of these adverse effects is more likely in patients who previously had hearing or balance disorders, patients with impaired liver function, those treated with other medicines causing hearing damage, patients not receiving sufficient fluids, and those receiving high doses of Gentamicin Bialmed for a prolonged period. (See section 2 "Important information before using Gentamicin Bialmed")

• Increased thirst and more frequent or less frequent urination than usual

These may be symptoms of kidney dysfunction, which occurs more frequently in elderly patients, women, patients who previously had kidney function disorders and those receiving insufficient fluids, as well as patients treated with other nephrotoxic medicines.

Effects occurring rarely (in 1 to 10 out of 1,000 patients):

• Hypersensitivity reactions (rash)

Effects occurring very rarely (in 1 to 10 out of 10,000 patients):

• Breathing difficulties, low blood pressure, motor restlessness, weak rapid heartbeat, sweaty skin (anaphylactic reaction)
• Severe and prolonged diarrhoea, which may be a symptom of a specific type of colitis (pseudomembranous colitis)
• Acute kidney failure
• High levels of phosphates and amino acids in urine (a sign of acquired Fanconi syndrome associated with long-term administration of high doses of the drug)

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

• Transient and/or irreversible hearing loss, hearing impairment (See section 2 "Important information before using Gentamicin Bialmed")
• Fatigue
• Confusion
• Depression
• Unusual visions or sounds (hallucinations)
• Nerve damage (including convulsions, lack of energy, brain dysfunction caused by toxic substances or infection (encephalopathy))
• Nerve damage in hands and feet causing pain or numbness, burning, and tingling (peripheral neuropathy)
• Inflammation of the mucous membrane of the mouth

Allergic reactions (including severe allergic reactions such as anaphylaxis), which may include:

• Itchy, bumpy rash or hives
• Swelling of hands, feet, ankles, face, lips, or throat, which may cause difficulty swallowing or breathing
• Fainting, dizziness, feeling faint (low blood pressure)
• Infection with microorganisms resistant to gentamicin
• Diarrhoea with or without blood and (or) stomach cramps

Severe skin and mucous membrane allergic reaction, accompanied by blisters and skin redness, which in very severe cases may affect internal organs and may be life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome)).

Other adverse effects
Effects occurring not very common (in 1 to 10 out of 100 patients):

• Dizziness, nystagmus
• Nausea, vomiting, diarrhoea
• Increased serum creatinine and urea levels, protein in urine

Effects occurring rarely (in 1 to 10 out of 1,000 patients):

• Decreased levels of calcium, potassium, and magnesium in blood
• Muscle weakness (neuromuscular blockade)

Effects occurring very rarely (in 1 to 10 out of 10,000 patients):

• Decreased white blood cell and platelet counts (leukopenia, thrombocytopenia), increased eosinophil count (a type of white blood cell), anaemia, decreased haemoglobin concentration
• Headache, fatigue, sensory disturbances (e.g. tingling sensation)
• Vision disturbances
• Increased bilirubin levels and increased liver enzyme (aminotransferase) activity
• Elevated body temperature, palpitations

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist.
Adverse effects can be reported directly to the Department of Monitoring 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
Reporting adverse effects helps to collect more information on the safety of the medicine.

5. How to store Gentamicin Bialmed

Keep this medicine out of sight and reach of children.
Store below 30°C in the original packaging. Do not store in the refrigerator or freeze.
Do not use this medicine after the expiry date stated on the carton and ampoule following EXP.
The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Gentamicin Bialmed contains

• The active substance is gentamicin. Each 2 ml ampoule of injection/infusion solution contains 80 mg gentamicin as gentamicin sulfate.
• Other ingredients are: methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), disodium edetate, sodium metabisulphite (E 223), water for injections. See section 2 "Gentamicin Bialmed contains methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216).", "Gentamicin Bialmed contains sodium metabisulphite (E 223).", "Gentamicin Bialmed contains sodium."

What Gentamicin Bialmed looks like and contents of the pack
Gentamicin Bialmed is a clear, colourless or slightly yellowish solution, free from visible mechanical particles.
Pack contains 10 ampoules with 2 ml of injection/infusion solution (80 mg/2 ml).
For more detailed information, please contact the marketing authorisation holder or the parallel importer.

Marketing Authorisation Holder in Romania, country of export:
E.I.P.I.CO MED S.R.L.
B-dul Unirii nr.6, Bl. 8C sc.1, ap 9, Sector 4
Bucharest, Romania

Manufacturer:
FELSIN Farm. S.R.L.
Str. Drumul Piscul Cerbului, nr.20-28, etaj P
camerele 1-9 şi etaj, sector 1
Bucharest, Romania

Parallel Importer:
Bialmed Sp. z o.o.
ul. Kazimierzowska 46/48/35
02-546 Warsaw, Poland

Repackaged in:
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warsaw, Poland
LABOR Przedsiębiorstwo Farmaceutyczno-Chemiczne Sp. z o.o.
ul. Długosza 49
51-162 Wrocław, Poland

Marketing Authorisation Number in Romania, country of export: 8064/2015/01
Parallel Import Licence Number: 294/24
[parallel importer logo]

Information intended exclusively for healthcare professionals:

Dosage in patients with renal impairment
The initial dose is the same as in patients with normal renal function. During continued treatment, the intervals between doses should be prolonged or the dose reduced.
The table below shows gentamicin dosing in patients with renal impairment.

| Blood urea concentration | Serum creatinine concentration | Creatinine clearance | Doses and intervals between doses | |--------------------------|-------------------------------|------------------------|-----------------------------------| | mg/100 ml | μmol/l | ml/min | ml/s | mg/100 ml | μmol/l | | <40 | <6-7 | >70 | >1.16 | <1.4 | <124 | 80 mg* every 8 hours | | | | | | 1.4–1.9 | 124–168 | 80 mg* every 12 hours | | 40–100 | 6–17 | 30–70 | 0.5–1.16 | 1.9–2.8 | 168–248 | 80 mg* every 18 hours | | | | | | 2.8–3.7 | 248–327 | 80 mg* every 24 hours | | 100–200 | 17–34 | 10–30 | 0.16–0.5 | 3.7–5.3 | 327–469 | 80 mg* every 36 hours | | | | | | 5.3–7.2 | 469–636 | 80 mg* every 48 hours | | >200 | >34 | 5–10 | 0.08–0.16 | | | |

* Patients weighing less than 60 kg should receive 60 mg of gentamicin.

Reducing the dose or increasing the intervals between doses is equally appropriate. However, it should be noted that the doses indicated are only approximate, and despite administering the same doses, serum concentrations of the active substance may vary among different patients. Therefore, in critically ill patients, serum gentamicin concentrations should be monitored and doses adjusted accordingly. Serum gentamicin concentration measured 30 to 60 minutes after intravenous or intramuscular administration should be at least 5 μg/ml.

After hemodialysis, gentamicin should be administered at a dose of 1 to 1.5 mg/kg body weight.

Patients undergoing peritoneal dialysis should receive 1 mg gentamicin/kg body weight in 2 liters of dialysis fluid.

Administration method
Intravenous and intramuscular administration.

Gentamicin is administered either intramuscularly or intravenously. In both cases, the drug dose is identical.

Due to the prolonged post-antibiotic effect of gentamicin, the efficacy of each subsequent dose administered during the post-antibiotic effect period is reduced, because bacteria are less susceptible to gentamicin at this time. Therefore, once-daily administration of the drug is doubly beneficial from the standpoint of antibacterial efficacy:

• due to the high initial serum concentration of gentamicin, its bactericidal effect is stronger,
• due to the longer interval between doses, the antibacterial effect of the next dose is enhanced.

Once-daily gentamicin administration is not recommended in patients with impaired immunity (neutropenia), severe renal impairment, cystic fibrosis, ascites, infective endocarditis, extensive burns (affecting more than 20% of body surface area), and in pregnant women.

In neonates, infants, and children, serum gentamicin concentrations after administration of the same doses (adjusted per body weight) as in adults are lower than in adults. Therefore, therapeutic doses in these patients are slightly higher. For safety reasons, daily monitoring of serum gentamicin concentration is recommended in children. Serum concentration measured one hour after administration should be at least 4 μg/ml.

If the daily dose of gentamicin is divided into multiple doses, the serum concentration prior to the next dose should not exceed 2 μg/ml. If the daily dose is administered as a single dose, the serum concentration prior to the next dose should not exceed 1 μg/ml.

Intravenous administration
Gentamicin may be administered directly into a vein or via a venous catheter. The injection time should be 2 to 3 minutes. When administering a single daily dose, the infusion should last 30 to 60 minutes.

Prior to short intravenous infusion, gentamicin should be diluted in 100 to 200 ml of 0.9% sodium chloride injection solution or 5% glucose injection solution. The concentration of gentamicin in the solution should not exceed 1 mg/ml.

Incompatibilities
β-lactam antibiotics may inactivate gentamicin in vitro; therefore, they should not be mixed in the same infusion bottle with gentamicin.

Gentamicin should also not be mixed with erythromycin, heparin, or sodium bicarbonate.