Amikacin Noridem

Package leaflet: Information for the patient

Amikacina Noridem 125 mg/ml injection/infusion solution, 250 mg/ml injection/infusion solution

amikacin
Generic medicine
Please read all of this leaflet carefully before you start taking this medicine, because it contains
important information for you.

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

Contents of this leaflet

1. What Amikacina Noridem is and what it is used for
2. What you need to know before taking Amikacina Noridem
3. How to take Amikacina Noridem
4. Possible side effects
5. How to store Amikacina Noridem
6. Contents of the pack and other information

1. What Amikacina Noridem is and what it is used for

Amikacina Noridem belongs to a group of antibiotics called "aminoglycosides".
This medicine is used for the short-term treatment of serious infections caused by strains of
susceptible bacteria.
Amikacina Noridem may be given to you to treat the following infections:

• Lung and lower respiratory tract infections, including pneumonia
• Bone and joint infections
• Central nervous system infections (including meningitis)
• Skin and soft tissue infections, including burn wounds
• Intra-abdominal infections, including inflammation of the peritoneum (the membrane lining the abdominal cavity and its organs)
• Infections following abdominal surgery
• Kidney, urinary tract, and bladder infections
• Bacterial inflammation of the inner lining of the heart (endocarditis)

This medicine may also be used to treat patients with systemic inflammatory response occurring in association with any of the listed infections, or when such an association is suspected.

2. What you should know before taking Amikacina Noridem

Do not take Amikacina Noridem:

• if you are allergic to amikacin or any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to other similar substances (other aminoglycosides)
• if you are being treated with ataluren (a medicine used for Duchenne muscular dystrophy, a rare genetic neuromuscular disease)

Warnings and precautions
Talk to your doctor before taking this medicine if:

• you have kidney problems
• you have previously had kidney or hearing problems after taking other antibiotics
• you have hearing disorders or dizziness (tinnitus)
• you suffer from muscle disorders such as severe myasthenia gravis (a disease causing muscle weakness) or parkinsonism
• you are elderly
• in case of advanced-stage hepatic cirrhosis (a severe chronic liver disease)
• if you or your family members have a mitochondrial mutation disease (a genetic condition) or hearing loss caused by taking antibiotics; in this case, we recommend informing your doctor or pharmacist before taking an aminoglycoside, as certain mitochondrial mutations may increase the risk of hearing loss when taking this product. Your doctor may recommend genetic testing before administering Amikacina Noridem.

If any of the above conditions apply to you, please discuss them with your doctor before taking this
medicine.
Other medicines and Amikacina Noridem
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
Some medicines may interact with others. Inform your doctor if you are taking:

• diuretics such as furosemide or ethacrynic acid
• other medicines that may have harmful effects on the kidneys or hearing, such as bacitracin, cisplatin, amphotericin B, cyclosporine, tacrolimus, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides
• penicillin-like medicines
• bisphosphonates (used to treat osteoporosis and other similar diseases)
• vitamin B1
• platinum-derived medicines
• muscle relaxants
• indomethacin, an anti-inflammatory drug that may increase the amount of amikacin absorbed in newborns
• ataluren (used for Duchenne muscular dystrophy, a rare genetic neuromuscular disease)

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Your doctor will prescribe this medicine only if the expected benefits outweigh the potential risks to the
baby.
Ask your doctor for advice before taking any medicine.
Driving and using machines
Do not drive or operate machinery if you experience adverse effects (such as dizziness) that could impair your reaction ability.
Amikacina Noridem contains sodium metabisulfite and sodium
This medicine contains sodium metabisulfite, which may rarely cause severe hypersensitivity reactions (serious allergies) and bronchospasm (difficulty breathing).
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. it is essentially “sodium-free”.

3. How to take Amikacina Noridem

This medicine is usually administered by injection into the muscle. It may also be given intravenously (into a vein) either as an injection or (after dilution) as an infusion (intravenous drip).
Dosage
Your doctor will determine the appropriate dose of amikacin for you and how often you should receive it.
The dose depends on your body weight, age, the type of infection, kidney function, any hearing problems, and other medicines you may be taking.
The medicine is usually given once or twice daily for up to 10 days.
During treatment, you may need to have blood tests to monitor kidney function and blood levels of amikacin, and you may be asked to provide urine samples.
You may also be required to have a hearing test before and during treatment to check for any possible side effects. Your doctor may adjust your dose based on these results.
Use in children
Amikacina Noridem, like all aminoglycosides, must be used with caution in newborns and premature infants.
If you take more Amikacina Noridem than you should
If you think you have been given too much of this medicine, inform your doctor or nurse immediately.
Overdose may cause kidney damage, damage to the nerves of the ear, or muscle function blockage (paralysis). In such cases, amikacin infusion must be stopped immediately.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following side effects, contact your doctor immediately:
Very rare (may affect up to 1 in 10,000 people)

• respiratory paralysis

Not known (frequency cannot be estimated from the available data)

• swelling of the face, lips, or tongue, skin rash, difficulty breathing, as these may be signs of an allergic reaction
• ringing in the ears or hearing loss (deafness)
• kidney problems, including reduced urine output (acute kidney failure)
• paralysis

Other side effects include:
Uncommon (may affect up to 1 in 100 people):

• infections or growth of resistant bacteria
• nausea, vomiting
• dizziness, vertigo
• involuntary eye movement (nystagmus)
• damage to renal tubular cells, kidney dysfunction

Rare (may affect up to 1 in 1,000 people):

• abnormal blood cell and platelet counts, such as anaemia, eosinophilia, leucopenia, granulocytopenia, thrombocytopenia
• hypomagnesaemia (low levels of magnesium in the blood)
• tremors, hallucinations, headache, loss of balance
• blindness, retinal infarction
• tinnitus, hearing loss
• hypotension (low blood pressure)
• itching, urticaria, rash, exanthema
• arthralgia (joint pain), muscle contractions
• decreased urine output, elevated serum creatinine, albuminuria, azotemia, red blood cells in urine, white blood cells in urine
• pyrexia (fever)
• migraine
• respiratory depression
• increased aspartate aminotransferase, increased alanine aminotransferase, increased alkaline phosphatase (mild and transient)

Very rare (may affect up to 1 in 10,000 people):

• neuromuscular blockade
• respiratory paralysis (isolated cases) – severe or complete weakness of respiratory muscles

Not known (frequency cannot be estimated from the available data):

• anaphylactic reaction, anaphylactic shock and anaphylactoid reaction, hypersensitivity
• paralysis
• deafness, sensorineural deafness
• apnoea (a disorder causing breathing interruptions during sleep), bronchospasm
• acute kidney failure, toxic nephropathy (kidney damage caused by medicines or toxic chemicals), urinary epithelium abnormalities

Injecting Amikacin Noridem directly into the eye may cause serious vision problems.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Amikacin Noridem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "EXP". The expiry date refers to the last day of that month.
Store the medicine at a temperature not exceeding 25°C.
Do not use this medicine if you notice the presence of particles in the vial or if the solution is not colourless to pale yellow in appearance.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package Contents and Other Information

What Amikacina Noridem Contains

• The active substance is amikacin sulfate. Each ml of injectable/infusion solution contains 125 mg of amikacin (as sulfate). Each ml of injectable/infusion solution contains 250 mg of amikacin (as sulfate). Each 2 ml vial contains 250 mg of amikacin. Each 2 ml vial contains 500 mg of amikacin.
• The other components are disodium citrate dihydrate, sodium metabisulfite, sulfuric acid (for pH adjustment), water for injections.

Description of the Appearance of Amikacina Noridem and Package Contents
Amikacina is a clear, colourless to pale yellow solution, free from visible particles, contained in glass vials.
Pack sizes: 1 and 10 vials
Not all pack sizes may be marketed.
Marketing Authorisation Holder:
Noridem Enterprises Limited
Evagorou & Makariou, Mitsi Building 3, Office 115,
1065 Nicosia, Cyprus
Manufacturer:
DEMO S.A. PHARMACEUTICAL INDUSTRY,
21st Km National Road Athens – Lamia
14568 Krioneri, Attiki, Greece,
Τ: +30 210 8161802, F: +30 210 8161587.
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Ireland Amikacin 125 mg/ml Solution for injection/infusion
Amikacin 250 mg/ml Solution for injection/infusion
Greece BRUSE
BRUSE
Romania Amikacină Noridem 125 mg/ml injectable/perfusion solution
Amikacină Noridem 250 mg/ml injectable/perfusion solution
Czech Republic Amikacin Noridem
Amikacin Noridem
Spain Amikacina Noridem 125 mg/ml Solución inyectable y para perfusión EFG
Amikacina Noridem 250 mg/ml Solución inyectable y para perfusión EFG
Italy Amikacina Noridem
Amikacina Noridem
Poland Amikacinum Noridem
Amikacinum Noridem
Slovakia Amikacin Noridem 125 mg/ml Injekčný/infúzny roztok
Amikacin Noridem 250 mg/ml Injekčný/infúzny roztok
France AMIKACINE NORIDEM 125 mg/mL, solution injectable/pour perfusion
AMIKACINE NORIDEM 250 mg/mL, solution injectable/pour perfusion
Hungary Amikacin Noridem 125 mg/ml Oldatos injekció/infúzió
Amikacin Noridem 250 mg/ml Oldatos injekció/infúzió
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The following information is intended exclusively for medical or healthcare professionals:
Dosage and Method of Administration
Amikacin is generally used in combination with other appropriate antibiotics. The dose of amikacin depends on the infection, the patient's condition, and renal function. Local guidelines should be consulted.
Dosage
To calculate the correct dosage, the patient's body weight must be known before treatment.
Renal function should be assessed based on measurement of serum creatinine concentration or calculation of endogenous creatinine clearance. Renal function should be periodically re-evaluated during therapy. Blood urea nitrogen measurement is much less reliable for this purpose.
Serum concentrations of amikacin should be measured whenever possible to ensure adequate but not excessive levels. During treatment, it is advisable to intermittently measure both peak and trough concentrations. Peak concentrations (30–90 minutes after injection) should not exceed 35 mcg/ml, and trough concentrations (just before the next dose) should not exceed 10 mcg/ml. Dosage should be adjusted accordingly. In patients with normal renal function, a single daily dose may be used. In such cases, peak concentrations may exceed 35 mcg/ml (see Single Daily Dosing and Renal Impairment below).
Adults and children over 12 years:
The recommended dose by intramuscular or intravenous infusion in adults and adolescents with normal renal function (creatinine clearance ≥50 ml/min) is 15 mg/kg/day, which may be administered as a single daily dose or divided into two equal doses of 7.5 mg/kg every 12 hours. The total daily dose must not exceed 1.5 g. In the treatment of endocarditis and in febrile neutropenic patients, the dose should be divided into two daily administrations, as there are insufficient data to support once-daily dosing.
Children aged 4 to 12 years:
The recommended dose by intramuscular or intravenous infusion (slow intravenous infusion) in children with normal renal function is 15–20 mg/kg/day, which may be administered as a single dose of 15–20 mg/kg once daily or in doses of 7.5 mg/kg every 12 hours. In the treatment of endocarditis and in febrile neutropenic patients, the dose should be divided into two daily administrations, as there are insufficient data to support once-daily dosing.
Neonates:
An initial loading dose of 10 mg/kg followed by doses of 7.5 mg/kg every 12 hours (see sections 4.4 and 5.2).
Premature neonates:
The recommended dose in premature neonates is 7.5 mg/kg every 12 hours (see sections 4.4 and 5.2).
Data on single daily dosing in patients with other systemic infections are limited (see also above regarding monitoring of peak and trough amikacin concentrations).
Treatment duration is 7 to 10 days. In most cases, aminoglycosides are indicated only at the beginning of treatment when the inoculum is potentially high, when there is uncertainty about treatment efficacy, and for treatment durations ≤ 5 days due to the benefit/risk ratio (bactericidal activity/treatment duration-related toxicity). For all routes of administration, the total daily dose must not exceed 20 mg/kg/day. In cases of difficult and complicated infections for which treatment beyond 10 days is considered, the use of amikacin should be re-evaluated, and if continued, renal, auditory, and vestibular function, as well as serum amikacin levels, must be monitored.
With the recommended dosage regimen, uncomplicated infections caused by amikacin-sensitive organisms should respond within 24–48 hours. If no definite clinical response is observed after 3–5 days, treatment should be discontinued and the pathogen's antibiotic sensitivity rechecked. Lack of response may be due to microbial resistance or the presence of septic foci requiring surgical drainage.
Impaired Renal Function
In patients with impaired renal function (creatinine clearance <50 ml/min), administration of the recommended daily dose of amikacin as a single dose is not recommended, as these patients will have prolonged exposure to high trough concentrations. For dosage adjustment in patients with impaired renal function, see below.
In patients with impaired renal function receiving the usual two or three daily doses, serum amikacin concentrations should be monitored whenever possible using appropriate analytical procedures. In patients with impaired renal function, the dosage regimen should be adjusted by administering normal doses at extended intervals or reduced doses at fixed intervals.
Both methods are based on the patient's creatinine clearance or serum creatinine values, as these have been observed to correlate with aminoglycoside half-lives in patients with reduced renal function. These dosage regimens should be used in conjunction with careful clinical and laboratory monitoring of the patient and modified as necessary, e.g., if the patient undergoes dialysis.
Normal Dose at Extended Intervals
If creatinine clearance is not available and the patient's condition is stable, the dosing interval in hours for the normal single dose (i.e., the dose that would be administered to patients with normal renal function on a twice-daily regimen, 7.5 mg/kg) is calculated as nine times the patient's serum creatinine level. For example, if the creatinine concentration is 2 mg/100 ml, the recommended single dose (7.5 mg/kg) should be administered every 18 hours.
Reduced Dose at Fixed Dosing Intervals
When amikacin must be administered at fixed intervals in patients with impaired renal function, the dose should be reduced. In such patients, serum amikacin concentrations should be measured to ensure accurate administration and avoid excessive serum concentrations. If serum level determinations are not available and the patient's condition is stable, serum creatinine or creatinine clearance values are the most readily available indicators of the degree of renal impairment to guide dosing.
Begin treatment by administering the normal dose, 7.5 mg/kg, as a loading dose. As indicated above, this is the same dose generally administered to a patient with normal renal function.
To determine maintenance doses to be administered every 12 hours, the loading dose should be reduced proportionally to the reduction in the patient's creatinine clearance rate:
Maintenance dose every 12 hours =
Observed CrCl in ml/min × calculated loading dose in mg
Normal CrCl in ml/min
(CrCl = creatinine clearance rate)
An alternative method to determine reduced dosing at 12-hour intervals (for patients with known steady-state serum creatinine values) is to divide the normally recommended dose by the patient's serum creatinine level.
The dosage regimens above are not intended as rigid recommendations but are provided as guidance for dosing when measurement of serum amikacin levels is not feasible.
Obese Patients
Amikacin distribution into adipose tissue is poor. The appropriate dose may be calculated from the patient's estimated ideal body weight, to which 40% of the excess weight is added to obtain the weight used to determine mg/kg.
Dose should be adjusted based on plasma concentration monitoring. The maximum dose of 1.5 g per day must not be exceeded. Treatment duration should be limited to 7–10 days.
Patients with Ascites
Due to the relatively larger distribution in the extracellular fluid compartment, higher doses are required to achieve adequate serum concentrations.
Method of Administration
Amikacina Noridem may be administered intramuscularly or intravenously. Local guidelines should be consulted.
Intravenous Administration
In adults, it may be administered by standard infusion (2–3 minutes) or slow infusion over 30–60 minutes.
A 30-minute slow infusion with measurement of serum amikacin concentrations 30 minutes after the end of the infusion may be considered appropriate, taking into account pharmacokinetic/pharmacodynamic targets and monitored drug concentrations at appropriate timepoints, using a standardized approach.
Special recommendations apply for intravenous administration in the paediatric population.
In paediatric patients, the amount of diluent used will depend on the amount of amikacin tolerated by the patient. The solution should normally be infused over 30–60 minutes. Young children should receive an infusion over 1–2 hours.
Amikacin must not be mixed with other medicinal products but may be administered separately according to the recommended dose and route.
For instructions on dilution of the medicinal product before administration, see the "Instructions for Handling" section below.
Incompatibilities
This medicinal product must not be mixed with other medicinal products (except those mentioned in the "Instructions for Handling" section below).
Mixing aminoglycosides with beta-lactam antibiotics (penicillins or cephalosporins) in an infusion solution may lead to significant mutual inactivation. A reduction in serum activity may also be observed even when an aminoglycoside or a penicillin-type antibiotic is administered in vivo via separate routes. Aminoglycoside inactivation is clinically relevant only in patients with severely impaired renal function. Inactivation may persist in body fluid samples taken for analysis, leading to erroneous aminoglycoside measurements. Samples must be properly treated (direct analysis, freezing, or addition of beta-lactamase).
Chemical incompatibilities are known with amphotericin, chlorothiazides, erythromycin, heparin, nitrofurantoin, novobiocin, phenytoin, sulfadiazine, thiopentone, chlortetracycline, vitamin B, and vitamin C. Amikacin must not be pre-mixed with these medicinal products.
Overdose
Overdose may cause nephrotoxic, ototoxic, or neurotoxic reactions (neuromuscular blockade). Neuromuscular blockade with respiratory arrest requires appropriate treatment, including administration of ionic calcium (e.g., as gluconate or lactobionate in a 10–20% solution). In cases of overdose or toxic reactions, peritoneal dialysis or haemodialysis may be performed to accelerate amikacin removal from the blood.
Continuous arteriovenous haemofiltration may also help reduce amikacin levels.
In neonates, exchange transfusion may be considered.
Instructions for Handling
Intravenous Administration: Preparation of the Solution
The solution for intravenous use should be prepared by adding the desired dose to 100 ml or 200 ml of sterile solvent, e.g., 0.9% sodium chloride solution, 5% dextrose in water, or any other compatible solution.
Amikacin 125 mg/ml and amikacin 250 mg/ml should be aseptically diluted with:

• 5% dextrose injection
• 5% dextrose and 0.2% sodium chloride injection
• 5% dextrose and 0.45% sodium chloride injection
• 0.9% sodium chloride injection
• Lactated Ringer's injection
• Lactated Ringer's injection with 5% dextrose

In paediatric patients, the volume of liquid used will depend on the amount tolerated by the patient. It should be sufficient for amikacin infusion over 30–60 minutes.
After Dilution:
Diluted solutions with final concentrations below 2.5 mg/ml must be used immediately.
Chemical and physical in-use stability has been demonstrated for 24 hours at 23–27 °C under artificial light and at 2–8 °C with 0.9% sodium chloride injections and lactated Ringer's injections, at amikacin concentrations of 2.5 mg/ml, 5.0 mg/ml, 7.5 mg/ml, and 15.0 mg/ml.
Chemical and physical in-use stability has been demonstrated for 3 hours at 23–27 °C under artificial light and for 12 hours at 2–8 °C with 5% dextrose injections, 5% dextrose and 0.2% sodium chloride injections, 5% dextrose and 0.45% sodium chloride injections, and lactated Ringer's with 5% dextrose injections, at amikacin concentrations of 2.5 mg/ml, 5.0 mg/ml, and 7.5 mg/ml.
Chemical and physical in-use stability has been demonstrated for 6 hours at 23–27 °C under artificial light and for 24 hours at 2–8 °C with 5% dextrose injections, 5% dextrose and 0.2% sodium chloride injections, 5% dextrose and 0.45% sodium chloride injections, and lactated Ringer's with 5% dextrose injections, at amikacin concentrations of 15.0 mg/ml.
From a microbiological standpoint, unless the method of opening excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the times and conditions of storage during use are the responsibility of the user.
The medicinal product should be visually inspected for the presence of particles or discoloration before administration.
Use only clear solutions free from particles.
For single use only.
Unused solution must be discarded.
Unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with current local regulations immediately after use.