AMICACIN B BRAUN 10 mg/ml SOLUTION FOR INTRAVENOUS INFUSION

2. What you need to know before you use Amikacin B. Braun 10 mg/ml

Do not use Amikacin B. Braun 10 mg/ml:

If you are allergic (hypersensitive) to amikacin or other aminoglycoside antibiotics or to any of the other components of this medicine (listed in section 6). It should not be administered with other medicines that are toxic to the ear or kidney, or with potent diuretics (medicines used to increase urine elimination).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Amikacin B. Braun 10 mg/ml.

Inform your doctor of any allergy or medical problem you have or have had, especially:

• if you are allergic to amikacin or other aminoglycoside antibiotics,
• if your kidneys do not work well, as it may increase the risk of toxicity,
• if you have muscle disorders, such as myasthenia gravis or Parkinson's disease, as it may worsen muscle weakness,
• if you are taking diuretics that can be toxic to the ear,
• if symptoms of ear toxicity such as dizziness, vertigo, tinnitus (ringing in the ears), buzzing in the ears, and hearing loss or kidney toxicity symptoms appear,
• if you or your family members have a mitochondrial mutation disease (a genetic disease) or hearing loss due to antibiotics, you are advised to inform your doctor or pharmacist before taking an aminoglycoside; certain mitochondrial mutations can increase your risk of hearing loss with this medicine. Your doctor may recommend genetic tests before administration of Amikacin B. Braun 5 mg/ml solution for infusion,
• Amikacin can produce alterations in the analysis values of some substances such as urea nitrogen, transaminases, alkaline phosphatase, bilirubin, creatinine, lactate dehydrogenase, sodium, potassium, magnesium, and calcium.

Use in children

This medicine will be administered with caution, and only if there is no other alternative, in premature and newborn infants because these patients have incomplete kidney development.

Use in elderly patients

This medicine should be administered with caution in these patients, as they are likely to have decreased kidney function and, therefore, a higher risk of generalized toxicity (systemic).

Use of Amikacin B. Braun 10 mg/ml with other medicines

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine.

The administration of this medicine with the following medicines may require modifying the dose of one of them or interrupting treatment.

• Other antibiotics of the same type as amikacin, aminoglycosides (gentamicin, tobramycin…), or capreomycin.
• Amphotericin (a medicine to treat fungal infections), vancomycin (an antibiotic), agents that decrease immunity, cytotoxic agents (toxic to cells such as cyclosporine or cisplatin), cephalosporins (cefalotin), or potent diuretics (to increase urine elimination).
• Anesthetics of the type halogenated hydrocarbons administered by inhalation, massive blood transfusions citrated, and neuromuscular blockers.
• Antihistamines (medicines for allergies).
• Buclizine, cyclizine, meclozine, or trimethobenzamide (medicines to control nausea and vomiting).
• Loxapine (for schizophrenia).
• Phenothiazines, thioxanthenes (drugs used in psychiatry).
• Anti-myasthenic (medicines to treat myasthenia gravis - muscle weakness)
• Indomethacin (a type of anti-inflammatory medicine).
• Malathion (a pesticide).
• Antibiotics of the type polypeptides (colistin, polymyxin).
• Opioid analgesics (opium derivatives used for pain treatment).
• Antibiotics of the type beta-lactam (penicillin).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Treatment during pregnancy is not recommended, although your doctor will assess the convenience of its use. If the medicine is used during pregnancy, or if the patient becomes pregnant during treatment, she should be informed of the possible risks.

During breastfeeding, your doctor will assess the possible benefit versus the risk of amikacin administration to the infant and will inform you whether you should interrupt breastfeeding during treatment.

Driving and using machines

There is no evidence of effects on the ability to drive vehicles or use machines. However, this ability may be altered if adverse reactions such as dizziness, vertigo, etc. appear.

Amikacin B. Braun 10 mg/ml contains sodium

This medicine contains 354 mg of sodium (main component of cooking/table salt) in each 100 ml bottle. This is equivalent to 17.7% of the maximum daily sodium intake recommended for an adult.

3. How to use Amikacin B. Braun 10 mg/ml

Follow exactly the administration instructions of this medicine as indicated by your doctor. In case of doubt, consult your doctor again.

Your doctor will decide the duration of your treatment.

Your doctor will determine the most suitable dose for you, and this will depend on your age, weight, general condition, severity of the infection, and kidney function. Kidney function should be monitored during treatment.

As a general rule, the usual dose in adults with normal kidney function is 15 mg/kg/day, administered as a single daily dose or divided into two or three equal doses administered at equivalent intervals, i.e., 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours.

It is administered by slow intravenous infusion.

If you use more Amikacin B. Braun 10 mg/ml than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

In case of a toxic reaction due to administration of more doses than prescribed or accumulation, the application of peritoneal dialysis or hemodialysis may favor the elimination of the antibiotic. This should be considered especially in patients with severe kidney failure.

If a hypersensitivity reaction occurs, its administration will be discontinued, and the patient will receive specific treatment according to the nature and intensity of the reaction (antihistamines, corticosteroids, adrenaline...).

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequency of side effects is classified into the following categories:

Very common (may affect more than 1 in 10 people)

• Nephrotoxicity: increased urea nitrogen and non-protein nitrogen and creatinine in blood, albuminuria (loss of albumin protein in urine), presence of red and white blood cells in urine…
• Neurotoxicity-ototoxicity: toxicity of the VIII cranial nerve: hearing loss, vertigo, cochlear damage (part of the inner ear) including high-frequency hearing loss.

Dizziness, ataxia (disorder affecting voluntary movements), vertigo, tinnitus, buzzing in the ears, and hearing loss may occur.

• Neurotoxicity-neuromuscular blockade: acute muscle paralysis and apnea (suspension of breathing), numbness, tingling, muscle spasms, and convulsions.

Uncommon (may affect up to 1 in 100 people):

• Headache, tremors.
• Skin rash, redness, and increased temperature at the injection site
• Nausea, vomiting.
• Paresthesia (sensation of numbness, tingling, or burning in the skin), arthralgia (joint pain).
• Pain at the injection site.

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

• Eosinophilia (abnormally high amount of eosinophils - a type of white blood cell - in the blood), anemia (low red blood cell concentration).
• Hypotension (low blood pressure); hypomagnesemia (low magnesium level).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Amikacin B. Braun 10 mg/ml

Keep this medicine out of the sight and reach of children.

No special storage conditions are required. Store in the original packaging.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month indicated.

The contents should be used immediately after opening. Once the pack is opened, discard the unused portion of the solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition ofAmikacin B. Braun 10 mg/ml

• The active ingredient is amikacin (as sulfate). Each 5 ml of solution contains 50 mg of amikacin (as sulfate). Each ml of solution contains 10 mg of amikacin (as sulfate). Each 100 ml bottle contains 1000 mg of amikacin (as sulfate).
• The other components (excipients) are sodium chloride, sodium hydroxide (pH adjustment), and water for injectable preparations.

Appearance of the Product and Container Content

It is presented in containers containing 1 and 20 plastic bottles of 100 ml, packaged in a cardboard box.

Marketing Authorization Holder and Manufacturer

• Braun Medical, S.A.

Ctra. de Terrassa, 121

08191 Rubí (Barcelona)

Spain

Date of the Last Review of this Prospectus: February 2015

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

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This information is intended only for doctors or healthcare professionals:

Renal function and auditory nerve function should be carefully monitored in patients with renal insufficiency when used for long periods or when administered in doses higher than recommended, as disorders of the VIII cranial nerve and renal function have been reported. The appearance of signs of nephrotoxicity or ototoxicity will determine a readjustment of the dosage or suspension of treatment according to the cases.

As a general rule, the usual dose in adults with normal renal function is 15 mg/kg/day, administered as a single daily dose or divided into two or three equal doses administered at equivalent intervals, i.e., 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours.

Amikacin plasma levels should be studied, adjusting the dosage to avoid prolonged levels above 35 micrograms/ml. Urine should be examined to detect increases in protein excretion, the presence of cells or cylinders, and a decrease in density.

Ototoxicity in children is not well determined.

In the event of superinfections produced by resistant microorganisms, treatment should be suspended and appropriate therapy applied.

Patients should be well hydrated during treatment.

Amikacin B. Braun 10 mg/ml is a ready-to-use solution and therefore should not be diluted before administration. However, it can be administered simultaneously in the same intravenous line with 0.9% sodium chloride or 5% glucose solutions.

Dosage and Administration

Before starting treatment with amikacin, it is advisable to perform an antibiogram. If the severity of the process requires it and the clinical picture allows suspicion of an infection by microorganisms sensitive to amikacin, therapy with amikacin can be initiated before knowing the result of the antibiogram (see section 4.4).

The dose and administration schedule are established according to the severity of the infection, the sensitivity of the responsible microorganism, the age, weight, and general condition of the patient. In patients with severe infections and in cases of renal insufficiency, monitoring of amikacin plasma levels is advisable.

The state of renal function should be established by determining the serum creatinine concentration or the endogenous creatinine clearance rate. The determination of blood urea nitrogen is less reliable in this case. Renal function should be monitored during treatment.

Whenever possible, amikacin serum concentrations should be determined to ensure adequate but not excessive levels. It is recommended to measure intermittent minimum and maximum serum concentrations during treatment. Maximum concentrations (30-90 minutes after injection) above 35 mg/ml and minimum concentrations (just before the next dose) above 10 mg/ml should be avoided. The dose will be adjusted as indicated.

Dosage

Patient withNormal Renal Function

Patients with normal renal function can be administered a single daily dose, as long as the maximum concentration does not exceed 35 mg/ml.

Adults, Adolescents (12 to less than 18 years) and Children (2 to 11 years)

The recommended intravenous dose for adults is 15 mg/kg/day, administered as a single daily dose or divided into two or three equal doses administered at equivalent intervals, i.e., 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours. Treatment in patients with high body mass should not exceed 1.5 g/day.

Infants (28 days to 23 months)

The recommended intravenous dose in children over 2 weeks is 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours.

Neonates (0 to 27 days)

The loading dose is 10 mg/kg, followed by doses of 7.5 mg/kg every 12 hours.

Premature Infants

The recommended intravenous dose is 7.5 mg/kg every 12 hours.

Single Daily Dose

Administration as a single daily dose (15 mg/kg/day) by intravenous infusion for 60 minutes is an alternative dosing regimen in non-neutropenic adult patients and immunocompetent patients with normal renal function.

In patients with normal renal function, reflected by a creatinine clearance ≥ 50 ml/min, a single daily intravenous dose of 15 mg/kg/day can be administered in adults, or 20 mg/kg/day in children (from 4 weeks of age or older) for the treatment of bacteremia, sepsis, respiratory tract infections, complicated urinary tract infections, intra-abdominal infections, and in cases of febrile neutropenia. There is not enough information about the use of a single daily dose in patients with impairment of other organs or systems.

When amikacin is indicated for uncomplicated urinary tract infections, a total daily dose of 500 mg can be administered as a single dose or divided into two doses (250 mg BID).

The duration of treatment is 7-10 days. The total daily dose should not exceed 15 mg/kg/day. In difficult and complicated infections that require treatment for more than 10 days, the use of this medication should be reconsidered. If continued, it is recommended to monitor renal, auditory, and vestibular functions and amikacin serum levels.

Uncomplicated infections caused by microorganisms sensitive to amikacin should respond within 24-48 hours. If a definitive clinical response is not obtained within 3-5 days, therapy should be suspended and the sensitivity of the microorganism to the antibiotic should be reviewed. Treatment failure may be due to resistance of the microorganism or the presence of a septic focus that requires surgical drainage.

Patient with Altered Renal Function

In patients with renal insufficiency, reflected by a creatinine clearance <50 ml min, the administration of amikacin in a single dose is not recommended, as these patients will have prolonged exposure to high trough concentrations. (see adjustment with renal insufficiency).< p>

In patients with renal insufficiency who receive daily divided doses, whenever possible, amikacin serum concentrations should be monitored by appropriate analysis procedures. Doses can be adjusted in patients with renal insufficiency by administering normal doses at prolonged intervals or by administering reduced doses at fixed intervals.

Both possibilities are based on the patient's creatinine clearance or serum creatinine values, as a correlation has been observed between these values and the half-life of aminoglycosides in patients with decreased renal function. These dosing schedules can be used along with careful clinical and laboratory observation of the patient and should be modified when necessary, even when dialysis is to be performed.

Normal Dose at Prolonged Dosing Intervals

If the creatinine clearance is not available and the patient is stable, the dosing interval in hours for a single dose (i.e., given to patients with normal renal function in a BID scheme, 7.5 mg/kg) can be calculated by multiplying the creatinine value by 9. For example, if the serum creatinine value is 2 mg/100 ml, a single dose of 7.5 mg/kg would be administered every 18 hours.

Reduced Dose at Fixed Dosing Intervals

When renal function is altered and it is advisable to administer this medication at fixed intervals, the dose should be reduced. In these patients, amikacin serum concentrations should be determined to ensure accurate administration and avoid excessive concentrations. If serum determinations cannot be performed and the patient is stable, serum creatinine and creatinine clearance values are the most easily available indicators of the degree of renal damage to use as a guide for dosing.

Initially, the normal dose of 7.5 mg/kg will be administered as a loading dose. This dose is the same as the normal recommended dose, which should be calculated for a patient with normal renal function, as mentioned earlier.

To determine the maintenance dose every 12 hours, the base dose should be reduced in proportion to the reduction in creatinine clearance:

Maintenance dose (every 12 hours):

1. Observed C.C. in ml/min
2. --------------------------------x loading dose (mg)
3. Normal C.C. in ml/min

C.C. = creatinine clearance

An alternative approximate guide for determining the reduced dose at 12-hour intervals (for patients with known steady-state serum creatinine values) is to divide the recommended usual dose by the patient's serum creatinine value.

These dosing schedules are not intended to be strict recommendations but rather a dosing guide when it is not possible to determine amikacin serum levels.

In the event that the patient's serum creatinine value is known, the way to determine the doses is to divide the normal dose (7.5 mg/kg) by the creatinine value. These dosages are not considered strict recommendations but are recommended when it is not possible to determine amikacin serum levels.

Other Risk Populations

Elderly Patients

May require lower maintenance doses than in younger patients to achieve therapeutic plasma concentrations.

The dose should be adjusted according to body weight and renal function. In obese patients, the initial dose should be calculated based on ideal body weight plus 40% of excess weight.

Patients with BurnsandPatients with Severe Infections

May require greater administration or intervals of four to six hours because, in these cases, the half-life of the drug is shorter.

Form of Administration

Intravenous route. Administration by intravenous infusion over a period of 30-60 minutes.