Leaflet: information for the user

Amicacina B. Braun5 mg/ml infusion solution

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• Ifyou have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What isAmicacina B. Braun 5 mg/mland what it is used for

2. What you need to know before you start usingAmicacina B. Braun 5 mg/ml

3. How to useAmicacina B. Braun 5 mg/ml

4. Possible side effects

5. Storage ofAmicacina B. Braun 5 mg/ml

6. Contents of the pack and additional information

This medication contains an antibiotic that belongs to the group of aminoglycosides, amikacin

It is used for the short-term treatment of severe infections caused by sensitive microorganisms.

• Blood infection, also known as sepsis,
• Severe respiratory tract infections, including patients with cystic fibrosis,
• Central nervous system infections (including meningitis and ventriculitis),
• Gastrointestinal tract infections, including peritonitis,
• Complicated and recurrent urinary tract infections,
• Soft tissue and skin infections (including burns),
• Bone and joint infections, including arthritis,
• Infections following surgical intervention.

No use Amikacin B. Braun 5 mg/ml:

If you are allergic (hypersensitive) to amikacin or to other aminoglycoside antibiotics or to any of the other components of this medication (listed in section 6). Do not administer with other medications that are toxic to the ear or kidney, or with potent diuretics (medications used to increase urine elimination))potent.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Amikacin B. Braun 5 mg/ml.

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

• if you are allergic to amikacin or to other aminoglycoside antibiotics,
• if your kidneys do not function well, as it may increase the risk of toxicity,
• if you have muscle disorders, such as myasthenia gravis or Parkinson, as it may worsen muscle weakness,
• if you are taking diuretics that may be toxic to the ear,
• if you experience symptoms of ear toxicity such as dizziness, vertigo, tinnitus (ringing in the ears), buzzing in the ears, and hearing loss or symptoms of kidney toxicity,
• if you or your family members have a mitochondrial 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 may increase your risk of hearing loss with this medication. Your doctor may recommend genetic testing before administration of Amikacin B. Braun 5 mg/ml solution for infusion,
• Amikacin may cause alterations in the values of some substances such as: urea nitrogen, transaminases, alkaline phosphatase, bilirubin, creatinine, lactate dehydrogenase, sodium, potassium, magnesium, and calcium.

Use in children

This medication will be administered with caution, and only if there is no other alternative, in premature and newborn children due to the incomplete development of their kidneys.

Usein elderly patients

This medication should be administered with caution in this type of patient, as they are likely to have a decrease in kidney function and, consequently, a higher probability of systemic toxicity.

Use of Amikacin B. Braun 5 mg/ml with other medications

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

The administration of this medication with the following medications may require modification of the dose of one of them or interruption of treatment.

-Other antibiotics of the same type as amikacin, aminoglycosides (gentamicin, tobramycin…), or capreomycin.

-Ampicillin (medication to treat infections caused by fungi), vancomycin (antibiotic), immunosuppressive agents, cytotoxic agents (toxic to cells such as cyclosporine or cisplatin), cephalosporins (cephalothin) or potent diuretics (to increase urine elimination).

-Anesthetics of the type halogenated hydrocarbons that are administered by inhalation, massive blood transfusions with citrate, and neuromuscular blockers.

-Antihistamines (allergy medications).

-Buclizine, cyclizine, meclozine, or trimethobenzamide (medications to control nausea and vomiting).

-Loxapine (for schizophrenia).

-Phenothiazines, thioxanthenes (medications used in psychiatry).

-Anti-myasthenic medications (medications to treat myasthenia gravis - muscle weakness).

-Indomethacin (anti-inflammatory medication).

-Malathion (pesticide).

-Aminopeptidase antibiotics (colistin, polymyxin).

-Opioid analgesics (derivatives of opium used to treat pain).

-Beta-lactam antibiotics (penicillin).

Pregnancy and lactation

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medication.

This medication is not recommended during pregnancy, although your doctor will evaluate the need for its use. If the medication is used during pregnancy, or if the patient becomes pregnant during treatment, she should be informed of the possible risks.

During lactation, your doctor will evaluate the possible benefit versus the risk of administering amikacin to the infant and will inform you if you should interrupt breastfeeding during treatment.

Driving and operating machines

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

Amikacin B. Braun 5 mg/ml contains sodium

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

Follow exactly the administration instructions for this medication as indicated by your doctor. If in 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.

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.

It is administered via slow intravenous infusion.

If you use more Amicacina B. Braun 5 mg/ml than you should

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

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

If an allergic reaction occurs, administration will be suspended, and the patient will be treated with the specific treatment appropriate to the nature and intensity of the reaction (antihistamines, corticosteroids, adrenaline, etc.).

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

Like all medications, this medication may produce adverse effects, although not all people will experience them.

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

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

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

They may cause dizziness, ataxia (disorder affecting voluntary movements), vertigo, tinnitus, ear buzzing, and hearing loss.

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

Rare (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 (pain in joints).
• Pain at the injection site.

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

• Eosinophilia (presence of an abnormally high number of eosinophils – a type of white blood cell – in the blood), anemia (low concentration of red blood cells).
• Hypotension (low blood pressure); hypomagnesemia (low magnesium level).

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keepthis medicationout of the sight and reach of children.

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

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

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Amikacin B. Braun 5 mg/ml

• The active ingredient is amikacin (as sulfate). Each 5 ml of solution contains 25 mg of amikacin (as sulfate). Each ml of solution contains 5 mg of amikacin (as sulfate). Each bottle of 100 ml contains 500 mg of amikacin (as sulfate).
• The other components (excipients) are sodium chloride, sodium hydroxide (pH adjustment) and water for injection preparations.

Appearance of the product and contents of the package

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

Holder of the marketing authorization and responsible for manufacturing

B. Braun Medical, S.A.

Ctra. de Terrassa, 121

08191Rubí (Barcelona)

Spain

Last review date of this leaflet: February 2015

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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This information is intended solely for doctors or healthcare professionals:

They should carefully observe the renal and auditory nerve functions in patients with renal insufficiency when using it for long periods or when administered in doses higher than recommended, as ototoxicity and renal dysfunction have been reported. The appearance of signs of nephro or ototoxicity will determine a dosage adjustment or suspension of treatment, as appropriate.

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 h or 5 mg/kg every 8 h.

The plasma levels of amikacin should be studied, adjusting its 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 decreased density.

The ototoxicity in children is not well determined.

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

Patients should be well hydrated during treatment.

Amikacin B. Braun 5 mg/ml is a ready-to-use solution and should not be diluted before administration. However, it can be administered in the same intravenous line simultaneously with sodium chloride 0.9% 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 suspecting an infection by microorganisms sensitive to amikacin, treatment can be initiated with amikacin before knowing the result of the antibiogram (see section 4.4.).

The dose and administration schedule should be 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, it is advisable to monitor the plasma levels of amikacin.

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

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

Dosage

Patients withnormal renal function

Patients with normal renal function can be administered a single daily dose, provided that 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 h or 5 mg/kg every 8 h. The treatment in patients with a large 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 h or 5 mg/kg every 8 h.

Newborns (0 to 27 days)

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

Preterm infants

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

Single daily dose

The administration as a single daily dose (15 mg/kg/day) by intravenous infusion over 60 minutes is an alternative dosing regimen in non-neutropenic adults 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 to adults, or 20 mg/kg/day to children (4 weeks of age or older) for the treatmentof bacteremia, sepsis, respiratory tract infections, complicated urinary tract infections, intra-abdominal infections, and in cases of neutropenic fever. There is not enough information about the use of a single daily dose in patients with other organ or system damage

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. In the case of continuing, it is recommended to monitor renal, auditory, and vestibular functions and serum amikacin levels.

Uncomplicated infections produced by microorganisms sensitive to amikacin should respond in 24-48 hours. If no definitive clinical response is obtained in 3-5 days, treatment 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.

Patients with altered renal function

In patients with renal insufficiency reflected by a creatinine clearance <50

In patients with renal insufficiency who receive usual daily doses divided into two or three times, whenever possible, serum amikacin concentrations should be monitored by appropriate analytical 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 in patients with decreased renal function, a correlation has been observed between these values and the half-life of aminoglycosides. These dosing regimens can be used along with careful clinical and laboratory observations of the patient and should be modified as needed, even when dialysis is planned.

Normal dose at prolonged dosing intervals

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

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, serum amikacin concentrations should be determined to ensure exact administration and avoid excessive concentrations. If serum determinations cannot be made and the patient is stable, serum creatinine values and creatinine clearance are the most easily available indicators of renal damage to use as a guide for dosing.

Initially, the normal dose of 7.5 mg/kg should 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 written earlier.

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

1. A.C. observed in ml/ min
2. --------------------------------x dose of loading (mg)
3. A.C. normal in ml/ min

A.C.= creatinine clearance

An alternative approximate guide for determining the reduced dose every 12 hours (for patients with known serum creatinine values in a steady state) is to divide the usual recommended dose by the patient's serum creatinine value.

These dosing regimens do not aim to be strict compliance recommendations, but rather a dosing guide when it is not possible to determine serum amikacin levels.

When 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 patient's serum creatinine value. These dosages are not considered to be strict compliance, but are recommended when it is not possible to determine serum amikacin levels.

Other populations at risk

Older patients

They may need lower maintenance doses than young people to obtain therapeutic plasma concentrations.

The dose should be adjusted according to body weight and renal function. Inobese patientsthe initial dose should be calculated at the ideal weight plus a 40% excess of weight.

Burn patientsandpatients with severe infections

They may need a greater administration or intervals of four to six hours due to the shorter half-life of the drug in these cases.

Administration route

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