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Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

PACKAGE LEAFLET: INFORMATION FOR THE USER

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

Amikacin

Read all of this leaflet carefully before you start taking this medicine.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor

In this leaflet:

1.    What Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml is and what it is used for

2.    Before you are given Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml

3.    How Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml is given

4.    Possible Side Effects

5.    Storing Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml

6.    Further information

1. WHAT AMIKACIN2.5 MG/ML, 5 MG/ML, 10 MG/ML IS AND WHAT IT IS USED FOR

Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml belong to a group of medicines called antibiotics, that is, they are used to treat severe infections with bacteria that can be killed by the active substance Amikacin. Amikacin belongs to a group of substances called aminoglycosides.

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

You may receive Amikacin to treat the following diseases:

-    Infections of lungs and lower airways occurring during in-patient treatment, including severe pneumonia

-    Infections within the belly, including inflammation of the peritoneum

-    Complicated and recurrent infections of kidneys, urinary ducts and bladder

-    Infections of skin and soft tissues, including severe burns

-    Bacterial inflammation of the inner lining of the heart

-    Infections after belly operations

Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml can also be used in the treatment of patients with an inflammation of the entire body that occurs in association with, or is suspected to be associated with, any of the infections listed above.

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

2. BEFORE YOU ARE GIVEN AMIKACIN 2.5 MG/ML, 5 MG/ML, 10 MG/ML

You must not receive Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml

-    if you are allergic (hypersensitive) to amikacin, other similar substances (other aminoglycosides) or any of the other ingredients of the medicinal products.

-    if you have Myasthenia gravis.

Special care with Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml should be taken

Your doctor should know if you have

-    impaired kidney function,

-    impaired hearing,

-    Parkinson’s disease.

-    already had a treatment with another antibiotic similar to amikacin.

Your doctor will exercise particular caution if any of these applies.

Your doctor will also exercise particular caution if you are 60 years old or older or you have a body water deficit.

Caution is also necessary when giving the medicine to pre-term or term new-born babies.

Monitoring will include

-    kidney function, especially if you are 60 years old or older or have kidney impairment,

-    hearing,

-    blood levels of amikacin, if necessary.

Daily doses will be reduced and/or the time between doses lengthened if signs of kidney impairment appear or if kidney impairment worsens. If kidney impairment becomes severe, amikacin will be stopped.

Amikacin therapy should also be stopped if ear noise or hearing loss develops.

To avoid the risk of damage to your kidneys, ear nerve and muscle function, treatment with amikacin will not be extended beyond 10 days unless your doctor considers it necessary.

It will be made sure during treatment that you have sufficient fluid supply.

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

If you undergo any rinsing procedures with solutions containing amikacin or a similar antibiotic on wounds during surgery, this will be taken into account for your amikacin dose.

Taking or using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

The following should be paid attention to:

The damaging effect of amikacin on kidneys and ear nerve may be increased by:

-    other antibiotic substances similar to amikacine

-    other substances used to treat infections like bacitracin, amphotericin B, cephalosporins, vancomycin, kanamycin, paromomycin, polymyxin B, colistin

-    anti-cancer drugs: carboplatin at high doses, cisplatin, oxaliplatin (particularly in cases of already existing kidney impairment)

-    substances suppressing undesirable immune reactions: ciclosporin, tacrolimus

-    rapid acting medicines increasing urine flow: furosemide or ethacrynic acid. Irreversible deafness may result.

Administration of these together with or after amikacin should be avoided as far as possible.

When amikacin must be combined with such substances, hearing and kidney function will be monitored very often and carefully. In the case of use of amikacin together with rapid acting medicines increasing urine flow your fluid balance will be followed up.

The following should also be paid attention to:

Methoxyflurane anaesthesia

The anaesthetist should know if you have received or are receiving amikacin or a similar antibiotic before performing anaesthesia with methoxyflurane (an anaesthetic gas) and avoid to use this agent if ever possible, because of an increased risk of severe kidney and nerve damage

Concurrent treatment with amikacin and a muscle-relaxant drug (e.g. d-tubocurarin), other agents acting like curare, botulinus toxin or narcotic gases e.g. halothane:

In the event of surgery the anaesthetist should be informed that you are being treated with amikacin because there is a risk that the blockade of nerve and muscle functions may become much stronger. Should a nerve and muscle blockade be caused by the aminoglycoside, this can be reversed by calcium salts.

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

In new-borns receiving amikacin the blood level of amicakin will be carefully controlled if indomethacin is administered concurrently because indomethacin may make the amikacin blood level rise.

Other antibiotics

Combination therapy with suitable antibiotics may markedly strengthen the effect of the treatment.

Pregnancy and breast-feeding

Pregnancy

If you are pregnant your doctor will give you this medicine only if he/she considers it absolutely necessary.

Breast-feeding

Although it is rather unlikely that-amikacin is taken up through the gut by suckling babies, your doctor will carefully consider whether nursing or amikacin therapy should be discontinued.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed. In the case of administration to outpatients, caution is advised when driving and using machines in view of the possible undesired effects such as dizziness and vertigo.

Important information about some of the ingredients of Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml

This medicinal product contains 354 mg (or 15 mmol) sodium per 100 ml in the form of normal salt. To be taken into consideration by patients on a controlled sodium diet.

3.    HOW AMIKACIN 2.5 MG/ML, 5 MG/ML, 10 MG/ML IS GIVEN

Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml are administered by a drip directly into a vein (intravenous infusion). The contents of one bottle are administered over a period of 30 - 60 minutes.

Your doctor will determine the appropriate dose for you. The following are commonly used doses:

Dosage in patients with normal kidney function

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Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

•    Adults and adolescents over 12 years (over 33 kg body weight):

The usual dose is 15 mg of amikacin per kg body weight (BW) per 24 hours, divided in 2 equal doses: 7.5 mg per kg BW every 12 hours

As a maximum you may receive up to 1.5 grams per day over a short period if there is an absolute need for such high doses and you will then be carefully and constantly monitored during treatment.

The total amount of amikacin you may receive during the whole treatment will not exceed 15 grams.

•    Infants, toddlers and children :

A single daily dose of amikacin of 15-20 mg/kg or a dose of 7.5 mg/kg every 12 hours.

•    Dosage for new-borns:

The starting dose is 10 mg of amikacin per kg BW, and 12 hours later 7.5 mg of amikacin per kg BW. Treatment continues with 7.5 mg of amikacin per kg BW every 12 hours.

• Dosage for pre-term babies:

7.5 mg of amikacin per kg BW every 12 hours.

This, however, does not apply to patients with weakened immunity, kidney failure, cystic fibrosis, water in the belly, inflammation of the inner lining of the heart, extensive burns (more than 20 per cent of the skin), elderly patients, and in pregnancy.

Time of treatment

Usually you will receive treatment with Amikacin over 7 - 10 days, only in cases of severe and complicated infections longer. Your therapy will normally show an effect within 24 to 48 hours, otherwise your medicine may have to be changed.

Your blood levels of the amikacin will be carefully monitored and your dose will carefully be adjusted throughout your therapy.

Dosage in patients with kidney function impairment

If you have kidney function impairment the amikacin level in the blood and your kidney function will be monitored carefully and frequently in order to adjust your amikacin dose adequately. Your doctor knows how to calculate the doses you are going to receive.

Patients undergoing haemodialysis or peritoneal dialysis receive one dose at half the normal strength at the end of the dialysis procedure.

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

Elderly patients may require lower doses of amikacin than younger patients to achieve therapeutic plasma concentrations. Your renal function will be assessed whenever possible and your dose adjusted if necessary.

Severely overweight patients

In these patients the dose is calculated according to the ideal body weight plus 40 per cent of weight excess. Later on your dose might be adjusted according to your blood levels of amikacin. The maximum dose is 1.5 g per day. The usual duration of treatment is 7 to 10 days.

Patients with water in the belly

Higher doses must be given in order to obtain adequate blood levels.

If you received more Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml than you should

Overdosing may cause damage to kidneys and the ear nerves or a blockage of muscle function (paralysis). In such a case the infusion of amikacin has to be stopped. Urine excretion will be increased to remove the amikacin from your blood if necessary. Further measures may include dialysis procedures or, in new-borns, blood exchange, however, expert advice must be sought before such a measure is implemented.

Calcium salts may be used to abolish the paralysing effect. Mechanical ventilation may be necessary in breathing paralysis.

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

4. POSSIBLE SIDE EFFECTS

Like all medicines, Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml can cause side effects, although not everybody gets them.

Under certain conditions amikacin (and also other similar substances) show toxic effects on ear nerve and kidneys. Kidney impairment is uncommonly observed in patients treated with Amikacin and will usually resolve afterwithdrawal of the drug. In most cases kidneydamage is associated with an excessively high dosage or long-lasting treatment, already existing kidney abnormalities or is associated with other substances also having a damaging effect on kidneys. Adverse reactions can largely be avoided by strictly obeying the preacautions and careful dosing according to instructions.

The adverse reactions that might be due to treatment are listed below by absolute frequency. Frequencies are defined as:

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Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

affects more than 1 user in 10 affects 1 to 10 user in 100

affects 1 to 10 user in 1,000

affects 1 to 10 user in 10,000

affects less than 1 user in 10,000

frequency cannot be estimated from the available data

The following adverse reactions, which may occur only rarely, may be serious and demand immediate treatment:

-    severe acute hypersensitivity (allergic) reactions with shock

-    deafness

-    breathing paralysis

-    acute kidney failure

Other side effects are:

Uncommon side effects:

•    Dizziness, vertigo.

•    Trembling of eyeballs.

•    Noise in the ears, pressure in the ears, hearing impairment.

•    Feeling sick.

•    Damage to certain parts of the kidney, impairment of kidney function.

Rare side effects:

•    Additional infection or colonisation (with resistant microbes or yeast-like fungi).

•    Abnormally low counts of white or red blood cells or blood platelets, increased count of a certain type of white blood cells (eosinophils).

•    Hypersensitivity (allergic) reactions, skin rash, itching, hives.

•    Low level of magnesium in the blood.

•    Headache, migraine, numbness, trembling.

•    Low blood pressure.

•    Breathing depression.

•    Sickness.

•    Joint pain.

•    Drug-related fever.

•    Increased blood levels of some enzymes located in the liver.

Very rare side effects:

•    Severe acute hypersensitivity (allergic) reaction with shock (isolated cases).

•    Deafness (isolated cases).

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

•    Breathing paralysis (isolated cases).

•    Blockage of muscle function.

•    Severe kidney damage, acute kidney failure.

Not known:

•    Allergic reactions to all substances that are similar to amikacin.

If any of the side effects becomes serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

5. STORING AMIKACIN 2.5 MG/ML, 5 MG/ML, 10 MG/ML

Keep out of the reach and sight of children.

Do not use Amikacin 2.5 mg/ml, 5 mg/ml, 10mg/ml after the expiry date which is stated on the bottle and the outer carton The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

The solution for infusion should be used immediately. For single use only.

Discard any unused solution.

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

6. FURTHER INFORMATION

What Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml contains

- The active substance is Amikacin.

1 ml of Amikacin 2.5 mg/ml solution for infusion contains 2.5 mg of Amikacin, as Amikacin sulphate.

1 bottle of 100 ml contains 250 mg of Amikacin.

1 ml of Amikacin 5 mg/ml solution for infusion contains 5 mg of Amikacin, as Amikacin sulphate.

1 bottle of 100 ml contains 500 mg of Amikacin.

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

1 ml of Amikacin 10 mg/ml solution for infusion contains 10 mg of Amikacin, as Amikacin sulphate.

1 bottle of 100 ml contains 1,000 mg of Amikacin.

- The other ingredients are:

Sodium chloride, sodium hydroxide (for pH adjustment), water for injections.

What Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml looks like and contents of the pack

Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml are solutions for infusion; i.e. they are administered as a drip through a small tube or cannula placed in a vein.

They are clear colourless solutions.

They come in polyethylene bottles of 100 ml.

They are supplied in packs of 10 and 20 bottles

Not all pack sizes may be marketed.

Marketing Authorisation Holder

B. Braun Melsungen AG Carl-Braun-Strasse 1 34212 Melsungen Germany

Phone: +49/5661/71-0 Fax: +49/5661/71-4567

Postal address:

34209 Melsungen Germany

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

Manufacturer

B. Braun Medical S. A.

Carretera de Terrassa 121 08191 Rubi (Barcelona)

Spanien

This leaflet was last approved in 02/2011.

The following information is intended for medical or healthcare professionals only:

Incompatibilities

Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml are ready-to-use formulations and must not be mixed with any other medicinal products but must be administered separately, in accordance with the recommended dose and method for administration.

On no account may aminoglycosides be mixed in an infusion solution with beta-lactam antibiotics (e.g. penicillins, cephalosporins), as this may cause chemical-physical inactivation of the combination partner.

Chemical incompatibilities are known for 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.

Inactivation when aminoglycosides and beta-lactam antibiotics are mixed may also persist when samples are taken to measure the serum levels of antibiotics and may result in considerable underestimation with dosage errors and risks of toxicity as a consequence. Samples must be handled rapidly and placed in ice or beta-lactamase should be added.

Shelf-life

Unopened: 3 years.

Package Leaflet

Amikacin 2.5 mg/ml solution for infusion Amikacin 5 mg/ml solution for infusion Amikacin 10 mg/ml solution for infusion

PL 03551/0130 PL 03551/0131 PL 03551/0132

In-use shelf-life (after opening):

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8° C.

Special precautions for disposal and other handling For single use only.

Discard any unused solution.

The reconstitution/dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter and discoloration prior to administration. The solution should only be used if the solution is clear and free from particles.

Storage information

See section 5 'How to store Amikacin'

Method of administration

See section 3 'How Amikacin is given'.

Posology

See section 3 'How Amikacin is given'.

Infusion volumes in patients with normal renal function:

Body weight

Amikacin 2.5 mg / ml (100 ml = 250 mg)

	2.5kg	5kg	10kg	12.5kg	20kg	30kg	40kg	50kg	60kg	70kg	80kg	90kg	100kg
Amikacin in mg
7.5	7.50	15.00	30.00	37.50	60.00	90.00	120.00	150.00	180.00	210.00	240.00	270.00	300.00	ml
15	15.00	30.00	60.00	75.00	120.00	180.00	240.00	300.00	360.00	420.00	480.00	540.00	600.00
20	20.00	40.00	80.00	100.00	160.00	240.00	320.00	400.00	480.00	560.00	640.00	720.00	800.00

Body weight

Amikacin 5 mg / ml (100 ml = 500 mg)

7.5	3.75	7.50	15.00	18.75	30.00	45.00	60.00	75.00	90.00	105.00	120.00	135.00	150.00	ml
15	7.50	15.00	30.00	37.50	60.00	90.00	120.00	150.00	180.00	210.00	240.00	270.00	300.00
20	10.00	20.00	40.00	50.00	80.00	120.00	160.00	200.00	240.00	280.00	320.00	360.00	400.00
	Body weight
Amikacin 10 mg / ml (100 ml = 1000 mg)
	2.5kg	5kg	10kg	12.5kg	20kg	30kg	40kg	50kg	60kg	70kg	80kg	90kg	100kg
Amikacin in mg
7.5	1.88	3.75	7.50	9.38	15.00	22.50	30.00	37.50	45.00	52.50	60.00	67.50	75.00	ml
15	3.75	7.50	15.00	18.75	30.00	45.00	60.00	75.00	90.00	105.00	120.00	135.00	150.00
20	5.00	10.00	20.00	25.00	40.00	60.00	80.00	100.00	120.00	140.00	160.00	180.00	200.00

Accuracy of dosing is improved if Amikacin 2.5 mg/ml, 5 mg/ml, 10 mg/ml solution for infusion is administered with an infusion pump.

This is a ready to use formulation which should not be diluted prior to administration and which is for single use only.

To avoid overdosing especially in children, the most appropriate available strength should be chosen.

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