AMICASIL 500 mg /2 Ml Injectable Solution

Зміст інструкції

1. AMICASIL 500 mg/2 ml injectable solution
   1. What is AMICASIL and what is it used for
   2. What you need to know before using AMICASIL
   3. How to use AMICASIL
   4. Possible side effects
   5. How to store AMICASIL
   6. Contents of the pack and other information

AMICASIL 500 mg/2 ml injectable solution

Amikacin sulfate

Read this leaflet carefully before using this medicine as 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.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is AMICASIL and what is it used for

AMICASIL contains the active ingredient amikacin belonging to the group of medicines called antibiotics
(aminoglycoside antibiotics) used for the treatment of infections caused by bacteria.
This medicine is used for the short-term treatment of serious infections caused by some bacteria
(Gram-negative).
In particular AMICASIL is indicated for the treatment of:

• blood infections (bacteremia, septicemia), neonatal sepsis (when sensitivity tests indicate that another aminoglycoside cannot be used);
• severe and frequent urinary and genital tract infections;
• respiratory tract infections;
• infections of the bones and/or joints (osteoarticular infections);
• infections of the central nervous system, including meningitis;
• infections that may occur following a burn;
• internal abdominal infections (endo-abdominal infections), including peritonitis (infection of the tissue lining the abdomen);
• infections that occur after surgery;
• infections caused by staphylococci, it can be adopted as an initial therapy in case of confirmed or suspected staphylococcal infections, when the patient is allergic to other antibiotics, or there is a mixed infection by staphylococci and Gram-negatives

This medicine is effective against several types of bacteria (for example Proteus rettgeri, Providencia stuartii,
Serratia mercescens and Pseudomonas aeruginosa), which are resistant to other antibiotics, such as gentamicin
or tobramycin.

2. What you need to know before using AMICASIL

Do not use AMICASIL

• if you are allergic to amikacin, to other similar substances (other aminoglycosides), or to any of the other ingredients of this medicine (listed in section 6);
• if you have previously suffered an allergy or have experienced toxic reactions after using an antibiotic of the same class as AMICASIL (aminoglycoside antibiotics).

Warnings and precautions
Consult your doctor, pharmacist or nurse before taking AMICASIL.
Before starting treatment with this medicine, it is recommended to perform an antibiogram.
Treatment can be started when the results of the antibiogram are not available and a
bacterial infection of a particular type is suspected (Gram-negative). The doctor will determine whether it is necessary
to continue therapy.
Particular caution must be exercised with AMICASIL if:

• you have impaired kidney function,
• you have impaired hearing,
• you have nervous and muscular disorders, such as a particular type of muscle weakness called myasthenia gravis
• you have Parkinson's disease,
• you have already been treated with another antibiotic similar to amikacin. In all these cases, the doctor must be particularly careful.

If you or your family members have a genetic disease that causes mitochondrial mutation or hearing loss caused by
taking antibiotics, we advise you to inform your doctor or pharmacist before
taking an aminoglycoside, as some mitochondrial mutations associated with this product may
increase the risk of hearing loss. Your doctor may recommend genetic testing before
administration of Amicasil.
If you suffer from any of the following conditions, you may be at higher risk of developing harmful effects
to your hearing or your nerves:

• impaired kidney function
• advanced age
• dehydration
• administration of high doses of this medicine
• prolonged therapy for more than 5-7 days, even in healthy patients.

The first signs of harmful effects to your hearing or your nerves after taking this medicine
may be:

• difficulty hearing high-pitched sounds (high-frequency hearing loss)
• dizziness
• numbness, tingling skin, muscle spasms, convulsions.

After the administration of this medicine, breathing (respiratory paralysis)
and muscle and nerve functions (neuromuscular block) may be blocked. Your doctor will take appropriate
countermeasures.
During therapy with this medicine, your doctor will keep you under close observation, paying particular
attention to your hearing ability and kidney function.
The observation will include:

• kidney function, especially if you have kidney failure or signs indicating its onset during treatment;
• hearing and amikacin levels in the blood, if necessary.

If signs of kidney damage appear or if kidney damage worsens, the doctor will reduce the daily doses and/or
extend the intervals between administrations.
If kidney damage becomes severe, amikacin will be discontinued.
Therapy with amikacin must also be discontinued if ringing in the ears or
hearing loss is observed.
If you undergo irrigation of wounds with solutions
containing amikacin or a similar antibiotic during surgery, this must be taken into account for dosage purposes
of amikacin.
As with other antibiotics, the use of this medicine may promote the occurrence of other infections caused by
bacteria or fungi to which AMICASIL is not effective (superinfections). If this should occur, it is
appropriate to discontinue treatment with this medicine and consult your doctor, who will indicate a
suitable therapy.
The use of AMICASIL consecutively or concurrently with other medicines (taken systemically, orally,
topically) that may promote problems with the kidneys or nerves (nephrotoxicity, neurotoxicity) must
be avoided (see section Other medicines and AMICASIL).
Elderly patients
If you are an elderly patient, your doctor will pay particular attention to your kidney function, and
may conduct several tests to ensure that your kidneys are not impaired, as elderly patients are more prone to having impaired kidney function.

Children
Caution is required when administering the medicine to newborns and premature infants due to the not yet mature
kidney function.

Other medicines and AMICASIL
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.
Do not use this medicine if you are taking:

• medicines that promote the elimination of fluids (diuretics), such as ethacrylic acid and furosemide, because they increase the toxic effect of AMICASIL on hearing.

Be particularly careful and inform your doctor if you are taking or are to take any of the following
medicines:

• anesthetics (medicines that induce a reduction in pain sensitivity and sedation) and neuromuscular blockers (such as succinylcholine, decamethonium, atracurium, rocuronium, vecuronium) or citrate (used as an anticoagulant in blood bags); in these cases, paralysis of the muscles and/or respiratory block may occur;
• medicines that may be toxic to the nervous system, to the ear or to the kidneys (neurotoxic, ototoxic and nephrotoxic medicines), such as kanamycin, tobramycin, bacitracin, cephaloridine, paromomycin, vancomycin, streptomycin, polymyxin B, colistin, neomycin, gentamicin and viomycin or other aminoglycosides (antibiotics used to treat infections caused by bacteria), amphotericin B (an antifungal used to treat infections caused by fungi), cisplatin (a medicine used for the treatment of tumors), cyclosporine and tacrolimus (medicines used for the treatment of autoimmune diseases or to prevent rejection after transplantation). Avoid using the above-mentioned medicines and AMICASIL at the same time or consecutively;
• medicines belonging to the cephalosporin group of antibiotics and administered intravenously or intramuscularly (parenterally), as this may increase the toxic effect on the kidneys and may give a false increase in creatinine levels in the blood;
• antibacterial medicines (aminoglycoside or penicillin antibiotics) as the action of AMICASIL may be reduced;
• bisphosphonates, medicines used for the treatment of some bone diseases; in this case, concomitant use may cause a decrease in calcium levels (hypocalcemia);
• platinum-based medicines as they may increase the risk of toxicity to the kidneys and hearing;
• vitamin B1 (thiamine), as when administered together with AMICASIL, it may lose its effect;
• indometacin, used for the treatment of inflammation, as when administered to a newborn it may increase the levels of amikacin in the newborn's blood.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine.
If you are pregnant or are planning a pregnancy, you will receive this medicine only if strictly
necessary and under the direct supervision of your doctor, as AMICASIL crosses the placenta and can cause
irreversible damage to the fetus (hearing loss).
If you are breastfeeding, consult your doctor, who will assess the need to discontinue breastfeeding with
breast milk or treatment with this medicine.
Studies in animals have not shown an effect on fertility.

Driving and operating machinery
The use of this medicine may cause side effects, such as disturbances of balance, vision and
hearing, which may impair your ability to drive vehicles and operate machinery (see section
Possible side effects), it is recommended to avoid driving and operating machinery.

AMICASIL contains sodium and sodium metabisulfite
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.
This medicine contains sodium metabisulfite which rarely may cause serious hypersensitivity reactions and
bronchospasm.

3. How to use AMICASIL

This medicine will be administered to you by a doctor or nurse.

Intramuscular and intravenous administration
Administration into a muscle (intramuscular administration) is preferable to direct administration
into a vein (intravenous administration).
The same dosage can be used for both routes of administration.

Use in adults and children
The recommended dose, for administration into muscle or vein, is 15 mg per kg of body weight per
day, to be taken in 2 equal administrations of 7.5 mg per kg of body weight every 12 hours.
High-risk infections and/or those caused by the Pseudomonas bacterium:
the initial dose in adults may be increased to 500 mg every 8 hours without exceeding the maximum dose of 1.5
g per day or prolonging therapy for more than 10 days.
The maximum total dose is 15 g.
Uncomplicated urinary tract infections (excluding infections caused by Pseudomonas):
the recommended dose is 7.5 mg per kg of body weight, in a single daily administration.

Use in newborns and/or premature infants
The recommended initial dose is 10 mg per kg of body weight, followed by a dose of 7.5 mg per kg of
body weight every 12 hours (see section Children).

Use in patients with kidney problems
If you have kidney problems (renal dysfunction), your doctor will assess a reduction in the daily dose and/or
an increase in the interval between administrations.
Duration of treatment
The duration of treatment is 3 - 7 days in case of administration into a vein (intravenous administration) and 7 - 10 days for administration into a muscle (intramuscular administration).
At the recommended doses, less severe infections caused by susceptible organisms respond to therapy within

• 24 - 48 hours.

Administration by intravenous infusion
Amikacin should not be mixed with other substances to be infused, but administered alone, according to the
established dosage regimen.

Use in adults
The contents of one vial must be diluted in 100-200 ml of a suitable solvent (physiological saline,
5% glucose solution and Ringer's lactate solution).
Administration into a vein must be carried out over a period of 30 to 60 minutes.

Use in children
In children, the amount of solvent (physiological saline, 5% dextrose, Ringer's lactate) must be established
by the doctor based on the dose of AMICASIL to be administered.
Administration into a vein must be carried out over a period of 30 to 60 minutes; in smaller children, a longer duration (1 to 2 hours) is recommended.

If you are given more AMICASIL than you should
This medicine will be administered to you by a doctor or nurse, so an overdose is unlikely.
However, if you think that you have been given an excessive amount of this medicine, warn
your doctor immediately or go to the nearest hospital.
In case of overdose, damage to hearing, kidneys and the nervous system (ototoxicity,
nephrotoxicity and neurotoxicity) and muscle contraction disorders (neuromuscular block) associated with
respiratory block may occur.
In such cases, mechanical filtration of the blood to remove the
medicine from the body (peritoneal dialysis or hemodialysis and continuous artero-venous hemofiltration) may be considered.
In case of neuromuscular block with respiratory block, the doctor will administer
the necessary treatment including the application of ionic calcium (e.g. gluconate or lactobionate in 10-20% solution).
In newborns, a transfusion (exchange transfusion) may be considered.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Amikacin and all other similar substances can cause toxic effects on hearing, kidneys, nerves and
muscles (neuromuscular blocking).
These effects are more often observed in patients:

• who already have kidney problems,
• treated with other medicines that can cause toxic effects on the kidneys and hearing (see section Warnings and precautions),
• who receive prolonged treatment or doses higher than those recommended of this medicine.

The following side effects may occur:

Uncommon(may affect up to 1 in 100 people)

• development of infections by resistant microbes (bacteria or yeasts to which AMICASIL is not effective);
• nausea, vomiting;
• skin rash.

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

• changes in the levels of red blood cells and white blood cells in the blood (anemia, eosinophilia);
• decrease in magnesium levels (hypomagnesemia);
• tremors, sensation of decreased sensitivity in the legs and arms (paresthesia);
• headache and balance disorders;
• perception of noises and/or ringing in the ears (tinnitus), hearing loss (hypoacusis);
• decrease in blood pressure (hypotension);
• itching, skin irritation (urticaria);
• joint pain (arthralgia);
• repeated muscle contractions (spasms);
• decreased urine production (oliguria);
• increased creatinine levels in the blood;
• high concentration of albumin in the urine (albuminuria);
• increased nitrogen levels in the blood (azotemia);
• presence of red blood cells and white blood cells in the urine; presence of casts in the urine sediment;
• alteration of blood tests (increased blood creatinine, azotemia);
• fever (pyrexia or iatrogenic fever);
• loss of vision and problems with the retina (retinal infarction) if AMICASIL is administered by injection into the eye (intravitreal injection).

Not known(frequency cannot be estimated from available data)

• severe allergic reactions (anaphylactic reaction, anaphylactic shock, and anaphylactoid reaction), hypersensitivity;
• muscle blocking (paralysis);
• deafness, even associated with nerve damage (sensorineural deafness);
• temporary interruption of breathing (apnea), difficulty breathing (bronchospasm);
• kidney problems (acute renal failure);
• toxic nephropathy, presence of cells in the urine.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly through
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 AMICASIL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after “Expiry”. The expiry date refers to the last day of that month.
Do not dispose of any medicine in the wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What AMICASIL contains

• The active ingredient is amikacin sulfate. Each vial contains 667.5 mg of amikacin sulfate corresponding to 500 mg of amikacin.
• The other ingredients are sodium citrate, sodium metabisulfite, sulfuric acid (as a pH adjuster), sodium hydroxide (as a pH adjuster), water for injections.

Description of the appearance of AMICASIL and contents of the pack
Pack of 10 vials of 2 ml.

Marketing Authorisation Holder
Pharmatex Italia srl - Via San Paolo 1, - 20121 Milan

Manufacturer
Officina Farmaceutica Fisiopharma s.r.l. - Industrial Area - 84020 Palomonte (SA)
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The following information is intended exclusively for healthcare professionals:
Additional warnings:
It is advisable to perform an antibiogram before starting therapy.
Amikacin can be adopted as initial therapy when a gram-negative etiology is suspected in an infection and the results of the antibiogram are not yet available. However, the decision to
continue therapy with this antibiotic may be based on the results of sensitivity tests, the severity
of the infection, the patient's response and taking into account the warnings reported below.
Caution should be exercised in patients with pre-existing renal insufficiency, or with pre-existing hearing or
vestibular damage. Patients treated with aminoglycosides parenterally should be placed in
close clinical observation due to the potential ototoxicity and nephrotoxicity associated with their use. The
safety of the medicinal product has not been established for treatment periods longer than 14 days.

Neuro/ototoxicity
Neurotoxicity, which manifests as vestibular and/or auditory bilateral ototoxicity, can
occur in patients treated with aminoglycosides. The risk of aminoglycoside-induced ototoxicity is
greater in patients with impaired renal function, or in those whose therapy is prolongedbeyond
5-7 days of treatment, even in healthy patients. High-frequency hearing loss usually occurs first and
can only be detected by audiometric tests. Vertigo may occur and may be a symptom of
vestibular damage. Other manifestations of neurotoxicity may include numbness, tingling of the
skin, muscle spasms and convulsions. Patients who develop cochlear or vestibular damage may not
have symptoms during therapy indicating the development of eighth nerve toxicity, and total or partial
bilateral deafness or disabling vertigo may occur even after the drug has been
discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.
There is an increased risk of ototoxicity in patients with mitochondrial DNA mutations (in
particular at nucleotide 1555 with a substitution of A with G in the 12S rRNA gene), even if serum levels
of aminoglycosides are within the recommended range during treatment. In these patients, alternative therapeutic options should be considered.
Patients with a family history of relevant mutations or aminoglycoside-induced deafness should be
considered for alternative treatments or genetic testing before administration.

Neuromuscular toxicity
Cases of neuromuscular blockade and respiratory paralysis have been reported following parenteral
injection, topical use (as in orthopedics and abdominal irrigation or in local treatment of
empyema), and after oral use of aminoglycosides. The possibility of respiratory paralysis must be taken into
consideration for all routes of administration of aminoglycosides, especially in patients treated with
anesthetics, and muscle relaxants. If neuromuscular blockade occurs, calcium salts may reverse respiratory paralysis, but mechanical ventilation may be necessary. Neuromuscular blockade and
muscle paralysis have been demonstrated in laboratory animals treated with high doses of amikacin.
Aminoglycosides should be used with caution in patients with muscle diseases such as myasthenia gravis
or parkinsonism as these drugs may worsen muscle weakness due to their
potential curare-like effect on the neuromuscular junctions.

Renal toxicity
Aminoglycosides are potentially nephrotoxic. Renal toxicity is independent of plasma concentration
peak (Cmax). The risk of nephrotoxicity is greater in patients with impaired renal function,
and in those who receive high doses of the drug, or in those whose therapy is prolonged.
Patients should be well hydrated during treatment and renal function should be assessed using
standard methods before starting therapy and daily during the course of treatment. We would like to point out
that when the patient is well hydrated and renal function is normal, the risk of nephrotoxic reactions with
amikacin is reduced, if you stay within the recommended doses. A dose reduction is necessary if
phenomena of renal dysfunction occur, such as the presence of urinary cylinders, white blood cells or
red blood cells, albuminuria, decreased creatinine clearance, decreased urine specific gravity, increased BUN, serum creatinine, and oliguria. If azotemia increases, or if
a progressive decrease in diuresis occurs, treatment should be discontinued.
Elderly patients may have reduced renal function that may not be evident in routine screening tests such as BUN or serum creatinine measurement. A creatinine clearance determination may be more useful. Monitoring of renal function in elderly patients during
treatment with aminoglycosides is particularly important.
Renal and eighth cranial nerve function should be carefully monitored, particularly in
patients with known or suspected renal insufficiency at the start of therapy, and also in those whose
renal function is initially normal, but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when possible to ensure adequate levels
and avoid potentially toxic levels (greater than 35 gamma/ml for long periods). Urine should
be examined for decreased specific gravity, increased protein excretion, and the presence of
cells or deposits. Blood urea nitrogen, serum creatinine or
creatinine clearance should be measured periodically. If possible, serial audiograms should be performed in patients old
enough to be tested, particularly in high-risk patients. Any symptoms of ototoxicity
(dizziness, vertigo, tinnitus, ringing in the ears, and hearing loss) or nephrotoxicity require
discontinuation or dosage adjustment of the drug.
Systemic, oral or topical concomitant and/or sequential administration of other neurotoxic or
nephrotoxic products should be avoided. Other factors that may increase the risk of toxicity are advanced age and
dehydration.
The inactivation of aminoglycosides is clinically significant only in patients with severe impairment
of renal function. Inactivation can continue in samples of biological fluids collected for analysis,
causing inaccurate aminoglycoside results. Such samples should be treated appropriately
(immediately frozen or treated with beta-lactamase).

Allergic reactions
Amikacin sulfate in injectable vials contains sodium metabisulfite, a sulfite that can cause allergic reactions including anaphylactic symptoms and asthmatic episodes that can be life-threatening in some
predisposed subjects or give rise to episodes of lesser severity. The overall prevalence of sulfite sensitivity in the general population is uncommon and probably low. Sulfite sensitivity is seen more
frequently in asthmatic subjects than in non-asthmatic subjects. Cross-allergy with other
aminoglycosides is possible.

Other
Aminoglycosides are rapidly and almost completely absorbed when applied locally,
except for the urinary bladder, in association with surgical procedures. Irreversible deafness, renal failure and death due to neuromuscular blockade have been reported after
irrigation of both small and large surgical fields with an aminoglycoside preparation.
In cases where amikacin is indicated in combination with other antibiotics, it is advisable to avoid mixing such
agents in syringes or infusion bottles.
As with other antibiotics, the use of amikacin can lead to the proliferation of non-susceptible organisms. If this occurs, appropriate therapy should be initiated.
Aminoglycosides should be used with caution in neonates and premature infants due to the immature
development of the renal system of these patients and the resulting prolongation of the plasma half-life of
these drugs.
The potential ototoxicity of amikacin in children is unknown. Until more data are available,
this antibiotic should be used in pediatrics only when sensitivity tests indicate that other aminoglycosides cannot be used and when the child can be closely monitored for the onset of toxicity at that level.
Cases of macular infarction with subsequent vision loss have sometimes occurred after intra-vitreal (injection into the eye) administration of amikacin.
Interference with laboratory tests

Dosage
Patients with impaired renal function
A recommended method for establishing the doses to be administered to patients with decreased, suspected or confirmed renal function is to multiply serum creatinine concentrations by 9: the result obtained
represents the interval, expressed in hours, between one dose and the next.
Example: if the serum creatinine level is 2 mg, the recommended dose should be administered every 18
hours.