Mikan

Package leaflet: Information for the user

MIKAN 1 g/4 ml injectable solution

Amikacin sulfate
Generic medicine
Please read all of this leaflet carefully before you start using 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4. Contents of this leaflet:
  1. What MIKAN is and what it is used for
  2. What you need to know before using MIKAN
  3. How to use MIKAN
  4. Possible side effects
  5. How to store MIKAN
  6. Contents of the pack and other information

1. What MIKAN is and what it is used for

MIKAN contains the active substance amikacin, which belongs to a group of medicines called antibiotics
(aminoglycoside antibiotics) used to treat infections caused by bacteria.
This medicine is used for short- and long-term treatment of serious infections caused by certain bacteria
(Gram-negative organisms), particularly for the treatment of infections:

• characterized by the presence of bacteria in the blood (bacteraemia, septicaemia), including in newborns;
• severe and recurrent infections of the urinary and genital tracts, respiratory tract, bones and/or joints (ostearticular infections), and central nervous system, including meningitis;
• of the skin, including infections developing after a burn (cutaneous and subcutaneous infections);
• inside the abdomen (intra-abdominal infections), including infection of the tissue lining the abdominal cavity (peritonitis);
• occurring after surgery.

2. What you should know before using MIKAN

Do not use MIKAN

• if you are allergic to amikacin, to other similar antibiotics (other aminoglycosides), to sodium metabisulfite (see section MIKAN contains sodium and sodium metabisulfite), or to any of the other ingredients of this medicine (listed in section 6);
• if you have previously experienced an allergic reaction or toxic reactions after using an antibiotic of the same class as MIKAN (aminoglycoside antibiotics).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using MIKAN.
As with other antibiotics, the use of this medicine may promote the development of other infections caused by bacteria or fungi to which MIKAN is not effective (superinfections). If this occurs, it is advisable to discontinue treatment with this medicine and consult your doctor, who will recommend appropriate therapy.
Use MIKAN cautiously and consult your doctor if you suffer from muscle disorders (myasthenia gravis, parkinsonism), as it may increase the sensation of muscle weakness.

Hearing problems (ototoxicity) and nervous system problems (neurotoxicity)
The use of this medicine may cause damage to hearing, kidneys, and the nervous system, especially if:

• you have kidney problems (renal insufficiency); in this case, the risk of severe hearing damage and deafness is much higher, and it is necessary to reduce the dose and increase the interval between administrations. If kidney problems occur during treatment (increased NPN, BUN, creatinine levels, or oliguria), contact your doctor, who will monitor your hearing (audiometric tests) and may decide to discontinue treatment;
• you already have hearing damage (auditory or vestibular damage);
• you are a healthy individual receiving prolonged therapy for 5–7 days with this medicine. Therefore, during treatment with this medicine, you must be closely monitored by your doctor, especially if you are elderly or if you are receiving doses exceeding 15 g of MIKAN, as hearing damage (ototoxic reactions) may occur. Deafness (high-frequency hearing loss) may occur early in treatment and can be detected by hearing tests (audiometry). In general, hearing damage caused by this medicine is irreversible, and the risk is greater if, in addition to MIKAN, you are taking another medicine, ethacrynic acid, used to treat high blood pressure (see section Other medicines and MIKAN).

Nervous system damage (neurotoxicity) may manifest as:

• hearing damage (ototoxicity affecting both vestibular and bilateral acoustic nerves); in some cases, hearing damage (cochlear or vestibular) may occur without symptoms;
• partial or total irreversible deafness, even after discontinuation of treatment;
• severe dizziness that may interfere with normal daily activities (disabling vertigo);
• dizziness (indicative of vestibular damage);
• reduced sensitivity and reflex response (numbness);
• skin tingling sensations;
• involuntary and repeated muscle contractions (spasms);
• seizures.

If you have kidney problems and have been prescribed treatment with this medicine for 5 days or more, hearing monitoring (audiogram) is recommended before starting therapy and should be repeated during treatment.
Discontinue treatment with MIKAN if you experience noises and/or ringing in the ear (tinnitus), notice a decrease in hearing, or if hearing tests show reduced perception of high-pitched sounds.
During treatment with this medicine, significant alterations in kidney function may occur; therefore, periodic monitoring of creatinine levels—a substance indicating proper kidney function—is necessary. If creatinine levels are abnormal, the frequency of administration must be adjusted.

Nerve and muscle problems (neuromuscular toxicity)
The use of this medicine may cause nerve and muscle problems (neuromuscular blockade) and respiratory paralysis (respiratory blockage). These effects are more likely if, together with MIKAN, you are using other medicines such as anesthetics or neuromuscular blockers used to reduce pain and muscle contractions during surgery (see section Other medicines and MIKAN).
In case of respiratory blockage, calcium salts may be administered, and respiratory support (mechanical ventilation) may be required.

Kidney problems
The use of MIKAN may cause kidney toxicity (nephrotoxicity), especially if you already have kidney problems, are undergoing prolonged treatment, or are receiving high doses of this medicine.
During treatment with this medicine, it is recommended to drink large amounts of fluids and to monitor kidney function before starting therapy and, once therapy has begun, daily. The dose should be reduced if blood tests show impaired kidney function (presence of urinary casts, red and white blood cells, albuminuria, reduced creatinine clearance, reduced urine specific gravity, increased blood urea nitrogen (BUN) and serum creatinine, or oliguria). Your doctor will advise you to discontinue MIKAN treatment if blood nitrogen levels increase (azotemia) or if the need to urinate progressively decreases.
If you are elderly, specific tests (creatinine clearance) are necessary to monitor kidney function, as standard tests may not be sufficient.

Be especially cautious and consult your doctor if:

• your kidney function is reduced or kidney damage is suspected before starting MIKAN therapy;
• your kidneys function normally before taking this medicine, but kidney problems develop during treatment.
  In these cases, the following are recommended:
• blood tests to determine medicine levels;
• specific urine tests (reduced specific gravity, increased protein excretion, presence of cells or urinary casts);
• periodic blood and urine tests (blood urea nitrogen, serum creatinine, or creatinine clearance);
• hearing tests if you are at high risk of developing kidney or hearing problems (serial audiograms).

If you experience dizziness, vertigo, hearing problems (tinnitus, acouphene, hearing loss), or kidney problems, consult your doctor, who will assess whether to reduce the dose or discontinue treatment.
Advanced age and low fluid levels (dehydration) may further increase the risk of the toxic effects described above.
Concurrent or sequential use of MIKAN with other medicines (administered systemically, orally, or topically) that may increase the risk of kidney or nerve problems (nephrotoxicity, neurotoxicity) should be avoided (see section Other medicines and MIKAN).

Children
This medicine should be administered only if strictly necessary and under direct medical supervision in newborns and premature infants.

Other medicines and MIKAN
Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicine.
Do not use this medicine if you are taking:

• medicines that promote fluid elimination (diuretics), such as ethacrynic acid, furosemide, sodium mercurithiazide, sodium mercaptomerin, and mannitol, as they increase the toxic effect of MIKAN on hearing.

Use this medicine with caution and consult your doctor if you are taking any of the following medicines:

• medicines used to reduce pain and muscle contractions during surgery (anesthetic and neuromuscular blocking agents), such as tubocurarine, succinylcholine, decamethonium, atracurium, rocuronium, and vecuronium; in these cases, muscle paralysis and/or respiratory blockage may occur;
• medicines that may cause nervous system, hearing, or kidney problems (neurotoxic, ototoxic, and nephrotoxic medicines), such as certain antibiotics (bacitracin, cephaloridine, paromomycin, vancomycin, streptomycin, polymyxin B, polymyxin E (colistin), neomycin, gentamicin, viomycin, or other aminoglycosides), amphotericin B (used to treat fungal infections), cisplatin (a medicine used in cancer treatment), and ciclosporin and tacrolimus (used to treat autoimmune diseases or in transplant patients); in these cases, avoid using the above-mentioned medicines concurrently or consecutively with MIKAN;
• antibiotic medicines belonging to the cephalosporin group administered intravenously or intramuscularly (parenterally), as they may increase kidney toxicity and may alter blood test results (false elevation of blood creatinine levels);
• antibacterial medicines prescribed together with MIKAN for the treatment of mixed infections or other infections caused by germs not sensitive to MIKAN (superinfections); in these cases, MIKAN must not be mixed with other medicines in the same syringe or infusion vial; in some cases, concomitant use of another antibiotic is not recommended even if administered separately;
• bisphosphonates, medicines used to treat bone problems; in this case, concurrent use may cause decreased calcium levels (hypocalcemia);
• platinum-based medicines, as they may increase the risk of kidney and hearing toxicity;
• vitamin B1, used to treat vitamin B1 deficiency; when administered together with MIKAN, it may lose its effect;
• indomethacin, when administered to a newborn for the treatment of inflammation; indomethacin may increase MIKAN blood levels in the newborn.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Use this medicine during pregnancy or when planning pregnancy only if strictly necessary and under direct medical supervision, as MIKAN crosses the placenta and may cause irreversible harm to the fetus (deafness).
If you are breastfeeding, consult your doctor, who will assess whether to discontinue breastfeeding or treatment with this medicine.
Reproductive toxicity studies in mice and rats have not shown effects on fertility or fetal toxicity.

Driving and using machines
The use of this medicine may cause adverse effects that may impair your ability to drive or operate machinery (see section Possible side effects); in this case, avoid driving and using machinery.

MIKAN contains sodium and sodium metabisulfite
This medicine contains less than 1 mmol (23 mg) of sodium per maximum dose, i.e., it is practically 'sodium-free'.
This medicine contains sodium metabisulfite, which may rarely cause severe hypersensitivity reactions and bronchospasm.

3. How to use MIKAN

This medicine will be administered to you by a doctor or a nurse.
At the recommended doses, in cases of non-severe infections caused by susceptible organisms,
an improvement in symptoms is usually observed within 1-2 days of treatment with this medicine.
The duration of treatment is 3-7 days for intravenous administration and 7-10 days for intramuscular administration.

Use in adults and adolescents (over 12 years of age)
The recommended dose for intramuscular or intravenous administration in adults and adolescents with normal renal function (creatinine clearance ≥ 50 ml/min) is 15 mg per kg of body weight per day. This dose may be given as a single dose or divided into two equal doses of 7.5 mg per kg of body weight every 12 hours.
The maximum daily dose of 1.5 g must not be exceeded.
If you have an infection of the inner lining of the heart (endocarditis) or if your white blood cell levels are low and you have fever, the recommended dose is 15 mg per kg of body weight divided into two daily administrations and not as a single dose.

Use in children (from 4 weeks to 12 years of age)
The recommended dose for intramuscular or intravenous administration (slow intravenous infusion) in children with normal renal function is 15–20 mg per kg of body weight per day. This dose may be given as a single dose or divided into two equal doses of 7.5 mg per kg of body weight every 12 hours.
If the child has an infection of the inner lining of the heart (endocarditis) or if their white blood cell levels are low and they have fever, the recommended dose is 15 mg per kg of body weight divided into two daily administrations and not as a single dose.

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

Use in premature newborns
The recommended dose is 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), consult your doctor, as it may be necessary to reduce the dose and/or increase the interval between doses.

If you use more MIKAN than you should
This medicine will be administered to you by a doctor or nurse, so overdose is unlikely. However, if you think that you have been given an excessive amount of this medicine, contact your doctor immediately or go to the nearest hospital.
In case of overdose, hearing damage, kidney damage, and nervous system disorders (ototoxicity, nephrotoxicity, and neurotoxicity) as well as muscle contraction disturbances (neuromuscular blockade) associated with respiratory arrest may occur. These effects should be appropriately treated with calcium salts (e.g. 10–20% gluconate or lactobionate solution), or mechanical blood filtration may be considered to remove the medicine from the body (peritoneal dialysis, hemodialysis, or continuous arteriovenous hemofiltration). In newborns, exchange transfusion (exsanguino-transfusion) may be considered.

If you forget to use MIKAN
Do not use a double dose to make up for a forgotten dose.
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 will experience them.
All antibiotics belonging to the same class as MIKAN may cause toxicity to the ear, kidneys, nerves, and muscles (neuromuscular blockade), especially if you already have kidney problems, are undergoing prolonged treatment, are using doses higher than those recommended for this medicine, or are taking other medicines that may cause kidney or ear toxicity (see section Warnings and precautions).

The following side effects may occur:
Uncommon (may affect up to 1 in 100 people)

• development of infections caused by bacteria or fungi to which MIKAN is not effective (see section Warnings and precautions);
• nausea, vomiting;
• skin irritation (rash).

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

• changes in levels of red and white blood cells in the blood (anaemia, eosinophilia);
• decreased levels of magnesium in the blood (hypomagnesaemia);
• tremors, sensation of reduced sensitivity in the legs and arms (paraesthesia);
• headache (cephalalgia) and balance disorders;
• perception of noises and/or ringing sounds in the ear (tinnitus), reduced hearing (hearing loss, see section Warnings and precautions);
• decreased blood pressure (hypotension);
• itching, skin irritation (urticaria);
• joint pain (arthralgia);
• repeated muscle contractions (spasms);
• reduced need to urinate (oliguria), changes in urine tests (albuminuria, red blood cells in urine, white blood cells in urine);
• changes in blood tests (increased blood creatinine, azotemia);
• fever;
• loss of vision and retinal problems (retinal infarction) if MIKAN 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, anaphylactoid reaction), hypersensitivity;
• muscle block (paralysis, see section Warnings and precautions);
• deafness and/or loss of balance, sometimes associated with nerve damage (sensorineural deafness, see section Warnings and precautions);
• kidney problems, usually reversible upon discontinuation of treatment (acute kidney failure);
• nervous system disorders (toxic neuropathy, see section Warnings and precautions);
• changes in urine tests (presence of cells in urine);
• apnoea, bronchospasm.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MIKAN

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

6. Package contents and other information

What MIKAN contains

• The active substance is amikacin sulfate. Each vial contains 1335.00 mg of amikacin sulfate, equivalent to 1000 mg of amikacin.
• The other components are sodium citrate, sodium metabisulfite, sulfuric acid, water for injections.

Description of the appearance of MIKAN and contents of the pack
Pack containing 1 vial of 4 ml.
Marketing Authorization Holder
S.F. Group S.r.l., Via Beniamino Segre 59, 00134 Roma
Manufacturer
Officina Farmaceutica Fisiopharma s.r.l. - Industrial Area - 84020 Palomonte (SA)

The following information is intended exclusively for healthcare professionals:

Preparation of the solution for direct intravenous administration (intravenous infusion)
It is recommended to dilute the contents of one vial in 100-200 ml of an appropriate solvent (physiological saline, 5% glucose solution, or Ringer's lactate solution). In children, the volume of solvent should be determined by the physician according to the dose of MIKAN to be administered. Intravenous administration should be carried out over a period of 30 to 60 minutes; in younger children, a longer duration (1-2 hours) is recommended.