Gentamicin sulfate Italfarmaco

Package leaflet: Information for the patient

Gentamicin sulfate Italfarmaco 80 mg/2 ml injectable solution

Gentamicin sulfate
Please read this leaflet carefully before you are given 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 effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Gentamicin sulfate Italfarmaco is and what it is used for
2. What you need to know before you are given Gentamicin sulfate Italfarmaco
3. How Gentamicin sulfate Italfarmaco is administered
4. Possible side effects
5. How to store Gentamicin sulfate Italfarmaco
6. Contents of the pack and other information

1. What Gentamicina solfato Italfarmaco is and what it is used for

Gentamicina solfato Italfarmaco contains the active substance gentamicin sulfate, which belongs to a
group of medicines called aminoglycoside antibiotics.
This medicine is indicated for the treatment of the following infections caused by bacteria that can be
eliminated by gentamicin:

• Respiratory tract infections (infections of the pleura and lungs);
• Acute and chronic kidney, urinary tract, bladder, and prostate infections;
• Systemic infections, for example, those in which bacteria are persistently present in the blood;
• Nervous system infections, such as inflammation of the membranes surrounding the brain (meningitis), infections of the brain and its surrounding membranes (meningoencephalitis), etc.;
• Post-surgical infections: localized infections (abscesses), localized infections that may spread to nearby organs (phlegmons), bone and bone marrow infections (osteomyelitis), infections following trauma;
• Ear, nose, and throat infections: middle ear infections (purulent otitis media), paranasal sinus infections (sinusitis), infections of the posterior portion of the temporal bone, called the mastoid (mastoiditis), tonsil infections (tonsillitis), pharynx and tonsil infections (pharyngotonsillitis);
• Obstetrical and gynecological infections: infections causing premature termination of pregnancy (septic abortion), infections of the uterus and surrounding tissues (metritis, parametritis), infections of the fallopian tubes and ovaries (salpingitis, salpingo-oophoritis), infections of the internal abdominal cavities (pelvi-peritonitis), breast infections (mastitis), etc.;
• Infections due to severe burns and following skin grafts. In these cases, Gentamicina solfato Italfarmaco may be used, if necessary, in combination with the locally acting pharmaceutical form.

Furthermore, in severe, life-threatening infections, Gentamicina solfato Italfarmaco may be
used in combination with other antibiotics:

• beta-lactam antibiotics such as carbenicillin or similar antibiotics in case of infections caused by Pseudomonas aeruginosa;
• penicillin-type antibiotics in case of inflammation of the inner lining of the heart (endocarditis) caused by group D Streptococcus infections.

2. What you should know before being administered Gentamicina solfato Italfarmaco

Do not be administered Gentamicina solfato Italfarmaco if:

• you are allergic to gentamicin sulfate or to any of the other ingredients of this medicine (listed in section 6);
• you are allergic to other aminoglycoside antibiotics (medicines of the same class as Gentamicina solfato Italfarmaco), as you may also be allergic to gentamicin (cross-allergy);
• you have a disease called Myasthenia gravis;
• you are pregnant or breastfeeding (see "Pregnancy and breastfeeding").

Warnings and precautions
Talk to your doctor or nurse before being administered Gentamicina solfato Italfarmaco.

During treatment with Gentamicina solfato Italfarmaco, you must remain under close medical supervision due to the potential toxicity associated with the use of aminoglycoside antibiotics (especially affecting the kidneys and ears). Symptoms of ototoxic effects include: dizziness, perception of ringing or rushing noises in the ear (tinnitus), vertigo, and less commonly, hearing loss. Elderly patients may have reduced kidney function, which might not be immediately evident. Your doctor may periodically monitor kidney function through routine laboratory tests such as blood urea nitrogen or serum creatinine, as well as liver and ear function. Additionally, periodic urine tests and monitoring of electrolyte levels and blood concentration of the medicine may be necessary.

In some patients (adults and children) treated with gentamicin, a condition affecting the passage of certain substances through the kidney, known as Fanconi-like syndrome, has been reported, characterized by excretion of protein derivatives in the urine (aminoaciduria) and accumulation of acids in the body (metabolic acidosis).

Exercise particular caution with Gentamicina solfato Italfarmaco and consult your doctor if:

• you are elderly or a child, as you may be particularly sensitive; during treatment, you must remain under close medical supervision;
• you have kidney problems or need to receive high doses or prolonged treatment, due to an increased risk of kidney and/or ear toxicity (both balance and hearing). If you experience signs of ear toxicity (confusion, vertigo, tinnitus, ringing in the ears, or hearing loss) or kidney problems, your doctor will need to adjust the dose of Gentamicina solfato Italfarmaco or discontinue treatment;
• you have lost excessive amounts of water from your body (if you are dehydrated);
• you have any condition affecting nerve and muscle function, such as myasthenia gravis (muscle weakness and fatigue), parkinsonism (a disease characterized by movement disorders such as tremors, rigidity, and slowness of movement), or infantile botulism (botulinum toxin poisoning in children), as use of this medicine could worsen muscle weakness;
• you develop a new infection during treatment, as treatment with this medicine may lead to excessive growth of bacteria resistant to gentamicin. In this case, contact your doctor, as it may be necessary to discontinue treatment with Gentamicina solfato Italfarmaco and start appropriate therapy. If you have asthma or develop an allergic reaction, including anaphylaxis (a severe, rapidly developing allergic reaction) or asthma (airway obstruction), even very severe reactions, as Gentamicina solfato Italfarmaco contains sodium bisulfite, a substance that may cause allergic-type reactions;
• you develop a skin reaction after administration of the medicine, as severe skin toxic reactions have been reported, including Stevens-Johnson syndrome (an acute reaction involving skin and mucous membranes) and toxic epidermal necrolysis (death of the outer layer of the skin);
• you are taking other antibiotics at the same time and develop diarrhea during or after treatment with Gentamicina solfato Italfarmaco, due to the risk of colon inflammation caused by bacterial toxins (pseudomembranous colitis). If you experience severe diarrhea and/or bloody diarrhea, stop treatment with Gentamicina solfato Italfarmaco and contact your doctor to start appropriate therapy. Drugs that inhibit peristalsis must not be administered (see section on undesirable effects).

Children
In very early infancy, this medicine should be administered only when strictly necessary and under direct medical supervision (see "How Gentamicina solfato Italfarmaco is administered").

Other medicines and Gentamicina solfato Italfarmaco
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

In particular, inform your doctor if you are taking:

• other aminoglycoside antibiotics, due to the risk of allergic reaction (cross-allergy) and increased risk of kidney toxicity;
• other medicines potentially toxic to the kidneys, for example:
  • high-dose methotrexate (a medicine used to treat rheumatoid arthritis, psoriasis, and some cancers);
  • cisplatin, organoplatinum compounds, ifosfamide (anticancer medicines). With cisplatin-containing medicines, note that gentamicin nephrotoxicity may increase even 3-4 weeks after administration;
  • polymyxin B, colistin, streptomycin, vancomycin, kanamycin, amikacin, neomycin, paromomycin, tobramycin, pentamidine, certain cephalosporins (antibiotics);
  • acyclovir, ganciclovir, adefovir, cidofovir, tenofovir, foscarnet (antiviral medicines);
  • amphotericin B (used against certain fungal infections);
  • cyclosporine or tacrolimus (immunosuppressive medicines);
  • iodinated contrast media (substances used in radiological imaging);
  • potent diuretics (medicines that increase urine production, such as ethacrynic acid and furosemide). The concomitant use of ethacrynic acid or furosemide with Gentamicina solfato Italfarmaco is contraindicated also due to the possible ototoxicity. Moreover, when administered intravenously, they may increase gentamicin toxicity by altering its blood and tissue concentrations;
• beta-lactam antibiotics (penicillins or cephalosporins), due to the risk of reduced efficacy;
• carbenicillin, if you have severe kidney problems (renal failure), as the efficacy of gentamicin may be reduced.

Aminoglycosides may enhance the harmful renal effects of methoxyflurane. When used concomitantly, severe nephropathies may occur. The anaesthetist must be informed of aminoglycoside use before surgery.

Additionally, inform your doctor that you are taking Gentamicina solfato Italfarmaco if you are scheduled for surgery, as this medicine may interfere with certain medicines used in anaesthesia (succinylcholine, tubocurarine, decamethonium), since such interactions may cause neuromuscular blockade and respiratory paralysis. Also inform your doctor if you are scheduled to receive massive blood transfusions containing citrate as an anticoagulant. Due to the increased risk, such patients must be monitored particularly closely.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before being administered this medicine.

Pregnancy
Aminoglycoside antibiotics may cause fetal harm. Therefore, this medicine will not be administered during pregnancy unless your doctor considers it absolutely necessary due to the severity of your illness.

Although no serious adverse effects on the mother, fetus, or newborn have been reported following gentamicin treatment during pregnancy, you must be informed of the potential risks before administration of Gentamicina solfato Italfarmaco, as aminoglycoside antibiotics cross the placenta and may harm the fetus. In newborns of mothers treated during pregnancy with certain aminoglycoside antibiotics, irreversible bilateral deafness has been reported. If you receive Gentamicina solfato Italfarmaco during pregnancy or discover you are pregnant while taking it, you must be informed of the potential risk to the fetus. In cases of gentamicin exposure during pregnancy, monitoring of the newborn's kidney and hearing function is recommended.

Breastfeeding
Due to the potential risk of serious adverse effects in the infant, such as sensitization, diarrhea, and fungal infections of mucous membranes caused by aminoglycosides in breast milk, your doctor will carefully evaluate whether to discontinue breastfeeding or discontinue treatment with Gentamicina solfato Italfarmaco, depending on the severity of your condition.

Driving and using machines
This medicine may impair your ability to drive or operate machinery. If you experience adverse effects such as dizziness, vertigo, hearing loss, or drowsiness, do not drive or use machinery (see "Possible side effects").

Gentamicina solfato Italfarmaco contains sodium metabisulfite, parabens, and sodium
This medicine contains sodium metabisulfite, which may cause severe hypersensitivity reactions and bronchospasm (narrowing of the airways causing breathing difficulty).

Gentamicina solfato Italfarmaco contains parabens (preservatives) such as methyl p-hydroxybenzoate and propyl p-hydroxybenzoate, which may cause allergic reactions (including delayed reactions) and, rarely, bronchospasm.

This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially "sodium-free".

3. How Gentamicina solfato Italfarmaco is administered

Gentamicina solfato Italfarmaco will be administered to you by a doctor or nurse at a hospital or clinic.
The medicine can be given into the muscle (intramuscular route) or into a vein (intravenous route). The recommended doses are the same in both cases.
Intravenous administration is recommended when intramuscular administration is not possible (for example, if you are in shock, or have severe bleeding, blood disorders, severe burns, reduced muscle mass, or suffer from serious bone marrow diseases). In these cases, intravenous administration should preferably be performed by infusion over 1-2 hours.
The dose of medicine you will receive and the frequency of administration will depend on the reason for treatment, your age, body weight, and any kidney problems you may have.
The usual duration of treatment is 7-10 days. In severe or complicated infections, a longer treatment period may be necessary. In such cases, the risk of adverse effects may increase; therefore, your doctor will pay particular attention to monitoring kidney function, hearing, and balance. However, it is generally advisable to continue therapy for at least 48 hours after the fever has subsided.

Use in children
In very early infancy, the medicine should be administered only when strictly necessary and under direct medical supervision.

Use in patients with impaired kidney function
Gentamicina solfato Italfarmaco is mainly eliminated through the kidneys; therefore, the dose and frequency of administration will be determined by your doctor based on your kidney function and body weight.

If you are given more Gentamicina solfato Italfarmaco than you should
In case of accidental overdose or administration of an excessive dose of Gentamicina solfato Italfarmaco, inform your doctor immediately or go to the nearest hospital.
In cases of overdose or toxic reactions, blood filtration (dialysis) allows rapid removal of gentamicin from the blood. In newborns, blood transfusions may be performed.
These procedures are particularly important in patients with kidney failure.

If you forget to take Gentamicina solfato Italfarmaco
If you miss an injection, it should be given as soon as possible. However, if it is almost time for the next scheduled injection, skip the missed dose. Do not take a double dose (two injections together) to make up for a forgotten dose. In any case, consult your doctor or nurse.

If you stop taking Gentamicina solfato Italfarmaco
Do not stop taking Gentamicina solfato Italfarmaco unless instructed by your doctor.
If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

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

Very rare

• Acute renal failure.
• High levels of phosphate and amino acids in the urine (so-called Fanconi-like syndrome, associated with administration of high doses over long periods).

Frequency not known (frequency cannot be estimated from the available data):

• Kidney disorders such as presence in urine of casts, cells or proteins, increased blood urea nitrogen, non-protein nitrogen and creatinine, decreased urine output (oliguria), particularly in elderly and pediatric patients and in patients with renal impairment or treated for longer periods and/or with higher than recommended doses;
• Hearing disorders including noises such as ringing, buzzing, hissing, pulsations, etc. (tinnitus), reduced hearing sensitivity (even irreversible), and balance disturbances (vestibular) (also irreversible), particularly in patients with renal impairment or undergoing prolonged treatment and/or with high doses. Other factors that may increase the risk of medicine-induced ear damage (ototoxicity) include: dehydration, concomitant administration of medicines that increase urine production (diuretics) such as ethacrynic acid and furosemide, or previous administration of other ototoxic substances affecting the ear and labyrinth (the site of the balance organ).
• Irreversible hearing loss, deafness;
• seizures;
• hallucinations;
• dizziness;
• epileptic fits;
• numbness, drowsiness;
• altered sensation in limbs or other parts of the body (paraesthesia);
• muscle twitching (fasciculation), severe muscle weakness (myasthenia gravis-like syndrome);
• fever;
• headache;
• confusion, depression;
• polyneuropathies, encephalopathy, neuromuscular blockade;
• breathing problems (respiratory depression);
• vision disturbances;
• loss of appetite (anorexia), weight loss;
• nausea, vomiting;
• excessive saliva production (sialorrhea);
• mouth inflammation (stomatitis);
• temporary enlargement of the liver (hepatomegaly);
• high blood pressure (hypertension);
• low blood pressure (hypotension);
• hypersensitivity reactions of variable severity, such as drug fever, severe acute hypersensitivity reactions (anaphylaxis), anaphylactic shock;
• allergic-type skin rashes or reactions due to a substance present in the medicine (idiosyncratic reaction);
• changes in certain laboratory tests: increased serum transaminases (AST, ALT), lactate dehydrogenase (LDH), alkaline phosphatase and bilirubin;
• reduced levels of calcium, magnesium, potassium and sodium in the blood;
• alterations in kidney function tests;
• excretion of protein metabolites in the urine (aminoaciduria) and accumulation of acids in the body (metabolic acidosis);
• anaemia;
• blood dyscrasias;
• decrease or increase in white blood cells in the blood (leucopenia, granulocytopenia, transient agranulocytosis, eosinophilia);
• increase or decrease in certain red blood cells called reticulocytes;
• decrease in platelets in the blood (thrombocytopenia);
• pain and/or signs of irritation at the injection site, thinning of tissues under the skin (subcutaneous atrophy);
• excessive sleepiness (lethargy);
• depression;
• swelling of the larynx (laryngeal oedema);
• skin redness with possible more severe skin manifestations (erythema multiforme);
• severe skin toxic reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• haemorrhagic manifestations in tissues characterised by spots of varying size (purpura);
• increased pressure inside the skull (pseudotumor cerebri);
• degeneration of the brain (acute organic brain syndrome); alteration of lung tissue (pulmonary fibrosis); loss of hair and body hair (alopecia); joint pain; temporary enlargement of the spleen (splenomegaly); chronic inflammation of the intestinal colon (pseudomembranous colitis).

Following the instructions provided in this leaflet reduces the risk of side effects.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gentamicin Sulfate Italfarmaco

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. The expiry date refers to the product in its original sealed packaging, correctly stored.
Store this medicine in its original packaging to protect it from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Gentamicina solfato Italfarmaco contains

• The active substance is gentamicin sulfate. 1 vial of 2 ml contains 96.9 mg of gentamicin sulfate (equivalent to 80 mg of gentamicin base).
• The other components are: methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, sodium metabisulfite, water for injections, diluted sulfuric acid (pH adjuster), diluted sodium hydroxide (pH adjuster).

Description of the appearance of Gentamicina solfato Italfarmaco and package contents
Gentamicina solfato Italfarmaco is a sterile solution for injection.
The pack contains 1 vial of 80 mg/2 ml for intramuscular or intravenous use.
Marketing Authorization Holder
Italfarmaco S.p.A. - Viale Fulvio Testi, 330 - 20126 Milan
Manufacturer
Officina Farmaceutica Biologici Italia Laboratories S.r.l. - Via Filippo Serpero, 2 - 20060 Masate (MI)

The following information is intended exclusively for healthcare professionals:

Read carefully also the information contained in sections 1-6.
Warnings and precautions
Excessive peaks and/or excessively high blood concentrations of aminoglycosides may increase the risk of renal or eighth cranial nerve toxicity.
Prolonged peaks above 12 mcg/mL and trough levels prior to the next injection exceeding 2 mcg/mL should be avoided by spacing out administrations or reducing the dosage when necessary.
Other medicines and Gentamicin sulfate Italfarmaco
The product must not be mixed in the same syringe with other medicines.
How to administer Gentamicin sulfate Italfarmaco
Intravenous administration should preferably be performed by infusion over 1-2 hours, using the same doses indicated for intramuscular route.
Each single dose should be diluted in 100-200 mL of physiological saline or 5% dextrose solution; in children, the volume of diluent should be reduced. In any case, the concentration of Gentamicin sulfate Italfarmaco should not exceed 1 mg/mL (0.1%).
Gentamicin sulfate Italfarmaco may be administered intravenously without dilution (however, this method should be limited to exceptional cases).
Intrathecal administration
Patients considered for intrathecal gentamicin treatment are usually simultaneously receiving systemic gentamicin therapy. All warnings and precautions for this or other concurrently administered products must be observed, and the possibility of additive effects should be considered. Furthermore, the risk of directly administering a potentially neurotoxic drug into the cerebrospinal fluid spaces of the central nervous system must be weighed against the potential benefit derived from this route of administration. Safety and efficacy have not been established in children under three months of age. The safety of intrathecal injection of gentamicin during pregnancy has not been defined.
A) Patients with normal renal function
Adults: The recommended dose for the treatment of systemic infections is 3 mg/kg/day (1 mg/kg every 8 hours or 1.5 mg/kg every 12 hours).
In life-threatening infections, a dosage regimen of up to 5 mg/kg/day administered in 3 or 4 divided doses is recommended for the first 2-3 days of treatment; thereafter, the dose should be reduced to 3 mg/kg/day.
For urinary tract infections and moderate extra-urinary infections, 2 mg/kg/day in two divided doses may be sufficient.
Guideline dosing schedule for patients weighing over 50 kg:

• 80 mg, three times daily.
• 80 mg, twice daily for urinary tract infections and moderate extra-urinary infections.

Children: In early infancy, the product should be administered only when strictly necessary and under direct medical supervision.
The recommended dose varies according to age, as follows:

Dosage adjustments must be made according to the patient's age, type and severity of infection.
In obese patients, the dosage should be calculated based on their ideal body weight.
The usual duration of treatment is 7–10 days. In severe or complicated infections, a longer treatment period may be required. In such cases, the risk of adverse effects may increase; therefore, particular attention should be paid to monitoring renal, auditory, and vestibular function.
Nevertheless, it is advisable to continue therapy for at least 48 hours after the fever has subsided.
B) Patients with impaired renal function
As with all drugs that are predominantly eliminated via the renal route, the dosing frequency should be adjusted according to renal function, following the scheme below:

The frequency of administrations can be approximately calculated by multiplying the serum creatinine by 8, according to the following formula:
Serum creatinine in mg/100 ml × 8 = interval between two consecutive administrations (in hours).
Hemodialysis. In adult patients with renal failure undergoing hemodialysis, the amount of gentamicin removed from plasma may vary depending on several factors, including the dialysis method employed. A six-hour hemodialysis session can reduce plasma gentamicine levels by approximately 50%.
Recommended doses at the end of each dialysis range between 1–1.7 mg/kg, depending on the severity of the infection. In children, doses of 2–2.5 mg/kg may be administered. Aminoglycoside antibiotics are removed from the blood during peritoneal dialysis, but to a lesser extent than with hemodialysis.
The medicinal product must not be mixed in the same syringe with other medicinal products.
In vitro, the combination of an aminoglycoside with a beta-lactam antibiotic (penicillins or cephalosporins) may result in mutual inactivation.
Recommended monitoring:
Monitoring of serum gentamicin concentration is recommended. Excessively high peaks and/or persistently elevated blood levels of aminoglycosides may increase the risk of renal or eighth cranial nerve toxicity.
Prolonged peak levels exceeding 12 mcg/ml and trough levels before the next injection exceeding 2 mcg/ml should be avoided by increasing the interval between administrations or reducing the dosage, when necessary.
Overdose
In cases of overdose or toxic reactions, hemodialysis allows rapid removal of gentamicin from plasma. The percentage of removal is considerably lower with peritoneal dialysis. In neonates, blood transfusions may be performed. These procedures are particularly important in patients with renal failure.
Treatment of neuromuscular blockade:
In case of neuromuscular blockade (usually caused by interactions, see section Other medicinal products and Gentamicin Sulfate Italfarmaco), administration of calcium chloride is recommended and, if necessary, artificial ventilation should be instituted.