Gentamicin sulfate L.F.M.

Package leaflet: Information for the user

GENTAMICIN SULFATE L.F.M. 80 mg/2ml Solution for injection

Equivalent 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 effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Gentamicin Sulfate L.F.M. is and what it is used for
2. What you need to know before using Gentamicin Sulfate L.F.M.
3. How to use Gentamicin Sulfate L.F.M.
4. Possible side effects
5. How to store Gentamicin Sulfate L.F.M.
6. Contents of the pack and other information

1. What Gentamicina Solfato L.F.M. is and what it is used for

Gentamicina Solfato L.F.M. contains the active substance gentamicin sulfate, belonging to a group of medicines called aminoglycoside antibiotics, used to treat infections caused by bacteria.
This medicine is used to treat many infections that can be eradicated by gentamicin, such as those affecting the chest (lungs and pleura), urinary tract, kidneys and bladder, bloodstream, following surgical procedures, nervous system, throat, ears and nose (otorhinolaryngological infections), during pregnancy and childbirth, and in infections of the female genital tract (obstetric-gynecological infections) as well as infections of the skin and soft tissues (infections following severe burns and skin grafts).
Gentamicina Solfato L.F.M. may be considered a first-line treatment when the infection is caused by bacteria known as Gram-negative organisms.
If a very severe and life-threatening infection is present, your doctor may prescribe this medicine in combination with another antibiotic (a beta-lactam antibiotic, for example carbenicillin or similar, indicated for infections caused by the bacterium Pseudomonas aeruginosa, and a penicillin-type antibiotic, indicated for endocarditis, heart infections, caused by bacteria called Group D Streptococci).

2. What you need to know before using Gentamicina Solfato L.F.M.

Do not use Gentamicina Solfato L.F.M.

• if you are allergic to gentamicin or to any of the other ingredients of this medicine (listed in section 6);
• if you have previously experienced allergic or toxic reactions after using antibiotics belonging to the same class as Gentamicina Solfato L.F.M.;
• if you suffer from myasthenia gravis;
• if you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Gentamicina Solfato L.F.M.
If you have kidney problems (severe renal impairment) or ear problems (previous inner ear deafness), your doctor will prescribe gentamicin only if considered essential. Your doctor will reduce the frequency or dose if you have impaired kidney function (see section 3 “How to use Gentamicina Solfato L.F.M.”).
During treatment with gentamicin, renal failure (e.g. reduced glomerular filtration) may develop, which usually resolves upon discontinuation of therapy. The main risk factors are high total dose, prolonged treatment, increased serum levels (high trough levels); additional possible risk factors include age, reduced circulating blood volume (hypovolemia), and shock. Acute renal failure may occur in isolated cases (see also section 4 “Possible side effects”).
Your doctor will periodically assess your kidney function and serum electrolyte levels if you are being treated with Gentamicina Solfato L.F.M. for more than 7–10 days for severe infections or if you may receive higher doses than recommended based on age, weight, or presumed renal function.
Like other aminoglycosides, Gentamicina Solfato L.F.M. injectable solution may cause kidney damage (nephrotoxic effect). This risk increases if you have impaired kidney function and if you receive high doses or prolonged treatment.
If you are elderly, you may have reduced kidney function, which may not be evident with routine laboratory tests (e.g. blood urea nitrogen, serum creatinine). Measurement of creatinine clearance may be more useful. Your doctor will monitor your kidney function during treatment with gentamicin, as with other aminoglycosides.
Drink plenty of fluids during treatment with this medicine.
Damage to the vestibulocochlear nerve (eighth cranial nerve) may occur, potentially affecting balance and hearing. The most common ototoxic reaction is vestibular damage. Hearing loss initially manifests as reduced hearing acuity at high frequencies and is usually irreversible. Important risk factors include pre-existing kidney dysfunction or a history of damage to the eighth cranial nerve; additionally, the risk increases proportionally with total and daily dose levels or with concomitant use of potentially ototoxic substances.
Symptoms of ototoxic effects include: dizziness, ringing or roaring sounds in the ears (tinnitus), vertigo, and, less commonly, hearing loss.
Gentamicin may affect the vestibular mechanism if trough blood levels exceed 2 µg/ml. This is usually reversible if detected promptly and if your doctor adjusts the dose (see also section 4 “Possible side effects”).
To reduce the risk of adverse effects associated with the use of Gentamicina Solfato L.F.M. (nephrotoxicity and ototoxicity), your doctor will perform careful monitoring of kidney function (serum creatinine, creatinine clearance), hearing (vestibular and cochlear function), and liver function before, during, and after treatment, especially in children and elderly patients and if you have low fluid levels (dehydration). Additionally, your doctor may monitor blood levels of the medicine (serum gentamicin concentration) and adjust the dose accordingly, particularly in elderly patients, newborns, and patients with impaired kidney function.
If you have extensive skin burns, your doctor will adjust the dose based on blood gentamicin levels.
In patients with significant obesity, your doctor will monitor blood gentamicin concentrations and may reduce the dose.
During treatment with this medicine, the following may occur:

• infections caused by microorganisms to which this medicine is not effective (superinfections); if you notice signs of infection, consult your doctor, who will recommend appropriate therapy for these symptoms;
• increased acidity and presence of amino acids in urine (Fanconi-like syndrome with metabolic acidosis and aminoaciduria), in both adults and children.

Children
The use of this medicine in early infancy is recommended only when absolutely necessary and under direct medical supervision.

Other medicines and Gentamicina Solfato L.F.M.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Avoid using Gentamicina Solfato L.F.M. if you are already taking the following medicines, as they may increase the risk of kidney problems (nephrotoxicity) or hearing problems (ototoxicity):

• other antibiotics (polymyxin B, colistin, viomycin, streptomycin, vancomycin, other aminoglycosides, other penicillin-group antibiotics, and certain cephalosporins such as cephaloridine);
• medicines used to treat immune system disorders or in transplant patients (immunosuppressants such as cyclosporine);
• medicines used to treat certain types of cancer (cisplatin);
• medicines used to promote fluid elimination from the body (potent diuretics such as ethacrynic acid and furosemide), since these diuretics have ototoxic properties. If use of the above medicines is necessary, your doctor must carefully monitor kidney function.

Use this medicine with caution and inform your doctor if you are undergoing the following treatments with Gentamicina Solfato L.F.M.:

• blood transfusions (with citrate-containing blood as anticoagulant) or if you are using anesthetic medicines or medicines used during surgery to reduce muscle contractions (succinylcholine, tubocurarine, or other anesthetic medicines). In these cases, muscle blockade may occur, which can be treated by administering calcium salts.
• if you are to receive methoxyflurane before surgery. Gentamicin may increase its kidney toxic effects.
• if you have severe kidney problems (severe renal insufficiency) and carbenicillin, an antibiotic medicine, is prescribed together with Gentamicina Solfato L.F.M., as this may reduce the effectiveness of Gentamicina Solfato L.F.M.
• if you are taking oral anticoagulant medicines, because gentamicin may enhance effects reducing a substance called thrombin involved in blood clotting (hypoprothrombinemic effects).
• if you are taking medicines known as bisphosphonates, because this increases the risk of low calcium levels in the blood (hypocalcemia).
• if botulinum toxin is administered concurrently, as this may increase the risk of toxicity due to neuromuscular blockade.
• if you are taking neostigmine and pyridostigmine, because these medicines counteract the effects of gentamicin.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
This medicine crosses the placenta and may harm the fetus.
If Gentamicina Solfato L.F.M. is administered during pregnancy or if you become pregnant while taking Gentamicina Solfato L.F.M., you must be informed of the potential risk to the fetus.
In case of exposure to gentamicin during pregnancy, monitoring of the newborn’s kidney and hearing function is recommended.
Cases of irreversible bilateral congenital deafness have been reported in children whose mothers received aminoglycosides, including Gentamicina Solfato L.F.M., during pregnancy.
Inform your doctor if you are breastfeeding. In breastfeeding women, Gentamicina Solfato L.F.M. is excreted in breast milk in small amounts. The breastfed newborn may develop diarrhea and fungal infections of mucous membranes, which may require discontinuation of breastfeeding.
Be aware of the possibility of sensitization. Due to the potentially serious adverse reactions associated with aminoglycosides, a decision must be made whether to discontinue breastfeeding or discontinue the treatment, taking into account the importance of the medicine for the mother.
Your doctor will assess whether it is necessary to discontinue breastfeeding or stop treatment with this medicine.

Driving and using machines
This medicine may affect your ability to drive and use machinery because it may cause side effects such as dizziness, vertigo, hearing loss, and reduced reflexes. If you experience these symptoms, avoid driving and using machinery.

Gentamicina Solfato L.F.M. contains hydroxy-benzoates, sodium metabisulfite, and sodium
This medicine contains parahydroxy-benzoates, which may cause allergic reactions (including delayed reactions) and, rarely, bronchospasm.
This medicine contains sodium metabisulfite, which may rarely cause severe hypersensitivity reactions and bronchospasm.
This medicine contains less than 23 mg (1 mmol) of sodium per dose, i.e., it is practically "sodium-free".

3. How to use Gentamicin Sulfate L.F.M.

This medicine will be administered to you by a doctor or nurse, into a muscle (intramuscular route) or into a vein (intravenous route). The doctor will adjust the dose according to your age, type and severity of infection.

A) Patients with normal renal function

Adults:
The recommended dose is 3 mg per kg of body weight per day. This dose may be divided into three daily administrations every 8 hours (1 mg per kg of body weight), or into two daily administrations every 12 hours (1.5 mg per kg of body weight).

In severe, life-threatening infections, the maximum recommended daily dose is 5 mg per kg of body weight, administered in 3 or 4 divided doses for the first 2–3 days of treatment. Subsequently, the daily dose should be reduced to 3 mg per kg of body weight.

For the treatment of moderate urinary and extrarenal infections, the recommended daily dose is 2 mg per kg of body weight, given in two divided doses.

Suggested dosage regimen for patients weighing over 50 kg:

• 80 mg, three times daily.
• 80 mg, twice daily in urinary tract infections and moderate extrarenal infections.

If you are overweight, your doctor will adjust the dose accordingly.

Children: In the earliest stages of infancy, this product should be administered only when strictly necessary and under direct medical supervision.

The recommended dose varies according to age as follows:

Total daily dose | Single dose
---|---
Premature infants and full-term neonates up to 1 week of age | 5–6 mg/kg/day | 2.5–3 mg/kg every 12 hours
Infants and neonates over 1 week of age | 7.5 mg/kg/day | 2.5 mg/kg every 8 hours
Children | 6–7.5 mg/kg/day | 2–2.5 mg/kg every 8 hours

Practical dosing guidelines:

Full-term neonates with body weight between 3.5 and 5 kg: The recommended dose ranges from 2 to 2.8 mg per kg of body weight every 12 hours.

Children weighing 5 to 10 kg: The recommended dose ranges from 2 to 4 mg per kg of body weight every 8–12 hours.

Children weighing 11 to 20 kg: The recommended dose is 40 mg every 8–12 hours.

In overweight children, the doctor will adjust the dose accordingly.

The doctor will adapt the dosage according to the patient's age, type and severity of infection. In obese patients, dosing should be based on 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, the doctor must pay particular attention to monitoring renal, auditory, and vestibular function. It is generally advisable to continue therapy for at least 48 hours after defervescence.

B) Patients with impaired renal function

As with all drugs that are primarily eliminated via the kidneys, the frequency of administration will be determined by the doctor according to renal function, following the table below:

The frequency of administrations can be approximately calculated by multiplying the
serum creatinine by 8, according to the following formula:
mg/100 ml serum creatinine x 8 = interval between two consecutive administrations (in hours).
Hemodialysis. In adult patients with renal failure undergoing mechanical blood filtration sessions (hemodialysis), the amount of gentamicin removed from plasma may vary depending on several factors, including the dialysis method used. A 6-hour hemodialysis session may reduce plasma gentamicin levels by approximately 50%.
Recommended doses at the end of each dialysis session 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 compared to hemodialysis.
The medicine must not be mixed in the same syringe with other drugs.
If you use more Gentamicina Solfato L.F.M. than you should
This medicine will be administered by a doctor or nurse, so it is unlikely that an overdose will occur. However, if you think you have been given too much of this medicine, inform your doctor immediately or go to the nearest hospital.
Treatment of overdose may include mechanical blood filtration (hemodialysis) to remove the medicine from the body.
In case of overdose in newborns, treatment includes blood transfusion.
These procedures are particularly important in patients suffering from kidney problems (renal failure).
Treatment of neuromuscular blockade:
In case of neuromuscular blockade (normally caused by interactions, see section “Other medicines and Gentamicina Solfato L.F.M.”), administration of calcium chloride is recommended and, if necessary, artificial ventilation should be performed.
If you forget to use Gentamicina Solfato L.F.M.
Do not use a double dose to make up for the forgotten dose.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
There are insufficient data available to determine the frequency of individual side effects listed below.
The following side effects may occur:

• presence of protein in the urine (proteinuria);
• impaired renal function, acute renal failure, increased acidity, high levels of phosphates and amino acids in the urine (so-called Fanconi-like syndrome associated with administration of high doses over long periods), reversible increase in blood nitrogen (azotemia);
• hearing and labyrinth problems presenting as vestibular damage, hearing loss, Ménière's disease, perception of ringing in the ear (tinnitus), reduced hearing (which may be irreversible), irreversible hearing loss, deafness, vertigo;
• breathing problems (respiratory depression);
• joint pain;
• confusion, depression, hallucinations, severe brain damage (acute organic brain syndrome);
• visual disturbances;
• decreased appetite (anorexia) and body weight;
• low or high blood pressure (hypotension, hypertension);
• nausea, vomiting, excessive salivation (sialorrhea), fungal infection of the mouth (stomatitis), transient alteration in liver size (hepatomegaly), inflammation of the intestine (pseudomembranous colitis);
• superinfection (by germs resistant to gentamicin);
• changes in laboratory test results (increased serum transaminases (AST, ALT), lactate dehydrogenase (LDH), alkaline phosphatase and bilirubin; decreased blood levels of calcium, magnesium, potassium and sodium), alterations in kidney function tests;
• hypersensitivity reactions of varying severity, from skin rash and itching, drug fever to severe acute hypersensitivity reactions (anaphylaxis) up to anaphylactic shock;
• fever and headache (cephalalgia), pain or irritation at the injection site, subcutaneous atrophy or signs of local irritation;
• encephalopathy, diseases affecting peripheral nerves (polyneuropathies), neuromuscular blockade, dizziness, reduced reflexes (numbness), tingling sensation in arms and/or legs (paresthesia), involuntary muscle contractions (fasciculation), convulsions, epileptic seizures, other muscle disorders (myasthenia gravis);
• changes in white blood cell levels (leukopenia, granulocytopenia, transient agranulocytosis, eosinophilia), changes in red blood cell levels (anemia, increased or decreased reticulocytes), decreased platelet levels (thrombocytopenia), alteration in blood composition (dyscrasia);
• various types of skin rashes due to allergy or to a substance present in the medicine (idiosyncratic reaction), swelling of the throat due to fluid accumulation (laryngeal edema), severe skin disorders (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), irritation associated with skin bleeding (purpura), hair loss (alopecia).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at the following address:
http://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 L.F.M.

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

6. Package contents and other information

What Gentamicina Solfato L.F.M. contains
The active substance is gentamicin sulfate. Each vial contains 96.9 mg of gentamicin sulfate equivalent to 80 mg of gentamicin.

• Other components are: methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, edetate sodium, sodium metabisulfite, sodium hydroxide, diluted hydrochloric acid as buffering agent, water for injections q.s. to 2 ml.

Description of the appearance of Gentamicina Solfato L.F.M. and package contents
Gentamicina Solfato L.F.M. 80 mg/2 ml Solution for injection: pack of 3 vials containing 80 mg/2 ml.
Marketing Authorization Holder and Manufacturer
LABORATORIO FARMACOLOGICO MILANESE S.r.l. - Via Monterosso 273, 21042 Caronno Pertusella (VA).

The following information is intended exclusively for healthcare professionals:

DOSAGE AND ADMINISTRATION
Gentamicin Sulfate L.F.M. can be administered intramuscularly or intravenously. The dosage is the same for both routes.
The intravenous route is recommended when intramuscular administration is not feasible (patients in shock, with hemorrhagic manifestations, hematological disorders, severe burns, reduced muscle mass, or with myeloproliferative disorders).
Intravenous administration should preferably be performed by infusion over 1-2 hours, using the same doses indicated for intramuscular administration. Each single dose must 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 L.F.M. must not exceed 1 mg/ml (0.1%).
Gentamicin Sulfate L.F.M. has also been administered intravenously without dilution (this method, however, should be limited to exceptional cases).

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).
For life-threatening infections, a dosage of up to 5 mg/kg/day is recommended, administered in 3 or 4 divided doses during 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.

Suggested dosage regimen 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, this product should be administered only when strictly necessary and under direct medical supervision. The recommended dose varies according to age, as follows:

Total daily dose  Single dose
Premature infants and full-term neonates
up to 1 week of age  5–6 mg/kg/day  2.5–3 mg/kg every 12 hours
Infants and neonates
beyond 1 week of age  7.5 mg/kg/day  2.5 mg/kg every 8 hours
Children  6–7.5 mg/kg/day  2–2.5 mg/kg every 8 hours

Practical dosage regimen:
Full-term neonates (3.5–5 kg): 2 mg/kg – 2.8 mg/kg every 12 hours.
Children from 5 to 10 kg: 2–4 mg/kg every 8–12 hours.
Children from 11 to 20 kg: 40 mg every 8–12 hours.

Dosage adjustments should be made according to the patient's age, type, and severity of infection. In obese patients, dosing should be based on ideal body weight.
The usual duration of treatment is 7–10 days. In severe or complicated infections, a longer treatment course may be necessary. In such cases, the risk of adverse effects increases; therefore, particular attention should be paid to monitoring renal, auditory, and vestibular function. It is advisable, in any case, to continue therapy for at least 48 hours after defervescence.

B) Patients with impaired renal function
As with all drugs primarily eliminated via the kidneys, the dosing frequency must be adjusted according to renal function, as shown in the following table:

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 x 8 = interval between two consecutive administrations (in hours).

Monitoring recommendations
Patients receiving aminoglycoside therapy must remain under close clinical monitoring due to the potential toxicity associated with their use. Since elderly patients and children may be particularly at risk, careful clinical monitoring is advised.
Urine should be examined for possible reduction in specific gravity, increased protein excretion, and presence of cells or cast precipitates. Blood urea nitrogen and non-protein nitrogen should be determined periodically, as well as serum creatinine or creatinine clearance. If feasible, serial audiograms are recommended, especially in high-risk patients.
In case of evident ototoxicity (confusion, vertigo, tinnitus, ringing in the ears, or hearing loss) or nephrotoxicity, dosage adjustment or discontinuation of the drug should be considered.
As with other aminoglycosides, in rare cases, changes in renal function or in the eighth cranial nerve may manifest only after completion of therapy.
Whenever possible, serum concentrations of aminoglycosides should be monitored to ensure adequate levels and to avoid potentially toxic levels. When peak gentamicin concentrations are monitored, doses should be adjusted to avoid prolonged levels above 12 mcg/mL. When trough gentamicin concentrations are monitored, doses should be adjusted to avoid levels above 2 mcg/mL.
Excessively high peaks and/or elevated serum aminoglycoside concentrations may increase the risk of renal or eighth cranial nerve toxicity.
In patients with extensive burns, altered pharmacokinetics may result in reduced serum aminoglycoside concentrations. In such patients treated with gentamicin, serum concentration monitoring is recommended as a basis for dosage adjustment.

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 used. A 6-hour hemodialysis session may reduce plasma gentamicin levels by approximately 50%.
Recommended doses at the end of each dialysis session 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 MEDICINE MUST NOT BE MIXED IN THE SAME SYRINGE WITH OTHER DRUGS.

During treatment, patients should be well hydrated.

Interactions
Cross-allergenicity among aminoglycosides has been demonstrated.
As with other aminoglycosides, concomitant and/or sequential systemic or topical administration of other nephrotoxic and/or neurotoxic drugs should be avoided.
Concomitant and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs should be avoided. If such combinations are necessary, renal function should be closely monitored with appropriate laboratory tests. Advanced age and dehydration are additional factors that may increase the risk of toxicity in patients.
When using drugs containing cisplatin, it should be noted that gentamicin-induced nephrotoxicity may increase even 3–4 weeks after administration of these substances.
Increased nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and certain cephalosporins.
Concomitant use of gentamicin and potent diuretics such as ethacrynic acid or furosemide is contraindicated, as these diuretics possess intrinsic ototoxicity. Moreover, when administered intravenously, diuretics may increase aminoglycoside toxicity by altering their serum and tissue concentrations.
Neurotoxic and nephrotoxic antibiotics may be significantly absorbed from body surfaces following local application or irrigation. The potential toxicity of antibiotics administered in this manner must be taken into account.
Although no cases of neuromuscular blockade have been reported in clinical practice either with gentamicin or with other aminoglycosides, the neuromuscular blocking activity of aminoglycosides may be enhanced by ether, muscle relaxants such as succinylcholine or tubocurarine, or during massive transfusions of citrated blood. When gentamicin is administered during or immediately after surgery, neuromuscular blockade may be intensified and prolonged if non-depolarizing muscle relaxants are used. These interactions may lead to neuromuscular blockade and respiratory paralysis. Due to the increased risk, such patients must be monitored particularly closely. If blockade occurs, it may be reversed by administration of calcium salts. Concomitant administration—even topical, especially if intracavitary—of other antibiotics potentially nephrotoxic and ototoxic may increase the risk of such effects.
Aminoglycosides may enhance the renal damage caused by methoxyflurane. When used concomitantly, extremely severe nephropathies are possible. The anesthesiologist must be informed about aminoglycoside use prior to surgery.
Neuromuscular blockade and respiratory paralysis have been reported in cats treated with high doses (40 mg/kg) of gentamicin. The possibility of such events occurring in humans should be considered when gentamicin is administered by any route to patients receiving neuromuscular blocking agents such as succinylcholine, tubocurarine, or decamethonium, anesthetics, or massive transfusions of citrated blood as anticoagulant. If neuromuscular blockade occurs, administration of calcium salts may reverse the effect.
Aminoglycosides should be used with caution in patients with neuromuscular disorders such as myasthenia gravis, parkinsonism, or infantile botulism, since these drugs may theoretically worsen muscle weakness due to their potential curare-like effect at neuromuscular junctions.
Gentamicin treatment may lead to overgrowth of microorganisms insensitive to the drug. If this occurs, appropriate therapy should be initiated.
Very rarely, following the use of aminoglycosides including gentamicin, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
Diarrhea and pseudomembranous colitis have been observed when gentamicin is used in combination with other antibiotics. These diagnoses should be considered in any patient who develops diarrhea during or immediately after treatment. Gentamicina Solfato L.F.M should be discontinued if severe diarrhea and/or bloody diarrhea occurs during treatment, and appropriate therapy should be initiated. Drugs that inhibit peristalsis must not be administered.
In vitro, the combination of an aminoglycoside with a beta-lactam antibiotic (penicillins or cephalosporins) may result in mutual inactivation. Even when an aminoglycoside and a penicillin-like antibiotic are administered via different routes, a reduction in the half-life or plasma levels of the aminoglycoside has been observed in patients with renal impairment and also in some subjects with normal renal function. A reduced plasma half-life of gentamicin has been observed in patients with severe renal failure receiving concomitant carbenicillin.
In neonates, indomethacin may increase plasma concentrations of gentamicin.
Concomitant use with oral anticoagulants may increase hypoprothrombinemic effects.
Concomitant administration with bisphosphonates may increase the risk of hypocalcemia.
Gentamicin administered concomitantly with botulinum toxin may increase the risk of toxicity due to neuromuscular blockade.
Neostigmine and pyridostigmine antagonize the effect of gentamicin.

OVERDOSE
In case 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.

Please refer to the Summary of Product Characteristics for further prescribing details.