Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

In patients with advanced renal impairment or with pre-existing inner ear deafness, gentamicin should be used only if its use is considered essential by the physician. The frequency or dose of administration should be reduced in patients with impaired renal function (see section 4.2).

Renal impairment
Renal impairment such as restriction of glomerular filtration is observed in approximately 10% of patients treated with gentamicin and is usually reversible. The most important risk factors are high total dose, long duration of therapy, raised serum level (high trough level); in addition, other potential risk factors are age, hypovolemia and shock.

Clinical signs of renal damage are: proteinuria, cylindruria, hematuria, oliguria, raised creatinine and urea concentrations in serum. In isolated cases, acute renal failure may occur (see also section 4.8).

Neuromuscular disorders
Since gentamicin has neuromuscular blocking properties, particular caution should be exercised in patients with pre- existing neuromuscular diseases (e.g., Parkinson's disease). Particularly careful monitoring is mandatory (see also section 4.8).

Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anaesthesia. These patients should also be monitored very carefully (see also section 4.8).

Effect on vestibulocochlear nerve
Damage to the vestibulocochlear nerve (eighth cranial nerve), whereby both balance and hearing may be affected, is possible. Vestibular damage is the most common ototoxic reaction. Hearing loss is manifested initially by diminution of high-tone acuity and is usually irreversible. Important risk factors are pre-existing renal impairment or a history of damage to the eighth cranial nerve; in addition, the risk increases in proportion to the level of the total and daily dose or by association with potentially ototoxic substances.
Symptoms of ototoxic effects are: dizziness, ringing/roaring in the ears (tinnitus), vertigo and less common hearing loss.
With gentamicin the vestibular mechanism may be affected if trough levels of 2 µg/ml are exceeded. This is usually reversible if observed promptly and the dose adjusted (see also section 4.8).

Antibiotic-associated diarrhoea, pseudomembranous colitis
Antibiotic-associated diarrhoea and pseudomembranous colitis have been reported with the use of gentamicin. These diagnoses should be considered in any patient who develops diarrhoea during or shortly after treatment. Gentamicin should be discontinued if severe and/or bloody diarrhoea occurs during treatment and appropriate therapy instituted. Drugs that inhibit peristalsis must not be given (see section 4.8).

Pregnancy and lactation
Gentamicin should be used in pregnancy and during lactation only after careful benefit risk assessment (see section 4.6).

Once daily dosing of gentamicin in elderly patients
There is limited experience with once daily dosing of gentamicin in elderly patients.
Once daily dosing of gentamicin may not be suitable and therefore, close monitoring is warranted in these patients.

Excipients
This medicine contains 0.78 mg of sodium per ampoule (less than 23 mg per ampoule), i.e., it is essentially sodium free.

Cross-allergenicity/-resistance
Cross-resistance and hypersensitivity to aminoglycosides may occur.

Monitoring
To avoid adverse events, continuous monitoring (before, during and after treatment) of renal function (serum creatinin, creatinin clearance), control of function of vestibule and cochlea, as well as hepatic and laboratory parameters is recommended.

In order to reduce the risk of nephrotoxicity and ototoxicity, the following instructions should be considered:

– Regular assessment of auditory, vestibular and renal function is particularly necessary in patients with additional risk factors. Impaired hepatic function or auditory function, bacteremia and fever have been reported to increase the risk of ototoxicity. Volume depletion or hypotension and liver disease have been reported as additional risk factors for nephrotoxicity.

– Monitoring of renal function before, during and after treatment.

– Dosage strictly according to creatinin clearance (or serum creatinine concentration). In patients with impaired renal function, the dosage must be adjusted according to renal performance (see section 4.2).

– In patients with impaired renal function additionally receiving gentamicin locally (inhalation, intratracheal, instillation), the amount of gentamicin absorbed after local administration must also be taken into account for dose adjustment of systemic treatment.

– Monitoring of serum gentamicin concentrations during therapy in order to avoid that peak levels exceed 10 µg/ml (toxic threshold for the cochleo-vestibular system) with conventional multiple daily dosing or trough levels exceed 2 µg/ml (see section 4.2), when administrating gentamicin twice daily and 1 mg/l for a once daily dosing.

– In patients with pre-existing inner ear damage (hearing impairment or balance function impairment), or where treatment is long-term, additional monitoring of the balance function and hearing is required.

– Prolonged treatment should be avoided. If possible, the duration of therapy should be limited to 7 – 10 days (see section 4.2).

– Avoid therapy with aminoglycosides immediately subsequent to previous aminoglycoside treatment; if possible, there should be an interval of 7 – 14 days between treatments.

– If possible, avoid concurrent administration of other potentially ototoxic and nephrotoxic substances. If this is unavoidable, particular careful monitoring of renal function is indicated (see section 4.5).

– Ensure adequate hydration and urine production.

Effects on Driving

4.7 Effects on ability to drive and use machines

Caution is advised when driving and using machines in view of the possible undesired effects such as dizziness and vertigo.