In patients with advanced renal impairment or with pre-existing inner ear deafness, Gentalyn 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.
Renal impairment
Renal impairment such as restriction of glomerular filtration is observed in approximately 10% of patients treated with Gentalyn 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, hypovolaemia and shock.
Clinical signs of renal damage are: proteinuria, cylindruria, haematuria, oliguria, raised creatinine and urea concentrations in serum.)
Neuromuscular disorders
Since Gentalyn has neuromuscular blocking properties, particular caution should be exercised in patients with pre- existing neuromuscular diseases (e.g.)
Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anaesthesia.)
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 Gentalyn the vestibular mechanism may be affected if trough levels of 2 µg/ml are exceeded.)
Antibiotic-associated diarrhoea, pseudomembranous colitis Antibiotic-associated diarrhoea and pseudomembranous colitis have been reported with the use of Gentalyn. These diagnoses should be considered in any patient who develops diarrhoea during or shortly after treatment. Gentalyn should be discontinued if severe and/or bloody diarrhoea occurs during treatment and appropriate therapy instituted. Drugs that inhibit peristalsis must not be given.
Pregnancy and lactation
Gentalyn should be used in pregnancy and during lactation only after careful benefit risk assessment.
Once daily dosing of Gentalyn in elderly patients:
There is limited experience with once daily dosing of Gentalyn in elderly patients. Once daily dosing of Gentalyn 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.
Sodium metabisulphite, one of the excipients of this medicinal product, may rarely cause severe hypersensitivity reactions and bronchospasm.
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, bacteraemia 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 creatinine clearance (or serum creatinine concentration). In patients with impaired renal function, the dosage must be adjusted according to renal performance.
- In patients with impaired renal function additionally receiving Gentalyn locally (inhalation, intratracheal, instillation), the amount of Gentalyn absorbed after local administration must also be taken into account for dose adjustment of systemic treatment.
- Monitoring of serum Gentalyn 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 when administrating Gentalyn 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.
- 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.
- Ensure adequate hydration and urine production.
WARNINGS
NOT FOR INJECTION INTO THE EYE. Gentamicin Sulfate Ophthalmic Solution is not for injection. It should never be injected subconjunctivally, nor should it be directly introduced into the anterior chamber of the eye.
PRECAUTIONS
General
Prolonged use of topical antibiotics may give rise to overgrowth of nonsusceptible organisms including fungi. Bacterial resistance to gentamicin may also develop. If purulent discharge, inflammation, or pain becomes aggravated, the patient should discontinue use of the medication and consult a physician.
If irritation or hypersensitivity to any component of the drug develops, the patient should discontinue use of this preparation, and appropriate therapy should be instituted.
Information for Patients
To avoid contamination, do not touch tip of container to the eye, eyelid, or any surface.
Carcinogenesis, Mutagenesis, Impairment of Fertility
There are no published carcinogenicity or impairment of fertility studies on gentamicin. Aminoglycoside antibiotics have been found to be nonmutagenic.
Pregnancy
Pregnancy Category C: Gentamicin has been shown to depress body weights, kidney weights, and median glomerular counts in newborn rats when administered systemically to pregnant rats in daily doses approximately 500 times the maximum recommended ophthalmic human dose. There are no adequate and well-controlled studies in pregnant women. Gentamicin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pediatric Use
Safety and effectiveness in neonates have not been established.
