1. Name Of The Medicinal Product
Genticin® Injectable.
2. Qualitative And Quantitative Composition
Gentamicin sulphate Ph. Eur.
3. Pharmaceutical Form
Solution for injection.
Each ampoule contains a sterile, clear, colourless to pale yellow liquid. The solution is preservative free.
4. Clinical Particulars
4.1 Therapeutic Indications
Genticin Injectable ampoules are indicated for the treatment of systemic infections due to susceptible bacteria such as, bacteraemia, septicaemia, urinary-tract infections and severe chest infections.
Consideration should be given to official local guidance on the appropriate use of antibacterial agents.
4.2 Posology And Method Of Administration
Genticin is normally administered intramuscularly but may be given intravenously as a slow intravenous injection over at least 3 minutes or short infusion if required. Genticin should not be given as a slow infusion or mixed with other drugs before use (see Incompatibilities).
The daily recommended dose in children, adolescents and adults with normal renal function is 3-6 mg/kg body weight per day as one (preferred) up to two single doses.
The daily dose in infants after the first month of life is 4.5-7.5 mg/kg body weight per day as one (preferred) up to two single doses.
The daily dose in newborns is 4-7 mg/kg body weight per day. Due to the longer half-life, newborns are given the required daily dose in one single dose.
In cases of impaired renal function a reduction in dosage frequency is recommended. The following table is a guide to recommended dosage schedules:
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In life-threatening infections the frequency of dosage may need to be increased to 6-hourly and the quantity of each dose may also be increased at the discretion of the clinician up to a total dosage of 5mg/kg in 24 hours. In such cases it is advisable to monitor gentamicin serum levels.
If renal function is not impaired, 160mg once daily may be used in some cases.
Monitoring advice:
Serum concentration monitoring of gentamicin is recommended, especially in elderly, in newborns and in patients with impaired renal function. Samples are taken at the end of a dosing interval (trough level). Trough levels should not exceed 2 μg/ml administering gentamicin twice daily and 1 μg/ml for a once daily dose.
Prolonged use should be avoided and whenever possible the treatment should not exceed 7 days.
Caution is advised in significant obesity as gentamicin is poorly distributed into fatty tissue. The dosage calculation should be based on an estimate of lean body weight. Serum levels should be monitored closely and the dose possibly adjusted (see 4.4).
4.3 Contraindications
Hypersensitivity to gentamicin, any other ingredient or to other aminoglycosides.
Myasthenia gravis.
4.4 Special Warnings And Precautions For Use
Where renal function is impaired through disease or old age the frequency, but not the amount, of each dose should be reduced according to the degree of impairment. Gentamicin is excreted by simple glomerular filtration, and dosage frequency may be predicted by assessing serum creatinin, creatinine clearance rates or blood urea and reducing the frequency accordingly.
It is also advisable to check serum levels to confirm that peak (1 hour) levels do not exceed 10 micrograms/ml and that trough levels (before next injection) do not exceed 2 micrograms/ml when administering gentamicin twice daily and 1 microgram/ml for a once daily dose.
Caution is required in Parkinsonism and other conditions characterised by muscular weakness.
To avoid adverse events, continuous monitoring (before, during and after) of renal function (serum creatinin, creatinin clearance), control of function of vestibule and cochlea as well as hepatic and laboratory parameters is recommended. Regular assessment of auditory, vestibular, renal and hepatic 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.
Caution is advised in significant obesity (see 4.2).
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Gentamicin should not be used concurrently with other potentially nephrotoxic or ototoxic drug substances unless considered essential by the physician. The potential nephrotoxicity of other aminoglycosides, vancomycin and some cephalosporins, ciclosporin, cisplatin, fludarabine and amphotericin may be increased in the presence of gentamicin and monitoring of renal function is therefore recommended.
Furosemide (frusemide) and piretanide may potentiate the ototoxicity of gentamicin, and etacrynic acid, which is ototoxic in its own right, should be avoided with gentamicin.
Aminoglycosides, including gentamicin, may induce neuromuscular blockade and respiratory paralysis and should therefore only be used with great caution in patients receiving curare-type muscle relaxants.
Aminoglycosides antagonise the effects of cholinergic agents such as neostigmine and pyridostigmine.
Indometacin has been reported to increase the plasma concentrations of aminoglycosides when given concomitantly.
Bacteriostatic antibiotics may give an antagonistic interaction, but in some cases (e.g. with clindamycin and lincomycin) the disadvantage of antagonism may be outweighed by the addition of activity against anaerobic organisms. Synergistic action has been demonstrated with penicillin. However, if penicillins (such as ticarcillin) are used with gentamicin the drugs should not be physically mixed and patients with poor renal function should be monitored for effectiveness of the gentamicin. Cross-sensitivity with aminoglycosides may occur.
4.6 Pregnancy And Lactation
Safety for use in pregnancy and lactation has not been established. Gentamicin crosses the placenta and there is a risk of ototoxicity (auditory or vestibular nerve damage) in the foetus. Gentamicin should only be used where the seriousness of the mother's condition justifies the risk and use is considered essential by the physician. In such cases, serum gentamicin concentration monitoring is essential. Some animal studies have shown a teratogenic effect.
Gentamicin is excreted in breast milk, but is unlikely to be a hazard to the infant except in the presence of maternal renal insufficiency when breast-feeding should be avoided, as the levels in breast milk then rise appreciably.
4.7 Effects On Ability To Drive And Use Machines
None.
4.8 Undesirable Effects
As with all aminoglycosides, at critical levels gentamicin exhibits toxicity.
Blood and lymphatic system disorders
Blood dyscrasias have been reported infrequently.
Electrolyte disturbances (e.g. hypomagnesaemia) have occurred rarely.
Immune system disorders
Hypersensitivity reactions and allergic rashes have occurred. Very rarely, anaphylactic reactions to gentamicin have occurred.
Nervous system disorders
Vestibular damage or hearing loss may occur, particularly after exposure to ototoxic drugs or in the presence of renal dysfunction. With gentamicin the vestibular mechanism may be affected when peak serum levels of 10 micrograms/ml or trough levels of 2 micrograms/ml are exceeded. This is usually reversible if observed promptly and the dose adjusted. In patients with normal renal function these levels are unlikely at standard dosage.
Gentamicin can cause neuromuscular blockade which may unmask or aggravate myasthenia gravis and cause postoperative respiratory distress.
Central neurotoxicity, including encephalopathy, convulsions, confusion, hallucinations and mental depression has been reported with gentamicin therapy, but this is extremely rare.
Gastrointestinal disorders
Infrequent effects reported include nausea, vomiting and stomatitis.
Gentamicin has rarely been associated with pseudomembranous colitis and usually in these cases other antibiotics are also involved.
Hepatobiliary disorders
Signs of liver dysfunction such as transient elevation of serum aminotransferase values and increased serum bilirubin concentration have been reported infrequently.
Renal and urinary disorders
Nephrotoxicity may occur, resulting in a gradual reduction in creatinine clearance after several days of treatment. This is usually reversible if the drug is withdrawn. Nephrotoxicity is more common if trough serum concentrations exceed 2 micrograms/ml and where there is pre-existing renal disease or concomitant treatment with other nephrotoxic agents.
4.9 Overdose
Symptoms include dizziness, vertigo and hearing loss if overdose accidentally given parenterally.
If the reaction is severe consider haemodialysis as treatment.
Gentamicin may be removed from the body by haemodialysis or peritoneal dialysis. Calcium salts given intravenously have been used to counter the neuromuscular blockade caused by gentamicin.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Gentamicin is a bactericidal aminoglycoside antibiotic which acts by inhibiting protein synthesis.
5.2 Pharmacokinetic Properties
Gentamicin is rapidly absorbed following intramuscular injection, giving peak plasma concentrations after 30 minutes - 1 hour. Effective concentrations are still present 4 hours after injection. An injection of 1mg/kg body weight results in a peak plasma concentration of approximately 4 micrograms/ml.
> 90% gentamicin is excreted in the urine by glomerular filtration.
< 10% is bound to plasma protein.
T½ = 2 - 3 hours in individuals with normal kidney function, but can be increased in individuals with renal insufficiency.
Distribution
The distribution volume of gentamicin is about equivalent to the volume of extracellular water. In the newborn water makes up 70 to 75% of bodyweight, compared with 50 to 55% in adults. The extracellular water compartment is larger (40% of body weight compared with 25% of body weight in adults). Therefore, the volume of distribution of gentamicin per kg bodyweight is affected and decreases with increasing age from 0.5 to 0.7 L/kg for a premature newborn to 0.25 L/kg for an adolescent. The larger volume of distribution per kg bodyweight means that for adequate peak blood concentration a higher dose per kg bodyweight needs to be administered.
Elimination
Gentamicin is not metabolized in the body but is excreted unchanged in microbiologically active form predominantly via the kidneys. In patients with normal renal function the elimination half-life is about 2 to 3 hours. In neonates elimination rate is reduced due to immature renal function.
Elimination half-life averages approximately 8 hours in neonates at a gestational age of 26 to 34 weeks compared with about 6.7 hours in neonates at a gestational age of 35 to 37 weeks.
Correspondingly, clearance values increase from about 0.05 L/h in neonates at a gestational age of 27 to 0.2 L/h in neonates at a gestational age of 40 weeks.
5.3 Preclinical Safety Data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Water for Injections, Sulphuric acid.
6.2 Incompatibilities
In general, mixing Genticin Injectable with other drugs prior to administration is not advised. In particular the following are incompatible in mixed solution: penicillins, cephalosporins, erythromycin, lipiphysan, heparins and sodium bicarbonate. In the latter case carbon dioxide may be liberated on addition of the two solutions. Normally this will dissolve in the solution, but under some circumstances small bubbles may form.
Dilution in the body will obviate the danger of physical and chemical incompatibility and enable Genticin Injectable to be given concurrently with the drugs listed above either as a bolus injection into the drip tubing with adequate flushing, or at separate sites. However, in the case of carbenicillin and gentamicin they should only be given at separate sites.
6.3 Shelf Life
4 years.
6.4 Special Precautions For Storage
Do not store above 25°C. Do not freeze.
6.5 Nature And Contents Of Container
Genticin Injectable is available in colourless, Type I glass ampoules containing 2ml, in boxes of 10 ampoules.
6.6 Special Precautions For Disposal And Other Handling
Discard any portion of the contents remaining after use.
Administrative Data
7. Marketing Authorisation Holder
Amdipharm PLC
Regency House
Miles Gray Road
Basildon
Essex
SS14 3AF
United Kingdom
8. Marketing Authorisation Number(S)
PL 20072/0056
9. Date Of First Authorisation/Renewal Of The Authorisation
28 May 2002
10. Date Of Revision Of The Text
December 2010
LEGAL STATUS
POM |
Genticin is a registered trade mark Item Code
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