As in the case of other aminoglycosides, toxicity is associated with serum levels above a critical value. In patients with normal renal function it is unlikely that toxic serum levels (in excess of 10 micrograms/ml) will be reached after administration of recommended doses. Where higher levels occur because of renal impairment, dosage should be reduced. In the event of an overdose or toxic reaction, peritoneal dialysis or haemodialysis will lower serum gentamicin levels. Calcium salts given intravenously have been used to counter the neuromuscular blockade caused by gentamicin.
36 months.
Patients being treated with gentamicin should be under close clinical observation because of its potential toxicity.
Hypersensitivity to gentamicin, any other ingredient or other aminoglycosides.
Myasthenia gravis.
Gentamicin should be used with caution in premature infants because of their renal immaturity, in elderly people and generally in patients with impaired renal function. Diabetes, auditory vestibular dysfunctions, otitis media, a history of otitis media, previous use of ototoxic drugs and a genetically determined high sensitivity to aminoglycoside induced ototoxicity, are other main factors which may pre-dispose the patient to toxicity.
Gentamicin Injection should not be mixed with other drugs before injection and where co-administration of penicillins, cephalosporins, erythromycin, sulphadiazine, furosemide and betalactam antibiotics and heparin is necessary, the drugs should be administered separately, either as bolus injections into the tubing of the giving set or at separate sites. Addition of gentamicin to solutions containing bicarbonate may lead to the release of carbon dioxide.
Sodium metabisulphite
Disodium edetate
Methyl hydroxybenzoate
Propyl hydroxybenzoate
Water for Injections
Sulphuric acid (2.5N)
Sodium hydroxide (2.5N)
Ototoxicity and nephrotoxicity are the most common side effects associated with Gentamicin therapy. Both effects are related to renal impairment and hence the dosage in such patients should be altered as suggested. In addition, there have been rare reports of changes in electrolyte balance including hypocalcaemia and hypokalaemia caused by renal tubular dysfunction.
Ear and labyrinth disorders:
Vestibular damage and ototoxicity may occur. This is usually reversible if observed promptly and the dose adjusted. Frequency Unknown (cannot be estimated from the available data): Irreversible hearing loss, deafness
Renal and urinary disorders
Nephrotoxicity. Frequency Very rare (< 1/10,000).: Acute renal failure, Fanconi-like syndrome in patients treated with a prolonged course of high-dose
Immune system disorders
Hypersensitivity, anaphylactic reactions associated with gentamicin containing therapy.
Blood and lymphatic system disorder
Anemia, blood dyscrasias, granulocytopenia (reversible)
Nervous system disorders
Convulsions, central nervous system toxicity (including encephalopathy, confusion, lethargy, mental depression and hallucinations), neuromuscular blockade
Hepatobiliary disorders
Hepatic function abnormal
Metabolism and nutrition disorders
Hypomagnesaemia (on prolonged therapy)
Infections and infestations
Combinations of antibiotics containing gentamicin have been associated with rare reports of Clostridium difficile diarrhoea.
Gastrointestinal disorders
Stomatitis, nausea, vomiting
Skin and subcutaneous tissue disorders:
Urticaria, allergic contact dermatitis, purpura
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard
There is no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Gentamicin is usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drug appears to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.
In general, gentamicin is active against many aerobic gram-negative bacteria and some aerobic gram-positive bacteria. Gentamicin is inactive against fungi, viruses, and most anaerobic bacteria.
In vitro, gentamicin concentrations of 1-8 µg/ml inhibit most susceptible strains of Escherichia coli, Haemophilus influenzae, Moraxella lacunata, Neisseria, indole positive and indole negative Proteus, Pseudomonas (including most strains of Ps. aeruginosa), Staphylococcus aureus, S. epidermidis, and Serratia. However, different species and different strains of the same species may exhibit wide variations in susceptibility in vitro. In addition, in vitro susceptibility does not always correlate with in vivo activity. Gentamicin is only minimally active against Streptococci.
Natural and acquired resistance to gentamicin has been demonstrated in both gram-negative and gram-positive bacteria. Gentamicin resistance may be due to decreased permeability of the bacterial cell wall, alteration in the ribosomal binding site, or the presence of a plasmid-mediated resistance factor which is acquired by conjugation. Plasmid-mediated resistance enables the resistant bacteria to enzymatically modify the drug by acetylation, phosphorylation, or adenylation and can be transferred between organisms of the same or different species. Resistance to other aminoglycosides and several other anti-infectives (e.g. chloramphenicol, sulphonamides, tetracycline) may be transferred on the same plasmid.
There is partial cross-resistance between gentamicin and other aminoglycosides.
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 halflife 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.
05/2018
Hospira UK Limited
Horizon, Honey Lane
Hurley
Maidenhead, SL6 6RJ
United Kingdom
Do not store above 25°C.
80 mg/2 ml - Clear, Type I glass vials in packs of 5 vials.
PL 04515/0037
Patients being treated with gentamicin should be under close clinical observation because of its potential toxicity.
As with other aminoglycosides toxicity is related to serum concentration. At serum levels more than 10 micrograms/ml the vestibular mechanism may be affected. Toxicity can be minimised by monitoring serum concentrations and it is advisable to check serum levels to confirm that peak levels (one hour) do not exceed 10 micrograms/ml and that trough levels (one hour before next injection) do not exceed 2 micrograms/ml when administering Gentamicin twice daily and 1µg/ml for a once daily dose. Evidence of toxicity requires adjustment of dosage or withdrawal of the drug.
As there is some evidence that the risk of both ototoxicity and nephrotoxicity is related to the level of total exposure, duration of therapy should be the shortest possible compatible with clinical recovery.
In some patients with impaired renal function, there has been a transient rise in blood- urea-nitrogen, which has usually reverted to normal during or following cessation of therapy. It is important to adjust the frequency of dosage according to the degree of renal function.
Gentamicin should be used with care in conditions characterised by muscular weakness.
In cases of significant obesity gentamicin serum concentrations should be closely monitored and a reduction in dose should be considered.
Concurrent use of other neurotoxic and/or nephrotoxic drugs can increase the possibility of gentamicin toxicity. Co-administration with the following agents should be avoided:
Neuromuscular blocking agents such as succinylcholine and tubocurarine.
Other potentially nephrotoxic or ototoxic drugs such as cephalosporins and methicillin.
Potent diuretics such as ethacrynic acid and furosemide.
Other aminoglycosides.
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.
Sulphites can cause allergic-type reactions including anaphylactic symptoms and bronchospasm in susceptible people, especially those with a history of asthma or allergy.
The vial stopper contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
Not applicable.
Not applicable.
5th February 1998
