GENTAMICIN Solution for injection Ref.[6852] Active ingredients: Gentamicin

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.

1. Antibacterials: increased risk of nephrotoxicity with cephalosporins notably cephalothin.
2. Gentamicin has been known to potentiate anticoagulants such as warfarin and phenindione.
3. Antifungals: increased risk of nephrotoxicity with amphotericin B.
4. Cholinergics: antagonism of effect of neostigmine and pyridostigmine.
5. Cyclosporin, cisplatin: increased risk of nephrotoxicity.
6. Cytotoxics: increased risk of nephrotoxicity and possible risk of ototoxicity with cisplatin.
7. Diuretics: increased risk of ototoxicity with loop diuretics.
8. Muscle relaxants: effect of non-depolarising muscle relaxants such as tubocurarine enhanced. Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anesthesia.
9. Indomethacin possibly increases plasma concentrations of gentamicin in neonates.
10. Concurrent use of bisphosphonates may increase the risk of hypocalcaemia.
11. Concurrent use of the Botulinum Toxin and gentamicin may increase the risk of toxicity due to enhanced neuromuscular block.

Use in Pregnancy

Although no teratogenic effects have been observed, gentamicin is known to cross the placenta. Ototoxicity in the foetus is also a potential hazard. The benefits should, therefore, be weighed against such hazards to the foetus before using gentamicin during pregnancy.

Use in Lactation

Small amounts of gentamicin have been reported in breast milk. Because of the potential for serious adverse reactions to an aminoglycoside in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. In the absence of gastro-intestinal inflammation, the amount of gentamicin ingested from the milk is unlikely to result in significant blood levels in breast-fed infants.

Not applicable.

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

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.