Gentamicin

Dosage is adjusted for patients with renal impairment to minimise the risk of toxicity. The first dose should be as normal – after this, doses should be given less frequently, the interval being determined by results of renal function tests as below.

Renal Function Tests:

* 60 mg if body weight <60 kg.

Frequency of dosage in hours may also be approximated as serum creatinine (mg%) x eight or in SI units, as serum creatinine (µmol/l) divided by 11. If these dosage guides are used, peak serum levels must be measured. Peak levels of gentamicin occur approximately one hour after intra muscular injection and intravenous injection. Trough levels are measured just prior to the next injection. Assay of peak serum levels gives confirmation of adequacy of dosage and also serves to detect levels above 10 mg/l, at which the possibility of ototoxicity should be considered. One hour concentrations of gentamicin should not exceed 10 mg/l (but should reach 4 mg/l), while the pre-dose trough concentration should be less than 2 mg/l.

There is increased risk of ototoxicity in co-administration of gentamicin with loop diuretics.

There is increased risk of nephrotoxicity in co-administration of gentamicin with cephalosporins notably cephalothin.

Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anesthesia.

Concurrent use of gentamicin with bisphosphonates may increase the risk of hypocalcaemia.

There is increased risk of nephrotoxicity in co-administration of gentamicin with amphotericin B.

Concurrent use of the botulinum toxin and gentamicin may increase the risk of toxicity due to enhanced neuromuscular block.

There is increased risk of nephrotoxicity in co-administration of gentamicin with ciclosporin.

There is increased risk of nephrotoxicity and possible risk of ototoxicity in co-administration of gentamicin with cisplatin.

Gentamicin has been known to potentiate anticoagulants such as warfarin and phenindione.

Indometacin possibly increases plasma concentrations of gentamicin in neonates.

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.

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.

Patients should be advised that the use of gentamicin in the eye may cause transient blurring of vision. If affected, patients should not drive or operate machinery until vision has cleared.

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.

In the event of irritation, sensitivity or super-infection, treatment should be discontinued and appropriate therapy instituted.