Cidomycin^TM Adult Injectable 80mg/2ml.

Each ampoule or vial (2ml) contains Gentamicin Sulphate Ph Eur equivalent to 80mg Gentamicin base.

For excipients, see section 6.1

Solution for Injection.

Clear, colourless solution.

Gentamicin is an aminoglycoside antibiotic with broad-spectrum bactericidal activity. It is usually active against most strains of the following organisms : Escherichia coli, Klebsiella spp., Proteus spp. (indole positive and indole negative), Pseudomonas aeruginosa, Staphylococci, Enterobacter spp., Citrobacter spp and Providencia spp.

Gentamicin injection and gentamicin paediatric injection are indicated in urinary-tract infections, chest infections, bacteraemia, septicaemia, severe neonatal infections and other systemic infections due to sensitive organisms.

ADULTS :

Serious infections: If renal function is not impaired, 5mg/kg/daily in divided doses at six or eight hourly intervals. The total daily dose may be subsequently increased or decreased as clinically indicated.

Systemic infections: If renal function is not impaired, 3-5mg/kg/day in divided doses according to severity of infection, adjusting according to clinical response and body weight.

Urinary tract infections: As “Systemic infections”. Or, if renal function is not impaired, 160mg once daily may be used.

CHILDREN:

Premature infants or full term neonates up to 2 weeks or age: 3mg/kg 12 hourly.

2 weeks to 12 years: 2mg/kg 8 hourly.

THE ELDERLY:

There is some evidence that elderly patients may be more susceptible to aminoglycoside toxicity whether secondary to previous eighth nerve impairment or borderline renal dysfunction. Accordingly, therapy should be closely monitored by frequent determination of gentamicin serum levels, assessment of renal function and signs of ototoxicity.

RENAL IMPAIRMENT:

Gentamicin is excreted by simple glomerular filtration and therefore reduced dosage is necessary where renal function is impaired. Nomograms are available for the calculation of dose, which depends on the patient's age, weight and renal function. The following table may be useful when treating adults.

*60mg if body weight <60kg. Frequency of dosage in hours may also be approximated as serum creatinine (mg%) x eight or in si units, as serum creatinine (umol/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 10mg/l, at which the possibility of ototoxicity should be considered. One hour concentrations of gentamicin should not exceed 10mg/l (but should reach 4mg/l), while the pre dose trough concentration should be less than 2mg/l.

The recommended dose and precautions for intramuscular and intravenous administration are identical. Gentamicin when given intravenously should be injected directly into a vein or into the drip set tubing over no less than three minutes. If administered by infusion, this should be over no longer than 20 minutes and in no greater volume of fluid than 100ml.

Hypersensitivity; Myasthenia Gravis.

Ototoxicity has been recorded following the use of gentamicin. Groups at special risk include patients with impaired renal function, infants and possibly the elderly. Consequently, renal, auditory and vestibular functions should be monitored in these patients and serum levels determined so as to avoid peak concentrations above 10mg/l and troughs above 2mg/l. As there is some evidence that 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 only be used in pregnancy if considered essential by the physician (see section 4.6 Pregnancy and Lactation.)

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 administration of gentamicin and other potentially ototoxic or nephrotoxic drugs should be avoided. Potent diuretics such as etacrynic acid and furosemide are believed to enhance the risk of ototoxicity whilst amphotericin B, cisplatin and ciclosporin are potential enhancers of nephrotoxicity.

Any potential nephrotoxicity of cephalosporins, and in particular cephaloridine, may also be increased in the presence of gentamicin. Consequently, if this combination is used monitoring of kidney function is advised.

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

Indometacin possibly increases plasma concentrations of gentamicin in neonates.

Concurrent use with oral anticoagulants may increase the hypothrombinanaemic effect.

Concurrent use of bisphosphonates may increase the risk of hypocalcaemia.

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

Antagonism of effect may occur with concomitant administration of gentamicin with either neostigmine or pyridostigmine.

There are no proven cases of intrauterine damage caused by gentamicin. However, in common with most drugs known to cross the placenta, usage in pregnancy should only be considered in life threatening situations where expected benefits outweigh possible risks. 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 known.

Side-effects include vestibular damage or hearing loss, particularly after exposure to ototoxic drugs or in the presence of renal dysfunction. Nephrotoxicity (usually reversible) and occasionally acute renal failure, hypersensitivity, anaemia, blood dycrasias, purpura, stomatitis, convulsions and effects on liver function occur occasionally.

Rarely hypomagnesia on prolonged therapy and antibiotic–associated colitis have been reported.

Nausea, vomiting and rash have also been reported.

Central neurotoxicity, including encephalopathy, confusion, lethargy, mental depression and hallucinations, has been reported in association with gentamicin therapy but this is extremely rare.

Haemodialysis and peritoneal dialysis will aid the removal from blood but the former is probably more efficient. Calcium salts given intravenously have been used to counter the neuromuscular blockade caused by gentamicin.

Gentamicin is a mixture of antibiotic substances produced by the growth of micromonospora purpurea. It is bactericidal with greater antibacterial activity than streptomycin, neomycin or kanamycin.

Gentamicin exerts a number of effects on cells of susceptible bacteria. It affects the integrity of the plasma membrane and the metabolism of RNA, but its most important effects is inhibition of protein synthesis at the level of the 30s ribosomal subunit.

Gentamicin is not readily absorbed from the gastro-intestinal tract. Gentamicin is 70-85% bound to plasma albumin following administration and is excreted 90% unchanged in urine. The half-life for its elimination in normal patients is 2 to 3 hours.

Effective plasma concentration is 4-8 µg/ml.

The volume of distribution (vd) is 0.3 l/kg.

The elimination rate constant is :

0.02 hr^-1 for anuric patients *

0.30 hr^-1 normal

* Therefore in those with anuria care must be exercised following the usual initial dose, any subsequent administration being reduced in-line with plasma concentrations of gentamicin.

Not applicable.

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Disodium Edetate

Water for Injections

2M Sodium Hydroxide

1M Sulphuric Acid

In general, gentamicin injection should not be mixed. In particular the following are incompatible in mixed solution with gentamicin injection : penicillins, cephalosporins, erythromycin, heparins, sodium bicarbonate. * Dilution in the body will obviate the danger of physical and chemical incompatibility and enable gentamicin 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. In the case of carbenicillin, administration should only be at a separate site.

* 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.

3 years

Do not store above 25°C. Do not refrigerate or freeze.

Cidomycin Adult Injectable is supplied in ampoules and vials.

Not applicable.

Sanofi-aventis

One Onslow Street

Guildford

Surrey

UK

PL 0109/5065R

24^th January 1991

July 2007

POM