INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo BEECHAM GENTAMICIN Ampoules 80 mg/2 mL (injection)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

BEECHAM GENTAMICIN Ampoules 80 mg/2 mL (injection)

COMPOSITION:
Each 2 mL ampoule contains 80 mg
gentamicin as gentamicin sulphate and sodium metabisulphite 0,32% m/v.

PHARMACOLOGICAL CLASSIFICATION:
A.20.1.1 Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION:
Gentamicin acts by inhibiting protein synthesis in susceptible bacteria. The antibacterial activity is primarily directed against Gram-negative bacteria. With the exception of Staphylococcus aureus, gentamicin sulphate is not active against Gram-positive ,organisms.
Micro-organisms sensitive in vitro to gentamicin are:
  Staphylococcus aureus
  Escherichia coli
  Proteus mirabilis
  Pseudomonas aeruginosa
  Klebsiella pneumoniae
  Enterobacter species and
  Serratia marcescens
In vitro sensitivity does not necessarily imply in vivo efficacy.
Resistance to gentamicin develops quickly when gentamicin is not used in combination with other antibiotics in the treatment of staphylococcal infections.
After intramuscular administration, peak serum levels are obtained within 1 to 4 hours. The half-life in adults with normal renal function is 2 to 3 hours.
Gentamicin sulphate does not penetrate the cerebrospinal fluid in significant amounts - not even in the presence of meningitis. Gentamicin sulphate does not penetrate the eye.
Gentamicin sulphate crosses the placenta and small amounts are excreted in the milk.
Gentamicin sulphate has neuromuscular blocking activity.

INDICATIONS:
Gentamicin is indicated for the treatment of the following conditions when caused by the following susceptible organisms Pseudomonas aeruginosa, Proteus, Escherichia coli, Klebsiella, Enterobacter and Serratia.
1. urinary tract infections (except uncomplicated urinary tract infections)
2. infected burns
3. respiratory tract infections
4. severe systemic infections such as peritonitis and sepsis
5. bone and soft tissue infections including osteomyelitis and wound infections.

CONTRA-INDICATIONS:
Gentamicin is contra-indicated in patients with a known history of allergy to it and to other aminoglycosides, and to sodium metabisulphite.
Gentamicin should not be administered to pregnant patients.

WARNINGS:
Due to the risk of ototoxicity and neurotoxicity with prolonged use of the aminoglycosides, gentamicin must be restricted to the therapy of life-threatening infections in which a less toxic antimicrobial agent is not suitable.
Serum peak levels (the level obtained directly after an intravenous infusion or 1 to 4 hours after intramuscular administration) of 10 µg/mL must be avoided as this could be toxic. Serum trough levels (the level directly before the next dose) of more than 2 µg/mL may be the best indication of accumulation of gentamicin sulphate which may be associated with toxicity.
To ensure safe and effective therapy, dosages should be monitored with serum peak and trough levels. Where practical, regular determination of plasma creatinine levels is advised.
Toxic levels may be reached when gentamicin sulphate is administered in normal doses in patients with impaired renal function.

DOSAGE AND DIRECTIONS FOR USE:
Gentamicin is usually given intramuscularly. Intravenous administration is generally reserved for those circumstances in which the intramuscular route is not feasible. The course of treatment should generally be limited to 7 to 10 days and plasma concentrations should not exceed 10 µg/mL.
Dosage and dosage intervals must be determined preferably for each patient with serum peak and trough levels of gentamicin.
The following dosage regimes are recommended where plasma levels cannot be determined:

Loading dose: 1,5 - 2 mg/kg bodymass.

Maintenance therapy: Patients with normal renal function.

Intramuscular Administration:
Adults: 3 mg/kg bodymass per day, one third being given every 8 hours. In life-threatening infections the dosage may be increased, to a maximum of 5 mg/kg bodymass daily, in three equally divided doses.

Children up to two years: 2 - 2,5 mg/kg bodymass every 8 hours.

Neonates (with severe infection): 6 mg/kg bodymass daily, divided into two or three equally spaced doses.

Intravenous Administration:
The recommended doses for intravenous administration are the same as those used intramuscularly.
Intravenous administration may be carried out slowly over 3 minutes or may be infused over a period of 20 to 30 minutes up to 2 hours.

Patients with impaired renal function:
Dosage must be adjusted in patients with impaired renal function. Plasma concentrations of gentamicin should be checked frequently in these patients and the dosage should be adjusted if the plasma concentration approaches 10 µg/mL or if the concentration immediately before the next dose exceeds 2 µg/mL.
The loading dose is the same as in patients with normal renal function. Thereafter dosages and dosage intervals must he adjusted according to serum peak and trough levels.
In the absence of serum the following table could serve as a general guideline for administration of gentamicin. The dosage intervals vary, alternatively, the dosage can be adapted according to the degree of renal impairment.

Maintenance dose as % of loading dose according to creatinine clearance:
Creatinine Clearance (mL/min) Half-Life (Hours) 8-hourly 12-hourly 24-hourly
90 3,1 84% - -
80 3,4 80% 91% -
70 3,9 76% 88% -
60 4,5 71% 84% -
50 5,3 65% 79% -
40 6,5 57% 72% 92%
30 8,4 48% 63% 86%
25 9,9 43% 57% 81%
20 11,9 37% 50% 75%
17 13,6 33% 46% 70%
15 15,1 31% 42% 67%
12 17,9 27% 37% 61%
10 20,4 24% 34% 56%
5 31,5 16% 23% 41%

Serum creatinine levels must be determined regularly in patients with renal function impairment. Thereby, an early deterioration in renal function will be noticed and ototoxicity prevented. When kidney function deteriorates gentamicin therapy should be withdrawn as a decrease in dosage only, could lead to further renal damage.

Compatibility with other medicines:
Gentamicin is incompatible with amphotericin, cephalosporins, erythromycin, heparin, penicillin, sodium bicarbonate and sulphadiazine.
When gentamicin is administered together with penicillin, the two, medicines must be administered at different sites.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The most significant clinical side-effects are renal function impairment and ototoxicity. These side-effects are related to the dosages used, existing renal function, peak and trough levels and the total dosage administered.

Ototoxicity:
Patients with renal impairment are especially susceptible to ototoxicity; high doses of gentamicin and previous exposure to other ototoxic medicines are contributory factors. Patients with pre-existing auditory impairment are also more likely to develop hearing loss following exposure to gentamicin.
Symptoms include dizziness, tinnitus and hearing loss. Ototoxicity is often not reversible as a result of cumulative damage to the eighth cranial nerve.

Nephrotoxicity:
Nephrotoxicity may be precipitated or worsened and acute renal failure has been reported, often in association with the concurrent administration of a cephalosporin antibiotic and diuretics.
Nephrotoxicity may be reversible if treatment is withdrawn in time.
Other side-effects include paraesthesia, muscle twitching, numbness, and convulsions. Hypersensitivity reactions (rash and urticaria), headache, increased or decreased reticulocyte count, granulocytopenia, anaemia, purpura, increased serum bilirubin and serum transaminase may occur.
Gentamicin should be given with care and in reduced dosage to patients with impaired renal function. Plasma concentrations of gentamicin should be checked frequently in these patients and the dosage should be adjusted if the plasma concentration approaches 10 µg/mL or if the concentration immediately before the next dose exceeds 2 µg/mL. Meticulous attention to drug clearance and concentrations in plasma is critically important for the effective and safe use of gentamicin.
It is recommended that patients receiving gentamicin be carefully monitored for ototoxicity, since the initial symptoms may be reversible; however, deafness may occur several weeks after therapy is discontinued.
Concurrent use of gentamicin with other potentially neurotoxic and/or nephrotoxic drugs, particularly streptomycin, neomycin, kanamycin, cephalosporins, viomycin, polymyxin B and polymyxin E, should be avoided.
Concurrent use of gentamicin with diuretics such as ethacrynic acid and furosemide could potentiate ototoxicity.
Anti-emetics can mask ototoxic symptoms.
Neuromuscular block and respiratory paralysis may occur with gentamicin, especially if it is administered to patients receiving neuromuscular blocking agents such as succinylcholine or tubocurarine.
Patients with myasthenia gravis are particularly susceptible to neuromuscular blockade.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
In the event of overdosage or toxic reactions, gentamicin may be removed by haemodialisis or peritoneal dialisis.

IDENTIFICATION:
A clear, colourless to slightly yellow solution contained in a sealed clear glass ampoule.

PRESENTATION:
Cartons containing 5 or 10, 2 mL clear glass ampoules.

STORAGE INSTRUCTIONS:
Store below 25°C.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
W/20.1.1/76

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Ltd.
6 Carey Street, Wynberg Ext. 6,
Johannesburg 2090.

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
06.l1.1990.

        P0903

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