INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
Q-MED TOBRAMYCIN 20 mg/2 mL INJECTION
Q-MED TOBRAMYCIN 80 mg/2 mL INJECTION

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

Q-MED TOBRAMYCIN 20 mg/2 mL INJECTION
Q-MED TOBRAMYCIN 80 mg/2 mL INJECTION

COMPOSITION:
Q-Med Tobramycin 20 mg/2 mL        -        Each 2 mL contains 20 mg tobramycin as the sulphate.
Q-Med Tobramycin 80 mg/2 mL        -        Each 2 mL contains 80 mg tobramycin as the sulphate.
Both concentrations contain benzyl alcohol 0,9% v/v as preservative and 0,32% m/v sodium metabisulphite as antioxidant.

PHARMACOLOGICAL CLASSIFICATION:
A 201.1 Broad and medium Spectrum Antibiotics.

PHARMACOLOGICAL ACTION:
Tobramycin is an aminoglycoside antibiotic with bactericidal activity against gram negative aerobic organisms, including Pseudomonas aeruginosa which results mainly from inhibition of protein synthesis in susceptible micro-organisms. Bacterial resistance to tobramycin may rapidly occur and cross-resistance between aminoglycosides may exist. Peak plasma concentrations is obtained 30 to 90 minutes following intramuscular injection, which are similar to those found 30 minutes following intravenous infusion. It has a half life of 2,2 hours and is negligibly plasma protein bound. High concentrations are found only in the renal cortex and in the endolymph and perilymph of the inner ear. After repeated administration only, is it found in the pleural and synovial fluid at concentrations approximating plasma levels. Excretion is almost entirely by glomerular filtration.

INDICATIONS:
Tobramycin sulphate is used usually in combination, to treat life-threatening infections due to sensitive gram-negative organisms. It is also used in the treatment and prophylaxis of endocarditis due to streptococci, enterococci, and sometimes staphylococci.
It may be given with an anti-pseudomonas penicillin or cephalosporin for the treatment of pseudomonas infections, with ampicillin or benzylpenicillin for enterococcal and streptococcal infections, or with metronidazole or clindamycin for mixed aerobic-anaerobic infections. Tobramycin and other antibiotics should be administered separately.
Bacterial cultures should be obtained prior to and during treatment to isolate and identify the causative organisms and to test their susceptibility to tobramycin.

CONTRA-INDICATIONS:
A history of allergy to tobramycin and to other aminoglycosides.
Pregnancy and lactation
It should be avoided in patients with myasthenia gravis. Use of tobramycin during pregnancy may damage the 8th cranial nerve of the foetus.

WARNINGS:
Due to the risk of ototoxicity and neurotoxicity with prolonged use of aminoglycosides, tobramycin must be restricted to the therapy of life-threatening infections in which a less toxic antimicrobial agent is not suitable. Serum peak levels of 10 µg/mL must be avoided as this could be toxic. Serum trough levels of more than 2 µg/mL may be the best indication of accumulation of tobramycin 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 tobramycin administered in normal doses to patients with impaired renal function.

DOSAGE AND DIRECTIONS FOR USE:
Tobramycin may be given intramuscularly, or intravenously over 20 to 60 minutes in 50 to 100 mL of sterile sodium chloride 0,9%. Proportionately less fluid should be given to children. Diluted solutions must be used within 24 hours after dilution and stored below 25°C.
Tobramycin should not be physically premixed with other medicines but should be administered separately.
Patients with normal renal function:
Children:
6 mg/kg/day to 7,5 mg/kg/day in three or four equally divided doses.
Premature or full term neonates 1 week of age or /less:
Up to 4 mg/kg/day may be administered in two equally divided doses every 12 hours.
Adults with serious infections:
3 mg/kg/day, administered in three equally divided doses every 8 hours. (See table 1 ).
Adults with life-threatening infections:
Up to 5 mg/kg/day may be administered in three or four equally divided doses (See table 1 ).
TABLE 1: Dosage schedule guide for adults with normal renal function

Patients Mass	Usual dose for serious infections 1 mg/kg 8 hourly (Total: 3 mg/kg/day)		Maximum dose for life-threatening infections (reduce as soon as possible) 1,66 mg/kg 8 hourly (Total: 5 mg/kg/day)
	mg/dose	mL/dose*	mg/dose	mL/dose*
	8 hourly		8 hourly
120 kg 100 kg 80 kg 60 kg 40 kg	120 mg 100 mg 80 mg 60 mg 40 mg	3,0 mL 2,5 mL 2,0 mL 1,5 mL 1,0 mL	200 mg 166 mg 133 mg 100 mg 66 mg	5,0 mL 4,0 mL 3,0 mL 2,5 mL 1,6 mL

* Applicable to 40 mg/mL product forms.
Treatment should generally continue for not longer than 7 to 10 days.
In all patients, dosage should be adjusted according to plasma-tobramycin concentrations and particularly where factors such as age, renal impairment, or high dose may predispose to toxicity.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
It can produce irreversible, cumulative ototoxicity affecting both the cochlea (manifest as hearing loss on higher tones) and more common, the vestibular system (manifest as dizziness and vertigo). Concurrent use of an anti-emetic eg. dimenhydrinate may mask the early symptoms of vestibular ototoxicity. Reversible nephrotoxicity may occur and acute renal failure has been reported, often in association with the concurrent administration of other nephrotoxic agents eg. other aminoglycosides, vancomycin, some cephalosporins, or potentially ototoxic agents such as ethacrynic acid and furosemide.
Renal impairment is usually mild, although acute tubular necrosis and interstitial nephritis have occurred. Decreased glomerular filtration rate is usually seen only after several days, and may even occur after therapy has been discontinued.
Tobramycin possesses a neuromuscular blocking action and respiratory depression and muscular paralysis have been reported and care is required when another neuromuscular blocking agent is given concomitantly. Neurotoxicity has occurred, both peripheral neuropathies and central systems including encephalopathy, confusion, lethargy, hallucinations, convulsions and central depression.
Cross-sensitivity may occur between aminoglycoside. Hypersensitivity reactions, anaphylactic reactions and endotoxic shock has been reported.
Infrequent effects reported include blood dyscrasias, purpura, nausea and vomiting, stomatitis, and signs of liver dysfunction eg. increased serum aminotransferase values and increased serum-bilirubin concentrations. Great care is required in patients with myasthenia gravis, parkinsonism and other conditions characterised by muscle weakness. It is desirable to determine dosage requirements by individual monitoring. Dosage should be adjusted to avoid peak plasma concentrations above 10 to 20 µg/mL, or trough concentrations exceeding 2 µg/mL. Monitoring is important in patients receiving high doses or prolonged courses, in infants and the elderly and in patients with renal failure.
Care should be exerted when it is given to patients receiving other medicines with a neuromuscular blocking activity or which are ototoxic or nephrotoxic. Anti-emetics may mask ototoxic symptoms. Patients with known renal impairment should be closely monitored for serum peak and trough levels. Regular plasma creatinine determination is advised.

KNOWN SYMPTOMS OF OVERDOSAGE AND ITS TREATMENT:
See Side Effects and Special Precautions.
In the event of overdosage or toxic reaction, haemodialysis or peritoneal dialysis will reduce serum levels. Treatment is symptomatic and supportive.

IDENTIFICATION:
A clear, colourless solution in clear colourless 2 mL vials.

PRESENTATION:
Q-Med Tobramycin 20 mg/2 mL vials in cartons of 10.
Q-Med Tobramycin 80 mg/2 mL vials in cartons of 10.

STORAGE INSTRUCTIONS:
Store below 25°C.
Keep out of reach of children.

REGISTRATION NUMBER:
20 mg/2 mL = 31/20.1.1/0155
80 mg/2 mL = 31/20.1 1/0156

NAME AND BUSINESS ADDRESS OF APPLICANT:
Quatromed Limited
10 Lindley Street
BETHLEHEM
9701

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
3/97                PTO0051/4-97

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