Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Hospira UK Limited, Horizon, Honey Lane, Hurley, Maidenhead, SL6 6RJ, UK
Pharmacotherapeutic group: Aminoglycoside Antibacterials
ATC Code: J01GB01
Tobramycin is bactericidal in activity. It enters the cells via complex active transport mechanism and exerts its activity primarily on the 30S ribosomal subunit, interfering with initial and subsequent steps in protein synthesis. It also acts to induce misreading of the genetic code of the mRNA template, resulting in incorporation of incorrect amino acids.
Tobramycin, in common with all other aminoglycosides, is primarily antibacterial against aerobic Gram-negative bacilli. Tobramycin is considered more active than most other aminoglycosides against Pseudomonas aeruginosa.
Tobramycin is usually active against most strains of the following organisms:
Proteus species (indole-positive and indole-negative) including:
Pr. mirabilis; Pr. morganii; Pr. rettgeri and Pr. vulgaris Escherichia coli
Klebsiella, Enterobacter, Serratia species Citrobacter species
Providencia species
Staphylococci, including Staph. aureus (coagulase-positive and coagulase-negative).
Aminoglycosides have a low order of activity against most Gram-positive organisms, including Streptococcus pyogenes, S. Pneumoniae and enterococci.
Some strains of Group D streptococci are susceptible in vitro although most strains of enterococci show resistance. In vitro studies have shown that an aminoglycoside combined with an antibiotic which interferes with cell wall synthesis affects some Group D streptococcal strains synergistically. The combination of benzylpenicillin and tobramycin results in a synergistic bactericidal effect in vitro against certain strains of S. faecalis. However, this combination is not synergistic against other closely related organisms, e.g. S. faecium. Specification of Group D streptococci alone cannot, therefore, be used to predict susceptibility. Susceptibility testing and tests for antibiotic synergism are emphasized.
Cross-resistance between aminoglycosides occurs and depends largely on inactivation by bacterial enzymes.
Following intramuscular administration of a single dose of tobramycin 1 mg/kg in adults with normal renal function, peak plasma tobramycin concentrations averaging 4-6 micrograms/ml are obtained within 30-90 minutes; plasma concentrations of the drug are 1 microgram/ml or less at 8 hours. Following intravenous infusion of the same dose over 30- 60 minutes, similar plasma concentrations of the drug are obtained. Tobramycin is poorly absorbed from the gastrointestinal tract.
After injection tobramycin has been detected in body fluids but concentrations in the cerebrospinal fluid are low even when there is meningeal inflammation. Most bodily compartments and tissues including the inner ear and kidneys become progressively saturated with aminoglycosides over the course of therapy, and the drug is slowly released from these areas. It has been postulated that this accumulation may account for the ototoxicity and nephrotoxicity associated with aminoglycosides. In general, aminoglycosides such as tobramycin readily cross the placenta. Small amounts of the drugs are also distributed into bile, saliva, sweat, tears, sputum, and milk.
The major route of elimination is renal and the drug is eliminated almost entirely by glomerular filtration. Protein binding of tobramycin has been reported as zero. The plasma elimination half-life of tobramycin is usually 2-3 hours in adults with normal renal function and is reported to range from 5 to 70 hours in adults with impaired renal function. In full- term infants the plasma elimination half-life is reported to average 4.6 hours and in low birth-weight infants it averages 8.7 hours.
Peak urine concentrations ranging from 75 to 100 microgram/ml have been observed after the intramuscular injection of a single dose of 1 mg/kg. After several days of treatment, the amount of tobramycin excreted in the urine approaches the daily amount administered. When renal function is impaired, excretion of tobramycin is slowed, and accumulation of the drug may cause toxic blood levels. In patients undergoing dialysis, 25 to 70% of the administered dose may be removed, depending on the duration and type of dialysis.
There are no preclinical data of relevance to the prescriber which are additional to the information already included in other sections of the SPC.
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