Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2022 Publisher: FDC International Ltd, Unit 6 Fulcrum 1, Solent Way, Whiteley, Fareham, Hampshire, PO15 7FE, United Kingdom
Pharmacotherapeutic group: Ophthalmological antibiotics
ATC Code: S01AA01
Chloramphenicol is a broad spectrum antibiotic with bacteriostatic activity and is effective against a wide range of gram-negative and gram-positive organisms.
Chloramphenicol exerts its antibacterial effect by binding to bacterial ribosomes and inhibiting bacterial protein synthesis at an early stage.
The following bacterial species are recognised conjunctival pathogens and may be susceptible to chloramphenicol. However due to the prevalence of acquired resistance to chloramphenicol in these species, the results of susceptibility testing should be taken into account if these are available. If no susceptibility test result is available, the choice of antibacterial agent should be influenced by local information on the likely prevalence of resistance to chloramphenicol in species that are commonly pathogenic in the eye.
Staphylococcus aureus
Streptococcus pyogenes
Streptococcus pneumoniae
Other beta-haemolytic streptococci
Haemophilius influenze
Moraxella catarrhalis
Neisseria gonorrhoeae
Acquired resistance to chloramphenicol has been described in all the above species. Most commonly this is mediated by bacterial production of a chloramphenicol acetyl transferase that inactivates the drug. Chloramphenicol is not generally active against the enterobacteriaceae and is not active against non-fermenters such as Pseudomonas aeruginosa.
Following topical application to the eye, chloramphenicol may be absorbed into the aqueous humour. Sufficient chloramphenicol may be absorbed from the eye to appear in the systemic circulation.
Specific data on systemic absorption from this dosage presentation is not available.
Chloramphenicol is readily absorbed when given by mouth. Blood concentrations of 10µg per ml or more may be reached about 1 or 2 hours after a single dose of 1g by mouth, and blood concentrations of about 18.5µg per ml have been reported after multiple 1g doses. Choramphenicol palmitate is hydrolysed to chloramphenicol in the gastrointestinal tract prior to absorption, and the sodium succinate, which is given parenterally is probably hydrolysed to free drug mainly in the liver, lungs, and kidneys; such hydrolysis may be incomplete in infants and neonates, contributing to the variable pharmacokinetics in this age group. Chloramphenicol sodium succinate is, even in adults, only partially and variably hydrolysed, so that blood concentrations of chloramphenicol obtained after parenteral administration of the sodium succinate are often lower than those obtained after administration of chloramphenicol by mouth, with up to 30% of a dose excreted unchanged in the urine before hydrolysis can take place.
Chloramphenicol is widely distributed in body tissues and fluids; it enters the cerebrospinal fluid, giving concentrations of about 50% of those existing in the blood even in the absence of inflamed meninges; it diffuses across the placenta into the foetal circulation, into breast milk, and into the aqueous and vitreous humours of the eye. Up to about 60% in the circulation is bound to plasma protein. The half-life of chloramphenicol has been reported to range from 1.5 to 4 hours; the half-life is prolonged in patients with severe hepatic impairment and is also much longer in neonates. Renal impairment has relatively little effect on the half-life of the active drug, due to its extensive metabolism, but may lead to accumulation of the inactive metabolites.
Chloramphenicol is excreted mainly in the urine but only 5 to 10% of an oral dose appears unchanged; the remainder is inactivated in the liver, mostly by conjugation with glucorinic acid. About 3% is excreted in the bile. However, most is reabsorbed and only about 1%, mainly in the inactive form, is excreted in the faeces.
The absorption, metabolism, and excretion of chloramphenicol are subject to considerable interindividual variation, especially in infants and children, making monitoring of plasma concentrations necessary to determine pharmacokinetics in a given patient.
Nothing of relevance which is not included in other sections of the SPC.
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