Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Rivopharm UK Ltd., 30<sup>th</sup> Floor, 40 Bank Street, Canary Wharf, London, El4 5NR, United Kingdom
Pharmacotherapeutic group: Lincosamides
ATC classification: J01FF01
Clindamycin is a lincosamide antibiotic with a primarily bacteriostatic action against Gram-positive aerobes and a wide range of anaerobic bacteria. Lincosamides such as clindamycin bind to the 50S subunit of the bacterial ribosome similarly to macrolides such as erythromycin and inhibit the early stages of protein synthesis. The action of clindamycin is predominantly bacteriostatic although high concentrations may be slowly bactericidal against sensitive strains.
Resistance to clindamycin usually occurs via macrolide-lincosamide-streptogramin B (MLSB) type of resistance, which may be constitutive or inducible.
The minimum inhibitory concentrations (MIC) breakpoints are as follows:
Eucast
Staphylococci: sensitive ≤0.5 resistant >0.5
Streptococci ABCG and pneumoniae: sensitive ≤0.5 resistant >0.5
Gram positive anaerobes: sensitive ≤4 resistant >4
Gram negative anaerobes: ≤4 resistant >4
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Susceptible:
Gram-positive aerobes:
Staphylococcus aureus*
Staphylococcus epidermidis
Streptococcus pneumonia
Streptococcus pyogenes
Streptococcus viridans
Anaerobes:
Bacteriodes fragilis group
Bacteroides melaninogenicus
Bifidobacterium spp.
Clostridium perfringens
Eubacterium spp
Fusobacterium spp.
Peptococcus spp.
Peptostreptococcus spp.
Propionibacterium spp.
Veillonella spp.
Resistant:
Clostridia spp.
Enterococci
Enterobacteriaceae
* Up to 50% of methicillin-susceptible S. aureus have been reported to be resistant to clindamycin in some areas. More than 90% of methicillin-resistant S.aureus (MRSA) are resistant to clindamycin and it should not be used while awaiting susceptibility test results if there is any suspicion of MRSA.
After oral administration clindamycin is absorbed quickly and almost completely (>90%). The absorption is not affected by food. The peak plasma concentration is achieved within approximately 45 minutes after oral administration. The bioavailability is non-linear and decreases with increasing doses. Following a 600 mg dose the absolute bioavailability is 53±14%.
Clindamycin is widely distributed in body fluids and tissues. It diffuses across the placenta but not the healthy blood-brain barrier. 68–93% of clindamycin in the circulation is bound to plasma proteins. Clindamycin is distributed very highly intracellular due to the lipophilic properties. The intracellular concentrations are 10-50 times higher than the extracellular concentrations.
Clindamycin undergoes metabolism, presumably in the liver, to the active N-demethyl and sulphoxide metabolites, and also some inactive metabolites and about 4% in the faeces: the remainder is excreted as inactive metabolites.
Half-life is approximately two and a half hour in children and approximately 3 hours in adults. Clindamycin is excreted as biological active and biological inactive metabolites in faeces, urine and bile. Faecal excretion is predominant. About 10% of the drug is excreted in the urine as active drug and about 4% in the faeces; the remainder is excreted as inactive metabolites.
The half-life, volume of distribution and clearance, and extent of absorption after administration of clindamycin phosphate are not altered by increased age.
In the presence of renal impairment, elimination half-life is prolonged; however, a dosage reduction is unnecessary in the event of mild to moderate impairment of renal function.
In patients with moderate to severe hepatic impairment the half life is prolonged, but when giving the dose every 8 hours, accumulation is rarely seen. Dose reduction is normally not necessary in patients with hepatic impairment.
Preclinical data reveal no special hazard for humans based on studies of repeat dose toxicity, reproductive toxicity or genotoxicity. Carcinogenicity studies have not been conducted.
In dogs, repeated high oral doses produced ulceration of the mucosa of the stomach and gall bladder.
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