Page 110 - 80 guidelines for the treatment of malaria_opt

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Guidelines for the treatment of malaria – 2 edition

Clindamycin is given parenterally as the phosphate either by the intramuscular or the
intravenous route. It is used for the treatment of anaerobic and Gram-positive bacterial
infections, babesiosis, toxoplasmosis and Pneumocystis carinii pneumonia.

Formulations
• Capsules containing 75 mg, 150 mg or 300 mg of clindamycin base as
hydrochloride.
Pharmacokinetics

About 90% of a dose is absorbed following oral administration. Food does not impede
absorption but may delay it. Clindamycin phosphate and palmitate hydrochloride are
rapidly hydrolysed to form the free drug. Peak concentrations may be reached within 1 h
in children and 3 h in adults. It is widely distributed, although not into the cerebrospinal
fluid. It crosses the placenta and appears in breast milk. It is 90% bound to plasma proteins
and accumulates in leukocytes, macrophages and bile. The half-life is 2–3 h but this may
be prolonged in neonates and patients with renal impairment. Clindamycin undergoes
metabolism to the active N-demethyl and sulfoxide metabolites, and also some inactive
metabolites. About 10% of a dose is excreted in the urine as active drug or metabolites
and about 4% in the faeces. The remainder is excreted as inactive metabolites. Excretion
is slow and takes place over many days. Clindamycin is not effectively removed from the
body by dialysis.
Toxicity

Diarrhoea occurs in 2–20% of patients. In some, pseudomembranous colitis may develop
during or after treatment, which can be fatal. Other reported gastrointestinal effects
include nausea, vomiting, abdominal pain and an unpleasant taste in the mouth. Around
10% of patients develop a hypersensitivity reaction. This may take the form of skin rash,
urticaria or anaphylaxis. Other adverse effects include leukopenia, agranulocytosis,
eosinophilia, thrombocytopenia, erythema multiforme, polyarthritis, jaundice and
hepatic damage. Some parenteral formulations contain benzyl alcohol, which may cause
fatal “gasping syndrome” in neonates.

Drug interactions
Clindamycin may enhance the effects of drugs with neuromuscular blocking activity
and there is a potential danger of respiratory depression. Additive respiratory depressant
effects may also occur with opioids. Clindamycin may antagonize the activity of
parasympathomimetics.

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