Therapeutic Indication
Typhoid fever and life threatening infections, particularly those caused by haemophilus influenza, where other antibiotics will not suffice.
Posology and method of administration
Normal dose for adults and elderly: 50 mg/kg body weight daily in 4 divided doses. For severe infections (meningitis, septicemia) this dose may be doubled initially, but it must be reduced as soon as clinically practical. Not recommended for children
| Image from Wikipedia |
Contraindications
Known hypersensitivity or toxic reaction to Chloramphenicol or to any of the excipients. Chloramphenicol is contraindicated in prophylaxis or treatment of minor infections; during active immunization and in porphyria patients. Chloramphenicol is contraindicated in patients taking drugs liable to depress bone marrow function. Chloramphenicol must not be used in breast-feeding mothers and during pregnancy or labour, due to a risk of foetal infant damage (Grey baby syndrome)
Special warning and precautions for use
Chloramphenicol should only be used if other treatments are ineffective and its use should always be carefully monitored. Dose reduction and plasma level monitoring may be required. Dose reduction and plasma level monitoring may be required in patients with hepatic or renal impairment; in the elderly and in patients concurrently treated with interacting drugs. Periodic blood testing should be conducted during prolonged or repeated treatment. Chloramphenicol should be discontinued if s significant detrimental effect is seen.
Pregnancy and lactation
The use of chloramphenicol is contraindicated as the drug crosses the placenta and is excreted in breast milk.
Effects on ability to drive and use machine
No significant effect on driving ability
Undesirable effects
The most serious undesirable effects that may arise are:
- A reversible dose related bone marrow depression
- An irreversible aplastic anemia with an estimated frequency between 1/4000 and 1/100000. Other undesirable effects are
- Increasing in bleeding time
- Immune system disorders
- Hypersensitivity reactions including allergic skin reactions
- Optic neuritis leading to blindness
- Ototoxicity
- Acidotic cardiovascular collapse
- Nausea, vomiting, glossitis, stomatitis, diarrhea, enterocolitis
- Pregnancy, puerperium and perinatal conditions
“Gray” syndrome, particulary in the newborn, which appears to be related to excessively high plasma levels. The Gray Baby Syndrome consists of abdominal distension, pallid cyanosis, vomiting, pregressing to vasomotor collapse, irregular respiration and death within a few hours of onset of symptoms. (These symptoms are thought to be dose related and rapid clearance of chloramphenicol has been associated with recovery)
Overdose
Where adverse effects show signs of developing administration must be stopped immediately and treatment is mainly supportive. If an allergy develops, oral antihistamines may be used. In severe overdose e.g. Gray baby syndrome, there is a need for a rapid reduction in plasma levels and it has been reported that resins haemoperfusion (XAD-4) substantially increases chloramphenicol clearance
Pharmacodynamics properties
Chloramphenicol is a broad spectrum antibiotic acting by interfering with bacterial protein synthesis. The most important action on the body tissue is the adverse one of bone marrow depression. There is significant Plasma Protein Binding and the drug is largely inactivated in the liver
Pharmacokinetic properties
Chloramphenicol is readily absorbed from the G.I. tract. Particle size may affect rate of absorption, but will not affect total absorption. Significant serum levels observable 30 minutes after ingestion and half-life may be 2-5 hours. Chloramphenicol is widely distributed in body tissues and fluids. It is found in cerebro-spinal fluid. It crosses the placental barrier and diffuses into breast milk. There is significant plasma protein binding (up to 60%). Excretion is mainly in the urine and largely inactivated in the liver
