Drugs List

• chloramphenicol 250mg capsules
• chloramphenicol syrup

Therapeutic Indications

Uses

Life-threatening infections untreatable with less toxic antimicrobials
Meningitis caused by haemophilus influenzae: treatment
Typhoid: treatment

Treatment of life-threatening infections including typhoid, meningitis caused by haemophilus influenzae, and other serious infections caused by susceptible bacteria where other antibiotics are inappropriate.

Chloramphenicol should not be used for trivial infections due to the possibility of severe and potentially fatal blood disorders.

Dosage

Children aged 1 month to 18 years (unlicensed)

12.5mg/kg every 6 hours. Dose may be doubled in severe infections, but should be reduced as soon as is clinically indicated.

Plasma chloramphenicol concentrations should be measured and high doses reduced as soon as is clinically indicated.

For young children other formulations of chloramphenicol may be more appropriate.

Contraindications

Neonates under 1 month
Breastfeeding
Porphyria
Pregnancy at term

Precautions and Warnings

Children 1 month to 18 years
Elderly
Hepatic impairment
Myelosuppression
Pregnancy
Renal impairment

Blood counts should be performed before and periodically during treatment
Monitor for signs of bone marrow depression
Monitor plasma levels and adapt dose in patients with hepatic impairment
Monitor plasma levels and adapt dose in patients with renal impairment
Avoid repeated or prolonged use

Chloramphenicol may cause severe bone marrow depression which can lead to aplastic anaemia. High doses, prolonged administration or repeated courses are usually associated with these effects but they may also occur at relatively low doses.

Pregnancy and Lactation

Pregnancy

Chloramphenicol should not be used during pregnancy unless there is a serious indication.

Schaefer suggests the drug should not be used in the last weeks of pregnancy as, owing to inadequate metabolism in the neonate, toxic concentrations can be reached. This may cause grey baby syndrome (feeding problems, vomiting, ash-grey skin, respiratory distress and cardiovascular collapse) which may be fatal in the neonate. If chloramphenicol has been taken in early pregnancy, it does not require termination of pregnancy or additional invasive diagnostic procedures. The manufacturers suggest chloramphenicol is contraindicated during breastfeeding.

Chloramphenicol is known to cross the placenta at term producing 30 to 106% of maternal levels. Cases of exposure during pregnancy have been reported but no evidence has been found to suggest a relationship to congenital malformations.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Chloramphenicol is contraindicated during breastfeeding.

The Drugs and Lactation Database (LactMed) suggests using an alternative drug or discontinuing breastfeeding. Milk levels are considered too low to cause grey baby syndrome but chloramphenicol-induced aplastic anaemia remains a possibility as this is not dose related. If the mother must receive chloramphenicol, it is advisable to monitor blood counts in the breastfed infant and check for gastrointestinal disturbances. The manufacturers suggest chloramphenicol is contraindicated during breastfeeding.

Chloramphenicol is known to be present in human breast milk.

The following have been noted in breastfed infants of chloramphenicol dosed mothers: refusal of milk, vomiting, excessive gas, falling asleep during feeding. Modification of infant bowel flora is also possible.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.

Side Effects

Aplastic anaemia
Blood disorders
Bone marrow depression
Cardiovascular collapse
Depression
Diarrhoea
Dry mouth
Enterocolitis
Erythema multiforme
Glossitis
Grey syndrome
Headache
Hypersensitivity reactions
Increased bleeding tendency
Leukaemia
Loss of vision(transient)
Nausea
Nocturnal haemoglobinuria
Optic neuritis
Ototoxicity
Peripheral neuritis
Stomatitis
Urticaria
Vomiting