CHLORAMPHENICOL SODIUM SUCCINATE

Chloromycetin

Reviewed by Dorothy Cooper
September 1998
Administration Newborn Drug Protocol Index Newborn Services Home Page

Dose and Administration

  1. Loading dose 20 mg/kg IV infusion by syringe pump over 30 minutes. Maintenance dose (begin 12 hours after loading dose):

Preterm infants less than 1 month of age:

2.5 mg/kg/dose every 6 hours

Preterm infants over 1 month of age:

5.0 mg/kg/dose every 6 hours

Full term infants less than 1 week of age:

5.0 mg/kg/dose every 6 hours

Full term infants over 1 week of age:

12.5 mg/kg/dose every 6 hours

Indications

  1. Neonatal CNS infections.
  2. After consultation with Paediatric Infectious Disease Consultant.

Contraindications and Precautions

  1. Caution in preterm infants, especially extreme immaturity.
  2. Caution in infants with liver, renal or gastrointestinal dysfunction.
  3. Caution in infants with G6PD deficiency.

Clinical Pharmacology

A wide spectrum bacteriostatic anti-microbial agent. Active against a wide range of gram negative and gram positive bacteria. It is particularly active against Salmonella typhii and Haemophilus influenzae. Also active against rickettsial organisms and the lymphogranuloma-psittacosis group. Acts by inhibition of protein synthesis in intact cells and in cell free systems. Development of resistance to chloramphenicol appears to be low in comparison with other antibiotics.

Absorbed rapidly from the gastrointestinal tract. Crosses tissue barriers readily, and diffuses widely and rapidly through nearly all body tissues and fluids. Chloramphenicol enters CSF even in the absence of meningeal inflammation. Hydrolysed for release of the active free base - the site of hydrolysis is unknown. The degree of hydrolysis can be unpredictable and variable from patient to patient with significant clinical consequences. Infants during the first month of life appear to hydrolyse the succinate ester less readily than do older infants and children. Some of the succinate ester is excreted by the kidneys prior to hydrolysis (9-40%). Free chloramphenicol is metabolised by hepatic glucuronyl transferases. Of administered or available free chloramphenicol, 85-90% is excreted via the kidney as the glucuronide.

Possible Adverse Effects

  1. Irritation, soft tissue injury at the site of IV injection.
  2. Fever, rash, urticaria and pruritus.
  3. Gastrointestinal disturbances (nausea, vomiting, diarrhoea).
  4. Haematological disturbances (anaemia, granulocytopaenia, thrombocytopaenia). A reversible type of bone marrow depression which is dose related, may occur. There is also an irreversible type of marrow suppression leading to aplastic anaemia.
  5. Neurological disturbances (headache, confusion and delirium, optic and peripheral neuritis).
  6. Grey syndrome (vomiting, refusal to suck, irregular and rapid respiration, abdominal distension, periods of cyanosis and passage of loose stools, flaccidity, an ashen grey colour, a decrease in temperature followed by circulatory collapse). There is no treatment of proved value in managing drug toxicity.

Interactions

  1. Anticoagulants, barbiturates, phenytoin, iron salts increase blood level with these agents.
  2. Penicillin synergistic effect may occur.
  3. Rifampicin may reduce chloramphenicol levels.

Special Considerations

  1. Rarely used in the newborn infant.
  2. Close monitoring of serum concentration is mandatory. Small changes in dose and interval can lead to disproportionately large changes in serum concentration. Therapeutic peak serum concentration 10-25 mg/L.
  3. Monitor FBC and reticulocyte counts.
  4. Assess hepatic and renal function.
  5. Sodium content = 2.25mEq (52mg)/g.