Clinical medicine profile
Chloramphenicol
Therapeutic agent (verify pharmacological class)
- Route
- INTRAVENOUS
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
WARNING Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia and granulocytopenia) are known to occur after the administration of chloramphenicol. In addition, there have been reports of aplastic anemia attributed to chloramphenicol which later terminated in leukemia. Blood dyscrasias have occurred after both short-term and prolonged therapy with this drug. Chloramphenicol must not be used when less potentially dangerous agents will be effective, as described in the INDICATIONS AND USAGE section. It must not be used in the treatment of trivial infections or where it is not indicated, as in colds, influenza, infections of the throat; or as a prophylactic agent to prevent bacterial infections. Precautions: It is essential that adequate blood studies be made during treatment with the drug. While blood studies may detect early peripheral blood changes, such as leukopenia, reticulocytopenia, or granulocytopenia, before they become irreversible, such studies cannot be relied on to detect bone marrow depression prior to development of aplastic anemia. To facilitate appropriate studies and observation during therapy, it is desirable that patients be hospitalized.
Contraindications
- CONTRAINDICATIONS: Chloramphenicol is contraindicated in individuals with a history of previous hypersensitivity and/or toxic reaction to it.
- It must not be used in the treatment of trivial infections or where it is not indicated, as in colds, influenza, infections of the throat
- or as a prophylactic agent to prevent bacterial infections.
Precautions
- Do routine blood examination, change parenteral administration to oral therapy as soon as possible, impaired liver and kidney functions.
- Must not be used in the treatment of trivial infections.
- Plasma concentration monitoring required in neonates and preferred in those under 4 years of age, in the elderly, and in hepatic impairment
- recommended peak plasma concentration (approx. 1 hour after intravenous injection or infusion) 1525mg/litre
- pre-dose (trough') concentration should not exceed 15mg/litre.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
By mouth or by intravenous injection or infusion, 50mg/kg daily in 4 divided doses [exceptionally, can be doubled for severe infections such as septicaemia and meningitis, providing high doses reduced as soon as clinically indicated]; child, haemophilus epiglottitis and pyogenic meningitis, 50-100mg/kg daily in divided doses [high dosages decreased as soon as clinically indicated]; neonate under 2 weeks 25mg/kg daily [in 4 divided doses]; infant 2 weeks1 year 50mg/kg daily [in 4 divided doses]. Note: Plasma concentration monitoring required in neonates and preferred in those under 4 years of age, in the elderly, and in hepatic impairment; recommended peak plasma concentration [approx. 1 hour after intravenous injection or infusion] 1525mg/litre; pre-dose [ trough'] concentration should not exceed 15mg/litre.
Pediatric Use Precaution should be used in therapy of premature and full-term neonates and infants to avoid “gray syndrome” toxicity. Due to immature metabolic processes in the neonate and infant, excessive blood levels may result from administration of the recommended dose. The dosage should be adjusted accordingly or, preferable, the blood concentration should be determined at appropriate intervals (see ADVERSE REACTIONS , "Gray Syndrome" ). See DOSAGE AND ADMINISTRATION for dosing information in the pediatric population.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- Serious infections where less potentially dangerous medicines are ineffective or contraindicated e.g. typhoid and paratyphoid fever, infections due to H. influenzae.
- Clinical selection for Chloramphenicol should follow culture results where relevant, Kenya STG/EML recommendations, and the current product SmPC.
- Class context: Therapeutic agent (verify pharmacological class).
- Confirm site-specific dose, duration and monitoring before prescribing.
Adverse effects
- ADVERSE REACTIONS: Blood Dyscrasias The most serious adverse effect of chloramphenicol is bone marrow depression.
- Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) are known to occur after the administration of chloramphenicol.
- An irreversible type of marrow depression leading to aplastic anemia with a high rate of mortality is characterized by the appearance weeks or months after therapy of bone marrow aplasia or hypoplasia.
- Peripherally, pancytopenia is most often observed, but in a small number of cases only one or two of the three major cell types (erythrocytes, leukocytes, platelets) may be depressed.
- A reversible type of bone marrow depression, which is dose related, may occur.
- This type of marrow depression is characterized by vacuolization of the erythroid cells, reduction of reticulocytes and leukopenia, and responds promptly to the withdrawal of chloramphenicol.
- An exact determination of the risk of serious and fatal blood dyscrasias is not possible because of lack of accurate information regarding 1) the size of the population at risk, 2) the total number of drug-associated dyscrasias, and 3) the total number of non-drug associated dyscrasias.
- In a report to the California State Assembly by the California Medical Association and the State Department of Public Health in January 1967, the risk of fatal aplastic anemia was estimated at 1:24,200 to 1:40,500 based on two dosage levels.
- There have been reports of aplastic anemia attributed to chloramphenicol which later terminated in leukemia.
- Paroxysmal nocturnal hemoglobinuria has been reported.
- Gastrointestinal Reactions Nausea, vomiting, glossitis and stomatitis, diarrhea and enterocolitis may occur in low incidence.
- Neurotoxic Reactions Headache, mild depression, mental confusion, and delirium have been described in patients receiving chloramphenicol.
- Optic and peripheral neuritis have been reported, usually following long-term therapy.
- If this occurs, the drug should be promptly withdrawn.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
Chloramphenicol is a broad-spectrum antibiotic originally isolated from Streptomyces venezuelae .
Read complete mechanism
Chloramphenicol is a broad-spectrum antibiotic originally isolated from Streptomyces venezuelae . It inhibits bacterial protein synthesis by interfering with the transfer of activated amino acids from soluble RNA to ribosomes. In vitro, chloramphenicol exerts mainly a bacteriostatic effect on a wide range of gram-negative and gram-positive bacteria. Antimicrobial Activity Chloramphenicol has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Aerobic gram-negative microorganisms Haemophilus influenzae Salmonella species, including Salmonella typhi Other microorganisms Lymphogranuloma-psittacosis group Rickettsia Susceptibility Testing Methods When available, the clinical
Product-specific
Product-specific
INTRAVENOUS
is not uniform. Highest concentrations are found in liver and kidney, and lowest concentrations are found in brain and cerebrospinal fluid. Chloramphenicol enters cerebrospinal fluid even in the absence of meningeal inflammation, appearing in concentrations about half of those fo...
of chloramphenicol in these studies ranged from a low of 68% to a high of 99% over a three-day period. From 8% to 12% of the antibiotic excreted is in the form of free chloramphenicol; the remainder consists of microbiologically inactive metabolites, principally the conjugate wit...
Pregnancy, lactation & diet
Pregnancy Pregnancy Category C – Animal reproduction studies have not been conducted with chloramphenicol. There are no adequate and well-controlled studies to establish safety of this drug in pregnancy. It is not known whether chloramphenicol can cause fetal harm when administered to a pregnant woman. Orally administered chloramphenicol has been shown to cross the placental barrier. Because of potential toxic effects on the fetus (see ADVERSE REACTIONS, “Gray Syndrome” ), chloramphenicol should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers Chloramphenicol is excreted in human milk following oral administration of the drug. Because of the potential for serious adverse reactions in nursing infants from chloramphenicol, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see ADVERSE REACTIONS, “Gray Syndrome” ).
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| Vanmycetin 0.5% Eye Drops | FDC Limited | Eye Drops | Unavailable |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.