BLACK BOX WARNING
- serious and fatal blood dyscrasias including aplastic anemia
- must not be used when less toxic antibiotics are effective
chloramphenicol
Brand: Chloromycetin
⚠ BBW TDM Required Prototype Drug
Drug Class: amphenicol antibiotic
Drug Family: antibiotic
Subclass: broad-spectrum bacteriostatic antibiotic (reserved)
Organ Systems: infectious-disease
Mechanism of Action
Binds the 50S ribosomal subunit at the peptidyl transferase center, inhibiting peptide bond formation; bacteriostatic (bactericidal against S. pneumoniae, H. influenzae, N. meningitidis). Excellent CNS penetration enables use in bacterial meningitis when beta-lactams are not tolerable.
50S ribosomal subunit (23S rRNA — peptidyl transferase center)
Indications
- bacterial meningitis (penicillin-allergic patients)
- Rocky Mountain spotted fever (alternative when doxycycline contraindicated)
- typhoid fever (Salmonella typhi)
- plague and tularemia (second-line)
- ophthalmic use (topical)
Contraindications
- chloramphenicol hypersensitivity
- routine use (reserve for life-threatening infections when no safer alternative)
Adverse Effects
Common
- bone marrow suppression (dose-related, reversible)
- GI upset
- peripheral neuropathy (prolonged use)
Serious
- aplastic anemia (idiosyncratic, irreversible — 1 in 25,000–40,000 courses)
- Gray baby syndrome (neonates/premature infants — cardiovascular collapse)
- hemolytic anemia (G6PD deficiency)
Pharmacokinetics (ADME)
| Absorption | ~80% oral bioavailability; widely used IV for serious infections |
| Distribution | widely distributed; excellent BBB and CSF penetration (45–90% of serum levels) |
| Metabolism | hepatic glucuronidation; immature glucuronyl transferase in neonates causes accumulation (Gray baby syndrome) |
| Excretion | renal (90% as glucuronide conjugate, 5–10% unchanged) |
| Half-life | 1.5–4 hours (adults); prolonged in neonates and liver disease |
| Onset | rapid |
| Peak | 1–3 hours (oral) |
| Duration | 6 hours |
| Protein Binding | 45–50% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| warfarin/phenytoin/sulfonylureas | inhibits CYP2C9; increases exposure and toxicity of these drugs | major |
| phenobarbital/rifampin | induction reduces chloramphenicol levels; treatment failure risk | moderate |
| other bone marrow suppressants | additive myelosuppression | major |
Nursing Considerations
- Monitor CBC with differential before and during therapy; dose-dependent bone marrow suppression (reversible) is common — obtain baseline then monitor twice weekly.
- Be alert for idiosyncratic aplastic anemia — any sign of anemia, leukopenia, or thrombocytopenia requires immediate discontinuation and hematology consultation.
- Never use in premature neonates or newborns without serum level monitoring; Gray baby syndrome (cardiovascular collapse, cyanosis, abdominal distension) results from immature glucuronidation and drug accumulation.
- Use only for infections where no safer effective alternative exists; document medical necessity in the chart.
Clinical Pearls
- Chloramphenicol's aplastic anemia risk (~1:25,000–40,000 treatment courses) is idiosyncratic and unpredictable; it is NOT dose-related, cannot be predicted by monitoring, and is often fatal — hence its relegation to last-resort status.
- Gray baby syndrome, unlike aplastic anemia, is dose-related and preventable by monitoring serum levels (therapeutic range 10–20 mcg/mL peak); it results from cardiovascular compromise due to drug accumulation from immature neonatal hepatic glucuronidation.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.