CHLORAMPHENICOL SODIUM SUCCINATE
Clinical safety rating: avoid
Potentiates effects of warfarin phenytoin and sulfonylureas by inhibiting their metabolism Associated with serious and fatal blood dyscrasias like aplastic anemia.
Reversibly binds to the 50S ribosomal subunit, inhibiting peptidyl transferase activity and blocking protein synthesis in bacteria.
| Metabolism | Primarily hepatic via glucuronidation; also hydrolyzed to active chloramphenicol base. Minor metabolism by reduction to aryl amines. |
| Excretion | Approximately 80-90% of the dose is excreted renally as unchanged drug and as the inactive chloramphenicol base (formed by hydrolysis in the liver and kidneys). Biliary excretion accounts for about 5-10%, with some enterohepatic circulation. Fecal excretion is negligible (<2%). |
| Half-life | Terminal elimination half-life is approximately 1.5-3.5 hours in adults with normal renal and hepatic function. In neonates (first 2 weeks of life), half-life is prolonged to 10-24 hours due to immature hepatic conjugation. In patients with severe hepatic impairment, half-life may exceed 12 hours, necessitating dose adjustment. |
| Protein binding | Approximately 50-60% bound to serum proteins, predominantly albumin. Binding is reversible and concentration-independent. |
| Volume of Distribution | Volume of distribution is 0.6-1.0 L/kg, indicating extensive distribution into total body water and tissues, including cerebrospinal fluid, brain, and aqueous humor. Penetration into CSF is 30-50% of serum levels even in non-inflamed meninges. |
| Bioavailability | Oral bioavailability of chloramphenicol base is 75-90% after oral administration, but chloramphenicol sodium succinate is a prodrug intended for parenteral use only. After intramuscular injection, bioavailability is approximately 70-80% due to incomplete hydrolysis to active free base at the injection site. |
| Onset of Action | Intravenous administration: Onset of action is rapid, with therapeutic serum concentrations achieved within 30-60 minutes after infusion. After intramuscular injection, peak concentrations occur at 1-2 hours but absorption may be erratic; onset is within 2-4 hours. |
| Duration of Action | Duration of action is approximately 6-12 hours following a single intravenous dose, correlating with serum concentrations above the minimum inhibitory concentration (MIC) for susceptible organisms. Prolonged in renal or hepatic impairment due to reduced clearance. |
| Molecular Weight | 445.2 Da (chloramphenicol sodium succinate) |
Intravenous, 50 mg/kg/day divided every 6 hours; maximum 4 g/day.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl <10 mL/min: 50 mg/kg loading dose, then 25 mg/kg/day divided every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: reduce dose by 50% and monitor serum levels. |
| Pediatric use | Neonates <7 days: 25 mg/kg/day IV every 24 hours; neonates >7 days: 50 mg/kg/day IV every 12 hours; infants and children: 50-75 mg/kg/day IV divided every 6 hours. |
| Geriatric use | Use with caution; monitor liver and renal function; consider lower end of dosing range due to decreased clearance. |
| 1st trimester | Avoid; known teratogen (gray baby syndrome) and associated with aplastic anemia. Use only for life-threatening infections when no alternative exists. |
| 2nd trimester | Avoid; risks of bone marrow suppression and gray baby syndrome in fetus. Use only if clearly needed and no safer alternative. |
| 3rd trimester | Avoid; risk of gray baby syndrome in neonate due to immature hepatic metabolism. Contraindicated in late pregnancy and during labor. |
Clinical note
Potentiates effects of warfarin phenytoin and sulfonylureas by inhibiting their metabolism Associated with serious and fatal blood dyscrasias like aplastic anemia.
| FDA category | Positive |
| Placental transfer | Chloramphenicol readily crosses the placenta, achieving fetal serum concentrations approximately 30-80% of maternal levels. |
■ FDA Black Box Warning
Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) have occurred with both short-term and prolonged therapy. Chloramphenicol should not be used when less potentially dangerous agents are effective.
| Common Effects | meningitis |
| Serious Effects |
History of serious hypersensitivity reaction (e.g., aplastic anemia) to chloramphenicolHistory of chloramphenicol-induced bone marrow depressionTreatment of trivial infections or prophylaxisPregnancy (especially third trimester) and lactationNeonates and premature infants (gray baby syndrome risk)
| Precautions | Bone marrow suppression including aplastic anemia and hypoplastic anemia, Gray baby syndrome in neonates due to immature hepatic glucuronidation, Hematologic monitoring required every 2 days during therapy, Potential for superinfection, Carcinogenicity and mutagenicity concerns |
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| Breastfeeding |
| Chloramphenicol is excreted into breast milk in small amounts. Potential serious adverse effects in nursing infants include bone marrow suppression and gray baby syndrome. Use is contraindicated during breastfeeding due to risk of idiosyncratic aplastic anemia. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Chloramphenicol crosses the placenta. First trimester: limited data, but animal studies show no teratogenicity at clinically relevant doses; avoid unless essential. Second/third trimester: Risk of gray baby syndrome (cardiovascular collapse, cyanosis, hypothermia) in neonate if administered near term. Not recommended in pregnancy unless no alternative. |
| Fetal Monitoring | Monitor maternal complete blood count (CBC) weekly for hematologic toxicity. In fetus/newborn: monitor for signs of gray baby syndrome (lethargy, pallor, hypothermia, cardiovascular instability) if exposure occurs near delivery. Consider therapeutic drug monitoring (target peak 15-25 mcg/mL, trough 5-10 mcg/mL) to avoid toxicity. |
| Fertility Effects | No specific studies on fertility in humans. In animal studies, high doses caused reversible testicular atrophy and impaired spermatogenesis. Clinical relevance unknown. |
| Food/Dietary |
| Avoid alcohol and alcohol-containing products during treatment and for 48 hours after last dose due to disulfiram-like reaction. No specific food restrictions. |
| Clinical Pearls | Chloramphenicol sodium succinate is a prodrug hydrolyzed to active chloramphenicol. Monitor CBC with differential and platelets every 2 days during therapy due to dose-dependent reversible bone marrow suppression and rare idiosyncratic aplastic anemia. Use with caution in neonates (gray baby syndrome) and hepatic impairment. Drug interactions: increases effects of warfarin, phenytoin, and sulfonylureas; decreases efficacy of oral contraceptives and iron supplements. |
| Patient Advice | Complete the full course of antibiotics even if you feel better. · Report any unusual bleeding, bruising, or signs of infection (fever, sore throat) immediately. · Avoid alcohol consumption during therapy and for 2 days after completion. · Notify your doctor if you are pregnant, breastfeeding, or planning to become pregnant. · Chloramphenicol may cause vision changes; report any blurry vision or visual disturbances. |