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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(klor am FEN i kole)
Generic Available (U.S.)
Yes
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of serious infections due to organisms resistant to other less toxic antibiotics or when its penetrability into the site of infection is clinically superior to other antibiotics to which the organism is sensitive; useful in infections caused by Bacteroides, H. influenzae, Neisseria meningitidis, Salmonella, and Rickettsia; active against many vancomycin-resistant enterococci
Pregnancy Considerations
Chloramphenicol crosses the placenta producing cord concentrations approaching maternal serum concentrations. An increased risk of teratogenic effects has not been identified for chloramphenicol and there have been no reports of fetal harm related to use of chloramphenicol in pregnancy. "Gray Syndrome" has occurred in premature infants and newborns receiving chloramphenicol. In most cases, chloramphenicol was started during the first 48 hours of life, but it has also occurred in older patients after high doses. Symptoms began after 3-4 days of therapy, starting with abdominal distention and continuing to progressive pallid cyanosis, vasomotor collapse, irregular respiration, and death within a few hours of symptom onset. Stopping therapy can reverse the process and allow complete recovery. There is one case report of an infant with gray baby syndrome after in utero exposure to a single maternal dose during labor, followed by a 10-fold overdose of chloramphenicol in the first day of life. The extent of the contribution of the single dose given during labor is unknown. The manufacturer recommends caution if used in a pregnant patient near term or during labor.
Lactation
Enters breast milk/use with caution (AAP rates “of concern”; AAP 2001 update pending)
Breast-Feeding Considerations
Chloramphenicol is excreted in human milk in both the active form and as inactive metabolites. Chloramphenicol is well absorbed following oral administration; however, metabolism and excretion are highly variable in infants and children. The half-life is also significantly prolonged in low birth weight infants. There have been documented toxicities in neonates and preterm infants when chloramphenicol has been used at therapeutic doses. The manufacturer recommends caution if using chloramphenicol in a breast-feeding infant. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to chloramphenicol or any component of the formulation; treatment of trivial or viral infections; bacterial prophylaxis
Warnings/Precautions
Boxed warnings:
• Blood dyscrasias: See “Concerns related to adverse effects” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Blood dyscrasias: [U.S. Boxed Warning]: Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) have occurred after both short-term and prolonged therapy. Monitor CBC frequently in all patients; discontinue if evidence of myelosuppression. Irreversible bone marrow suppression may occur weeks or months after therapy. Avoid repeated courses of treatment. Should not be used for minor infections or when less potentially toxic agents are effective.
• Gray syndrome: Characterized by circulatory collapse, cyanosis, acidosis, abdominal distention, myocardial depression, coma, and death. Reaction appears to be associated with serum levels ≥50 mcg/mL. May result from drug accumulation in patients with impaired hepatic or renal function.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced dosage recommended.
• Renal impairment: Use with caution in patients with renal impairment
Special populations:
• Glucose 6-phosphate dehydrogenase deficiency: Use with caution in patients with glucose 6-phosphate dehydrogenase deficiency.
• Neonates: Use with caution in neonates; due to risk of gray syndrome.
Adverse Reactions
Frequency not defined.
Central nervous system: Confusion, delirium, depression, fever, headache
Dermatologic: Angioedema, rash, urticaria
Gastrointestinal: Diarrhea, enterocolitis, glossitis, nausea, stomatitis, vomiting
Hematologic: Aplastic anemia, bone marrow suppression, granulocytopenia, hypoplastic anemia, pancytopenia, thrombocytopenia
Ocular: Optic neuritis
Miscellaneous: Anaphylaxis, hypersensitivity reactions, Gray syndrome
Metabolism/Transport Effects
Inhibits CYP2C9 (weak), 3A4 (weak)
Drug Interactions
Anticonvulsants (Hydantoin): Chloramphenicol may decrease the metabolism of Anticonvulsants (Hydantoin). Anticonvulsants (Hydantoin) may decrease the serum concentration of Chloramphenicol. Increased chloramphenicol concentrations have also been seen. Risk D: Consider therapy modification
Barbiturates: May increase the metabolism of Chloramphenicol. Chloramphenicol may decrease the metabolism of Barbiturates. Risk D: Consider therapy modification
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Cyanocobalamin: Chloramphenicol may diminish the therapeutic effect of Cyanocobalamin. The expected hematologic response for the treatment of anemia may be opposed. Risk D: Consider therapy modification
Rifampin: May increase the metabolism of Chloramphenicol. Risk D: Consider therapy modification
Sulfonylureas: Chloramphenicol may decrease the metabolism of Sulfonylureas. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Chloramphenicol may enhance the anticoagulant effect of Vitamin K Antagonists. Chloramphenicol may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voriconazole: Chloramphenicol may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: May decrease intestinal absorption of vitamin B12 may have increased dietary need for riboflavin, pyridoxine, and vitamin B12.
Storage
Store at room temperature prior to reconstitution. Reconstituted solutions remain stable for 30 days. Use only clear solutions. Frozen solutions remain stable for 6 months.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, fat emulsion 10%, LR, 1/2NS, NS.
Y-site administration: Compatible: Acyclovir, cyclophosphamide, enalaprilat, esmolol, foscarnet, hydromorphone, labetalol, magnesium sulfate, meperidine, morphine, perphenazine, tacrolimus. Incompatible Fluconazole.
Compatibility in syringe: Compatible: Ampicillin, diatrizoate meglumine and diatrizoate sodium, diatrizoate sodium, heparin, iohexol, iopamidol, iothalamate meglumine, ioxaglate meglumine and ioxaglate sodium, penicillin G sodium. Incompatible: Glycopyrrolate, metoclopramide.
Compatibility when admixed: Compatible: Amikacin, aminophylline, ascorbic acid injection, calcium chloride, calcium gluconate, colistimethate, corticotropin, cyanocobalamin, dimenhydrinate, dopamine, ephedrine, heparin, hydrocortisone sodium succinate, kanamycin, lidocaine, lincomycin, magnesium sulfate, metaraminol, methyldopate, methylprednisolone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, nafcillin, oxacillin, oxytocin, penicillin G potassium, penicillin G sodium, pentobarbital, phenylephrine, phenylephrine with sodium bicarbonate, phytonadione, plasma protein fraction, potassium chloride, ranitidine, sodium bicarbonate, thiopental, verapamil. Incompatible: Chlorpromazine, hydroxyzine, phenytoin, polymyxin B sulfate, prochlorperazine edisylate, prochlorperazine mesylate, promethazine, vancomycin. Variable (consult detailed reference): Ascorbic acid injection, erythromycin lactobionate, promazine, vitamin B complex with C.
Mechanism of Action
Reversibly binds to 50S ribosomal subunits of susceptible organisms preventing amino acids from being transferred to growing peptide chains thus inhibiting protein synthesis
Pharmacodynamics/Kinetics
Distribution: To most tissues and body fluids
Chloramphenicol: Vd: 0.5-1 L/kg
Chloramphenicol succinate: Vd: 0.2-3.1 L/kg; decreased with hepatic or renal dysfunction
Protein binding: Chloramphenicol: ~60%; decreased with hepatic or renal dysfunction and in newborn infants
Metabolism:
Chloramphenicol: Hepatic to metabolites (inactive)
Chloramphenicol succinate: Hydrolyzed in the liver, kidney and lungs to chloramphenicol (active)
Bioavailability:
Chloramphenicol: Oral: ~80%
Chloramphenicol succinate: I.V.: ~70%; highly variable, dependent upon rate and extent of metabolism to chloramphenicol
Half-life elimination:
Normal renal function:
Chloramphenicol: Adults: ~4 hours; Children 4-6 hours; Infants: Significantly prolonged
Chloramphenicol succinate: Adults: ~3 hours
End-stage renal disease: Chloramphenicol: 3-7 hours
Hepatic disease: Prolonged
Excretion: Urine (~30% as unchanged chloramphenicol succinate in adults, 6% to 80% in children; 5% to 15% as chloramphenicol)
Dosage
Neonates: Initial loading dose: I.V. (I.M. administration is not recommended): 20 mg/kg (the first maintenance dose should be given 12 hours after the loading dose)
Maintenance dose: Postnatal age:
≤7 days: 25 mg/kg/day once every 24 hours
>7 days, ≤2000 g: 25 mg/kg/day once every 24 hours
>7 days, >2000 g: 50 mg/kg/day divided every 12 hours
Children: Usual dosing range: I.V.: 50-100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day
Meningitis: I.V.: Infants >30 days and Children: 75-100 mg/kg/day divided every 6 hours
Adults: 50-100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day
Dosing adjustment in renal impairment: Use with caution; monitor serum concentrations
Dosing adjustment/comments in hepatic impairment: Use with caution; monitor serum concentrations
Administration: I.V.
Do not administer I.M.; can be administered IVP over at least 1 minute at a concentration of 100 mg/mL, or I.V. intermittent infusion over 15-30 minutes at a final concentration for administration of ≤20 mg/mL.
Administration: I.V. Detail
pH: 6.4-7.0
Monitoring Parameters
CBC with differential (baseline and every 2 days during therapy), periodic liver and renal function tests, serum drug concentration
Reference Range
Therapeutic levels:
Meningitis:
Peak: 15-25 mcg/mL; toxic concentration: >40 mcg/mL
Trough: 5-15 mcg/mL
Other infections:
Peak: 10-20 mcg/mL
Trough: 5-10 mcg/mL
Timing of serum samples: Draw levels 0.5-1.5 hours after completion of I.V. dose
Test Interactions
May cause false-positive results in urine glucose tests when using cupric sulfate (Benedict's solution, Clinitest®).
Dietary Considerations
May have increased dietary need for riboflavin, pyridoxine, and vitamin B12. Some products may contain sodium.
Patient Education
This medication is administered by infusion and you will be monitored during each infusion. Report immediately unusual chest tightness, difficulty breathing, or swallowing; itching or skin rash; back pain; acute headache; or redness, swelling, or pain at infusion site. You may experience a bitter taste during infusion; this will pass. May cause nausea or vomiting. Report persistent rash; unusual or persistent fatigue; diarrhea or vomiting; pain, burning, or numbness of extremities; signs of secondary infection (sore throat, vaginal itching or discharge, or mouth sores); unusual bleeding or bruising, petechiae, yellowing of skin or eyes, dark urine, or stool discoloration; CNS disturbances (nightmares or acute headache); or lack of improvement or worsening of condition.
Geriatric Considerations
Chloramphenicol has not been studied in the elderly. It is not necessary to adjust the dose based upon the decrease in renal function associated with age. Chloramphenicol should be reserved for serious infections and the oral form avoided.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Glossitis and stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause nightmares
Mental Health: Effects on Psychiatric Treatment
May cause bone marrow suppression; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess results of culture/sensitivity tests, patient allergy history, renal status, and hepatic status prior to beginning treatment. Discontinue therapy if evidence of myelosuppression exists. Observe closely for bone marrow depression or aplastic anemia (petechiae, sore throat, fatigue, unusual bleeding or bruising, abdominal or bone pain), circulatory collapse, CNS disturbances, and opportunistic infection. Teach patient to report CNS changes, opportunistic infection, and aplastic anemia (may occur weeks to months after initial exposure to chloramphenicol).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 1 g [contains sodium [~52 mg (2.25 mEq)/g]]
References
Ambrose PJ, “Clinical Pharmacokinetics Of Chloramphenicol And Chloramphenicol Succinate,” Clin Pharmacokinet, 1984, 9(3):222-38.
American Academy of Pediatrics Committee on Drugs, “Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.
Cocke JG Jr, “Chloramphenicol Optic Neuritis. Apparent Protective Effects of Very High Daily Doses of Pyridoxine and Cyanocobalamin,” Am J Dis Child, 1967, 114(4):424-6.
Doona M and Walsh JB, “Use of Chloramphenicol as Topical Eye Medication: Time to Cry Halt?” BMJ, 1995, 310(6989):1217-8.
Freundlich M, Cynamon H, Tamer A, et al, “Management of Chloramphenicol Intoxication in Infancy by Charcoal Hemoperfusion,” J Pediatr, 1983, 103(3):485-7.
Hammett-Stabler CA and Johns T, “Laboratory Guidelines for Monitoring of Antimicrobial Drugs. National Academy of Clinical Biochemistry,” Clin Chem, 1998, 44(5):1129-40.
Kunin CM, Glazko AJ, and Finland M, “Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. II. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Failure Disease or Hepatic Cirrhosis,” J Clin Invest, 1959, 38(9):1498-508.
Messick CR and Pendland SL, “In Vitro Activity of Chloramphenicol Alone and in Combination With Vancomycin, Ampicillin, or RP 59500 (Quinupristin/Dalfopristin) Against Vancomycin-Resistant Enterococci,” Diagn Microbiol Infect Dis, 1997, 29(3):203-5.
Montoro A, Cao A, Ordoqui E, et al, “Contact Sensitivity to Chloramphenicol,” J Allergy Clin Immunol, 1995, 95:291.
Nahata MC and Powell DA, “Bioavailability and Clearance of Chloramphenicol After Intravenous Chloramphenicol Succinate,” Clin Pharmacol Ther, 1981, 30(3):368-72.
Powell DA and Nahata MC, “Chloramphenicol: New Perspectives on an Old Drug,” Drug Intell Clin Pharm, 1982, 16(4):295-300.
Ramilo O, Kinane BT, and McCracken GH Jr, “Chloramphenicol Neurotoxicity,” Pediatr Infect Dis J, 1988, 7(5):358-9.
Smilack JD, Wilson WR, and Cockerill FR 3d, “Tetracyclines, Chloramphenicol, Erythromycin, Clindamycin, and Metronidazole,” Mayo Clin Proc, 1991, 66(12):1270-80.
Tunkel AR, Wispelwey B, and Scheld M, “Bacterial Meningitis: Recent Advances in Pathophysiology and Treatment,” Ann Intern Med, 1990, 112(8):610-23.
Vozeh S, Schmidlin O, and Taeschner W, “Pharmacokinetic Drug Data,” Clin Pharmacokinet, 1988, 15(4):254-82.
Yoshikawa TT, “Antimicrobial Therapy for the Elderly Patient,” J Am Geriatr Soc, 1990, 38(12):1353-72.
Yunis AA, “Chloramphenicol: Relation of Structure to Activity and Toxicity,” Annu Rev Pharmacol Toxicol, 1988, 28:83-100.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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