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Chloramphenicol

Pronunciation

Pronunciation

(klor am FEN i kole)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Generic: 1 g (1 ea)

Pharmacologic Category

  • Antibiotic, Miscellaneous

Pharmacology

Reversibly binds to 50S ribosomal subunits of susceptible organisms preventing amino acids from being transferred to growing peptide chains thus inhibiting protein synthesis

Distribution

To most tissues and body fluids; good CSF and brain penetration

CSF concentration with uninflamed meninges: 21% to 50% of plasma concentration

CSF concentration with inflamed meninges: 45% to 89% of plasma concentration

Vd: Chloramphenicol: 0.5-1 L/kg; Chloramphenicol succinate: 0.2-3.1 L/kg; decreased with hepatic or renal dysfunction

Metabolism

Chloramphenicol: Hepatic to metabolites (inactive); Chloramphenicol succinate: Hydrolyzed in the liver, kidney and lungs to chloramphenicol (active)

Excretion

Urine (~30% as unchanged chloramphenicol succinate in adults, 6% to 80% in children; 5% to 15% as chloramphenicol)

Half-Life Elimination

Neonates: 1-2 days: 24 hours; 10-16 days: 10 hours

Normal renal function:

Chloramphenicol: Infants: Significantly prolonged; Children 4-6 hours; Adults: ~4 hours

Chloramphenicol succinate: Adults: ~3 hours

End-stage renal disease: Chloramphenicol: 3-7 hours

Hepatic disease: Prolonged

Protein Binding

Chloramphenicol: ~60%; decreased with hepatic or renal dysfunction and 30% to 40% in newborn infants

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

Contraindications

Hypersensitivity to chloramphenicol or any component of the formulation; treatment of trivial or viral infections; bacterial prophylaxis

Dosing: Adult

Systemic infections: IV: 50-100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Other infections: Children: Usual dosing range: IV: 50-100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day

Meningitis: IV: Infants >30 days and Children: 75-100 mg/kg/day divided every 6 hours

Dosing: Renal Impairment

Use with caution; monitor serum concentrations.

Dosing: Hepatic Impairment

Use with caution; monitor serum concentrations.

Administration

Do not administer IM; can be administered IVP over at least 1 minute at a concentration of 100 mg/mL, or IV intermittent infusion over 15-30 minutes at a final concentration for administration of ≤20 mg/mL.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).

Dietary Considerations

May have increased dietary need for riboflavin, pyridoxine, and vitamin B12. Some products may contain sodium.

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: Incompatible with fluconazole.

Compatibility in syringe: Incompatible with glycopyrrolate, metoclopramide.

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.

Drug Interactions

Alcohol (Ethyl): Chloramphenicol may enhance the adverse/toxic effect of Alcohol (Ethyl). Monitor therapy

Barbiturates: Chloramphenicol may decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol. Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Carbocisteine: Chloramphenicol may enhance the adverse/toxic effect of Carbocisteine. Specifically, chloramphenicol may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Monitor therapy

CefTAZidime: Chloramphenicol may diminish the therapeutic effect of CefTAZidime. Management: Consider using a different combination of antimicrobials, especially if bactericidal activity is desired. If these agents are combined, monitor for reduced antimicrobial effectiveness and/or therapeutic failure. Consider therapy modification

Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification

Citalopram: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a strong CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Consider therapy modification

Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a strong CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

CycloSPORINE (Systemic): Chloramphenicol may increase the serum concentration of CycloSPORINE (Systemic). Management: Cyclosporine dose reductions will likely be required with initiation of concurrent chloramphenicol. Monitor cyclosporine concentrations and response closely following initiation and/or discontinuation of chloramphenicol. Consider therapy modification

CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Flibanserin: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Chloramphenicol. Fosphenytoin may increase the serum concentration of Chloramphenicol. Chloramphenicol may increase the serum concentration of Fosphenytoin. Monitor therapy

Phenytoin: May decrease the serum concentration of Chloramphenicol. Phenytoin may increase the serum concentration of Chloramphenicol. Chloramphenicol may increase the serum concentration of Phenytoin. Monitor therapy

Rifampin: May increase the metabolism of Chloramphenicol. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Sulfonylureas: Chloramphenicol may decrease the metabolism of Sulfonylureas. Monitor therapy

Tacrolimus (Systemic): Chloramphenicol may increase the serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose reductions will likely be required with initiation of concurrent chloramphenicol. Monitor tacrolimus concentrations and response closely following initiation and/or discontinuation of chloramphenicol. Consider therapy modification

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 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin B12: Chloramphenicol may diminish the therapeutic effect of Vitamin B12. Monitor therapy

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. Monitor therapy

Voriconazole: Chloramphenicol may increase the serum concentration of Voriconazole. Monitor therapy

Test Interactions

May cause false-positive results in urine glucose tests when using cupric sulfate (Benedict's solution, Clinitest®).

Adverse Reactions

Frequency not defined.

Central nervous system: Confusion, delirium, depression, headache

Dermatologic: Skin rash, urticaria

Gastrointestinal: Diarrhea, enterocolitis, glossitis, nausea, stomatitis, vomiting

Hematologic & oncologic: Aplastic anemia, bone marrow depression, granulocytopenia, hypoplastic anemia, pancytopenia, thrombocytopenia

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Ophthalmic: Optic neuritis

Miscellaneous: Fever, Gray syndrome

ALERT: U.S. Boxed Warning

Blood dyscrasias:

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 Indications. 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.

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.

Warnings/Precautions

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 in neonates (including premature) has resulted in “gray-baby syndrome" characterized by circulatory collapse, cyanosis, acidosis, abdominal distention (with or without emesis), myocardial depression, coma, and death; progression of symptoms is rapid; prompt termination of therapy required. Reaction result from drug accumulation possibly caused by the impaired neonatal hepatic or renal function.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).

Monitoring Parameters

CBC with differential (baseline and every 2 days during therapy), periodic liver and renal function tests, serum drug concentration

Pregnancy Considerations

Chloramphenicol crosses the placenta producing cord concentrations approaching maternal serum concentrations. An increased risk of teratogenic effects has not been associated with the use of chloramphenicol in pregnancy (Czeizel, 2000; Heinonen, 1977). "Gray Syndrome" has occurred in premature infants and newborns receiving chloramphenicol. The manufacturer recommends caution if used in a pregnant patient near term or during labor. Chloramphenicol may be used for the treatment of Rocky Mountain spotted fever in pregnant women although caution should be used when administration occurs during the third trimester (CDC, 2006).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache. Have patient report immediately to prescriber signs of infection, impaired wound healing, severe dizziness, passing out, loss of strength and energy, bruising, bleeding, illogical thinking, mood changes, vision changes, burning or numbness feeling, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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