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. 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.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Generic: 1 g (1 ea)
Pharmacology
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
Pharmacokinetics/Pharmacodynamics
Distribution
To most tissues and body fluids (Ambrose 1984); 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: 0.6 to 1 L/kg; Chloramphenicol succinate: 0.2 to 3.1 L/kg (Ambrose 1984)
Metabolism
Chloramphenicol: Hepatic to metabolites (inactive); Chloramphenicol succinate: Hydrolyzed in the liver, kidney and lungs to chloramphenicol (active) (Ambrose 1984)
Excretion
Urine (~30% as unchanged chloramphenicol succinate in adults, 6% to 80% in children; 5% to 15% as chloramphenicol) (Ambrose 1984; Powell 1982)
Half-Life Elimination
Neonates: 1 to 2 days: 24 hours; 10 to 16 days: 10 hours
Chloramphenicol: Infants: Significantly prolonged (Powell 1982); Children 4 to 6 hours; Adults: ~4 hours (Ambrose 1984)
Hepatic disease: Prolonged (Ambrose 1984)
Protein Binding
Chloramphenicol: ~60%; decreased with hepatic or renal dysfunction and 30% to 40% in newborn infants (Ambrose 1984)
Use: Labeled Indications
Serious infections: Treatment of serious infections, including cystic fibrosis exacerbations, bacterial meningitis, and bacteremia, caused by Chlamydiaceae, Haemophilus influenzae, Rickettsia, Salmonella spp. (acute infections), and other organisms when other less toxic agents are ineffective or contraindicated.
Guideline recommendations: Chloramphenicol may be considered for use as an alternative agent to doxycycline in the treatment of tickborne rickettsial diseases (eg, Rocky Mountain spotted fever [RMSF]); however, epidemiologic studies suggest that chloramphenicol-treated patients with RMSF are at a higher risk of death compared to tetracycline-treated patients. In addition, chloramphenicol is not effective in the treatment of human ehrlichiosis or anaplasmosis, therefore, use with caution in the empiric treatment of tickborne rickettsial diseases (CDC [Biggs 2016]).
Contraindications
Hypersensitivity to chloramphenicol or any component of the formulation; treatment of trivial or viral infections; bacterial prophylaxis
Dosage and Administration
Dosing: Adult
Serious infections: IV: 50 to 100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day (Moffa 2015).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Follow serum concentrations closely to monitor for toxicity. Use should be restricted to treatment of serious infections when less toxic drugs are ineffective (ie, resistance) or contraindicated.
Meningitis: Infants, Children, and Adolescents: IV: 18.75-25 mg/kg/dose every 6 hours (Bradley, 2012; Kliegman, 2011; Tunkel, 2004)
Severe infections: Infants, Children, and Adolescents: IV:
Manufacturer's labeling: 12.5 mg/kg/dose every 6 hours; in some cases higher doses up to 25 mg/kg/dose every 6 hours may be required; higher doses should be promptly decreased when able
Alternate dosing: 12.5-25 mg/kg/dose every 6 hours; maximum daily dose: 4000 mg/day (AAP, 2012)
Reconstitution
Reconstitute vial with 10 mL of SWFI or D5W to a final concentration of 100 mg/mL.
Administration
IV: For IV use only; do not administer IM. Can be administered IVP over at least 1 minute at a concentration of 100 mg/mL.
Dietary Considerations
May have increased dietary need for riboflavin, pyridoxine, and vitamin B12. Some products may contain sodium.
Storage
Store intact vials at 20°C to 25°C (68°F to 77°F).
Drug Interactions
Alcohol (Ethyl): Chloramphenicol (Systemic) may enhance the adverse/toxic effect of Alcohol (Ethyl). Monitor therapy
Barbiturates: Chloramphenicol (Systemic) may decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol (Systemic). 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 (Systemic) 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 (Systemic) 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
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
CycloSPORINE (Systemic): Chloramphenicol (Systemic) 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
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Fosphenytoin: May decrease the serum concentration of Chloramphenicol (Systemic). Fosphenytoin may increase the serum concentration of Chloramphenicol (Systemic). Chloramphenicol (Systemic) may increase the serum concentration of Fosphenytoin. Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Phenytoin: May decrease the serum concentration of Chloramphenicol (Systemic). Phenytoin may increase the serum concentration of Chloramphenicol (Systemic). Chloramphenicol (Systemic) may increase the serum concentration of Phenytoin. Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
RifAMPin: May increase the metabolism of Chloramphenicol (Systemic). 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 (Systemic) may decrease the metabolism of Sulfonylureas. Monitor therapy
Tacrolimus (Systemic): Chloramphenicol (Systemic) 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 (Systemic) may diminish the therapeutic effect of Vitamin B12. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Chloramphenicol (Systemic) may enhance the anticoagulant effect of Vitamin K Antagonists. Chloramphenicol (Systemic) may increase the serum concentration of Vitamin K Antagonists. Monitor therapy
Voriconazole: Chloramphenicol (Systemic) may increase the serum concentration of Voriconazole. Monitor therapy
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: Drug toxicity (Gray syndrome), fever
Warnings/Precautions
Concerns related to adverse effects:
- Blood dyscrasias: [US Boxed Warning]: Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) have occurred after both short-term and prolonged therapy; do not use for minor infections or when less potentially toxic agents are effective. Monitor CBC frequently in all patients; discontinue if evidence of myelosuppression. Irreversible bone marrow suppression may occur weeks or months after therapy. Avoid prolonged or repeated courses of treatment.
- Gray syndrome: Characterized by cyanosis, abdominal distention, vasomotor collapse (often with irregular respiration), and death. Reaction appears to be associated with serum levels ≥50 mcg/mL (Powell 1982).
- 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; reduced dosage and serum concentration monitoring is recommended.
- Renal impairment: Use with caution; reduced dosage and serum concentration monitoring is recommended.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Glucose 6-phosphate dehydrogenase deficiency: Use with caution in patients with glucose 6-phosphate dehydrogenase deficiency.
- Neonates: Use in premature and full-term neonates and infants has resulted in “gray syndrome" characterized by cyanosis, abdominal distention (with or without emesis), vasomotor collapse (often with irregular respiration), and death; progression of symptoms is rapid; prompt termination of therapy required. Reaction may result from drug accumulation caused by immature hepatic or renal function in neonates and infants.
Monitoring Parameters
CBC with differential (baseline and every 2 days during therapy), periodic hepatic and renal function tests, serum drug concentration
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted. 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. Chloramphenicol may be used as an alternative agent for the treatment of Rocky Mountain spotted fever in pregnant women although caution should be used when administration occurs during the third trimester (CDC [Biggs 2016]).
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, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), impaired wound healing, severe dizziness, passing out, loss of strength and energy, confusion, mood changes, vision changes, burning or numbness feeling, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea 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.
