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.
Serious infections: IV: 50 to 100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day (Moffa 2015).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be necessary. Use with caution; monitor serum concentrations.
There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustments may be necessary. Use with caution; monitor serum concentrations.
(For additional information see "Chloramphenicol: Pediatric drug information")
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. Chloramphenicol palmitate (oral formulation) is no longer available in the US; chloramphenicol sodium succinate (IV formulation) continues to be available.
Meningitis and nonmeningeal pneumococcal infections: Limited data available: Infants, Children, and Adolescents: IV: 18.75 to 25 mg/kg/dose every 6 hours; maximum daily dose: 4,000 mg/day (IDSA [Tunkel 2004]; Kliegman 2020; Red Book [AAP 2018]).
Severe infections: Infants, Children, and Adolescents: IV: 12.5 to 25 mg/kg/dose every 6 hours; maximum daily dose: 4,000 mg/day (Kliegman 2020; Red Book [AAP 2018]; manufacturer labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
All patients: There are no dosage adjustments provided in the manufacturer's labeling; use with caution, reduced dosage and serum concentration monitoring is recommended.
All patients: There are no dosage adjustments provided in the manufacturer's labeling; use with caution, reduced dosage and serum concentration monitoring is recommended.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Generic: 1 g (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Chloromycetin Succinate: 1 g (1 ea)
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.
Parenteral:
IV push: Administer over at least 1 minute.
Intermittent IV infusion: Infuse over 30 to 60 minutes (Klaus 1998). In neonates, some centers have administered as an intermittent IV infusion over 15 minutes (Prober 1990).
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) for preparation. Double gloving, a gown, and (if dosage form allows) CSTDs are required during administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
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]).
Chloromycetin may be confused with chlorambucil, Chlor-Trimeton
KIDs List: Chloramphenicol, when used in neonates, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of gray baby syndrome unless serum concentration monitoring used (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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
Hypersensitivity to chloramphenicol or any component of the formulation; treatment of trivial or viral infections; bacterial prophylaxis
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.
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.
Inhibits CYP2C9 (weak)
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Alcohol (Ethyl): Chloramphenicol (Systemic) may enhance the adverse/toxic effect of Alcohol (Ethyl). Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: 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. Risk C: 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. Risk D: Consider therapy modification
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: 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. Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: 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. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
PHENobarbital: May decrease the serum concentration of Chloramphenicol (Systemic). Chloramphenicol (Systemic) may increase the serum concentration of PHENobarbital. Risk C: 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. Risk C: Monitor therapy
Primidone: Chloramphenicol (Systemic) may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, the concentrations of phenobarbital may be increased. Primidone may decrease the serum concentration of Chloramphenicol (Systemic). Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
RifAMPin: May increase the metabolism of Chloramphenicol (Systemic). Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: 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. Risk D: Consider therapy modification
Sulfonylureas: Chloramphenicol (Systemic) may increase the serum concentration of Sulfonylureas. Risk C: 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. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin B12: Chloramphenicol (Systemic) may diminish the therapeutic effect of Vitamin B12. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): CYP2C9 Inhibitors (Weak) may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
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]).
Chloramphenicol and its inactive metabolites are present in breast milk.
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 (Powell 1982). Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. Other sources recommended avoiding use while breast-feeding, especially young infants (<34 weeks postconceptual age or <1 month of age) or when unusually large doses are needed (Atkinson 1988; Matsuda 1984; Plomp 1983; WHO 2002). In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Infants exposed to chloramphenicol from breast milk should be monitored for GI disturbances, hemolysis and jaundice (WHO 2002).
May have increased dietary need for riboflavin, pyridoxine, and vitamin B12. Some products may contain sodium.
CBC with differential (baseline and every 2 days during therapy), periodic hepatic and renal function tests, serum drug concentration
Therapeutic levels:
Pediatric:
Peak: Infants, Children, and Adolescents: 15 to 30 mcg/mL (Balbi 2004; Coakley 1992; Long 2012)
Trough: 5 to 15 mcg/mL
Adult:
Peak: 10 to 20 mcg/mL (Ambrose 1984; Hammet-Stabler 1998)
Trough: 5 to 10 mcg/mL (Ambrose 1984)
Timing of serum samples: Draw levels 0.5 to 1.5 hours after completion of IV dose (Hammet-Stabler 1998)
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 (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
Chloramphenicol: Vd: 0.6 to 1 L/kg (Ambrose 1984)
Chloramphenicol succinate: Vd: 0.2 to 3.1 L/kg (Ambrose 1984)
Protein binding: Chloramphenicol: ~60%; decreased with hepatic or renal dysfunction and 30% to 40% in newborn infants (Ambrose 1984)
Metabolism:
Chloramphenicol: Hepatic to metabolites (inactive) (Ambrose 1984)
Chloramphenicol succinate: Hydrolyzed in the liver, kidney, and lungs to chloramphenicol (active) (Ambrose 1984)
Bioavailability:
Chloramphenicol: Oral: ~80% (Ambrose 1984)
Chloramphenicol succinate: IV: ~70%; highly variable, dependent upon rate and extent of metabolism to chloramphenicol (Ambrose 1984)
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)
Excretion: Urine (~30% as unchanged chloramphenicol succinate in adults, 6% to 80% in children; 5% to 15% as chloramphenicol) (Ambrose 1984; Powell 1982)
Solution (reconstituted) (Chloramphenicol Sod Succinate Intravenous)
1 g (per each): $46.70
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