Chloramphenicol

Drug class: Antineoplastic Agents

Usage of Chloramphenicol

Meningitis

Alternative for treatment of meningitis caused by susceptible bacteria, including Haemophilus influenzae, Neisseria meningitidis, or Streptococcus pneumoniae. Generally used only when penicillins and cephalosporins are contraindicated or ineffective.

Despite evidence of in vitro activity against Listeria monocytogenes, has been ineffective for treatment of systemic infections caused by this organism.

Do not use for treatment of meningitis caused by gram-negative bacilli.

Rickettsial Infections

Possible alternative to tetracyclines for treatment of rickettsial infections. CDC and other experts state that doxycycline is the drug of choice for treatment of all rickettsial infections in all age groups (including children <8 years of age). Some of these infections can be rapidly progressive and may be fatal or lead to long-term sequelae; do not delay empiric treatment while waiting for confirmatory testing. If considering an alternative to doxycycline, consultation with an expert recommended.

Possible alternative to doxycycline for treatment of certain tickborne rickettsial diseases, including Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii. Doxycycline is drug of choice for treatment of RMSF, regardless of patient age. Consider chloramphenicol only in certain patients when doxycycline cannot be used (e.g., those with history of potentially life-threatening allergic reactions to doxycycline, pregnant women). There is some epidemiologic evidence that risk of death in patients with RMSF is higher in those treated with chloramphenicol than in those treated with a tetracycline; close monitoring required if chloramphenicol used.

Possible alternative to doxycycline for treatment of endemic typhus (murine typhus; fleaborne typhus) caused by R. typhi or R. felis and for treatment of epidemic typhus (louseborne typhus; sylvatic typhus) caused by R. prowazekii. Doxycycline is drug of choice for treatment of endemic typhus and epidemic typhus, regardless of patient age.

Has been used for treatment of scrub typhus caused by Orientia tsutsugamushi; recommended as possible alternative to doxycycline. Consider that chloramphenicol resistance and persistence or relapse reported.

Do not use for treatment of anaplasmosis caused by Anaplasma phagocytophilum (also known as human granulocytic anaplasmosis; HGA) or ehrlichiosis caused by Ehrlichia chaffeensis (also known as human monocytic ehrlichiosis; HME). Doxycycline is drug of choice for treatment of human ehrlichiosis and anaplasmosis, regardless of patient age. Chloramphenicol considered ineffective; use not supported by results of in vitro susceptibility testing.

Typhoid Fever and Other Severe Salmonella Infections

Has been used for treatment of typhoid fever (enteric fever) caused by susceptible Salmonella enterica serovar Typhi and treatment of paratyphoid fever caused by S. enterica serovar Paratyphi.

Although chloramphenicol was a drug of choice for treatment of infections caused by typhoidal Salmonella in the past, multidrug-resistant strains of S. enterica serovar Typhi (i.e., strains resistant to ampicillin, chloramphenicol, and/or co-trimoxazole) are reported worldwide and common in many regions of the world. Whenever possible, select anti-infectives for treatment of typhoid fever based on results of in vitro susceptibility testing.

Do not use to treat typhoid carrier state. Depending on susceptibility of the strain, a fluoroquinolone (e.g., ciprofloxacin), ampicillin, amoxicillin, or co-trimoxazole usually recommended to treat typhoid carrier state.

Do not use for treatment of uncomplicated Salmonella gastroenteritis.

Anthrax

Alternative for treatment of anthrax† [off-label].

Has in vitro activity against Bacillus anthracis, but limited clinical data exist regarding use in the treatment of anthrax.

Although chloramphenicol has been suggested as an alternative for treatment of naturally occurring anthrax in patients hypersensitive to penicillins or as one of several options for use in multiple-drug regimens for treatment of anthrax, WHO states chloramphenicol is no longer recommended for such infections because evidence of in vivo efficacy in treatment of severe anthrax is lacking and the drug is associated with serious adverse effects.

For treatment of inhalational anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism, CDC, AAP, and the US Working Group on Civilian Biodefense recommend initial treatment with a multiple-drug parenteral regimen that includes a fluoroquinolone (preferably ciprofloxacin) or doxycycline and 1 or 2 additional anti-infectives predicted to be effective (e.g., clindamycin, rifampin, a carbapenem [doripenem, imipenem, meropenem], chloramphenicol, vancomycin, penicillin, ampicillin, linezolid, gentamicin, clarithromycin).

For treatment of systemic anthrax with possible or confirmed meningitis, CDC and AAP recommend a regimen of IV ciprofloxacin with an IV bactericidal anti-infective (preferably meropenem) and an IV protein synthesis inhibitor (preferably linezolid). These experts recommend IV chloramphenicol as a possible alternative to linezolid, but use only if clindamycin and rifampin not available.

Burkholderia Infections

Has been used in patients with cystic fibrosis and has been recommended as an alternative for treatment of infections caused by Burkholderia cepacia† [off-label]. However, B. cepacia usually resistant to chloramphenicol in vitro. Optimum treatment regimens for chronic B. cepacia complex infections not identified; select treatment regimen based on in vitro susceptibility data and previous clinical responses. Anti-infectives that have been recommended include meropenem, imipenem, co-trimoxazole, ceftazidime, doxycycline, and chloramphenicol; some experts recommend use of multiple-drug regimens.

Has been used in conjunction with doxycycline and co-trimoxazole for treatment of melioidosis† [off-label] caused by B. pseudomallei. Ceftazidime or a carbapenem (either meropenem or imipenem) usually drugs of choice for initial treatment, followed by long-term treatment (≥3 months) with an oral anti-infective (e.g., co-trimoxazole, amoxicillin and clavulanate potassium, doxycycline). B. pseudomallei may be difficult to eradicate and relapse of melioidosis may occur, especially if there is poor compliance with the follow-up regimen.

Plague

Alternative for treatment of plague† [off-label] caused by Yersinia pestis, including naturally occurring or endemic plague or pneumonic plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.

Streptomycin (or gentamicin) historically considered drug of choice for treatment of plague. Alternatives include fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), doxycycline (or tetracycline), chloramphenicol, or co-trimoxazole (may be less effective than other alternatives).

Chloramphenicol considered a drug of choice for treatment of plague meningitis.

Tularemia

Alternative for treatment of tularemia† [off-label] caused by Francisella tularensis, including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.

Streptomycin (or gentamicin) generally considered drug of choice for treatment of tularemia. Alternatives include tetracyclines (doxycycline), chloramphenicol, or ciprofloxacin.

Some clinicians state reserve chloramphenicol for treatment of tularemic meningitis (usually in conjunction with streptomycin) and do not use for other forms of tularemia.

Relate drugs

How to use Chloramphenicol

General

  • Because differences between therapeutic and toxic plasma concentrations of chloramphenicol are narrow and because of interindividual differences in metabolism and elimination of the drug, most clinicians recommend that plasma concentrations of chloramphenicol be monitored in all patients receiving the drug and dosage adjusted accordingly.
  • Blood samples to measure peak plasma concentrations of chloramphenicol usually obtained 0.5–1.5 hours after an IV dose.
  • Generally adjust chloramphenicol dosage to maintain plasma concentrations of 5–20 mcg/mL (usually 10–20 mcg/mL). In pediatric patients beyond the neonatal period, AAP suggests adjusting dosage to maintain target plasma concentrations of 15–25 mcg/mL. Some clinicians suggest adjusting dosage in pediatric patients to maintain peak plasma concentrations of 15–25 mcg/mL for treatment of meningitis or 10–20 mcg/mL for treatment of other infections.
  • Chloramphenicol plasma concentrations >25 mcg/mL have been associated with toxicity.
  • Use no longer than necessary to eradicate the infection with little or no risk of relapse; switch IV chloramphenicol to an appropriate oral anti-infective as soon as feasible.
  • Avoid repeated courses of chloramphenicol if possible.

    • Administration

    Administer IV.

    Has been administered IM†, but plasma concentrations unpredictable following IM injection. Manufacturer states do not give IM since this route may be ineffective.

    Has been administered orally as the base or palmitate; oral preparations no longer commercially available in US.

    IV Administration

    Reconstitution

    Reconstitute vial containing 1 g of chloramphenicol (as the sodium succinate) by adding 10 mL of aqueous diluent (e.g., sterile water for injection, 5% dextrose injection) to provide a solution containing 100 mg/mL.

    Rate of Administration

    Inject appropriate dose of reconstituted solution IV over ≥1 minute.

    Has been given by intermittent IV infusion† over 15–60 minutes.

    Dosage

    Available as chloramphenicol sodium succinate; dosage expressed in terms of chloramphenicol.

    Pediatric Patients

    General Dosage for Neonates IV

    Manufacturer states 25 mg/kg daily given in 4 equally divided doses every 6 hours usually provides and maintains blood and tissue concentrations adequate for most indications. After first 2 weeks of life, manufacturer states full-term neonates may receive up to 50 mg/kg daily given in 4 equally divided doses every 6 hours. If higher dosage required for treatment of severe infections, use such dosage only to maintain blood concentrations within a therapeutically effective range.

    Some clinicians recommend loading dose of 20 mg/kg followed 12 hours later by maintenance dosage based on age and weight. These clinicians recommend maintenance dosage of 25 mg/kg once every 24 hour in neonates ≤7 days of age. In neonates >7 days of age, these clinicians recommend maintenance dosage of 25 mg/kg once every 24 hours in those weighing ≤2 kg and 25 mg/kg once every 12 hours in those weighing >2 kg.

    Other clinicians recommend loading dose of 20 mg/kg followed 12 hours later by a different maintenance dosage based on age and weight. In premature neonates, these clinicians recommend maintenance dosage of 22 mg/kg once every 24 hours in those weighing ≤1.2 kg and 25 mg/kg once every 24 hours in those ≤1 week of age weighing ≤2 kg. In full-term neonates, these clinicians recommend maintenance dosage of 25 mg/kg daily in divided doses every 12 hours in those <2 weeks of age and 25–50 mg/kg daily in divided doses every 12 hours in those 2–4 weeks of age.

    Use with caution in neonates because immature metabolic processes in this age group may result in excessive plasma concentrations of chloramphenicol. (See Pediatric Use under Cautions.)

    General Dosage for Pediatric Patients Beyond the Neonatal Period IV

    Manufacturer states 50 mg/kg daily given in 4 divided doses every 6 hours provides blood concentrations adequate for most indications in pediatric patients. Manufacturer states up to 100 mg/kg daily may be required for severe infections (e.g., bacteremia, meningitis), especially when adequate CSF concentrations desired; reduce dosage to 50 mg/kg daily as soon as possible.

    AAP recommends 50–100 mg/kg daily given in 4 divided doses for severe infections.

    General Dosage for Pediatric Patients with Immature Metabolic Processes IV

    Manufacturer states 25 mg/kg daily usually produces therapeutic blood concentrations in young infants and other pediatric patients in whom immature metabolic functions are suspected.

    Carefully monitor chloramphenicol concentrations because high concentrations may occur and tend to increase with succeeding doses. (See Pediatric Use under Cautions.)

    Rickettsial Infections IV

    Children: 12.5–25 mg/kg every 6 hours for 5–10 days recommended by some clinicians.

    Known or suspected RMSF: Initiate anti-infective treatment promptly and continue for ≥3 days after fever subsides and until there is evidence of clinical improvement. Minimum duration of treatment is 5–7 days; longer duration may be required for severe or complicated disease.

    If considering chloramphenicol for treatment of rickettsial infection, expert consultation recommended. (See Rickettsial Infections under Uses.)

    Typhoid Fever and Other Severe Salmonella Infections IV

    Children ≥2 years of age: 60 mg/kg daily in 4 divided doses has been given until defervescence, followed by 40 mg/kg daily in 4 divided doses to complete 14 days of treatment.

    Children ≥14 years of age: 50 mg/kg daily in 4 divided doses (up to 3 g daily) has been given for 14 days.

    To lessen possibility of relapse, some clinicians recommend adjusting dosage to provide therapeutic plasma concentrations and continuing treatment for 8–10 days after patient becomes afebrile.

    Anthrax† Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)† IV

    Children: 50–75 mg/kg daily given in divided doses every 6 hours has been recommended. Usual duration is ≥14 days after symptoms abate.

    Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism)† IV

    Full-term or preterm neonates: AAP recommends 25 mg/kg daily given as a single daily dose in those ≤7 days of age and 50 mg/kg daily given in divided doses every 12 hours in those 1–4 weeks of age.

    Children ≥1 month of age: AAP recommends 100 mg/kg daily given in divided doses every 6 hours.

    Used as part of a multiple-drug regimen; continue parenteral regimen for ≥2–3 weeks until patient is clinically stable and can be switched to appropriate oral anti-infectives.

    Plague† Treatment of Plague (Biologic Warfare or Bioterrorism)† IV

    Children ≥2 years of age: 25 mg/kg 4 times daily (adjust dosage to maintain plasma concentrations of 5–20 mcg/mL) recommended by some experts (e.g., the US Working Group on Civilian Biodefense). Other experts (e.g., US Army Medical Research Institute of Infectious Diseases [USAMRIID]) recommend loading dose of 25 mg/kg followed by 15 mg/kg every 6 hours (adjust dosage based on plasma concentrations).

    Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 10–14 days.

    Tularemia† Treatment of Tularemia (Biologic Warfare or Bioterrorism)† IV

    Children: 15 mg/kg 4 times daily recommended by some experts (e.g., the US Working Group on Civilian Biodefense).

    Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 14–21 days.

    Treatment of Tularemic Meningitis† IV

    Children: 15 mg/kg every 6 hours (up to 4 g daily) given for 14–21 days in conjunction with streptomycin (or gentamicin).

    Adults

    General Dosage for Adults IV

    Manufacturer recommends 50 mg/kg daily given in divided doses every 6 hours.

    Infections caused by less susceptible organisms: Manufacturer states up to 100 mg/kg daily may be required. However, because of concern that toxic plasma chloramphenicol concentrations may occur with this high dosage, some clinicians suggest that 75 mg/kg daily be used initially for treatment of these infections. Reduce dosage to 50 mg/kg daily as soon as possible.

    Rickettsial Infections IV

    60–75 mg/kg daily in 4 divided doses for 5–10 days recommended by some clinicians.

    Scrub typhus caused by O. tsutsugamushi: 50–100 mg/kg daily (up to 3 g daily) in divided doses every 6 hours has been recommended.

    Known or suspected RMSF: Initiate anti-infective treatment promptly and continue for ≥3 days after fever subsides and until there is evidence of clinical improvement. Minimum duration of treatment is 5–7 days; longer duration may be required for severe or complicated disease.

    If considering chloramphenicol for treatment of rickettsial infection, expert consultation recommended. (See Rickettsial Infections under Uses.)

    Typhoid Fever and Other Salmonella Infections IV

    50 mg/kg daily in 4 divided doses given for 14 days has been used. Alternatively, 60 mg/kg daily in 4 divided doses has been given until defervescence, followed by 40 mg/kg daily in 4 divided doses to complete 14 days of treatment.

    To lessen possibility of relapse, some clinicians recommend adjusting dosage to provide therapeutic plasma concentrations and continuing treatment for 8–10 days after patient becomes afebrile.

    Anthrax† Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)† IV

    50–100 mg/kg daily in divided doses every 6 hours has been recommended. Usual duration is ≥14 days after symptoms abate.

    Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism)† IV

    1 g every 6–8 hours recommended by CDC. Used as part of a multiple-drug parenteral regimen; continue for ≥2–3 weeks until patient is clinically stable and can be switched to appropriate oral anti-infectives.

    Plague† Treatment of Plague (Biologic Warfare or Bioterrorism)† IV

    25 mg/kg 4 times daily (adjust dosage to maintain plasma concentrations of 5–20 mcg/mL) recommended by some experts (e.g., the US Working Group on Civilian Biodefense). Other experts (e.g., USAMRIID) recommend loading dose of 25 mg/kg followed by 15 mg/kg every 6 hours (adjust dosage based on plasma concentrations).

    Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 10–14 days.

    Tularemia† Treatment of Tularemia (Biologic Warfare or Bioterrorism)† IV

    15 mg/kg 4 times daily recommended by some experts (e.g., the US Working Group on Civilian Biodefense). Other experts (e.g., USAMRIID) recommend 15–25 mg/kg every 6 hours.

    Can be switched to an appropriate oral anti-infective when clinically indicated; total duration of treatment usually 14–21 days.

    Treatment of Tularemic Meningitis† IV

    15–25 mg/kg every 6 hours (up to 4 g daily) given for 14–21 days in conjunction with streptomycin (or gentamicin).

    Special Populations

    Hepatic Impairment

    Base dosage on plasma chloramphenicol concentrations, especially in pediatric patients, and adjust accordingly.

    Renal Impairment

    Base dosage on plasma chloramphenicol concentrations, especially in pediatric patients, and adjust accordingly.

    Geriatric Patients

    Select dosage with caution, usually starting at low end of dosage range. Consider greater frequency of decreased renal, hepatic, and/or cardiac function in geriatric patients; consider monitoring renal function. (See Geriatric Use under Cautions.)

    Warnings

    Contraindications

  • Hypersensitivity to chloramphenicol.
  • Previous toxic reaction to chloramphenicol.
  • Trivial infections or when not indicated (e.g., colds, influenza, throat infections, prophylaxis).

    • Warnings/Precautions

    Warnings

    Hematologic Effects

    Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) reported with both short-term and prolonged use. Aplastic anemia attributed to chloramphenicol, which later terminated in leukemia, has occurred.

    Two forms of hematologic toxicity may occur with chloramphenicol.

    Most common type is a dose-related, reversible bone marrow depression. Characterized by anemia, leukopenia, reticulocytopenia, thrombocytopenia, increased concentrations of serum iron, increased serum iron-binding capacity, and vacuolization of erythroid and myeloid precursors. More likely to occur in patients receiving chloramphenicol dosage ≥4 g daily and in those with plasma chloramphenicol concentrations >25 mcg/mL. Usually reversible after discontinuance of chloramphenicol.

    Second type is a rare, but often fatal, irreversible aplastic anemia that does not appear to be dose related. Has been associated with a mortality rate >50%. Bone marrow aplasia or hypoplasia may occur weeks or months after the drug was discontinued. Pancytopenia frequently observed peripherally, but in some cases only 1 or 2 major cell types (erythrocytes, leukocytes, platelets) may be depressed.

    Paroxysmal nocturnal hemoglobinuria reported. Hemolytic anemia reported when chloramphenicol used in patients with glucose-6-phosphate dehydrogenase deficiency.

    Perform adequate hematologic studies prior to and approximately every 2 days during chloramphenicol therapy. Patients should be hospitalized during treatment to facilitate appropriate laboratory studies and clinical observation. Consider that peripheral blood studies may detect leukopenia, reticulocytopenia, or granulocytopenia before these become irreversible, but cannot be relied on to detect bone marrow depression prior to development of aplastic anemia.

    Discontinue chloramphenicol if reticulocytopenia, leukopenia, thrombocytopenia, anemia, or any other hematologic abnormalities attributable to the drug occur.

    Sensitivity Reactions

    Hypersensitivity Reactions

    Hypersensitivity reactions, including anaphylaxis, rash (macular and vesicular), angioedema, urticaria, and fever, reported in patients receiving chloramphenicol.

    Herxheimer-like reactions reported in patients receiving the drug for treatment of typhoid fever.

    Other Warnings and Precautions

    Gray Syndrome

    A type of circulatory collapse, referred to as the gray syndrome, has occurred in neonates and premature infants receiving chloramphenicol. Most cases have occurred when the drug was initiated within first 48 hours of life; also reported in older infants and in infants born to mothers who received chloramphenicol during late pregnancy or during labor. (See Pediatric Use under Cautions.)

    Similar syndrome has been reported in older children and adults following chloramphenicol overdosage.

    May occur because chloramphenicol impairs myocardial contractility by directly interfering with myocardial tissue respiration and oxidative phosphorylation. Has been attributed to high plasma concentrations of the drug.

    Selection and Use of Anti-infectives

    Use only when other potentially less toxic anti-infectives cannot be used or would be ineffective. Do not use for trivial infections or when not indicated (e.g., for colds, influenza, throat infections, prophylaxis).

    When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

    May be initiated pending results of in vitro susceptibility testing, but discontinue if causative organism found to be susceptible to potentially less toxic anti-infectives. Base decision to continue chloramphenicol rather than switching to a less toxic anti-infective on severity of infection, comparative in vitro susceptibility, expected efficacy in the specific infection, and comparative safety profiles of the drugs.

    Continue chloramphenicol no longer than required to eradicate the infection with little or no risk or relapse. Avoid repeated courses of the drug if possible.

    Nervous System Effects

    Optic neuritis, rarely resulting in optic atrophy and blindness, reported, usually following long-term therapy. Symptoms tend to be reversible, but permanent vision loss may occur. Promptly discontinue chloramphenicol if optic neuritis occurs.

    Peripheral neuritis reported, usually following long-term therapy. Promptly discontinue chloramphenicol if peripheral neuritis occurs.

    Headache, ophthalmoplegia, depression, confusion, and delirium reported.

    Sodium Content

    Each 1 g of chloramphenicol in the reconstituted solution contains approximately 52 mg (2.25 mEq) of sodium.

    Superinfection

    As with other anti-infectives, overgrowth of nonsusceptible organisms, including fungi, may occur.

    Discontinue chloramphenicol and institute appropriate therapy if infection caused by nonsusceptible organisms occurs.

    Specific Populations

    Pregnancy

    No adequate and well-controlled studies evaluating chloramphenicol in pregnant women; no animal reproduction studies.

    Studies using oral chloramphenicol (no longer available in US) indicate the drug crosses the placenta.

    Use during late pregnancy and during labor has been associated with the gray syndrome and other adverse effects in the fetus or infant. (See Gray Syndrome under Cautions.)

    Because of potential toxic effects on the fetus, manufacturer states use chloramphenicol during pregnancy only if potential benefits justify potentials risks to the fetus.

    Lactation

    Studies using oral chloramphenicol (no longer available in US) indicate the drug is distributed into human milk.

    Potentially could cause serious adverse effects in breast-fed infants. (See Gray Syndrome under Cautions.)

    Manufacturer states discontinue nursing or the drug, taking into account importance of the drug to the woman.

    Pediatric Use

    Use with caution in premature and full-term neonates and infants because of potential toxicity.

    Gray syndrome has occurred in neonates and premature infants receiving chloramphenicol. Symptoms of gray syndrome in infants usually develop 2–9 days after initiation of chloramphenicol and include abdominal distension (with or without emesis), progressive pallid cyanosis, flaccidity, and vasomotor collapse (frequently accompanied by irregular respiration). Can be fatal within a few hours after onset of symptoms; may be reversible with complete recovery if chloramphenicol discontinued at early evidence of symptoms.

    Immature metabolic processes in neonates and infants or other pediatric patients may result in excessive chloramphenicol concentrations. Determine plasma concentrations of the drug at appropriate intervals and adjust dosage accordingly. (See General under Dosage and Administration.)

    Geriatric Use

    Insufficient experience in patients ≥65 years of age to determine whether geriatric adults respond differently than younger patients. Other reported clinical experience has not identified differences in responses between geriatric and younger adults.

    Substantially eliminated by kidneys; increased risk of adverse effects in those with impaired renal function. Select dosage with caution because of age-related decreases in renal, hepatic, and/or cardiac function and potential for concomitant disease and drug therapy. (See Geriatric Patients under Dosage and Administration.)

    Hepatic Impairment

    Excessive chloramphenicol concentration may occur in patients with impaired hepatic function. Determine chloramphenicol concentrations at appropriate intervals and adjust dosage accordingly.

    Renal Impairment

    Excessive chloramphenicol concentrations may occur in patients with impaired renal function. Determine chloramphenicol concentrations at appropriate intervals and adjust dosage accordingly.

    Common Adverse Effects

    Hematologic effects (blood dyscrasias, bone marrow depression), GI effects (nausea, vomiting, diarrhea, glossitis, stomatitis, enterocolitis).

    What other drugs will affect Chloramphenicol

    Inhibits CYP isoenzymes 2C9 and 3A4.

    Specific Drugs

    Drug

    Interaction

    Comments

    Aminoglycosides

    In vitro evidence of antagonistic antibacterial effects with chloramphenicol; clinical importance unclear

    Some clinicians state use concomitantly with caution or avoid concomitant use

    Antianemia agents

    Possible delayed response to iron preparations, vitamin B12, or folic acid

    Anticoagulants (warfarin)

    Warfarin: Possible prolonged warfarin half-life

    Anticonvulsants

    Fosphenytoin: Possible altered (increased or decreased) chloramphenicol concentrations

    Phenobarbital: Decreased chloramphenicol concentrations; possible increased phenobarbital concentrations

    Phenytoin: Possible altered (increased or decreased) chloramphenicol concentrations and potentially toxic chloramphenicol concentrations; possible prolonged phenytoin half-life and increased phenytoin concentrations

    Antidiabetic agents, sulfonylureas (e.g., chlorpropamide, tolbutamide)

    Possible increased half-lives of some sulfonylurea antidiabetic agents

    β-Lactam antibiotics

    Aztreonam: In vitro evidence of antagonistic antibacterial effects with chloramphenicol against Klebsiella pneumoniae

    Penicillins and cephalosporins: In vitro evidence of antagonistic antibacterial effects with chloramphenicol; clinical importance unclear

    Aztreonam: If used concomitantly, some clinicians suggest giving chloramphenicol a few hours after aztreonam

    Penicillins and cephalosporins: Some clinicians state use concomitantly with caution or avoid concomitant use

    Cyclophosphamide

    Possible prolonged cyclophosphamide half-life, decreased concentrations of active cyclophosphamide metabolite, and reduced effectiveness of the drug

    Fluoroquinolones

    In vitro evidence of antagonistic antibacterial effects with chloramphenicol; clinical importance unclear

    Some clinicians state use concomitantly with caution or avoid concomitant use

    Immunosuppressive agents (cyclosporine, tacrolimus)

    Cyclosporine: Possible increased cyclosporine concentrations and increased risk of renal dysfunction, cholestasis, and paresthesias

    Tacrolimus: Possible increased tacrolimus concentrations

    Myelosuppressive agents

    Potential additive bone marrow depression

    Avoid concomitant use with other drugs that may cause bone marrow depression

    Rifampin

    Possible increased clearance and decreased chloramphenicol concentrations

    Typhoid vaccine

    Typhoid vaccine live oral Ty21a: Possible decreased efficacy

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