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Chloramphenicol

Class: Chloramphenicol
VA Class: AM150
Molecular Formula: C15H15Cl2N2NaO8
CAS Number: 982-57-0

Medically reviewed by Drugs.com. Last updated on Jun 24, 2019.

Warning

  • Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur after short-term or prolonged therapy.112 Chloramphenicol-associated aplastic anemia (terminating in leukemia) has been reported.112 (See Hematologic Effects under Cautions.)

  • Must be used only for treatment of serious infections when other potentially less hazardous anti-infectives cannot be used or would be ineffective.112 Must not be used for trivial infections or when not indicated (e.g., for colds, influenza, throat infections, prophylaxis).112

  • It is essential that adequate blood studies be performed during chloramphenicol treatment.112 While such studies may detect early peripheral blood changes (e.g., leukopenia, reticulocytopenia, granulocytopenia) before they become irreversible, such studies cannot be relied on to detect bone marrow depression prior to development of aplastic anemia.112

  • To facilitate appropriate blood studies and clinical observation, patient should be hospitalized while receiving chloramphenicol.112

Introduction

Antibacterial; broad-spectrum anti-infective.104 110 112

Uses for Chloramphenicol

Meningitis

Alternative for treatment of meningitis caused by susceptible bacteria, including Haemophilus influenzae,110 112 418 Neisseria meningitidis,110 418 or Streptococcus pneumoniae.110 418 Generally used only when penicillins and cephalosporins are contraindicated or ineffective.101 102 104 105 110 197 418

Despite evidence of in vitro activity against Listeria monocytogenes, has been ineffective for treatment of systemic infections caused by this organism.475

Do not use for treatment of meningitis caused by gram-negative bacilli.475

Rickettsial Infections

Possible alternative to tetracyclines for treatment of rickettsial infections.104 110 112 197 292 500 525 526 529 530 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).292 500 525 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.292 500 525 If considering an alternative to doxycycline, consultation with an expert recommended.525

Possible alternative to doxycycline for treatment of certain tickborne rickettsial diseases, including Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii.292 500 525 Doxycycline is drug of choice for treatment of RMSF, regardless of patient age.292 500 525 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).292 500 525 530 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;292 500 527 close monitoring required if chloramphenicol used.292 500 527

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.197 292 529 530 Doxycycline is drug of choice for treatment of endemic typhus and epidemic typhus, regardless of patient age.292

Has been used for treatment of scrub typhus caused by Orientia tsutsugamushi;110 178 197 526 recommended as possible alternative to doxycycline.197 526 529 Consider that chloramphenicol resistance and persistence or relapse reported.110 178

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).159 500 Doxycycline is drug of choice for treatment of human ehrlichiosis and anaplasmosis, regardless of patient age.159 292 500 Chloramphenicol considered ineffective; use not supported by results of in vitro susceptibility testing.159 500

Typhoid Fever and Other Severe Salmonella Infections

Has been used for treatment of typhoid fever (enteric fever) caused by susceptible Salmonella enterica serovar Typhi104 110 112 134 136 139 140 173 174 175 183 197 and treatment of paratyphoid fever caused by S. enterica serovar Paratyphi.110 140 174

Although chloramphenicol was a drug of choice for treatment of infections caused by typhoidal Salmonella in the past,104 173 175 183 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.173 175 183 292 Whenever possible, select anti-infectives for treatment of typhoid fever based on results of in vitro susceptibility testing.175 292

Do not use to treat typhoid carrier state.104 110 112 Depending on susceptibility of the strain, a fluoroquinolone (e.g., ciprofloxacin), ampicillin, amoxicillin, or co-trimoxazole usually recommended to treat typhoid carrier state.173 175 197 292

Do not use for treatment of uncomplicated Salmonella gastroenteritis.104 110

Anthrax

Alternative for treatment of anthrax.104 668 670 671 672 673 680 683

Has in vitro activity against Bacillus anthracis,161 668 but limited clinical data exist regarding use in the treatment of anthrax.668 680

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,670 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.680

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).668 671 672 673 683

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).671 672 673 These experts recommend IV chloramphenicol as a possible alternative to linezolid, but use only if clindamycin and rifampin not available.671 672 673

Burkholderia Infections

Has been used in patients with cystic fibrosis112 and has been recommended as an alternative for treatment of infections caused by Burkholderia cepacia.197 However, B. cepacia usually resistant to chloramphenicol in vitro.104 110 Optimum treatment regimens for chronic B. cepacia complex infections not identified; select treatment regimen based on in vitro susceptibility data and previous clinical responses.177 Anti-infectives that have been recommended include meropenem, imipenem, co-trimoxazole, ceftazidime, doxycycline, and chloramphenicol;292 some experts recommend use of multiple-drug regimens.292

Has been used in conjunction with doxycycline and co-trimoxazole for treatment of melioidosis caused by B. pseudomallei.154 176 197 Ceftazidime or a carbapenem (either meropenem or imipenem) usually drugs of choice for initial treatment,104 110 152 153 154 156 180 197 292 followed by long-term treatment (≥3 months) with an oral anti-infective (e.g., co-trimoxazole, amoxicillin and clavulanate potassium, doxycycline).104 180 292 B. pseudomallei may be difficult to eradicate and relapse of melioidosis may occur, especially if there is poor compliance with the follow-up regimen.104 152 153 154 156 180

Plague

Alternative for treatment of plague 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.133 197 292 683 689

Streptomycin (or gentamicin) historically considered drug of choice for treatment of plague.104 197 292 683 688 Alternatives include fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), doxycycline (or tetracycline), chloramphenicol, or co-trimoxazole (may be less effective than other alternatives).104 292 683 688

Chloramphenicol considered a drug of choice for treatment of plague meningitis.104 292 683

Tularemia

Alternative for treatment of tularemia caused by Francisella tularensis,133 197 683 689 including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.683 689

Streptomycin (or gentamicin) generally considered drug of choice for treatment of tularemia.104 197 292 683 689 Alternatives include tetracyclines (doxycycline), chloramphenicol, or ciprofloxacin.197 292 683 689

Some clinicians state reserve chloramphenicol for treatment of tularemic meningitis (usually in conjunction with streptomycin)104 683 and do not use for other forms of tularemia.104

Chloramphenicol Dosage and Administration

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.101 102 104 105 107 108 109 110 112 114 115 179 184 301

  • Blood samples to measure peak plasma concentrations of chloramphenicol usually obtained 0.5–1.5 hours after an IV dose.179 184 301

  • Generally adjust chloramphenicol dosage to maintain plasma concentrations of 5–20 mcg/mL (usually 10–20 mcg/mL).101 102 104 105 107 108 110 179 In pediatric patients beyond the neonatal period, AAP suggests adjusting dosage to maintain target plasma concentrations of 15–25 mcg/mL.292 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.184

  • Chloramphenicol plasma concentrations >25 mcg/mL have been associated with toxicity.104 179

  • Use no longer than necessary to eradicate the infection with little or no risk of relapse;112 switch IV chloramphenicol to an appropriate oral anti-infective as soon as feasible.112

  • Avoid repeated courses of chloramphenicol if possible.112

Administration

Administer IV.112

Has been administered IM,104 108 110 113 but plasma concentrations unpredictable following IM injection.104 Manufacturer states do not give IM since this route may be ineffective.112

Has been administered orally as the base or palmitate;104 110 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.112

Rate of Administration

Inject appropriate dose of reconstituted solution IV over ≥1 minute.112

Has been given by intermittent IV infusion over 15–60 minutes.55 104 110 301

Dosage

Available as chloramphenicol sodium succinate; dosage expressed in terms of chloramphenicol.112

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.112 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.112 If higher dosage required for treatment of severe infections, use such dosage only to maintain blood concentrations within a therapeutically effective range.112

Some clinicians recommend loading dose of 20 mg/kg followed 12 hours later by maintenance dosage based on age and weight.184 These clinicians recommend maintenance dosage of 25 mg/kg once every 24 hour in neonates ≤7 days of age.184 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.184

Other clinicians recommend loading dose of 20 mg/kg followed 12 hours later by a different maintenance dosage based on age and weight.301 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.301 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.301

Use with caution in neonates because immature metabolic processes in this age group may result in excessive plasma concentrations of chloramphenicol.112 (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.112 Manufacturer states up to 100 mg/kg daily may be required for severe infections (e.g., bacteremia, meningitis), especially when adequate CSF concentrations desired;112 reduce dosage to 50 mg/kg daily as soon as possible.112

AAP recommends 50–100 mg/kg daily given in 4 divided doses for severe infections.292

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.112

Carefully monitor chloramphenicol concentrations because high concentrations may occur and tend to increase with succeeding doses.112 (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.526 530

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.292 500 Minimum duration of treatment is 5–7 days;292 500 longer duration may be required for severe or complicated disease.500

If considering chloramphenicol for treatment of rickettsial infection, expert consultation recommended.525 (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.134

Children ≥14 years of age: 50 mg/kg daily in 4 divided doses (up to 3 g daily) has been given for 14 days.140

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.112

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.670 Usual duration is ≥14 days after symptoms abate.670

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.671

Children ≥1 month of age: AAP recommends 100 mg/kg daily given in divided doses every 6 hours.671

Used as part of a multiple-drug regimen;671 continue parenteral regimen for ≥2–3 weeks until patient is clinically stable and can be switched to appropriate oral anti-infectives.671

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).688 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).683

Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 10–14 days.683 688

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).689

Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 14–21 days.689

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).104

Adults

General Dosage for Adults
IV

Manufacturer recommends 50 mg/kg daily given in divided doses every 6 hours.112

Infections caused by less susceptible organisms: Manufacturer states up to 100 mg/kg daily may be required.112 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.102 105 Reduce dosage to 50 mg/kg daily as soon as possible.112

Rickettsial Infections
IV

60–75 mg/kg daily in 4 divided doses for 5–10 days recommended by some clinicians.526 530

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.526

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.500 Minimum duration of treatment is 5–7 days;500 longer duration may be required for severe or complicated disease.500

If considering chloramphenicol for treatment of rickettsial infection, expert consultation recommended.525 (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.140 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.134

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.112

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.670 Usual duration is ≥14 days after symptoms abate.670

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

1 g every 6–8 hours recommended by CDC.672 673 Used as part of a multiple-drug parenteral regimen;672 673 continue for ≥2–3 weeks until patient is clinically stable and can be switched to appropriate oral anti-infectives.672 673

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).688 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).683

Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 10–14 days.683 688

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).689 Other experts (e.g., USAMRIID) recommend 15–25 mg/kg every 6 hours.683

Can be switched to an appropriate oral anti-infective when clinically indicated;689 total duration of treatment usually 14–21 days.689

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).104

Special Populations

Hepatic Impairment

Base dosage on plasma chloramphenicol concentrations, especially in pediatric patients, and adjust accordingly.110 112 301

Renal Impairment

Base dosage on plasma chloramphenicol concentrations, especially in pediatric patients, and adjust accordingly.110 112 301

Geriatric Patients

Select dosage with caution, usually starting at low end of dosage range.112 Consider greater frequency of decreased renal, hepatic, and/or cardiac function in geriatric patients;112 consider monitoring renal function.112 (See Geriatric Use under Cautions.)

Cautions for Chloramphenicol

Contraindications

  • Hypersensitivity to chloramphenicol.112

  • Previous toxic reaction to chloramphenicol.112

  • Trivial infections or when not indicated (e.g., colds, influenza, throat infections, prophylaxis).112

Warnings/Precautions

Warnings

Hematologic Effects

Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) reported with both short-term and prolonged use.112 Aplastic anemia attributed to chloramphenicol, which later terminated in leukemia, has occurred.112

Two forms of hematologic toxicity may occur with chloramphenicol.104 110 112

Most common type is a dose-related, reversible bone marrow depression.104 110 112 Characterized by anemia, leukopenia, reticulocytopenia, thrombocytopenia, increased concentrations of serum iron, increased serum iron-binding capacity, and vacuolization of erythroid and myeloid precursors.104 112 More likely to occur in patients receiving chloramphenicol dosage ≥4 g daily and in those with plasma chloramphenicol concentrations >25 mcg/mL.104 Usually reversible after discontinuance of chloramphenicol.104 110 112

Second type is a rare, but often fatal, irreversible aplastic anemia that does not appear to be dose related.104 110 112 Has been associated with a mortality rate >50%.104 110 Bone marrow aplasia or hypoplasia may occur weeks or months after the drug was discontinued.112 Pancytopenia frequently observed peripherally, but in some cases only 1 or 2 major cell types (erythrocytes, leukocytes, platelets) may be depressed.112

Paroxysmal nocturnal hemoglobinuria reported.112 Hemolytic anemia reported when chloramphenicol used in patients with glucose-6-phosphate dehydrogenase deficiency.104 110

Perform adequate hematologic studies prior to and approximately every 2 days during chloramphenicol therapy.112 Patients should be hospitalized during treatment to facilitate appropriate laboratory studies and clinical observation.112 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.112

Discontinue chloramphenicol if reticulocytopenia, leukopenia, thrombocytopenia, anemia, or any other hematologic abnormalities attributable to the drug occur.112

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis,112 rash (macular and vesicular),112 angioedema,112 urticaria,112 and fever,112 reported in patients receiving chloramphenicol.

Herxheimer-like reactions reported in patients receiving the drug for treatment of typhoid fever.112

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.104 110 112 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.110 112 (See Pediatric Use under Cautions.)

Similar syndrome has been reported in older children and adults following chloramphenicol overdosage.104 110

May occur because chloramphenicol impairs myocardial contractility by directly interfering with myocardial tissue respiration and oxidative phosphorylation.104 110 Has been attributed to high plasma concentrations of the drug.104 110 112

Selection and Use of Anti-infectives

Use only when other potentially less toxic anti-infectives cannot be used or would be ineffective.112 Do not use for trivial infections or when not indicated (e.g., for colds, influenza, throat infections, prophylaxis).112

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.112 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.112

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.112 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.112

Continue chloramphenicol no longer than required to eradicate the infection with little or no risk or relapse.112 Avoid repeated courses of the drug if possible.112

Nervous System Effects

Optic neuritis,104 110 112 rarely resulting in optic atrophy and blindness,104 110 reported, usually following long-term therapy.104 110 112 Symptoms tend to be reversible, but permanent vision loss may occur.104 110 Promptly discontinue chloramphenicol if optic neuritis occurs.112

Peripheral neuritis reported, usually following long-term therapy.104 110 112 Promptly discontinue chloramphenicol if peripheral neuritis occurs.112

Headache,104 110 112 ophthalmoplegia,104 110 depression,104 110 112 confusion,104 110 112 and delirium110 112 reported.

Sodium Content

Each 1 g of chloramphenicol in the reconstituted solution contains approximately 52 mg (2.25 mEq) of sodium.112

Superinfection

As with other anti-infectives, overgrowth of nonsusceptible organisms, including fungi, may occur.112

Discontinue chloramphenicol and institute appropriate therapy if infection caused by nonsusceptible organisms occurs.112

Specific Populations

Pregnancy

No adequate and well-controlled studies evaluating chloramphenicol in pregnant women;112 no animal reproduction studies.112

Studies using oral chloramphenicol (no longer available in US) indicate the drug crosses the placenta.110 112

Use during late pregnancy and during labor has been associated with the gray syndrome and other adverse effects in the fetus or infant.110 112 (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.112

Lactation

Studies using oral chloramphenicol (no longer available in US) indicate the drug is distributed into human milk.112

Potentially could cause serious adverse effects in breast-fed infants.112 (See Gray Syndrome under Cautions.)

Manufacturer states discontinue nursing or the drug, taking into account importance of the drug to the woman.112

Pediatric Use

Use with caution in premature and full-term neonates and infants because of potential toxicity.112

Gray syndrome has occurred in neonates and premature infants receiving chloramphenicol.104 110 112 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).104 110 112 Can be fatal within a few hours after onset of symptoms;112 may be reversible with complete recovery if chloramphenicol discontinued at early evidence of symptoms.112

Immature metabolic processes in neonates and infants or other pediatric patients may result in excessive chloramphenicol concentrations.104 110 112 Determine plasma concentrations of the drug at appropriate intervals and adjust dosage accordingly.110 112 (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.112 Other reported clinical experience has not identified differences in responses between geriatric and younger adults.112

Substantially eliminated by kidneys; increased risk of adverse effects in those with impaired renal function.112 Select dosage with caution because of age-related decreases in renal, hepatic, and/or cardiac function and potential for concomitant disease and drug therapy.112 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Excessive chloramphenicol concentration may occur in patients with impaired hepatic function.112 Determine chloramphenicol concentrations at appropriate intervals and adjust dosage accordingly.112

Renal Impairment

Excessive chloramphenicol concentrations may occur in patients with impaired renal function.112 Determine chloramphenicol concentrations at appropriate intervals and adjust dosage accordingly.112

Common Adverse Effects

Hematologic effects (blood dyscrasias, bone marrow depression), GI effects (nausea, vomiting, diarrhea, glossitis, stomatitis, enterocolitis).112

Interactions for Chloramphenicol

Inhibits CYP isoenzymes 2C9 and 3A4.104 110

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

In vitro evidence of antagonistic antibacterial effects with chloramphenicol;104 110 clinical importance unclear110

Some clinicians state use concomitantly with caution104 or avoid concomitant use110

Antianemia agents

Possible delayed response to iron preparations, vitamin B12, or folic acid104 110

Anticoagulants (warfarin)

Warfarin: Possible prolonged warfarin half-life104

Anticonvulsants

Fosphenytoin: Possible altered (increased or decreased) chloramphenicol concentrations104

Phenobarbital: Decreased chloramphenicol concentrations;58 59 104 possible increased phenobarbital concentrations104

Phenytoin: Possible altered (increased or decreased) chloramphenicol concentrations and potentially toxic chloramphenicol concentrations;104 110 possible prolonged phenytoin half-life and increased phenytoin concentrations104 110

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

Possible increased half-lives of some sulfonylurea antidiabetic agents104 110

β-Lactam antibiotics

Aztreonam: In vitro evidence of antagonistic antibacterial effects with chloramphenicol against Klebsiella pneumoniae116

Penicillins and cephalosporins: In vitro evidence of antagonistic antibacterial effects with chloramphenicol;104 110 clinical importance unclear110

Aztreonam: If used concomitantly, some clinicians suggest giving chloramphenicol a few hours after aztreonam116

Penicillins and cephalosporins: Some clinicians state use concomitantly with caution104 or avoid concomitant use110

Cyclophosphamide

Possible prolonged cyclophosphamide half-life, decreased concentrations of active cyclophosphamide metabolite, and reduced effectiveness of the drug104

Fluoroquinolones

In vitro evidence of antagonistic antibacterial effects with chloramphenicol;104 110 clinical importance unclear110

Some clinicians state use concomitantly with caution104 or avoid concomitant use110

Immunosuppressive agents (cyclosporine, tacrolimus)

Cyclosporine: Possible increased cyclosporine concentrations and increased risk of renal dysfunction, cholestasis, and paresthesias104

Tacrolimus: Possible increased tacrolimus concentrations104

Myelosuppressive agents

Potential additive bone marrow depression112

Avoid concomitant use with other drugs that may cause bone marrow depression112

Rifampin

Possible increased clearance and decreased chloramphenicol concentrations103 110

Typhoid vaccine

Typhoid vaccine live oral Ty21a: Possible decreased efficacy104

Chloramphenicol Pharmacokinetics

Absorption

Bioavailability

Chloramphenicol sodium succinate is a prodrug; inactive until hydrolyzed in vivo to active chloramphenicol.102 107 110

Bioavailability following IV administration varies; considerable interindividual variation in plasma chloramphenicol concentrations.101 102 107 109 110 114

Distribution

Extent

Widely distributed into body tissues and fluids, including ascitic fluid, pleural fluid, synovial fluid, saliva, and aqueous and vitreous humor.104 107 110 112 Highest concentrations attained in liver and kidneys.112

Distributed into CSF, even in absence of meningeal inflammation.55 104 110 112 CSF concentrations reported to be ≥50% of concurrent plasma concentrations in patients with uninflamed meninges.104 110 112 In 3 neonates 2–6 weeks of age, CSF concentrations were 45–89% of concurrent plasma concentrations.55

Crosses the placenta.104 107 110 112

Distributed into human milk.104 107 110 112

Plasma Protein Binding

Approximately 60%.107

Elimination

Metabolism

Chloramphenicol sodium succinate is hydrolyzed to active chloramphenicol, presumably by esterases in liver, kidneys, and lungs.102 107 110 Rate and extent of hydrolysis highly variable.101 102 107 109 110 114

Chloramphenicol is then metabolized principally in the liver to chloramphenicol glucuronide, an inactive metabolite.104 110

Elimination Route

Approximately 30% of an IV dose excreted unchanged in urine,102 107 but fraction excreted in urine varies considerably and may range from 6–80%.102 107 109 110

Small amounts of the dose (2–3%) eliminated in bile;104 110 about 1% eliminated in feces.104 110

Half-life

Adults with normal renal and hepatic function: 1.2–4.1 hours.101 104 107 110

Neonates and infants: Plasma half-life inversely related to age.110 In one study, plasma half-life was 10–36 hours in neonates 1–8 days of age and 5.5–15.7 hours in infants 11 days to 8 weeks of age.110 Premature infants and neonates have immature mechanisms for glucuronide conjugation and excretion which results in higher and more prolonged chloramphenicol concentrations.107 110 112

Special Populations

Impaired hepatic function: Elimination half-life prolonged and clearance decreased.107 110

Impaired renal function: Elimination half-life not substantially prolonged, but accumulation of inactive conjugated metabolite may occur.110

Stability

Storage

Parenteral

Powder for Injection

20–25°C.112

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 2.5, 5, or 10%

Dextrose 2.5% in half-strength Ringer's injection

Dextrose 5% in half-strength Ringer's injection, lactated

Dextrose 5% in Ringer's injection

Dextrose 2.5, 5, or 10% in Ringer’s injection, lactated

Dextrose 2.5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in sodium chloride 0.225, 0.45, or 0.9%

Ionosol B, MB, or M in dextrose 5%

Normosol R

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate 1/6 M

Drug Compatibility
Admixture CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Calcium chloride

Calcium gluconate

Colistimethate sodium

Cyanocobalamin

Dimenhydrinate

Dopamine HCl

Ephedrine sulfate

Fat emulsion, intravenous

Heparin sodium

Hydrocortisone sodium succinate

Lidocaine HCl

Lincomycin HCl

Magnesium sulfate

Methyldopate HCl

Methylprednisolone sodium succinate

Nafcillin sodium

Oxacillin sodium

Oxytocin

Penicillin G potassium

Penicillin G sodium

Pentobarbital sodium

Phenylephrine HCl

Phytonadione

Potassium chloride

Ranitidine HCl

Sodium bicarbonate

Verapamil HCl

Incompatible

Chlorpromazine HCl

Erythromycin lactobionate

Hydroxyzine HCl

Polymyxin B sulfate

Prochlorperazine edisylate

Prochlorperazine mesylate

Promethazine HCl

Vancomycin HCl

Variable

Ascorbic acid

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Cyclophosphamide

Enalaprilat

Esmolol HCl

Foscarnet sodium

Hydromorphone HCl

Labetalol HCl

Magnesium sulfate

Meperidine HCl

Morphine sulfate

Nicardipine HCl

Tacrolimus

Incompatible

Fluconazole

Actions and Spectrum

  • Usually bacteriostatic in action,104 110 112 but may be bactericidal against some organisms.104 110

  • Inhibits protein synthesis in susceptible organisms by reversibly binding to peptidyl transferase cavity of the 50S ribosomal subunit of bacterial 70S ribosomes.104 110 This prevents aminoacyl-tRNA from binding to the ribosome and terminates polypeptide chain synthesis.104 Also appears to inhibit protein synthesis in rapidly proliferating mammalian cells;26 29 110 dose-related bone marrow depression reported during chloramphenicol therapy may be the result of inhibition of protein synthesis in mitochondria of bone marrow cells.29 104 110 181

  • Chloramphenicol sodium succinate is a prodrug and is inactive until hydrolyzed in vivo to active chloramphenicol.102 107 110

  • Broad spectrum of activity.104 110 112 Active in vitro against many gram-positive and gram-negative aerobic bacteria, some anaerobic bacteria, and some other organisms (e.g., Rickettsia, Chlamydia, Mycoplasma).104 110 112 Inactive against Mycobacterium104 110 and protozoa.104 110

  • Gram-positive aerobes: Active in vitro against S. aureus (including some methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]),104 110 S. epidermidis,110 S. pneumoniae110 and other streptococci.110 Has in vitro activity against B. anthracis.104 110 161 167 668

  • Gram-negative aerobes: Active in vitro against some strains of H. influenzae,104 110 112 H. parainfluenzae,110 Moraxella catarrhalis,104 110 N. gonorrhoeae,104 and N. meningitidis.104 Active in vitro against some Enterobacteriaceae, including some Citrobacter, Enterobacter, Escherichia coli, Hafnia, Klebsiella, Proteus, Providencia, Salmonella, and Shigella,104 110 but susceptibility is variable and many strains are resistant.104 110 Aeromonas,110 Bordetella pertussis,110 Brucella,110 Burkholderia mallei,110 Campylobacter jejuni,110 F. tularensis,691 Helicobacter pylori,110 Legionella pneumophila,110 Pasteurella multocida,110 Vibrio parahaemolyticus,110 and Y. pestis110 usually susceptible. Although V. cholerae usually susceptible, resistance reported.110

  • Anaerobes: Active in vitro against Actinomyces,110 Bifidobacterium,110 Clostridium,104 110 Eubacterium,110 Lactobacillus,104 110 Peptococcus,110 Peptostreptococcus,104 and Propionibacterium.104 110 Also active against Bacteroides fragilis, Fusobacterium, Prevotella, and Veillonella.104 110

  • Other organisms: Active against some Rickettsia, including R. rickettsii and causative agents of various typhus fevers.110

  • Reported incidence of chloramphenicol resistance in clinical isolates varies considerably worldwide; may be reported more frequently in regions of the world where the drug is still commonly used and has not been reserved for treatment of serious infections.104 110

  • Resistance has been reported in staphylococci,104 110 S. pneumoniae,104 110 126 131 E. coli,110 Salmonella,110 and Shigella.110 Chloramphenicol-resistant H. influenzae104 110 125 and N. meningitidis110 142 reported rarely.

  • Several mechanisms of chloramphenicol resistance reported.104 A common mechanism is enzymatic acetylation and inactivation by chloramphenicol acetyltransferases (CATs);104 110 identified in many different bacteria and may be readily transmitted to other bacteria.110 Other mechanisms involve transmembrane efflux pumps, decreased membrane permeability, or alterations in the 50S ribosomal subunit.104 110

Advice to Patients

  • Advise patients that antibacterials (including chloramphenicol) should only be used to treat bacterial infections and should not be used to treat viral infections (e.g., the common cold).112

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.112

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.112

  • Importance of advising patients of other important precautionary information.112 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chloramphenicol Sodium Succinate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

1 g (of chloramphenicol)*

Chloramphenicol Sodium Succinate

AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 24, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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55. Dunkle LM. Central nervous system chloramphenicol concentration in premature infants. Antimicrob Agents Chemother. 1978; 13:427-9. http://www.ncbi.nlm.nih.gov/pubmed/400823?dopt=AbstractPlus

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