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Chloramphenicol (Systemic)

Medically reviewed by Drugs.com. Last updated on July 18, 2020.

Pronunciation

(klor am FEN i kole)

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)

Pharmacologic Category

  • Antibiotic, Miscellaneous

Pharmacology

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

Distribution

To most tissues and body fluids (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

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).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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. 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.

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

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

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). Monitor therapy

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

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). Monitor therapy

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 increase the serum concentration 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: 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. Consider therapy modification

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

Vitamin K Antagonists (eg, warfarin): CYP2C9 Inhibitors (Weak) may increase the serum concentration of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

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

ALERT: U.S. Boxed Warning

Blood dyscrasias:

Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) are known to occur after the administration of chloramphenicol. In addition, there have been reports of aplastic anemia attributed to chloramphenicol which later terminated in leukemia. Blood dyscrasias have occurred after both short-term and prolonged therapy with this drug. Chloramphenicol must not be used when less potentially dangerous agents will be effective. It must not be used in the treatment of trivial infections or where it is not indicated, as in colds, influenza, infections of the throat; or as a prophylactic agent to prevent bacterial infections.

It is essential that adequate blood studies be made during treatment with the drug. While blood studies may detect early peripheral blood changes, such as leukopenia, reticulocytopenia, or granulocytopenia, before they become irreversible, such studies cannot be relied on to detect bone marrow depression prior to development of aplastic anemia. To facilitate appropriate studies and observation during therapy, it is desirable that patients be hospitalized.

Warnings/Precautions

Concerns related to adverse effects:

• Blood dyscrasias: [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.

Monitoring Parameters

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Chloramphenicol crosses the placenta producing cord concentrations approaching maternal serum concentrations. An increased risk of teratogenic effects has not been associated with the use of chloramphenicol in pregnancy (Czeizel 2000; Heinonen 1977). "Gray Syndrome" has occurred in premature infants and newborns receiving chloramphenicol. 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

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like 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

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.