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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(klor am FEN i kole)
Generic Available (U.S.)
Yes
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of serious infections due to organisms resistant to other less toxic antibiotics or when its penetrability into the site of infection is clinically superior to other antibiotics to which the organism is sensitive; useful in infections caused by Bacteroides, H. influenzae, Neisseria meningitidis, Salmonella, and Rickettsia; active against many vancomycin-resistant enterococci
Pregnancy Considerations
Chloramphenicol crosses the placenta producing cord concentrations approaching maternal serum concentrations. An increased risk of teratogenic effects has not been identified for chloramphenicol and there have been no reports of fetal harm related to use of chloramphenicol in pregnancy. "Gray Syndrome" has occurred in premature infants and newborns receiving chloramphenicol. In most cases, chloramphenicol was started during the first 48 hours of life, but it has also occurred in older patients after high doses. Symptoms began after 3-4 days of therapy, starting with abdominal distention and continuing to progressive pallid cyanosis, vasomotor collapse, irregular respiration, and death within a few hours of symptom onset. Stopping therapy can reverse the process and allow complete recovery. There is one case report of an infant with gray baby syndrome after in utero exposure to a single maternal dose during labor, followed by a 10-fold overdose of chloramphenicol in the first day of life. The extent of the contribution of the single dose given during labor is unknown. The manufacturer recommends caution if used in a pregnant patient near term or during labor.
Lactation
Enters breast milk/use with caution (AAP rates “of concern”; AAP 2001 update pending)
Breast-Feeding Considerations
Chloramphenicol is excreted in human milk in both the active form and as inactive metabolites. 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. There have been documented toxicities in neonates and preterm infants when chloramphenicol has been used at therapeutic doses. The manufacturer recommends caution if using chloramphenicol in a breast-feeding infant. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to chloramphenicol or any component of the formulation; treatment of trivial or viral infections; bacterial prophylaxis
Warnings/Precautions
Boxed warnings:
• Blood dyscrasias: See “Concerns related to adverse effects” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Blood dyscrasias: [U.S. Boxed Warning]: Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) have occurred after both short-term and prolonged therapy. Monitor CBC frequently in all patients; discontinue if evidence of myelosuppression. Irreversible bone marrow suppression may occur weeks or months after therapy. Avoid repeated courses of treatment. Should not be used for minor infections or when less potentially toxic agents are effective.
• Gray syndrome: Characterized by circulatory collapse, cyanosis, acidosis, abdominal distention, myocardial depression, coma, and death. Reaction appears to be associated with serum levels ≥50 mcg/mL. May result from drug accumulation in patients with impaired hepatic or renal function.
• 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 in patients with hepatic impairment; reduced dosage recommended.
• Renal impairment: Use with caution in patients with renal impairment
Special populations:
• Glucose 6-phosphate dehydrogenase deficiency: Use with caution in patients with glucose 6-phosphate dehydrogenase deficiency.
• Neonates: Use with caution in neonates; due to risk of gray syndrome.
Adverse Reactions
Frequency not defined.
Central nervous system: Confusion, delirium, depression, fever, headache
Dermatologic: Angioedema, rash, urticaria
Gastrointestinal: Diarrhea, enterocolitis, glossitis, nausea, stomatitis, vomiting
Hematologic: Aplastic anemia, bone marrow suppression, granulocytopenia, hypoplastic anemia, pancytopenia, thrombocytopenia
Ocular: Optic neuritis
Miscellaneous: Anaphylaxis, hypersensitivity reactions, Gray syndrome
Metabolism/Transport Effects
Inhibits CYP2C19 (strong), CYP2C9 (weak), CYP3A4 (strong)
Drug Interactions
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): Chloramphenicol may decrease the metabolism of Anticonvulsants (Hydantoin). Anticonvulsants (Hydantoin) may decrease the serum concentration of Chloramphenicol. Increased chloramphenicol concentrations have also been seen. Risk D: Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Decrease aripiprazole dose to 50% of the usual dose with concomitant use of strong CYP3A4 inhibitors or to 25% of usual dose with concomitant use of strong CYP3A4 and 2D6 inhibitors or with use of a strong 3A4 inhibitor in a poor 2D6 metabolizer Risk D: Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk X: Avoid combination
Barbiturates: May increase the metabolism of Chloramphenicol. Chloramphenicol may decrease the metabolism of Barbiturates. Risk D: Consider therapy modification
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Risk C: Monitor therapy
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Risk C: Monitor therapy
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
Ciclesonide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ciclesonide. Specifically, concentrations of the active des-ciclesonide metabolite may be increased. Risk C: Monitor therapy
Citalopram: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a strong CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Risk D: Consider therapy modification
Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased. Risk X: Avoid combination
Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Risk X: Avoid combination
Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Monitor for signs and symptoms of adrenal suppression if inhaled budesonide or mometasone are coadministered with a strong CYP3A4 inhibitor. Avoid combining inhaled fluticasone with any strong CYP3A4 inhibitor. Exceptions: Beclomethasone; Beclomethasone (Oral Inhalation); Triamcinolone; Triamcinolone (Systemic). Risk C: Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Risk X: Avoid combination
Cyanocobalamin: Chloramphenicol may diminish the therapeutic effect of Cyanocobalamin. The expected hematologic response for the treatment of anemia may be opposed. Risk D: Consider therapy modification
CycloSPORINE: Chloramphenicol may increase the serum concentration of CycloSPORINE. 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
CycloSPORINE (Systemic): Chloramphenicol 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
CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Risk X: Avoid combination
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Risk C: Monitor therapy
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk X: Avoid combination
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Risk C: Monitor therapy
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Risk X: Avoid combination
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Decrease ivacaftor dose to 150 mg twice a week in patients also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Risk D: Consider therapy modification
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. Risk X: Avoid combination
Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. Risk C: Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Risk X: Avoid combination
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. Risk D: Consider therapy modification
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose titration and/or adjustments in patients receiving strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors) and monitor for increased steroid related adverse effects. Risk D: Consider therapy modification
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy
Pazopanib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pazopanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib adult dose to 400 mg. Further dose reductions may also be required. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Risk C: Monitor therapy
Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Rifampin: May increase the metabolism of Chloramphenicol. Risk D: Consider therapy modification
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Risk X: Avoid combination
Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: Reduce ruxolitinib initial adult dose to 10 mg twice daily in patients receiving strong CYP3A4 inhibitors whose platelet count is 100*10^9/L or greater. Avoid in patients with lower platelet count. Risk D: Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Management: Limit saxagliptin adult dose to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) when used with a strong CYP3A4 inhibitor. Monitor for decreased saxagliptin levels/effects if discontinuing CYP3A4 inhibitor. Risk D: Consider therapy modification
Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: When used for treatment of pulmonary arterial hypertension, use of sildenafil with strong CYP3A4 inhibitors should be avoided. When used for erectile dysfunction, starting dose should be reduced to 25 mg. Max dose with ritonavir is 25 mg per 48 hours. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Risk X: Avoid combination
SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. Risk C: Monitor therapy
Sulfonylureas: Chloramphenicol may decrease the metabolism of Sulfonylureas. Risk C: Monitor therapy
Tacrolimus: Chloramphenicol may increase the serum concentration of Tacrolimus. 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
Tacrolimus (Systemic): Chloramphenicol 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
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Recommendations regarding use of tadalafil in patients also receiving strong CYP3A4 inhibitors may vary based on indication and/or international labeling. Consult appropriate product labeling. Risk D: Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk X: Avoid combination
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended dose of long-acting tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Toremifene: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra, Staxyn) or by international labeling. Consult appropriate product labeling for specific recommendations. Risk D: Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Chloramphenicol may enhance the anticoagulant effect of Vitamin K Antagonists. Chloramphenicol may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voriconazole: Chloramphenicol may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: May decrease intestinal absorption of vitamin B12 may have increased dietary need for riboflavin, pyridoxine, and vitamin B12.
Storage
Store at room temperature prior to reconstitution. Reconstituted solutions remain stable for 30 days. Use only clear solutions. Frozen solutions remain stable for 6 months.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, fat emulsion 10%, LR, 1/2NS, NS.
Y-site administration: Compatible: Acyclovir, cyclophosphamide, cyclosporine, enalaprilat, esmolol, foscarnet, hydromorphone, labetalol, magnesium sulfate, meperidine, morphine, nicardipine, tacrolimus. Incompatible Fluconazole.
Compatibility in syringe: Compatible: Ampicillin, cloxacillin, heparin, iohexol, iopamidol, iothalamate meglumine, ioxaglate meglumine and ioxaglate sodium, penicillin G sodium. Incompatible: Glycopyrrolate, metoclopramide.
Mechanism of Action
Reversibly binds to 50S ribosomal subunits of susceptible organisms preventing amino acids from being transferred to growing peptide chains thus inhibiting protein synthesis
Pharmacodynamics/Kinetics
Distribution: To most tissues and body fluids
Chloramphenicol: Vd: 0.5-1 L/kg
Chloramphenicol succinate: Vd: 0.2-3.1 L/kg; decreased with hepatic or renal dysfunction
Protein binding: Chloramphenicol: ~60%; decreased with hepatic or renal dysfunction and in newborn infants
Metabolism:
Chloramphenicol: Hepatic to metabolites (inactive)
Chloramphenicol succinate: Hydrolyzed in the liver, kidney and lungs to chloramphenicol (active)
Bioavailability:
Chloramphenicol: Oral: ~80%
Chloramphenicol succinate: I.V.: ~70%; highly variable, dependent upon rate and extent of metabolism to chloramphenicol
Half-life elimination:
Normal renal function:
Chloramphenicol: Adults: ~4 hours; Children 4-6 hours; Infants: Significantly prolonged
Chloramphenicol succinate: Adults: ~3 hours
End-stage renal disease: Chloramphenicol: 3-7 hours
Hepatic disease: Prolonged
Excretion: Urine (~30% as unchanged chloramphenicol succinate in adults, 6% to 80% in children; 5% to 15% as chloramphenicol)
Dosage
Children: Usual dosing range: I.V.: 50-100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day
Meningitis: I.V.: Infants >30 days and Children: 75-100 mg/kg/day divided every 6 hours
Adults: 50-100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day
Dosing adjustment in renal impairment: Use with caution; monitor serum concentrations
Dosing adjustment/comments in hepatic impairment: Use with caution; monitor serum concentrations
Administration: I.V.
Do not administer I.M.; can be administered IVP over at least 1 minute at a concentration of 100 mg/mL, or I.V. intermittent infusion over 15-30 minutes at a final concentration for administration of ≤20 mg/mL.
Administration: I.V. Detail
pH: 6.4-7.0
Monitoring Parameters
CBC with differential (baseline and every 2 days during therapy), periodic liver and renal function tests, serum drug concentration
Reference Range
Therapeutic levels:
Meningitis:
Peak: 15-25 mcg/mL; toxic concentration: >40 mcg/mL
Trough: 5-15 mcg/mL
Other infections:
Peak: 10-20 mcg/mL
Trough: 5-10 mcg/mL
Timing of serum samples: Draw levels 0.5-1.5 hours after completion of I.V. dose
Test Interactions
May cause false-positive results in urine glucose tests when using cupric sulfate (Benedict's solution, Clinitest®).
Dietary Considerations
May have increased dietary need for riboflavin, pyridoxine, and vitamin B12. Some products may contain sodium.
Patient Education
This medication is administered by infusion and you will be monitored during each infusion. Report immediately unusual chest tightness, difficulty breathing, or swallowing; itching or skin rash; back pain; acute headache; or redness, swelling, or pain at infusion site. You may experience a bitter taste during infusion; this will pass. May cause nausea or vomiting. Report persistent rash; unusual or persistent fatigue; diarrhea or vomiting; pain, burning, or numbness of extremities; signs of secondary infection (sore throat, vaginal itching or discharge, or mouth sores); unusual bleeding or bruising, petechiae, yellowing of skin or eyes, dark urine, or stool discoloration; CNS disturbances (nightmares or acute headache); or lack of improvement or worsening of condition.
Geriatric Considerations
Chloramphenicol has not been studied in the elderly. It is not necessary to adjust the dose based upon the decrease in renal function associated with age. Chloramphenicol should be reserved for serious infections and the oral form avoided.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Glossitis and stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause nightmares
Mental Health: Effects on Psychiatric Treatment
May cause bone marrow suppression; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess results of culture/sensitivity tests, patient allergy history, renal status, and hepatic status prior to beginning treatment. Discontinue therapy if evidence of myelosuppression exists. Observe closely for bone marrow depression or aplastic anemia (petechiae, sore throat, fatigue, unusual bleeding or bruising, abdominal or bone pain), circulatory collapse, CNS disturbances, and opportunistic infection. Teach patient to report CNS changes, opportunistic infection, and aplastic anemia (may occur weeks to months after initial exposure to chloramphenicol).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 1 g [contains sodium [~52 mg (2.25 mEq)/g]]
References
Ambrose PJ, “Clinical Pharmacokinetics Of Chloramphenicol And Chloramphenicol Succinate,” Clin Pharmacokinet, 1984, 9(3):222-38.
American Academy of Pediatrics Committee on Drugs, “Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.
Cocke JG Jr, “Chloramphenicol Optic Neuritis. Apparent Protective Effects of Very High Daily Doses of Pyridoxine and Cyanocobalamin,” Am J Dis Child, 1967, 114(4):424-6.
Doona M and Walsh JB, “Use of Chloramphenicol as Topical Eye Medication: Time to Cry Halt?” BMJ, 1995, 310(6989):1217-8.
Freundlich M, Cynamon H, Tamer A, et al, “Management of Chloramphenicol Intoxication in Infancy by Charcoal Hemoperfusion,” J Pediatr, 1983, 103(3):485-7.
Hammett-Stabler CA and Johns T, “Laboratory Guidelines for Monitoring of Antimicrobial Drugs. National Academy of Clinical Biochemistry,” Clin Chem, 1998, 44(5):1129-40.
Kunin CM, Glazko AJ, and Finland M, “Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. II. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Failure Disease or Hepatic Cirrhosis,” J Clin Invest, 1959, 38(9):1498-508.
Messick CR and Pendland SL, “In Vitro Activity of Chloramphenicol Alone and in Combination With Vancomycin, Ampicillin, or RP 59500 (Quinupristin/Dalfopristin) Against Vancomycin-Resistant Enterococci,” Diagn Microbiol Infect Dis, 1997, 29(3):203-5.
Montoro A, Cao A, Ordoqui E, et al, “Contact Sensitivity to Chloramphenicol,” J Allergy Clin Immunol, 1995, 95:291.
Nahata MC and Powell DA, “Bioavailability and Clearance of Chloramphenicol After Intravenous Chloramphenicol Succinate,” Clin Pharmacol Ther, 1981, 30(3):368-72.
Powell DA and Nahata MC, “Chloramphenicol: New Perspectives on an Old Drug,” Drug Intell Clin Pharm, 1982, 16(4):295-300.
Ramilo O, Kinane BT, and McCracken GH Jr, “Chloramphenicol Neurotoxicity,” Pediatr Infect Dis J, 1988, 7(5):358-9.
Smilack JD, Wilson WR, and Cockerill FR 3d, “Tetracyclines, Chloramphenicol, Erythromycin, Clindamycin, and Metronidazole,” Mayo Clin Proc, 1991, 66(12):1270-80.
Tunkel AR, Wispelwey B, and Scheld M, “Bacterial Meningitis: Recent Advances in Pathophysiology and Treatment,” Ann Intern Med, 1990, 112(8):610-23.
Vozeh S, Schmidlin O, and Taeschner W, “Pharmacokinetic Drug Data,” Clin Pharmacokinet, 1988, 15(4):254-82.
Yoshikawa TT, “Antimicrobial Therapy for the Elderly Patient,” J Am Geriatr Soc, 1990, 38(12):1353-72.
Yunis AA, “Chloramphenicol: Relation of Structure to Activity and Toxicity,” Annu Rev Pharmacol Toxicol, 1988, 28:83-100.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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