In 1947, chloramphenicol was isolated from Streptomyces venezuelae, but it is now available synthetically for therapeutic use as either chloramphenicol, chloramphenicol palmitate, or chloramphenicol sodium succinate. Chloramphenicol palmitate is hydrolyzed in the GI tract to chloramphenicol; chloramphenicol sodium succinate is hydrolyzed to free chloramphenicol in vivo. Oral chloramphenicol was removed from the US market in July 2012 due to safety concerns, primarily bone marrow suppression and aplastic anemia, which may have a higher risk with the oral formulation; intravenous chloramphenicol continues to be an approved formulation. Chloramphenicol was approved by the FDA in 1950.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Powder Vials for Injection
Reconstitution
-Reconstitute 1 g with 10 mL of an aqueous diluent (i.e., Sterile Water for Injection or 5% Dextrose Injection) to yield 100 mg/mL.
Intermittent IV Push
-Inject IV over at least 1 minute.
The gray-baby syndrome is an adverse reaction seen in premature or newborn infants receiving chloramphenicol. It is believed that the infant's hepatic system is unable to conjugate or excrete the drug, resulting in a syndrome characterized by abdominal distension with or without emesis; progressive pallid cyanosis; and vasomotor collapse, possibly accompanied by irregular breathing. The syndrome can cause death in a few hours. Most cases result from institution of therapy within the first 48 hours of life and symptoms generally first appear after 3 to 4 days of continued treatment with high doses. Chloramphenicol should be discontinued at the first sign of this syndrome, which may reverse the process and lead to recovery. Progression of symptoms from onset to exitus can be accelerated with higher dose schedules.
Aplastic anemia, hypoplastic anemia, thrombocytopenia, pancytopenia, and neutropenia have all occurred following short-term and long-term therapy as a result of bone marrow suppression. Bone marrow toxicity may be dose-related. Non-dose-related, irreversible bone marrow suppression can result in aplastic anemia and has a high mortality rate. This type of aplasia or hypoplasia can develop months after the drug has been discontinued, or from a single dose. Reversible bone marrow suppression usually is dose-related and is characterized by anemia, reticulocytopenia, leukopenia, or thrombocytopenia. It is believed that bone marrow toxicity is more common when peak chloramphenicol serum concentrations are equal to or exceed 25 mcg/ml. There have also been reports of aplastic anemia attributed to chloramphenicol which later terminated in leukemia. Patients should be monitored for a declining hematocrit and a rising serum iron if chloramphenicol serum concentrations are not available. Paroxysmal nocturnal hemoglobinuria has also been reported.
Optic neuritis, which can cause blindness, or peripheral neuritis can result from long-term therapy and requires immediate discontinuation of chloramphenicol. Other adverse neurotoxic effects include headache, mild depression, confusion, and delirium. Patients should be monitored for other signs of peripheral neuropathy.
GI effects occur in low incidence during therapy with chloramphenicol but can include nausea, vomiting, diarrhea, glossitis, stomatitis, and enterocolitis. Adverse GI symptoms should be reported immediately because they can indicate more severe reactions.
Maculopapular rash, vesicular rash, fever, angioedema, anaphylactoid reactions, and urticaria can occur from administration of chloramphenicol. Herxheimer reaction have been reported during therapy for typhoid fever.
Interstitial nephritis, a hypersensitivity reaction, although uncommon, has been reported in a case report with chloramphenicol therapy.
Chloramphenicol has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with fever above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2-3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, pruritus, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome.
Chloramphenicol may reduce absorption of vitamin B12 leading to vitamin B12 deficiency. Supplementation of vitamin B12 should be considered during extended therapy.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with chloramphenicol. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.
Chloramphenicol should not be given to patients who have known toxic reactions to the drug. Some fatal reactions have occurred.
Systemic chloramphenicol is contraindicated for minor infections, colds and influenza, and as prophylaxis because of the potential for toxicity. Therapeutic benefits generally do not outweigh the risks. Administration of chloramphenicol should occur in a setting where appropriate serum level and patient monitoring can be undertaken. Serum concentrations and patient response are unpredictable. All patients receiving systemic chloramphenicol should have plasma concentrations monitored.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, such as chloramphenicol, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Chloramphenicol should be used with caution in patients with bone marrow suppression. Chloramphenicol is associated with serious and fatal blood dyscrasias such as aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia. Bone marrow suppression appears to be dose-related and has occurred after short- and long-term therapy. Chloramphenicol is also associated with aplastic anemia which later terminated in leukemia. Do not use chloramphenicol when less potentially dangerous agents will be effective. The drug must not be used for trivial infections or where it is not indicated, as in colds, influenza, throat infections; or in the prophylaxis of bacterial infections. During treatment, adequate blood studies must be performed. However, blood studies may detect early peripheral blood changes (i.e., leukopenia, reticulocytopenia, or granulocytopenia) before the become irreversible but they can not be reliable in detecting bone marrow depression prior to development of aplastic anemia. It is desirable to hospitalize the patient to aid in monitoring during chloramphenicol therapy. Risk-benefit should be considered before using chloramphenicol in patients who have received cytotoxic drug therapy or radiation therapy. Prolonged or repeated use of topical chloramphenicol should be avoided because it could be absorbed systemically, resulting in marrow hypoplasia, aplastic anemia, and, possibly, death. Toxicity also has been reported after ophthalmic use.
According to the manufacturer, chloramphenicol should be given during pregnancy only if the benefit outweighs the potential risk to the fetus. Although it is not known whether chloramphenicol can cause fetal harm, there are no adequate well-controlled studies to establish safety in pregnancy. Chloramphenicol crosses the placenta readily and should be used during pregnancy with extreme caution. It should not be used during pregnancy near term or during labor because of the possibility of "gray-baby syndrome"and bone marrow suppression of the neonate.
Chloramphenicol should be administered to infants with caution. Premature infants or neonates have hepatic systems that are unable to cope with conjugation or excretion of the drug. This can cause the 'gray-baby' syndrome characterized by a failure to feed; abdominal distension, with or without vomiting; progressive pallid cyanosis; and vasomotor collapse, possibly accompanied by irregular breathing. The syndrome can result in death in a few hours. Infants and children up to 2 years of age have been affected by this syndrome, although most cases result from institution of therapy within the first 48 hours of life. The drug should be discontinued at the first signs of this syndrome, which may reverse the process and lead to recovery.
According to the manufacturer, caution is warranted with the use of chloramphenicol in breast-feeding women. Chloramphenicol is excreted into human milk after systemic administration and is known to cause serious adverse events when administered directly to neonates. The American Academy of Pediatrics (AAP) suggests that chloramphenicol may be of concern in nursing mothers due to the potential of bone marrow suppression in the infant. After single-dose therapy of 500 mg PO, breast milk concentrations ranged from 3.1-4.2 mcg/ml. Adverse events reported in infants whose mothers were being treated with chloramphenicol include refusing to nurse, falling asleep during nursing, intestinal gas, and heavy vomiting after feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Chloramphenicol should be given with caution to patients with hepatic disease, renal impairment, or to those with glucose 6-phosphate dehydrogenase deficiency (G6PD deficiency). Chloramphenicol and metabolites are mainly excreted in the urine. Some adults have suffered a gray-baby syndrome-type reaction, and those with impaired hepatic function are most at risk.
Intramuscular injections should not be administered to patients with platelet counts < 50,000/mm3 who are receiving chloramphenicol. IM injections may cause bleeding, bruising, or hematomas due to thrombocytopenia secondary to chloramphenicol-induced bone marrow suppression.
Chloramphenicol can induce porphyria in patients with a history of acute intermittent porphyria, so it should be used with caution in these patients.
Chloramphenicol should be used with caution in patients with dental disease. Chloramphenicol can cause myelosuppression and there may be an increased risk of infection. Dental work should be performed prior to initiating chloramphenicol therapy or deferred until blood counts return to normal.
The geriatric adult may be more susceptible to bone marrow suppression and the hematologic adverse effects of systemic chloramphenicol; use should be avoided whenever possible. If use is clinically necessary, hematologic parameters and chloramphenicol concentrations should be closely monitored and dosages adjusted as indicated.
Due to the risk of potentially fatal toxicity, chloramphenicol must only be used to treat serious infections for which other antibiotics are ineffective or contraindicated.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Chlamydia sp., Chlamydophila psittaci, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Rickettsia rickettsii, Rickettsia sp., Salmonella enterica serotype Typhi , Salmonella sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Francisella tularensis, Yersinia pestis
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of serious infections for which less potentially dangerous drugs are ineffective or contraindicated, including various serious gram-negative bacterial infections causing bacteremia, H. influenzae infections, cystic fibrosis, and lymphogranuloma psittacosis group infections:
Intravenous dosage:
Adults: 50 mg/kg/day IV divided every 6 hours. For infections caused by moderately resistant organisms, doses up to 100 mg/kg/day may be required. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dose based on serum concentrations.
Infants, Children, and Adolescents: 50 mg/kg/day IV divided every 6 hours. For infections caused by moderately resistant organisms, doses up to 100 mg/kg/day may be required. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dose based on serum concentrations.
Neonates 8 days and older: 25 mg/kg/dose IV every 12 to 24 hours is supported by limited data in neonates and guideline. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger and up to 50 mg/kg/day IV divided every 6 hours in neonates older than 14 days; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
Neonates 0 to 7 days: 25 mg/kg/dose IV every 24 hours is supported by limited data in neonates and guidelines. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
For the treatment of salmonella infections, including salmonellosis and typhoid fever:
-for the treatment of salmonellosis:
Intravenous dosage:
Adults: 50 to 100 mg/kg/day IV divided every 6 hours. Reduce dosage to 50 mg/kg/day IV as soon as possible. Adjust dose based on serum concentrations.
Infants, Children, and Adolescents: 50 to 100 mg/kg/day IV divided every 6 hours. Reduce dosage to 50 mg/kg/day IV as soon as possible. Adjust dose based on serum concentrations.
Neonates 8 days and older: 25 mg/kg/dose IV every 12 to 24 hours is supported by limited data in neonates and guidelines. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger and up to 50 mg/kg/day IV divided every 6 hours in neonates older than 14 days; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
Neonates 0 to 7 days: 25 mg/kg/dose IV every 24 hours is supported by limited data in neonates and guidelines. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
-for the treatment of fully sensitive severe typhoid fever:
Intravenous dosage:
Adults: 100 mg/kg/day IV divided every 6 hours for 14 to 21 days as an alternative. Usual dose: 2 to 3 g/day. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dosage based on serum concentrations.
Infants, Children, and Adolescents: 100 mg/kg/day IV divided every 6 hours for 14 to 21 days as an alternative. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dosage based on serum concentrations.
Neonates 8 days and older: 25 mg/kg/dose IV every 12 to 24 hours for 14 to 21 days as an alternative is supported by limited data in neonates and guidelines. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger and up to 50 mg/kg/day IV divided every 6 hours in neonates older than 14 days; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
Neonates 0 to 7 days: 25 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative is supported by limited data in neonates and guidelines. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
For the treatment of plague* infection:
-for the treatment of bubonic or pharyngeal plague*:
Intravenous dosage:
Adults: 12.5 to 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.
Infants, Children, and Adolescents: 12.5 to 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
Neonates 15 days and older: 12.5 mg/kg/dose IV every 6 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
Neonates 0 to 14 days: 6.25 mg/kg/dose IV every 6 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
-for the treatment of pneumonic or septicemic plague*:
Intravenous dosage:
Adults: 12.5 to 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.
Infants, Children, and Adolescents: 12.5 to 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
Neonates 15 days and older: 12.5 mg/kg/dose IV every 6 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
Neonates 0 to 14 days: 6.25 mg/kg/dose IV every 6 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
-for the treatment of plague meningitis*:
Intravenous dosage:
Adults: 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours in combination with levofloxacin or moxifloxacin for 10 to 14 days. After clinical improvement, may decrease dose to 12.5 mg/kg/dose IV every 6 hours. For patients with secondary plague meningitis, chloramphenicol should be added to the existing antimicrobial regimen and the entire regimen should be continued for an additional 10 days.
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours in combination with levofloxacin or moxifloxacin for 10 to 14 days. For patients with secondary plague meningitis, chloramphenicol should be added to the existing antimicrobial regimen and the entire regimen should be continued for an additional 10 days.
Neonates 8 days and older: 25 mg/kg/dose IV every 12 hours in combination with levofloxacin for 10 to 14 days. For patients with secondary plague meningitis, chloramphenicol should be added to the existing antimicrobial regimen and the entire regimen should be continued for an additional 10 days.
Neonates 0 to 7 days: 25 mg/kg/dose IV every 24 hours in combination with levofloxacin for 10 to 14 days. For patients with secondary plague meningitis, chloramphenicol should be added to the existing antimicrobial regimen and the entire regimen should be continued for an additional 10 days.
For the initial treatment of tularemia* infection due to exposure to Francisella tularensis in individual patients or in a contained casualty setting:
NOTE: Streptomycin is the drug of choice to treat tularemia in most patients; gentamicin is the preferred agent in pregnant women. The risk of serious infection following tularemia exposure supports the use of chloramphenicol in pregnant women if necessary.
Intravenous dosage:
Adults, Adolescents, and Children > 2 years: 15 mg/kg IV every 6 hours for 14-21 days. Switch to oral antibiotic therapy when clinically indicated. Intravenous streptomycin or gentamicin, or, if antibiotic susceptibility testing allows, the third-line agents intravenous doxycycline or ciprofloxacin could be used as alternatives.
For the treatment of anthrax*:
-for the treatment of systemic anthrax* without aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Adults: 1 g IV every 6 to 8 hours for at least 14 days; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for at least 14 days; may consider step-down to oral therapy.
-for the treatment of systemic anthrax* with aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Adults: 1 g IV every 6 to 8 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Adults: 1 g IV every 6 to 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
For the treatment of serious Rickettsial infections, including Rocky Mountain spotted fever:
Intravenous dosage:
Adults: 50 to 100 mg/kg/day IV divided every 6 hours as an alternative. Reduce dosage to 50 mg/kg/day IV as soon as possible. Adjust dose based on serum concentrations.
Infants, Children, and Adolescents: 50 to 100 mg/kg/day IV divided every 6 hours as an alternative. Reduce dosage to 50 mg/kg/day IV as soon as possible. Adjust dose based on serum concentrations.
Neonates 8 days and older: 25 mg/kg/dose IV every 12 to 24 hours as an alternative is supported by limited data in neonates and guidelines. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger and up to 50 mg/kg/day IV divided every 6 hours in neonates older than 14 days; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
Neonates 0 to 7 days: 25 mg/kg/dose IV every 24 hours as an alternative is supported by limited data in neonates and guidelines. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
For the treatment of bartonellosis*, including Oroya fever*:
Intravenous dosage:
Adults: 500 mg IV every 6 hours for 14 days plus a beta-lactam as first-line therapy. Alternatively, 50 mg/kg/day IV divided every 6 hours for 3 days, then 25 mg/kg/day IV divided every 6 hours for 11 days.
Pregnant or Breast-Feeding Persons: 500 mg IV every 6 hours for 14 days as first-line therapy. Alternatively, 1 g IV every 8 hours for 5 days, then 500 mg IV every 6 hours for 11 days, or 50 to 100 mg/kg/day IV divided every 6 hours for 14 days. Add a beta-lactam.
Infants, Children, and Adolescents: 50 to 75 mg/kg/day IV divided every 6 hours for 14 days plus a beta-lactam as first-line therapy.
For the treatment of meningitis:
-for the treatment of meningococcal meningitis as well as meningitis due to H. influenzae:
Intravenous dosage:
Adults: 50 to 100 mg/kg/day (Max: 4 g/day) IV divided every 6 hours for 7 days. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dose based on serum concentrations.
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 4 g/day) IV divided every 6 hours for 7 days. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dose based on serum concentrations.
Neonates 8 days and older: 50 mg/kg/day IV divided every 12 to 24 hours for 7 days. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger and up to 50 mg/kg/day IV divided every 6 hours in neonates older than 14 days; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
Neonates 0 to 7 days: 25 mg/kg/dose IV every 24 hours for 7 days. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
-for the treatment of pneumococcal meningitis:
Intravenous dosage:
Adults: 50 to 100 mg/kg/day (Max: 6 g/day) IV divided every 6 hours for 10 to 14 days. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dose based on serum concentrations.
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 6 g/day) IV divided every 6 hours for 10 to 14 days. Reduce dosage to 50 mg/kg/day as soon as possible. Adjust dose based on serum concentrations.
Neonates 8 days and older: 50 mg/kg/day IV divided every 12 to 24 hours for 10 to 14 days. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger and up to 50 mg/kg/day IV divided every 6 hours in neonates older than 14 days; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
Neonates 0 to 7 days: 25 mg/kg/dose IV every 24 hours for 10 to 14 days. The FDA-approved dosage is 25 mg/kg/day IV divided every 6 hours in neonates 14 days and younger; however, dosing modifications for premature neonates are not specified and the frequency specified in the product labeling is higher than what is supported in pharmacokinetic studies in neonates. Adjust dose based on serum concentrations.
Therapeutic Drug Monitoring:
Serum concentrations must be monitored in low-birth weight infants because the pharmacokinetics of chloramphenicol are highly variable in this age group. Plasma concentrations should also be monitored at least weekly, or more often in patients with renal impairment, impaired or immature hepatic function, or in patients who are receiving other hepatically metabolized drugs. For infections other than meningitis, peak concentrations should be in the range 10-20 mcg/ml and trough concentrations 5-10 mcg/ml. For meningitis, peak concentrations of 15-25 mcg/ml and trough concentrations of 5-15 mcg/ml may be desired. Peak serum concentrations should be checked 1.5 hours and 3 hours after completion of IV or PO dosing. Trough levels should be drawn 1 hour prior to the next dose and may be preferable. Additionally, complete blood counts (CBCs) may be required frequently during chloramphenicol therapy to detect dose-related reversible bone marrow depression. Chloramphenicol therapy should be discontinued if reticulocytopenia, leukopenia, thrombocytopenia, anemia, or other blood dyscrasias are detected. However, CBCs are not useful for detecting aplastic anemia which usually occurs after completion of chloramphenicol therapy.
Maximum Dosage Limits:
-Adults
100 mg/kg/day IV.
-Geriatric
100 mg/kg/day IV.
-Adolescents
100 mg/kg/day IV.
-Children
100 mg/kg/day IV.
-Infants
100 mg/kg/day IV.
-Neonates
15 days and older: 50 mg/kg/day IV.
8 to 14 days: 25 mg/kg/day IV is FDA-approved; however, doses up to 50 mg/kg/day IV have been used off-label
0 to 7 days: 25 mg/kg/day IV.
Patients with Hepatic Impairment Dosing
Chloramphenicol is metabolized by the liver. Patients with hepatic impairment or immature hepatic function may require a dosage reduction especially if there is concomitant renal impairment. However, specific dosage adjustment guidelines are not available. Serum concentrations should be monitored.
Patients with Renal Impairment Dosing
No quantitative recommendations are available; however, dosage should be modified based on clinical response, degree of renal impairment, and serum chloramphenicol concentrations.
*non-FDA-approved indication
Abemaciclib: (Major) If coadministration with chloramphenicol is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If chloramphenicol is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of chloramphenicol. Abemaciclib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and chloramphenicol; significantly increased acalabrutinib exposure may occur. If short-term chloramphenicol use is unavoidable, interrupt acalabrutinib therapy. Wait at least 24 hours after chloramphenicol has been discontinued before resuming acalabrutinib at the previous dosage. Acalabrutinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In healthy subjects, the Cmax and AUC values of acalabrutinib were increased by 3.9-fold and 5.1-fold, respectively, when acalabrutinib was coadministered with another strong inhibitor for 5 days.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with chloramphenicol may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Chloramphenicol is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like chloramphenicol can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If chloramphenicol is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. If chloramphenicol is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like chloramphenicol can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If chloramphenicol is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Moderate) Monitor for an increase in adagrasib-related adverse effects during concomitant use of chloramphenicol. Avoid concomitant use during adagrasib therapy initiation (approximately 8 days); concomitant use before steady state is achieved may increase adagrasib exposure and the risk for adagrasib-related adverse reactions. Adagrasib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use of a single 200 mg dose of adagrasib with another strong CYP3A inhibitor increased adagrasib exposure by approximately 4-fold, however, no clinically significant differences in pharmacokinetics are predicted at steady state.
Ado-Trastuzumab emtansine: (Major) Avoid coadministration of chloramphenicol with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until chloramphenicol has cleared from the circulation (approximately 3 half-lives of chloramphenicol) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; chloramphenicol is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
Alfuzosin: (Contraindicated) Alfuzosin is contraindicated for use with chloramphenicol due to the potential for serious/life-threatening reactions, including hypotension. Alfuzosin is primarily metabolized by CYP3A4 hepatic enzymes; strong inhibitors of CYP3A4, such as chloramphenicol, block the metabolism of alfuzosin and increase systemic exposure to alfuzosin. Coadministration of another strong CYP3A4 inhibitor increased the alfuzosin AUC by 2.5-fold to 3.2-fold.
Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with chloramphenicol is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and chloramphenicol should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Alprazolam: (Contraindicated) Coadministration of chloramphenicol and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with chloramphenicol, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
Amiodarone: (Major) Avoid concomitant use of amiodarone and chloramphenicol due to the risk for increased amiodarone exposure which may increase the risk for adverse effects. Amiodarone is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Amlodipine: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Atorvastatin: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Benazepril: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Celecoxib: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Olmesartan: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Valsartan: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Amobarbital: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Apalutamide: (Moderate) Monitor for an increase in apalutamide-related adverse reactions if coadministration with chloramphenicol is necessary. Consider reducing the dose of apalutamide if necessary based on tolerability in patients experiencing grade 3 or higher adverse reactions or intolerable toxicities. Apalutamide is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with one strong CYP3A4 inhibitor decreased the Cmax of single-dose apalutamide by 22% and the AUC remained similar. Concomitant use with another strong CYP3A4 inhibitor is predicted to increase the single-dose apalutamide AUC by 24% but have no effect on Cmax; the steady-state Cmax and AUC are predicted to increase by 38% and 51%, respectively, with this inhibitor. The predicted steady-state exposure of the active moieties (unbound apalutamide plus potency-adjusted unbound N-desmethyl apalutamide) is predicted to increase by 28%.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of chloramphenicol with aprepitant due to substantially increased exposure of aprepitant. If coadministration cannot be avoided, use caution and monitor for an increase in aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Chloramphenicol is a strong CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of a single oral dose of aprepitant (125 mg) on day 5 of a 10-day ketoconazole regimen (strong CYP3A4 inhibitor) increased the aprepitant AUC approximately 5-fold, and increased the mean terminal half-life by approximately 3-fold.
Aripiprazole: (Major) Recommendations for managing aripiprazole and chloramphenicol vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; chloramphenicol is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and chloramphenicol vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; chloramphenicol is a strong CYP3A inhibitor.
Artemether; Lumefantrine: (Moderate) Chloramphenicol is an inhibitor and artemether a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased artemether concentrations. Concomitant use warrants caution due to the potential for increased side effects. (Moderate) Chloramphenicol is an inhibitor and lumefantrine a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation.
Asciminib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with chloramphenicol is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. If chloramphenicol is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like chloramphenicol can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If chloramphenicol is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Moderate) Caution is warranted when atazanavir is administered with chloramphenicol as there is a potential for elevated concentrations of atazanavir. Chloramphenicol is a CYP3A4 inhibitor; atazanavir is a substrate of CYP3A4.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when atazanavir is administered with chloramphenicol as there is a potential for elevated concentrations of atazanavir. Chloramphenicol is a CYP3A4 inhibitor; atazanavir is a substrate of CYP3A4. (Moderate) Caution is warranted when cobicistat is administered with chloramphenicol as there is a potential for elevated cobicistat concentrations. Chloramphenicol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4.
Atogepant: (Major) Avoid use of atogepant and chloramphenicol when atogepant is used for chronic migraine. Limit the dose of atogepant to 10 mg PO once daily for episodic migraine if coadministered with chloramphenicol. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of CYP3A and chloramphenicol is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor resulted in a 5.5-fold increase in atogepant overall exposure and a 2.15-fold increase in atogepant peak concentration.
Avacopan: (Major) Reduce the dose of avacopan to 30 mg once daily if concomitant use of chloramphenicol is necessary. Concomitant use may increase avacopan exposure and risk for avacopan-related adverse effects. Avacopan is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased avacopan overall exposure 2.19-fold.
Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including chloramphenicol, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Avapritinib: (Major) Avoid coadministration of avapritinib with chloramphenicol due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state.
Axitinib: (Major) Avoid coadministration of axitinib with chloramphenical due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after chloramphenical is discontinued. Axitinib is a CYP3A4/5 substrate and chloramphenical is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers.
Azelastine; Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Barbiturates: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as chloramphenicol, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, chloramphenicol may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of chloramphenicol with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and chloramphenicol is a CYP2C19 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with chloramphenicol may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of chloramphenicol in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Chloramphenicol is a strong inhibitor of CYP3A4.
Betamethasone: (Moderate) Monitor for corticosteroid-related adverse effects if coadministration is necessary. Chloramphenicol is a strong CYP3A4 inhibitor and betamethasone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like chloramphenicol; the risk of peripheral neuropathy may be additive.
Bosentan: (Moderate) Chloramphenicol is a potent inhibitor of CYP3A4. Chloramphenicol may increase the risk of toxicity from CYP3A4 substrates such as bosentan. Excessive bosentan dosage can result in hypotension or elevated hepatic enzymes.
Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as chloramphenicol. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Because brexpiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a moderate to strong CYP3A4 inhibitor and moderate to strong CYP2D6 inhibitor should have their brexpiprazole dose reduced to one-quarter (25%) of the usual dose. If the co-administered CYP inhibitor is discontinued, adjust the brexpiprazole dose to its original level.
Brigatinib: (Major) Avoid coadministration of brigatinib with chloramphenicol if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of chloramphenicol, resume the brigatinib dose that was tolerated prior to initiation of chloramphenicol. Brigatinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
Bromocriptine: (Major) When bromocriptine is used for diabetes, avoid coadministration with chloramphenicol ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; chloramphenicol is a strong inhibitor of CYP3A4.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and chloramphenicol may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; chloramphenicol inhibits CYP3A4.
Buprenorphine: (Major) The plasma concentrations of CYP3A4 substrates such as buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently with strong CYP3A4 inhibitors such as chloramphenicol. During co-administration, use the lowest buprenorphine starting dose and slowly titrate to desired effect. Monitoring for adverse effects, such as CNS side effects or respiratory depression, is advisable. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buprenorphine; Naloxone: (Major) The plasma concentrations of CYP3A4 substrates such as buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently with strong CYP3A4 inhibitors such as chloramphenicol. During co-administration, use the lowest buprenorphine starting dose and slowly titrate to desired effect. Monitoring for adverse effects, such as CNS side effects or respiratory depression, is advisable. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Butalbital; Acetaminophen: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Butalbital; Acetaminophen; Caffeine: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism. (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism. (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with chloramphenicol if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and chloramphenicol is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering chloramphenicol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib and chloramphenicol due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with chloramphenicol 2 to 3 days after discontinuation of chloramphenicol. Cabozantinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Capivasertib: (Major) Avoid coadministration of capivasertib with chloramphenicol due to increased capivasertib exposure which may increase the risk for capivasertib-related adverse effects. If coadministration is necessary, reduce the dose of capivasertib to 320 mg PO twice daily for 4 days followed by 3 days off; monitor for adverse reactions. Capivasertib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor is predicted to increase the overall exposure of capivasertib by up to 1.7-fold.
Capmatinib: (Moderate) Monitor for an increase in capmatinib-related adverse reactions if coadministration with chloramphenicol is necessary. Capmatinib is a CYP3A substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%.
Carbidopa; Levodopa; Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation, or intestinal beta-glucuronidation such as chloramphenicol. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as chloramphenicol, is initiated in a patient who is on a stable dose of cariprazine, reduce the cariprazine dosage by half. For adult patients taking cariprazine 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For adult patients taking cariprazine 1.5 mg daily, the dosing frequency should be adjusted to every other day. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased. When initiating cariprazine in a patient who is stable on a strong CYP3A4 inhibitor, the patient should be administered 1.5 mg of cariprazine on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, then increased to a maximum dose of 3 mg daily. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased.
Ceritinib: (Major) Avoid concomitant use of ceritinib with chloramphenicol due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After chloramphenicol is discontinued, resume the dose of ceritinib taken prior to initiating chloramphenicol. Ceritinib is a CYP3A substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like chloramphenicol can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If chloramphenicol is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received chloramphenicol within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as chloramphenicol, may diminish vaccine efficacy and result in suboptimal immune response. A duration of fewer than 14 days between stopping antibiotics and vaccination might also be acceptable in some clinical settings if travel cannot be avoided before 14 days have elapsed after stopping antibiotics.
Cinacalcet: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of chloramphenicol and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Citalopram: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with chloramphenicol, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of chloramphenicol as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4.
Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of chloramphenicol. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and chloramphenicol is an inhibitor of CYP2C19. Extrapolation from pharmacogenomic data indicate that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
Clopidogrel: (Moderate) Monitor for reduced clopidogrel efficacy during concomitant use of chloramphenicol. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19; chloramphenicol is a CYP2C19 inhibitor.
Clozapine: (Moderate) Caution is advisable during concurrent use of chloramphenicol and clozapine. Chloramphenicol is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with a CYP3A4 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with chloramphenicol as there is a potential for elevated cobicistat concentrations. Chloramphenicol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chloramphenicol due to the risk of cobimetinib toxicity. Cobimetinib is a CYP3A substrate in vitro, and chloramphenicol is a strong inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), another strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Codeine: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of chloramphenicol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If chloramphenicol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chloramphenicol is a strong inhibitor of CYP3A4.
Colchicine: (Major) Avoid concomitant use of colchicine and chloramphenicol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Conivaptan: (Contraindicated) Coadministration of conivaptan and chloramphenicol is contraindicated due to the potential for increased conivaptan exposure. Conivaptan is a sensitive CYP3A substrate; chloramphenicol is a strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the exposure of oral conivaptan by 11-fold.
Conjugated Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Copanlisib: (Major) Avoid the concomitant use of copanlisib and chloramphenicol if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; chloramphenicol is a strong CYP3A inhibitor.
Crizotinib: (Major) Avoid concomitant use of crizotinib and chloramphenicol due to the risk for increased crizotinib exposure which may increase the risk for crizotinib-related adverse effects. If concomitant use is necessary, a crizotinib dosage reduction is required; specific dosage adjustment recommendations are dependent on age, indication, and body surface area (BSA). For adult patients with non-small cell lung cancer (NSCLC) or inflammatory myofibroblastic tumor (IMT), decrease the crizotinib dose to 250 mg once daily. For pediatric patients or young adults with anaplastic large cell lymphoma (ALCL) or IMT, BSA-based dosage adjustments are recommended; consult product labeling for specific recommendations. Crizotinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with other strong CYP3A inhibitors has been observed to increase crizotinib overall exposure by 57% to 216%.
Cyanocobalamin, Vitamin B12: (Moderate) If use together is necessary, monitor for reduced efficacy of cyanocobalamin (vitamin B12), and if needed, consider an alternative therapy. Chloramphenicol can cause bone marrow depression and inhibit red blood cell maturation, which may reduce the efficacy of vitamin B12 in the treatment of anemia.
Cyclosporine: (Moderate) Increased cyclosporine trough concentrations have been reported in patients receiving chloramphenicol increasing the risk for cyclosporine toxicity. Close monitoring of cyclosporine concentrations appears to be warranted; cyclosporine dosage adjustments may be necessary during concurrent therapy.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as chloramphenicol. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Dapagliflozin; Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and chloramphenicol are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as chloramphenicol.
Daridorexant: (Major) Avoid concomitant use of daridorexant and chloramphenicol. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased daridorexant overall exposure by over 400%.
Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg PO when administered with chloramphenicol due to increased darifenacin exposure. Darifenacin is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor.
Darunavir: (Moderate) Caution is warranted when darunavir is administered with chloramphenicol as there is a potential for elevated concentrations of darunavir. Chloramphenicol is a CYP3A4 inhibitor; darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with chloramphenicol as there is a potential for elevated cobicistat concentrations. Chloramphenicol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with chloramphenicol as there is a potential for elevated concentrations of darunavir. Chloramphenicol is a CYP3A4 inhibitor; darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with chloramphenicol as there is a potential for elevated cobicistat concentrations. Chloramphenicol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with chloramphenicol as there is a potential for elevated concentrations of darunavir. Chloramphenicol is a CYP3A4 inhibitor; darunavir is a substrate of CYP3A4.
Dasatinib: (Major) Avoid coadministration of dasatinib and chloramphenicol due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to chloramphenicol with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of chloramphenicol in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue chloramphenicol or stop dasatinib until chloramphenicol is discontinued. Allow a washout of approximately 1 week after chloramphenicol is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with chloramphenicol. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Dexamethasone: (Moderate) Monitor for steroid-related adverse reactions if coadministration of chloramphenicol with dexamethasone is necessary, due to increased dexamethasone exposure; Cushing's syndrome and adrenal suppression could potentially occur with long-term use. Consider the use of corticosteroids such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A inhibitors, especially for long-term use. Dexamethasone is primarily metabolized by CYP3A and chloramphenicol is a strong CYP3A inhibitor. Another strong CYP3A inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Dienogest; Estradiol valerate: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Dihydroergotamine: (Contraindicated) Concomitant use of ergotamine with chloramphenicol is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Docetaxel: (Major) Avoid coadministration of docetaxel with chloramphenicol if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
Dolutegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering chloramphenicol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Doravirine: (Minor) Coadministration of doravirine and chloramphenicol may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; chloramphenicol is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Coadministration of doravirine and chloramphenicol may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; chloramphenicol is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doxazosin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with chloramphenicol. Chloramphenicol is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
Doxercalciferol: (Moderate) CYP450 enzyme inhibitors, like chloramphenicol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
Doxorubicin Liposomal: (Major) Chloramphenicol is a CYP3A4 inhibitor and doxorubicin is a major CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of chloramphenicol and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) Chloramphenicol is a CYP3A4 inhibitor and doxorubicin is a major CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of chloramphenicol and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Major) Use caution if coadministration of dronabinol with chloramphenicol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Moderate) Dronedarone is metabolized by CYP3A. Chloramphenicol is an inhibitor CYP3A4. No data exist regarding the appropriate dose adjustment needed to allow safe administration of dronedarone with CYP3A4 inhibitors; therefore, use caution when coadministering dronedarone with CYP3A4 inhibitors such as chloramphenicol.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Drospirenone; Estradiol: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as chloramphenicol. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
Duvelisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with chloramphenicol. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; chloramphenicol is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as chloramphenicol.
Elacestrant: (Major) Avoid concomitant use of elacestrant and chloramphenicol due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Elagolix: (Major) Concomitant use of elagolix 200 mg twice daily and chloramphenicol for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and chloramphenicol to 6 months. Elagolix is a CYP3A substrate; chloramphenicol is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Elagolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of elagolix 200 mg twice daily and chloramphenicol for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and chloramphenicol to 6 months. Elagolix is a CYP3A substrate; chloramphenicol is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Elbasvir; Grazoprevir: (Major) Concurrent administration of elbasvir with chloramphenicol should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Chloramphenicol is a strong inhibitor of the hepatic enzyme CYP3A, while elbasvir is metabolized by CYP3A. (Major) Concurrent administration of grazoprevir with chloramphenicol should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Chloramphenicol is a strong inhibitor of the hepatic enzyme CYP3A, while grazoprevir is metabolized by CYP3A.
Eletriptan: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of chloramphenicol due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
Elexacaftor; tezacaftor; ivacaftor: (Major) If chloramphenicol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to twice a week in the morning, approximately 3 to 4 days apart (i.e., Day 1 and Day 4) when coadministered with chloramphenicol; omit the evening dose of ivacaftor. Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; chloramphenicol is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with chloramphenicol; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); chloramphenicol is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of chloramphenicol and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both chloramphenicol and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Chloramphenicol is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as chloramphenicol, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with chloramphenicol as there is a potential for elevated cobicistat concentrations. Chloramphenicol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when elvitegravir is administered with chloramphenicol as there is a potential for elevated elvitegravir concentrations. Chloramphenicol is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with chloramphenicol as there is a potential for elevated cobicistat concentrations. Chloramphenicol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when elvitegravir is administered with chloramphenicol as there is a potential for elevated elvitegravir concentrations. Chloramphenicol is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering chloramphenicol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Close clinical monitoring is advised when administering chloramphenicol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Encorafenib: (Major) Avoid concomitant use of encorafenib and chloramphenicol due to the risk for increased encorafenib exposure which may increase the risk for adverse effects. If concomitant use is necessary, an encorafenib dosage reduction is required: reduce a daily dose of 450 mg to 150 mg, reduce the daily dose to 75 mg for all other dosages. Encorafenib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased encorafenib overall exposure by 3-fold.
Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation, or intestinal beta-glucuronidation such as chloramphenicol. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Entrectinib: (Major) Avoid coadministration of entrectinib with chloramphenicol due to increased entrectinib exposure which may increase the risk for entrectinib-related adverse effects. If coadministration is necessary in adults and pediatric patients 2 years and older, reduce the dose of entrectinib (600 mg/day to 100 mg/day; 400 mg or 300 mg/day to 50 mg/day; 200 mg/day to 50 mg every other day) and limit coadministration to 14 days or less. For pediatric patients with a starting dose less than 200 mg, avoid coadministration. Entrectinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased the overall exposure of entrectinib by 6-fold.
Eplerenone: (Contraindicated) Coadministration of chloramphenicol and eplerenone is contraindicated. Chloramphenicol potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and chloramphenicol due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Ergotamine: (Contraindicated) Concomitant use of ergotamine with chloramphenicol is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Ergotamine; Caffeine: (Contraindicated) Concomitant use of ergotamine with chloramphenicol is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Erlotinib: (Major) Avoid coadministration of erlotinib with chloramphenicol if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
Escitalopram: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with chloramphenicol, a CYP2C19 and potent CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Esterified Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives.
Estradiol; Levonorgestrel: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Estradiol; Norethindrone: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Estradiol; Norgestimate: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Estradiol; Progesterone: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) Use caution if coadministration of chloramphenicol with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Chloramphenicol is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Estropipate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Eszopiclone: (Major) The total dose of eszopiclone should not exceed 2 mg when administered with chloramphenicol. Coadministration may increase eszopiclone exposure resulting in increased risk of next-day psychomotor or memory impairment and decreased ability to perform tasks requiring full mental alertness such as driving. CYP3A4 is a primary metabolic pathway for eszopiclone; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased eszopiclone exposure by 2.2-fold.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Ethotoin: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of hydantoins. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of hydantoin.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Etonogestrel: (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as chloramphenicol may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol. (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as chloramphenicol may increase the serum concentration of etonogestrel.
Etrasimod: (Major) Avoid concomitant use of etrasimod and chloramphenicol in CYP2C9 poor metabolizers due to the risk for increased etrasimod exposure which may increase the risk for adverse effects. Etrasimod is a CYP2C9 and CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Everolimus: (Major) Avoid coadministration of everolimus with chloramphenicol due to the risk of increased everolimus-related adverse reactions. If concomitant use is unavoidable in patients receiving everolimus for either kidney or liver transplant, closely monitor everolimus whole blood trough concentrations. Everolimus is a sensitive CYP3A4 substrate and P-glycoprotein (P-gp) substrate. Chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4/P-gp inhibitor increased the AUC of everolimus by 15-fold.
Fedratinib: (Major) Avoid coadministration of fedratinib with chloramphenicol as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If chloramphenicol is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. If chloramphenicol is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like chloramphenicol can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If chloramphenicol is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with chloramphenicol. Avoid use of fesoterodine and chloramphenicol in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
Fexinidazole: (Major) Avoid concomitant use of fexinidazole and chloramphenicol and monitor for decreased fexinidazole efficacy if coadministration is necessary. Concomitant use may limit conversion of fexinidazole to its active metabolites. Fexinidazole is converted to its active metabolites via CYP3A and chloramphenicol is a strong CYP3A inhibitor.
Finerenone: (Contraindicated) Concomitant use of finerenone and chloramphenicol is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as chloramphenicol, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Salmeterol: (Major) Avoid concomitant use of salmeterol with chloramphenicol. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Umeclidinium; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Folic Acid, Vitamin B9: (Minor) Concurrent use of chloramphenicol with folic acid can antagonize the hematopoietic response to folic acid. Hematologic response should be monitored in patients requiring folic acid if chloramphenicol is administered concomitantly.
Food: (Major) Advise patients to avoid cannabis use during chloramphenicol treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A substrates and chloramphenicol is a strong CYP3A inhibitor. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inhibitor increased THC, 11-OH-THC, and CBD peak exposures by 1.3-, 3-, and 1.9-fold respectively.
Formoterol; Mometasone: (Moderate) Coadministration of mometasone with chloramphenicol may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Fosamprenavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with chloramphenicol. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Fosphenytoin: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of hydantoins. Hydantoin toxicity can occur; several cases are reported in the medical literature. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of hydantoin anticonvulsants, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Fostamatinib: (Moderate) Monitor for fostamatinib toxicities that may require fostamatinib dose reduction (i.e., elevated hepatic enzymes, neutropenia, high blood pressure, severe diarrhea) if given concurrently with a strong CYP3A4 inhibitor. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R406, which may increase the risk of adverse reactions. R406 is extensively metabolized by CYP3A4; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with chloramphenicol is necessary. Gefitinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
Gilteritinib: (Major) Consider an alternative to chloramphenicol during treatment with gilteritinib. Concurrent use may increase gilteritinib exposure resulting in treatment-related adverse events. If coadministration is required, frequently monitor for gilteritinib adverse reactions. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study.
Glasdegib: (Major) Consider an alternative to chloramphenicol during treatment with glasdegib. Concurrent use may increase glasdegib exposure resulting in treatment-related adverse events including QT prolongation. If coadministration cannot be avoided, monitor for increased adverse events; more frequent ECG monitoring is recommended. Glasdegib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study.
Glimepiride: (Moderate) Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
Glipizide: (Moderate) Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
Glipizide; Metformin: (Moderate) Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
Glyburide: (Moderate) Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
Glyburide; Metformin: (Moderate) Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
Guanfacine: (Major) Chloramphenicol may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. If chloramphenicol is discontinued, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and chloramphenicol is a strong CYP3A4 inhibitor.
Haloperidol: (Moderate) Chloramphenicol is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like chloramphenicol can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If chloramphenicol is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like chloramphenicol can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If chloramphenicol is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like chloramphenicol can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If chloramphenicol is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydroxocobalamin: (Major) Chloramphenicol can antagonize the hematopoietic response to hydroxocobalamin, vitamin B12 through interference with erythrocyte maturation.
Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with chloramphenicol. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ibrutinib: (Major) Avoid concomitant use of ibrutinib and chloramphenicol; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). If short-term use of chloramphenicol is necessary (e.g., 7 days or less), interrupt ibrutinib treatment. Resume ibrutinib at the previous dose when chloramphenicol is discontinued. Ibrutinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased ibrutinib exposure by 5.7-fold to 24-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. If chloramphenicol is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like chloramphenicol can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If chloramphenicol is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Idelalisib: (Major) Coadministration of idelalisib with chloramphenicol may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with chloramphenicol is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Chloramphenicol is a strong CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with chloramphenicol. If chloramphenicol is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Iloperidone is a CYP3A4 substrate. Chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the AUC of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively.
Infigratinib: (Major) Avoid concomitant use of infigratinib and chloramphenicol. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
Irinotecan Liposomal: (Major) Avoid administration of chloramphenicol during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates; chloramphenicol is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan and SN-38.
Irinotecan: (Major) Avoid administration of chloramphenicol during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates; chloramphenicol is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan and SN-38.
Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with chloramphenicol is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) It may be necessary to adjust the dosage of chloramphenicol if given concurrently with rifampin. Rifampin may induce the metabolism of chloramphenicol; coadministration may result in decreased chloramphenicol plasma concentrations.
Isoniazid, INH; Rifampin: (Moderate) It may be necessary to adjust the dosage of chloramphenicol if given concurrently with rifampin. Rifampin may induce the metabolism of chloramphenicol; coadministration may result in decreased chloramphenicol plasma concentrations.
Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with chloramphenicol as istradefylline exposure and adverse effects may increase. Chloramphenicol is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
Ivabradine: (Contraindicated) Coadministration of ivabradine and chloramphenicol is contraindicated. Ivabradine is primarily metabolized by CYP3A4; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If chloramphenicol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with chloramphenicol due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If chloramphenicol is discontinued, wait at least 5 half-lives of chloramphenicol before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and chloramphenicol due to increased ixabepilone exposure, which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of ixabepilone to 20 mg/m2. Ixabepilone is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ixabepilone exposure by 79%.
Ketoconazole: (Major) Avoid chloramphenicol for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may increase exposure of ketoconazole and increase the risk of adverse effects. If concomitant use is necessary, monitor closely for ketoconazole-related adverse reactions; a ketoconazole dose reduction may be necessary. Ketoconazole is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Lapatinib: (Major) Avoid coadministration of lapatinib with chloramphenicol due to increased plasma concentrations of lapatinib. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily. If chloramphenicol is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold.
Larotrectinib: (Major) Avoid coadministration of larotrectinib with chloramphenicol due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If chloramphenicol is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of chloramphenicol. Larotrectinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study.
Lefamulin: (Major) Avoid coadministration of chloramphenicol with oral lefamulin due to increased lefamulin exposure; chloramphenicol may be administered with intravenous lefamulin. Lefamulin is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and chloramphenicol as concurrent use may significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Leniolisib: (Major) Avoid concomitant use of leniolisib and chloramphenicol due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Levamlodipine: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Levoketoconazole: (Major) Avoid chloramphenicol for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may increase exposure of ketoconazole and increase the risk of adverse effects. If concomitant use is necessary, monitor closely for ketoconazole-related adverse reactions; a ketoconazole dose reduction may be necessary. Ketoconazole is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Levomilnacipran: (Major) The adult dose of levomilnacipran should not exceed 80 mg/day during concurrent use of strong CYP3A4 inhibitors. Chloramphenicol is considered a strong inhibitor of CYP3A4. Levomilnacipran is partially metabolized by CYP3A4, and decreased metabolism of the drug can lead to an increased risk of adverse effects such as urinary retention.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and chloramphenicol may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; chloramphenicol inhibits CYP3A4.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and chloramphenicol may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; chloramphenicol inhibits CYP3A4.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and chloramphenicol may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; chloramphenicol inhibits CYP3A4.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and chloramphenicol is contraindicated; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of lonafarnib by 425%.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with chloramphenicol. Concurrent use may increase loperamide exposure. Loperamide is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with chloramphenicol. Concurrent use may increase loperamide exposure. Loperamide is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of chloramphenicol with lopinavir may result in elevated lopinavir plasma concentrations, and subsequent adverse events. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; lopinavir is a substrate of this enzyme. Monitor patient for lopinavir-related adverse events. (Moderate) Concurrent administration of chloramphenicol with ritonavir may result in elevated plasma concentrations of ritonavir, and subsequent adverse events. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; ritonavir is a substrate of this enzyme. Monitor patient for ritonavir-related adverse events.
Lorlatinib: (Major) Avoid coadministration of lorlatinib with chloramphenicol due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If chloramphenicol is discontinued, resume the original dose of lorlatinib after 3 half-lives of chloramphenicol. Lorlatinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%.
Lumacaftor; Ivacaftor: (Major) If chloramphenicol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Use caution with the concomitant use of lumacaftor; ivacaftor and chloramphenicol as the exposure of ivacaftor may be increased. Lumacaftor; ivacaftor dosage adjustment is not required when chloramphenicol is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking chloramphenicol, reduce the dosage of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking chloramphenicol. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Chloramphenicol is a strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Although chloramphenicol is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
Lumacaftor; Ivacaftor: (Major) Use caution with the concomitant use of lumacaftor; ivacaftor and chloramphenicol as the exposure of ivacaftor may be increased. Lumacaftor; ivacaftor dosage adjustment is not required when chloramphenicol is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking chloramphenicol, reduce the dosage of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking chloramphenicol. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Chloramphenicol is a strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Although chloramphenicol is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
Lumateperone: (Major) Reduce the dose of lumateperone to 10.5 mg once daily if concomitant use of systemic chloramphenicol is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold.
Lurasidone: (Contraindicated) Concurrent use of lurasidone with strong CYP3A4 inhibitors, such as chloramphenicol, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Increased lurasidone plasma concentrations are expected when the drug is co-administered with inhibitors of CYP3A4.
Lurbinectedin: (Major) Avoid concomitant use of lurbinectedin and chloramphenicol due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Maraviroc: (Major) Coadministration of maraviroc, a CYP3A substrate, with chloramphenicol, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; also, coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with chloramphenicol (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with chloramphenicol due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and chloramphenicol is a moderate CYP2C19 inhibitor and strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Chloramphenicol is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Metformin; Repaglinide: (Moderate) Coadministration of repaglinide and chloramphenicol may increase plasma concentrations of repaglinide; if coadministration is necessary, repaglinide dosage adjustment may be required and an increased frequency of glucose monitoring is recommended. Repaglinide is a CYP3A4 substrate and chloramphenicol is an inhibitor of CYP3A4.
Metformin; Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and chloramphenicol are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as chloramphenicol.
Methohexital: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Methotrexate: (Minor) Chloramphenicol may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Chloramphenicol may also displace methotrexate from protein binding sites leading to increased methotrexate levels.
Methylergonovine: (Major) Avoid concomitant use of methylergonovine with chloramphenicol. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and chloramphenicol due to the risk of increased midostaurin exposure which may increase the incidence and severity of adverse reactions. If concomitant use cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity, particularly during the first week of midostaurin therapy for those with systemic mastocytosis/mast cell leukemia and during the first week of each cycle for those with acute myeloid leukemia. Midostaurin is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of one strong CYP3A4 inhibitor with a single dose of midostaurin increased the exposure of midostaurin and its active metabolites CGP62221 and CGP52421 by 10.4-fold, 3.5-fold, and 1.2-fold, respectively. Coadministration of another strong CYP3A4 inhibitor with twice daily doses of midostaurin increased Day 28 trough concentrations of midostaurin, CGP62221, and CGP52421 by 2.1-fold, 1.2-fold, and 1.3-fold respectively compared with day 21 trough levels with midostaurin alone.
Mifepristone: (Major) Caution is advised when administering chloramphenicol with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with chloramphenicol should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving chloramphenicol, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with chloramphenicol is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Mifepristone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor.
Mirvetuximab Soravtansine: (Moderate) Closely monitor for mirvetuximab soravtansine-related adverse reactions if concomitant use of chloramphenicol is necessary. DM4, the cytotoxic component of mirvetuximab soravtansine, is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use may increase unconjugated DM4 exposure.
Mitapivat: (Major) Avoid coadministration of mitapivat with chloramphenicol due to increased risk of adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with other strong CYP3A inhibitors increased mitapivat overall exposure by 3.6 to 4.9-fold.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and chloramphenicol. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions such as QT prolongation. Mobocertinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Use of a strong CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 374% to 419%.
Mometasone: (Moderate) Coadministration of mometasone with chloramphenicol may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with chloramphenicol. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor.
Naloxegol: (Contraindicated) Concomitant use of naloxegol with chloramphenicol is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as chloramphenicol, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with chloramphenicol is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and chloramphenicol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Neratinib: (Major) Avoid concomitant use of chloramphenicol with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
Nevirapine: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with chloramphenicol is necessary. Nevirapine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and chloramphenicol. If therapy with chloramphenicol is necessary, interrupt nilotinib therapy if possible. Monitor patients closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in patients with resistant or intolerant Ph+ CML or to 200 mg once daily in patients with newly diagnosed Ph+ CML. If chloramphenicol is discontinued, a washout period should be allowed before adjusting the nilotinib dosage upward to the indicated dose. Nilotinib is a substrate of CYP3A4 and chloramphenicol is a strong inhibitor of CYP3A4.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of chloramphenicol with ritonavir may result in elevated plasma concentrations of ritonavir, and subsequent adverse events. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; ritonavir is a substrate of this enzyme. Monitor patient for ritonavir-related adverse events.
Nirogacestat: (Major) Avoid concomitant use of nirogacestat and chloramphenicol due to the risk for increased nirogacestat exposure which may increase the risk for nirogacestat-related adverse effects. Nirogacestat is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with other strong CYP3A inhibitors is predicted to increase nirogacestat overall exposure by 3.46- to 8.2-fold.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with chloramphenicol due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Olaparib: (Major) Avoid coadministration of olaparib with chloramphenicol due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after chloramphenicol is discontinued. Olaparib is a CYP3A substrate and chloramphenicol is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and chloramphenicol is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and chloramphenicol may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If chloramphenicol is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Olopatadine; Mometasone: (Moderate) Coadministration of mometasone with chloramphenicol may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and chloramphenicol. If concomitant use is necessary, decrease omaveloxolone dose to 50 mg once daily. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased omaveloxolone overall exposure by 4-fold.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Osilodrostat: (Major) Reduce the dose of osilodrostat by one-half during coadministration of chloramphenicol; concurrent use may increase osilodrostat exposure and the risk of osilodrostat-related adverse reactions. Osilodrostat is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. If chloramphenicol is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like chloramphenicol can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If chloramphenicol is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with chloramphenicol is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Palbociclib: (Major) Avoid coadministration of chloramphenicol with palbociclib; significantly increased palbociclib exposure may occur. If concomitant use cannot be avoided, reduce the dose of palbociclib to 75 mg PO once daily and monitor for increased adverse reactions. If chloramphenicol is discontinued, increase the palbociclib dose (after 3 to 5 half-lives of chloramphenicol) to the dose used before initiation of chloramphenicol. Palbociclib is primarily metabolized by CYP3A4 and chloramphenicol is a strong CYP3A4 inhibitor. In a drug interaction trial, coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of palbociclib by 87% and 34%, respectively.
Palovarotene: (Major) Avoid concomitant use of palovarotene and chloramphenicol due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. Palovarotene is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased palovarotene overall exposure by 3-fold.
Paricalcitol: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as chloramphenicol. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
Pazopanib: (Moderate) Pazopanib is a substrate for CYP3A4. Chloramphenicol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and chloramphenicol is required.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and chloramphenicol due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If chloramphenicol is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of chloramphenicol. Pemigatinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%.
Pentobarbital: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Perindopril; Amlodipine: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and chloramphenicol due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If chloramphenicol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of chloramphenicol. Pexidartinib is a CYP3A substrate; chloramphenicol is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Phenobarbital: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Phenytoin: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenytoin. Phenytoin toxicity can occur. Phenytoin dosage adjustments may be necessary in some patients who receive chloramphenicol concurrently; monitor for signs of phenytoin toxicity.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 10 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as chloramphenicol. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
Pimozide: (Major) Concurrent use of pimozide and chloramphenicol should be avoided. Pimozide is metabolized primarily through CYP3A4, and chloramphenicol is a potent CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Pioglitazone; Glimepiride: (Moderate) Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
Pirtobrutinib: (Major) Avoid concomitant use of pirtobrutinib and chloramphenicol due to the risk of increased pirtobrutinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pirtobrutinib dose by 50 mg. If the current pirtobrutinib dosage is 50 mg once daily, interrupt pirtobrutinib treatment for the duration of chloramphenicol use. Resume the previous dose of pirtobrutinib after chloramphenicol is discontinued for 5 half-lives. Pirtobrutinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant with another strong CYP3A inhibitor increased pirtobrutinib overall exposure by 49%.
Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of chloramphenicol due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; chloramphenicol is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Ponatinib: (Major) Avoid coadministration of ponatinib and chloramphenicol due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of chloramphenicol and consider alternative therapy. After chloramphenicol has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting chloramphenicol. Ponatinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%.
Pralsetinib: (Major) Avoid concomitant use of chloramphenicol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Primidone: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and chloramphenicol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Progesterone: (Moderate) Use caution if coadministration of chloramphenicol with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Chloramphenicol is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Quetiapine: (Major) Coadministration of chloramphenicol, a potent CYP3A4 inhibitor, with quetiapine, a CYP3A4 substrate, may result in increased exposure to quetiapine. If administration of chloramphenicol is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If chloramphenicol is discontinued, increase the quetiapine dose by 6-fold.
Quizartinib: (Major) Avoid concomitant use of chloramphenicol with quizartinib due to the risk of increased quizartinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of quizartinib to 26.5 mg for patients taking a daily dose of 53 mg, and to 17.7 mg for patients taking a daily dose of 35.4 mg or 26.5 mg; interrupt quizartinib therapy for the duration of the strong CYP3A inhibitor use for patients already taking a daily dose of 17.7 mg. Quizartinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of quizartinib by 94%.
Ramelteon: (Moderate) The AUC and Cmax of ramelteon may be increased by strong CYP3A4 inhibitors such as chloramphenicol.
Ranolazine: (Contraindicated) Ranolazine is metabolized mainly by CYP3A. According to the manufacturer, ranolazine is contraindicated in patients receiving drugs known to be strong CYP3A inhibitors. Although not specifically mentioned by the manufacturer of ranolazine, chloramphenicol is known to be a strong inhibitor of CYP3A4. Inhibition of ranolazine metabolism could lead to increased ranolazine plasma concentrations and associated QTc prolongation. Do not use ranolazine with chloramphenicol due to the potential for reduced metabolism of ranolazine and the risk of QT prolongation.
Regorafenib: (Major) Avoid coadministration of regorafenib with chloramphenicol due to increased plasma concentrations of regorafenib and decreased plasma concentrations of the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as chloramphenicol may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events. Also, anti-infectives that disrupt the normal GI flora, including chloramphenicol, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol.
Repaglinide: (Moderate) Coadministration of repaglinide and chloramphenicol may increase plasma concentrations of repaglinide; if coadministration is necessary, repaglinide dosage adjustment may be required and an increased frequency of glucose monitoring is recommended. Repaglinide is a CYP3A4 substrate and chloramphenicol is an inhibitor of CYP3A4.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with chloramphenicol due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as chloramphenicol, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ribociclib: (Major) Avoid coadministration of chloramphenicol with ribociclib if possible due to increased ribociclib exposure resulting in a risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of ribociclib to 400 mg PO once daily; monitor ECGs for QT prolongation and monitor electrolytes. If chloramphenicol is discontinued, the original dose of ribociclib may be resumed after at least 5 half-lives of chloramphenicol. Ribociclib is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner. Chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ribociclib exposure in healthy subjects by 3.2-fold.
Ribociclib; Letrozole: (Major) Avoid coadministration of chloramphenicol with ribociclib if possible due to increased ribociclib exposure resulting in a risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of ribociclib to 400 mg PO once daily; monitor ECGs for QT prolongation and monitor electrolytes. If chloramphenicol is discontinued, the original dose of ribociclib may be resumed after at least 5 half-lives of chloramphenicol. Ribociclib is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner. Chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ribociclib exposure in healthy subjects by 3.2-fold.
Rifampin: (Moderate) It may be necessary to adjust the dosage of chloramphenicol if given concurrently with rifampin. Rifampin may induce the metabolism of chloramphenicol; coadministration may result in decreased chloramphenicol plasma concentrations.
Rifapentine: (Moderate) It may be necessary to adjust the dosage of chloramphenicol if given concurrently with rifapentine. Rifapentine may induce the metabolism of chloramphenicol; coadministration may result in decreased chloramphenicol plasma concentrations.
Rilpivirine: (Moderate) Close clinical monitoring is advised when administering chloramphenicol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Rimegepant: (Major) Avoid coadministration of rimegepant with chloramphenicol; concurrent use may significantly increase rimegepant exposure. Rimegepant is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of rimegepant with another strong CYP3A4 inhibitor increased rimegepant exposure by 4-fold.
Ripretinib: (Moderate) Monitor patients more frequently for ripretinib-related adverse reactions if coadministered with chloramphenicol. Coadministration may increase the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions. Ripretinib and DP-5439 are metabolized by CYP3A4 and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ripretinib and DP-5439 exposure by 99%.
Ritonavir: (Moderate) Concurrent administration of chloramphenicol with ritonavir may result in elevated plasma concentrations of ritonavir, and subsequent adverse events. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; ritonavir is a substrate of this enzyme. Monitor patient for ritonavir-related adverse events.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and chloramphenicol may result in increases in rivaroxaban exposure and may increase bleeding risk. Chloramphenicol is an inhibitor of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Chloramphenicol is an inhibitor of CYP3A4. Concurrent administration of romidepsin with an inhibitor of CYP3A4 may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary.
Ruxolitinib: (Major) Reduce the ruxolitinib dosage when coadministered with chloramphenicol in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur. No dose adjustments are necessary for patients with graft-versus-host disease; however, monitor blood counts more frequently for toxicity and adjust ruxolitinib dosage for adverse reactions. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Avoid the use of chloramphenicol in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily; alternatively, ruxolitinib therapy may be interrupted for the duration of chloramphenicol use. Ruxolitinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Salmeterol: (Major) Avoid concomitant use of salmeterol with chloramphenicol. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Saquinavir: (Moderate) Both saquinavir boosted with ritonavir and chloramphenicol are inhibitors of CYP3A4; an isoenzyme responsible for the metabolism of saquinavir. The use of saquinavir/ritonavir with chloramphenicol may result in large increases in saquinavir plasma concentrations, which could cause adverse events such as life threatening cardiac arrhythmias (e.g., torsades de pointes [TdP]).
Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and chloramphenicol are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as chloramphenicol.
Secobarbital: (Moderate) Chloramphenicol inhibits the cytochrome P-450 enzyme system and can affect the hepatic metabolism of phenobarbital. Phenobarbital levels rise modestly. It is also possible that plasma concentrations of chloramphenicol can be reduced by concomitant use of barbiturates, agents that are known to stimulate hepatic microsomal enzymes responsible for chloramphenicol metabolism.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol. (Minor) Coadministration of segesterone and strong CYP3A4 inhibitors such as chloramphenicol may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and chloramphenicol due to the risk of increased selpercatinib exposure which may increase the risk of adverse reactions, including QT prolongation. If coadministration is unavoidable, reduce the dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily, and to 80 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If chloramphenicol is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of chloramphenicol. Selpercatinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selpercatinib exposure by 133%.
Selumetinib: (Major) Avoid coadministration of selumetinib and chloramphenicol due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If chloramphenicol is discontinued, resume the original selumetinib dose after 3 elimination half-lives of chloramphenicol. Selumetinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selumetinib exposure by 49%.
Sildenafil: (Major) Coadministration of chloramphenicol is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving chloramphenicol. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Chloramphenicol is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Silodosin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as chloramphenicol may cause significant increases in silodosin plasma concentrations.
Siponimod: (Moderate) Concomitant use of siponimod and chloramphenicol may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Major) Avoid concomitant use of sirolimus and chloramphenicol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with chloramphenicol. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Chloramphenicol is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with chloramphenicol. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Chloramphenicol is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sonidegib: (Major) Avoid concomitant use of sonidegib and chloramphenicol as increased sonidegib plasma are expected, resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. Chloramphenicol is a strong CYP3A4 inhibitor and may significantly increase the level of the CYP3A4 substrate, sonidegib. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
Sparsentan: (Major) Avoid concomitant use of sparsentan and chloramphenicol. Concomitant use may increase sparsentan exposure and the risk for sparsentan-related adverse effects. Sparsentan is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased sparsentan overall exposure by 174%.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if chloramphenicol must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. If chloramphenicol is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like chloramphenicol can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If chloramphenicol is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) The risk for developing leukopenia and/or thrombocytopenia can be increased if other bone marrow depressants are used with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include chloramphenicol. If these agents are used concomitantly, close observation of blood counts is warranted.
Sulfonylureas: (Moderate) Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
Sunitinib: (Major) Avoid coadministration of chloramphenicol with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
Suvorexant: (Major) Coadministration of suvorexant and chloramphenicol is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
Tacrolimus: (Major) Decrease tacrolimus dose and closely monitor tacrolimus serum concentrations if coadministration with chloramphenicol is necessary; additional dosage reductions may be required. Concurrent use may increase tacrolimus serum concentration and increase the risk of toxicity. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; chloramphenicol is a strong CYP3A4 inhibitor.
Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as chloramphenicol. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and chloramphenicol. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as chloramphenicol, may increase exposure to tasimelteon with the potential for adverse reactions.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with chloramphenicol as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telmisartan; Amlodipine: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as chloramphenicol, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when chloramphenicol is coadministered with amlodipine; therapeutic response should be monitored.
Temsirolimus: (Major) Avoid coadministration of chloramphenicol with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week. Allow a washout period of approximately 1 week after discontinuation of chloramphenicol before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure, but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering chloramphenicol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; chloramphenicol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
Tezacaftor; Ivacaftor: (Major) If chloramphenicol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with chloramphenicol; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); chloramphenicol is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Thiotepa: (Major) Avoid the concomitant use of thiotepa and chloramphenicol if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; chloramphenicol is a strong CYP3A4 inhibitor.
Tisotumab Vedotin: (Moderate) Monitor for tisotumab vedotin-related adverse reactions if concomitant use with chloramphenicol is necessary due to increased monomethyl auristatin E (MMAE) exposure which may increase the incidence and severity of adverse reactions. MMAE, the active component of tisotumab vedotin, is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Clinical drug interaction studies have not been conducted for tisotumab vedotin. However, coadministration of another antibody-drug conjugate that contains MMAE with a strong CYP3A inhibitor increased unconjugated MMAE exposure by 34%.
Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with chloramphenicol. In patients receiving 5 mg or less twice daily, reduce to once daily dosing; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 22 mg once daily of the extended-release (XR) formulation, switch to 11 mg XR once daily; in patients receiving 11 mg XR once daily, switch to the immediate-release formulation at a dose of 5 mg once daily. Tofacitinib exposure is increased when coadministered with chloramphenicol. Chloramphenicol is a strong CYP3A4 inhibitor; tofacitinib is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold.
Tolterodine: (Major) Reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily if coadministered with chloramphenicol. Concurrent use may increase tolterodine exposure. Chloramphenicol is a strong CYP3A4 inhibitor. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers.
Tolvaptan: (Contraindicated) The concomitant use of tolvaptan and chloramphenicol is contraindicated. Concurrent use is expected to increase tolvaptan exposure. Tolvaptan is a sensitive CYP3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
Toremifene: (Major) Avoid coadministration of chloramphenicol with toremifene if possible due to increased plasma concentrations of toremifene which may result in QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner, and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased toremifene exposure by 2.9-fold; exposure to N-demethyltoremifene was reduced by 20%.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with chloramphenicol due to the risk of increased trabectedin exposure. If short-term chloramphenicol (less than 14 days) cannot be avoided, begin administration 1 week after the trabectedin infusion and discontinue it the day prior to the next trabectedin infusion. Trabectedin is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
Trazodone: (Major) Avoid coadministration of trazodone with chloramphenicol due to the potential for increased trazodone exposure and associated adverse effects including QT prolongation. If concurrent use cannot be avoided, consider a reduced dose of trazodone based on tolerability. Trazodone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of trazodone alone.
Triamcinolone: (Moderate) Chloramphenicol may inhibit the CYP3A4 metabolism of triamcinolone, resulting in increased plasma triamcinolone concentrations and reduced serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients receiving another strong CYP3A4 inhibitor with triamcinolone, resulting in systemic corticosteroid effects including, but not limited to, Cushing syndrome and adrenal suppression. Consider the benefit-risk of concomitant use and monitor for systemic corticosteroid side effects. Consider using an alternative treatment to triamcinolone, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). In some patients, a corticosteroid dose adjustment may be needed. If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
Triazolam: (Contraindicated) Coadministration of triazolam, a primary CYP3A4 substrate, with strong CYP3A4 inhibitors, such as chloramphenicol, is contraindicated by the manufacturer of triazolam due to the risk for increased and prolonged sedation and respiratory depression. Concurrent use is expected to produce large increases in systemic exposure to triazolam, with the potential for serious adverse effects.
Ubrogepant: (Contraindicated) Coadministration of ubrogepant and chloramphenicol is contraindicated as concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor resulted in a 9.7-fold increase in the exposure of ubrogepant.
Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and chloramphenicol is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
Upadacitinib: (Major) During concomitant use of upadacitinib and chloramphenicol reduce the upadacitinib dosage to 15 mg once daily. During induction for ulcerative colitis and Crohn's disease reduce the upadacitinib dosage to 30 mg once daily. Concomitant use may increase upadacitinib exposure and risk for adverse effects. Concomitant use with another strong CYP3A inhibitor increased upadacitinib overall exposure 1.75-fold.
Valbenazine: (Major) The dose of valbenazine should be reduced to 40 mg once daily during co-administration with a strong CYP3A4 inhibitor, such as chloramphenicol. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, valbenazine concentrations may be higher in patients taking a strong CYP3A4 inhibitor and QT prolongation may become clinically significant.
Vamorolone: (Major) Decrease the vamorolone dose to 4 mg/kg once daily (max: 200 mg) and monitor for adverse effects if concomitant use with chloramphenicol is necessary. Concomitant use may increase vamorolone exposure and the risk for vamorolone-related adverse effects. Vamorolone is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased vamorolone overall exposure by 44%.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with chloramphenicol due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold.
Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and chloramphenicol; vemurafenib exposure may be increased resulting in an increased risk of adverse events, including QT prolongation. If use with chloramphenicol cannot be avoided, consider a vemurafenib dose reduction; monitor patients closely for the development of adverse events and dose reduce or discontinue therapy based on manufacturer guidance. Vemurafenib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of vemurafenib by 40%.
Venetoclax: (Major) Coadministration of chloramphenicol with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of chloramphenicol. Specific venetoclax dosage adjustments are as follows: CLL/SLL patients at steady daily dose: 100 mg/day. AML patients: 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, then 100 mg/day starting on day 4. Venetoclax is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of strong CYP3A4 inhibitors increased the venetoclax AUC by 90% to 690% in drug interaction studies.
Vilazodone: (Major) Because CYP3A4 is the primary isoenzyme involved in the metabolism of vilazodone, the manufacturer of vilazodone recommends that the daily dose not exceed 20 mg/day during concurrent use of a strong CYP3A4 inhibitor, such as chloramphenicol. The original vilazodone dose can be resumed when the CYP3A4 inhibitor is discontinued.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with chloramphenicol is necessary. Vinblastine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Vincristine Liposomal: (Major) Chloramphenicol inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vincristine: (Major) Chloramphenicol inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with chloramphenicol is necessary. Vinorelbine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Vitamin B Complex Supplements: (Moderate) If use together is necessary, monitor for reduced efficacy of cyanocobalamin (vitamin B12), and if needed, consider an alternative therapy. Chloramphenicol can cause bone marrow depression and inhibit red blood cell maturation, which may reduce the efficacy of vitamin B12 in the treatment of anemia. (Minor) Concurrent use of chloramphenicol with folic acid can antagonize the hematopoietic response to folic acid. Hematologic response should be monitored in patients requiring folic acid if chloramphenicol is administered concomitantly.
Voclosporin: (Contraindicated) Concomitant use of voclosporin and chloramphenicol is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and chloramphenicol. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with chloramphenicol, a CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with a phenicol derivative, such as chloramphenicol, is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Phenicol derivatives are strong CYP3A4 inhibitors and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zaleplon: (Moderate) Zaleplon is partially metabolized by CYP3A4, and concurrent use of strong CYP3A4 inhibitors, such as chloramphenicol, may decrease the clearance of zaleplon. Routine dosage adjustments of zaleplon are not required. Dosage adjustments should be made on an individual basis according to efficacy and tolerability.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with chloramphenicol. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of chloramphenicol, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Zolpidem: (Moderate) Consider decreasing the dose of zolpidem if coadministration with chloramphenicol is necessary. Zolpidem is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with strong CYP3A4 inhibitors increased the AUC of zolpidem by 34% to 70%.
Zuranolone: (Major) Decrease the zuranolone dose to 30 mg once daily and monitor for zuranolone-related adverse effects if concomitant use with chloramphenicol is necessary. Concomitant use may increase zuranolone exposure and the risk for zuranolone-related adverse effects. Zuranolone is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased zuranolone overall exposure by 1.62-fold.
Chloramphenicol is usually bacteriostatic but may be bactericidal in high concentrations or against more susceptible organisms such as H. influenzae and S. pneumoniae. Antibiotic activity appears to result from inhibition of protein synthesis of bacterial cells. Chloramphenicol binds to the 50 S subunit of bacterial ribosomes, which inhibits peptide bond formation. Chloramphenicol also inhibits mitochondrial protein synthesis in both bacterial and mammalian cells via its effects on the 70 S ribosome at these sites. The protein synthesis of rapidly proliferating cells may be affected, especially mammalian erythrocytes, explaining the mechanism of reversible bone marrow depression.
The susceptibility interpretive criteria for chloramphenicol are delineated by pathogen. The MICs are defined for anaerobes, Staphylococcus sp., Enterococcus sp., Enterobacterales, B. cepacia, S. maltophilia, Vibrio sp., other non-Enterobacterales, Y. pestis, Leuconostoc sp., Pediococcus sp., Bacillus sp. (excluding B. anthracis), and Aeromonas sp. as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more. The MICs are defined for Pasteurella sp. as susceptible at 2 mcg/mL or less. The MICs are defined for F. tularensis as susceptible at 8 mcg/mL or less. The MICs are defined for S. pneumoniae, Abiotrophia sp., and Granulicatella sp. as susceptible at 4 mcg/mL or less and resistant at 8 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, N. meningitidis, and M. catarrhalis as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for beta-hemolytic Streptococcus sp., Streptococcus sp. Viridans group, Aggregatibacter sp., Cardiobacterium sp., E. corrodens, and Kingella sp. as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more.
Chloramphenicol is administered intravenously. It is widely distributed throughout most body tissues and fluids, with highest concentrations in the liver and kidneys. The lowest concentrations are found in the brain and CSF, with concentrations in the CSF at about half those found in the serum without the presence of inflamed meninges. Transport across the placental barrier occurs with somewhat lower concentrations in the cord blood of newborns as compared to maternal serum concentrations. About 60% is bound to plasma proteins. The plasma half-life is approximately 4.1 hours in adults with normal renal and hepatic function. Chloramphenicol is inactivated by hepatic glucuronyl transferase. Between 8 to 12% is excreted unchanged in the urine by glomerular filtration in patients with normal renal and hepatic function, the remainder being excreted by tubular secretion, mostly as inactive metabolites. Small amounts of the drug are found in the bile and feces.
Affected cytochrome P450 isoenzymes and drug transporter: CYP2C19, CYP2D6, CYP3A4
Chloramphenicol is a potent inhibitor of CYP2C19 and CYP3A4 and also weakly inhibits CYP2D6.
-Route-Specific Pharmacokinetics
Oral Route
Free chloramphenicol is rapidly absorbed from the GI tract. A single 1 g oral dose produces peak plasma concentrations of about 11 mcg/mL within 1 to 3 hours. Peak concentrations rise with repeated administration. Serum concentrations vary after administration of chloramphenicol palmitate because hydrolysis rates in the GI tract can vary. Small amounts of chloramphenicol are excreted unchanged in the bile and feces following oral administration. NOTE: Oral formulations were removed from the US market due to safety concerns.
Intravenous Route
Serum concentrations vary after administration or intravenous chloramphenicol. These variations may result from the hydrolysis rate of the chloramphenicol sodium succinate. Average peak serum concentrations of 11.2 mcg/mL occur after the first dose (1 g every 6 hours). A cumulative effect allows peaks to rise to 18.4 mcg/mL after the fifth dose. Mean serum concentrations over a 48 hour period range from 8 to 14 mcg/mL.
Intramuscular Route
Chloramphenicol is ineffective when administered via the intramuscular route.
-Special Populations
Hepatic Impairment
Plasma concentrations are increased following IV administration of chloramphenicol sodium succinate to patients with hepatic dysfunction.
Renal Impairment
Plasma concentrations are increased following IV dosage with chloramphenicol sodium succinate to patients with renal impairment, probably due to decreased renal clearance of the succinate ester.
Pediatrics
Neonates older than 14 days, Infants, and Children
The pediatric population may experience variations in the maturity of metabolic function of the liver and kidney, resulting in high or escalating chloramphenicol serum concentrations. Carefully monitor serum drug concentrations and reduce dose if necessary.
Premature Neonates and Neonates younger than 14 days
Premature and newborn infants have immature metabolic functions which may result in high and escalating chloramphenicol serum concentrations. Dose reductions and serum drug monitoring are required.