Drug-drug interaction of chloramphenicol

Chloramphenicol is a potent inhibitor of the cytochrome P450 isoforms CYP2C19 and CYP3A4 in the liver. Inhibition of CYP2C19 causes decreased metabolism and therefore increased levels of, for example, antidepressants, antiepileptics, proton pump inhibitors, and anticoagulants if they are given concomitantly. Inhibition of CYP3A4 causes increased levels of, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, azole antifungals, tricyclic antidepressants, macrolide antibiotics, SSRIs, statins, cardiac antiarrhythmics, antivirals, anticoagulants, and PDE5 inhibitors.

Tolbutamide, Diphenylhydantoin, and Dicoumarol:

Chloramphenicol has been shown to retard the biotransformation of tolbutamide, diphenylhydantoin, and dicoumarol in man leading to rise in the concentration of them in blood.

Phenytoin and phenobarbital:

Chloramphenicol reduce metabolic biotransformation of them leading to rise the concentration of them in blood. A reduction in dose of both phenytoin and phenobarbital was required to minimize adverse effects during the course of chloramphenicol therapy.

Chloramphenicol Disease Interactions

1. Bone Marrow Depression/Low Blood Counts:

Therapy with chloramphenicol should be administered cautiously, in patients with preexisting blood dyscrasias and/or bone marrow depression because Chloramphenicol may cause bone marrow depression and other hematologic toxicities, which can be irreversible or reversible. Bone marrow aplasia or hypoplasia may occur after a single dose but more often develops weeks or months after the drug has been discontinued. Complete blood counts and differential reticulocyte counts should be performed in all patients prior to initiating therapy and approximately every 2 days during therapy. Marked depression of blood counts and/or development of other hematologic abnormalities may be indication for withdrawal of chloramphenicol therapy.

2. Liver Disease, Renal Dysfunction:

Therapy with chloramphenicol should be administered cautiously in patients with significantly impaired renal and/or hepatic function, since drug accumulation may occur in such patients because Chloramphenicol is primarily inactivated by glucuronyl transferase in the liver and eliminated in the urine as both parent drug and metabolites.

The dosage should be reduced based on the degree of impairment as well as plasma drug concentrations.

3. Colitis/Enteritis (Noninfectious):

Therapy with broad-spectrum antibiotics and other agents with significant antibacterial activity should be administered cautiously in patients with a history of gastrointestinal diseases, particularly colitis because Antibiotic therapy can alter the normal flora of the colon and permit overgrowth of Clostridium difficile, whose toxin is believed to be a primary cause of antibiotic-associated colitis.

N.B:

PREGNANCY: There are no adequate studies done on chloramphenicol to determine safe and effective use in pregnant women.

NURSING MOTHERS: Chloramphenicol enters breast milk. Therefore, it should not be used in nursing mothers.