Tacrolimus Chloramphenicol

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

ANTIARRHYTHMICS - disopyramide, propafenone 2. ANTIBIOTICS-chloramphenicol, doxycycline, metronidazole, rifampicin, telithromycin 3. ANTICANCER AND IMMUNOMODULATING DRUGS - carmustine, cidosporin, corticosteroids, doxorubicin, etoposide, ima-tinib, lomustine, paditaxel, tacrolimus, tamoxifen, toremifene, vinca alkaloids 4. ANTICOAGULANTS - ORAL 5. ANTI-... 

TACROLIMUS CHLORAMPHENICOL Toxic blood levels of tacrolimus, usually on the second day of starting chloramphenicol Attributed to impaired clearance of tacrolimus by chloramphenicol. Dose i of nearly 80% of tacrolimus may be required to prevent toxicity. Watch for adverse effects. Monitor tacrolimus plasma concentrations... 

Inhibition of tacrolimus clearance has been observed in an adolescent renal transplant recipient who was treated with standard doses of chloramphenicol for vancomycin-resistant enterococci. Toxic concentrations of tacrolimus were observed on the second day of chloramphenicol treatment, requiring an 83% reduction in the dose of tacrolimus (81). 

A 47-year-old white man with a cadaveric liver transplant took chloramphenicol for a urinary tract infection due to a vancomycin-resistant Enterococcus and inadvertently received 1850 mg qds (roughly twice the maximum recommended dose). On day 4 he had a 12-hour trough tacrolimus concentration of over 60 ng/ml. 

Schulman SL, Shaw LM, Jabs K, Leonard MB, Brayman KL. Interaction between tacrolimus and chloramphenicol in a renal transplant recipient. Transplantation 1998 65(10) 1397-8. 

A marked rise in tacrolimus trough blood levels has been reported in several patients who were given systemic chloramphenicol. 

A retrospective study identified 3 patients taking tacrolimus who had received a total of 5 courses of intravenous chloramphenicol, each lasting for at least 12 days. Tacrolimus trough blood levels were doubled by day 2, and had risen by 207% at their peak, on day 6. The tacrolimus dose had been decreased by about one-third by day 12, and the tacrolimus levels returned to around the baseline value. ... 

Chloramphenicol (a known enzyme inhibitor) is thought to raise tacrolimus levels by rapidly reducing its metabolism. ... 

These appear to be the only reports of this interaction, but it is consistent with the known metabolic characteristics of both drugs and therefore it is expected to be an interaction of general importance. Monitor the outcome closely if systemic chloramphenicol is given to any patient taking tacrolimus, being alert for the need to reduce the tacrolimus dosage. It seems... 

Taber DJ, Dupuis RE, Hollar KD, Sttzalka AL, Johnson MW. Drug-drug interaction between chloramphenicol and tacrolimus in a liver transplant recipient. Trans ant Proc (2000) 32, 660-62. 

Bakri R, Breen C, Maclean D, Taylor J, Goldsmith D. Serious interaction between tacrolimus FK506 and chloramphenicol in a kidney-pancreas transplant recipient. Transpl Int (2003) 16, 441-3. 

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