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Drug Interactions between Chloromycetin Sodium Succinate and tacrolimus

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

chloramphenicol tacrolimus

Applies to: Chloromycetin Sodium Succinate (chloramphenicol) and tacrolimus

MONITOR CLOSELY: Chloramphenicol may significantly increase the blood concentrations and effects of tacrolimus. The proposed mechanism may include inhibition of CYP450 3A4-mediated metabolism of tacrolimus by chloramphenicol. In case reports, three adult kidney- or pancreas-transplant recipients received concomitant therapy with chloramphenicol and tacrolimus. Daily trough tacrolimus concentrations were compared with baseline tacrolimus concentrations before being coadministered with chloramphenicol. Administration of chloramphenicol increased tacrolimus trough levels to 99% above baseline on day 2, 151% on day 3, 161% on day 4, 191% on day 5, and to 207% on day 6. The increases in tacrolimus trough levels were considered by the investigators to be statistically significant. Nephrotoxicity and other adverse effects (e.g., hyperkalemia, hyperglycemia, hemolytic anemia, hemolytic uremic syndrome, neurotoxicity) in association with significantly elevated tacrolimus blood levels have been reported with concomitant use of potent CYP450 3A4 inhibitors, necessitating substantial reductions or interruptions in tacrolimus dosing.

MANAGEMENT: Frequent monitoring of tacrolimus whole blood levels should be performed during and after discontinuation of chloramphenicol therapy, and the tacrolimus dosage adjusted accordingly. Tacrolimus whole blood concentrations should be monitored within 1 to 3 days of initiating chloramphenicol. Patients should be closely monitored for the development of serious adverse effects including nephrotoxicity, malignancies, infections, diabetes, neurotoxicity (tremor, paraesthesia, encephalopathy, delirium, coma), hyperkalemia, QT prolongation, myocardial hypertrophy, and hypertension. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References (15)
  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Jensen C, Jordan M, Shapiro R, et al. (1994) "Interaction between tacrolimus and erythromycin." Lancet, 344, p. 825
  3. Osowski CL, Dix SP, Lin LS, Mullins RE, Geller RB, Wingard JR (1996) "Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients." Transplantation, 61, p. 1268-72
  4. Floren LC, Bekersky I, Benet LZ, et al. (1997) "Tacrolimus oral bioavailability doubles with coadministration of ketoconazole." Clin Pharmacol Ther, 62, p. 41-9
  5. Schulman SL, Shaw LM, Jabs K, Leonard MB, Brayman KL (1998) "Interaction between tacrolimus and chloramphenicol in a renal transplant recipient." Transplantation, 65, p. 1397-8
  6. Billaud EM, Guillemain R, Tacco F, Chevalier P (1998) "Evidence for a pharmacokinetic interaction between itraconazole and tacrolimus in organ transplant patients." Br J Clin Pharmacol, 46, p. 271-4
  7. Gomez G, Alvarez ML, Errasti P, Lavilla FJ, Garcia N, Ballester B, Garcia I, Purroy A (1999) "Acute tacrolimus nephrotoxicity in renal transplant patients treated with clarithromycin." Transplant Proc, 31, p. 2250-1
  8. Moreno M, Latorre A, Manzanares C, et al. (1999) "Clinical management of tacrolimus drug interactions in renal transplant patients." Transplant Proc, 31, p. 2252-3
  9. Taber DJ, Dupuis RE, Hollar KD, Strzalka AL, Johnson MW (2000) "Drug-drug interaction between chloramphenicol and tacrolimus in a liver transplant recipient." Transplant Proc, 32, p. 660-2
  10. Venkataramanan R, Zang S, Gayowski T, Singh N (2002) "Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant recipient and in human liver microsomes." Antimicrob Agents Chemother, 46, p. 3091-3
  11. Ibrahim RB, Abella EM, Chandrasekar PH (2002) "Tacrolimus-clarithromycin interaction in a patient receiving bone marrow transplantation." Ann Pharmacother, 36, p. 1971-1972
  12. Soltero L, Carbajal H, Rodriguez-Montalvo C, Valdes A (2003) "Coadministration of tacrolimus and ketoconazole in renal transplant recipients: cost analysis and review of metabolic effects." Transplant Proc, 35, p. 1319-21
  13. Kunicki PK, Sobieszczanska-Malek M (2005) "Pharmacokinetic interaction between tacrolimus and clarithromycin in a heart transplant patient." Ther Drug Monit, 27, p. 107-108
  14. (2023) "Product Information. Chloramphenicol (chloramphenicol)." Eramol (UK) Ltd
  15. Mathis AS, shah n, Knipp GT, Friedman GS (2002) "Interaction of chloramphenicol and the calcineurin inhibitors in renal transplant recipients" National Library of Medicine, 4, p. 169-174

Drug and food interactions

Moderate

tacrolimus food

Applies to: tacrolimus

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

References (2)
  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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