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Drug Interactions between Prograf and telithromycin

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

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Interactions between your drugs

Major

tacrolimus telithromycin

Applies to: Prograf (tacrolimus) and telithromycin

ADJUST DOSE: Coadministration with certain macrolide or ketolide antibiotics may significantly increase the oral bioavailability of tacrolimus. The proposed mechanism is inhibition of tacrolimus metabolism via intestinal CYP450 3A4. Inhibition of P-glycoprotein (P-gp) efflux transporter in gut wall may also contribute. There have been case reports of nephrotoxicity and other adverse effects (e.g., hyperkalemia, hyperglycemia, hemolytic anemia, hemolytic uremic syndrome, neurotoxicity) in association with significantly elevated tacrolimus blood levels within days following the addition of clarithromycin or erythromycin, which necessitated either a dosing adjustment or interruption of tacrolimus and/or discontinuation of the macrolide. Greater than 10-fold increases in tacrolimus blood levels have been observed in some cases. These reports are consistent with data derived from pharmacokinetic studies involving tacrolimus and other potent CYP450 3A4 inhibitors such as azole antifungal agents. Although data are not available for telithromycin, it is expected to interact similarly with tacrolimus due to its status as a potent CYP450 3A4/P-gp inhibitor.

MONITOR CLOSELY: Tacrolimus can cause concentration-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval such as macrolide and ketolide antibiotics may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is advised when tacrolimus is used with macrolide or ketolide antibiotics that significantly inhibit CYP450 3A4 such as clarithromycin, erythromycin, josamycin, and telithromycin. A preemptive dosage reduction for tacrolimus may be appropriate in some cases. Frequent monitoring of tacrolimus whole blood levels should be performed during and after discontinuation of macrolide antibiotic therapy, and the tacrolimus dosage adjusted accordingly. In addition, patients should be closely monitored for development of serious adverse effects such as nephrotoxicity, lymphoma and other 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

  1. (2002) "Product Information. Biaxin (clarithromycin)." Abbott Pharmaceutical
  2. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  3. Cakaloglu Y, Tredger JM, Devlin J, Williams R (1994) "Importance of cytochrome p-450IIIA activity in determining dosage and blood levels of FK 506 and cyclosporine in liver transplant recipients." Hepatology, 20, p. 309-16
  4. Jensen C, Jordan M, Shapiro R, et al. (1994) "Interaction between tacrolimus and erythromycin." Lancet, 344, p. 825
  5. Wolter K, Wagner K, Philipp T, Fritschka E (1994) "Interaction between FK 506 and clarithromycin in a renal transplant patient." Eur J Clin Pharmacol, 47, p. 207-8
  6. Furlan V, Perello L, Jacquemin E, Debray D, Taburet AM (1995) "Interactions between FK506 and rifampin or erythromycin in pediatric liver recipients." Transplantation, 59, p. 1217-8
  7. Shaeffer MS, Collier D, Sorrell MF (1994) "Interaction between FK506 and erythromycin." Ann Pharmacother, 28, p. 280-1
  8. 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
  9. 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
  10. Pea F, Furlanut M (2001) "Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions." Clin Pharmacokinet, 40, p. 833-868
  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. (2004) "Product Information. Ketek (telithromycin)." Aventis Pharmaceuticals
  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. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  15. Parissis H, Gould K, Dark J (2010) "Dangerous drug interactions leading to hemolytic uremic syndrome following lung transplantation." J Cardiothorac Surg, 5, p. 70
  16. Homma S, Takahashi KI, Nihei S, Kato F, Sugihara S, Nunoda S (2014) "The successful management of respiratory complications with long-term, low-dose macrolide administration in pediatric heart transplant recipients." Int Heart J
  17. Katari SR, Magnone M, Shapiro R, et al. (1997) "Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients." Clin Transplant, 11, p. 237-42
View all 17 references

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Drug and food interactions

Moderate

tacrolimus food

Applies to: Prograf (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

  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

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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.

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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.

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