Tacrograf Drug Interactions

Metabolism/transport effects: Substrate of CYP3A4 (major), P-glycoprotein; Note: Assignment of major/minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein.
QT Prolongation: An additive effect with other drugs that prolong the QT interval cannot be excluded. The following drugs are examples of agents that may prolong the QT interval and increase the risk of life-threatening cardiac arrhythmias, including torsades de pointes: antiarrhythmic agents (e.g., disopyramide, dofetilide, procainamide, quinidine, sotalol), arsenic trioxide, chlorpromazine, cisapride, citalopram, clarithromycin, dolasetron, droperidol, erythromycin, fluoxetine, levofloxacin, mesoridazine, moxifloxacin, pentamidine, pimozide, thioridazine, and ziprasidone. Unless contraindicated, coadminister these agents with caution.
Afatinib: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of afatinib.
Management: Per US labeling: reduce afatinib by 10 mg if not tolerated.
Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification.
Alcohol (ethyl): Alcohol (ethyl) may increase the absorption of tacrolimus (systemic). Consider therapy modification.
Antidepressants (serotonin reuptake inhibitor/antagonist (SARI)): Antidepressants (serotonin reuptake inhibitor/antagonist) may decrease the metabolism of tacrolimus (systemic).
Exceptions: trazodone. Consider therapy modification.
Antidiabetic agents: Hyperglycemia-associated agents may diminish the therapeutic effect of antidiabetic agents. Monitor therapy.
Aprepitant: Aprepitant may increase the serum concentration of CYP3A4 substrates. Monitor therapy.
Azithromycin (systemic): Azithromycin (systemic) may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Bacillus Calmette-Guérin (BCG) (intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (intravesical). Myelosuppressive agents may diminish the therapeutic effect of BCG (intravesical). Avoid combination.
Boceprevir: Boceprevir may increase the serum concentration of tacrolimus (systemic).
Management: Tacrolimus doses will need to be substantially reduced, and the tacrolimus dosing interval will likely need to be prolonged with concurrent boceprevir. Follow tacrolimus concentrations closely and monitor patients for evidence of tacrolimus toxicity. Consider therapy modification.
Bosentan: Bosentan may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Bosutinib: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of bosutinib. Avoid combination.
Brentuximab vedotin: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy.
Calcium channel blockers (dihydropyridine): Calcium channel blockers (dihydropyridine) may increase the serum concentration of tacrolimus (systemic).
Exceptions: clevidipine. Monitor therapy.
Calcium channel calcium blockers (non-dihydropyridine): Calcium channel blockers (non-dihydropyridine) may decrease the metabolism of tacrolimus (systemic).
Exceptions: bepridil. Monitor therapy.
Caspofungin: Caspofungin may decrease the serum concentration of tacrolimus (systemic).
Monitor therapy.
Chloramphenicol: Chloramphenicol may increase the serum concentration of tacrolimus (systemic).
Management: Tacrolimus dose reductions will likely be required with initiation of concurrent chloramphenicol. Monitor tacrolimus concentrations and response closely following initiation and/or discontinuation of chloramphenicol. Consider therapy modification.
Cinacalcet: Cinacalcet may decrease the serum concentration of tacrolimus (systemic). Monitor therapy.
Clotrimazole (oral): Clotrimazole (oral) may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Clotrimazole (topical): Clotrimazole (topical) may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Clozapine: Myelosuppressive agents may enhance the adverse/toxic effect of clozapine. Specifically, the risk for neutropenia may be increased. Monitor therapy.
Coccidioides immitis skin test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis skin test. Monitor therapy.
Colchicine: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased.
Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification.
Conivaptan: Conivaptan may increase the serum concentration of CYP3A4 Substrates. Avoid combination.
Crizotinib: Crizotinib may increase the serum concentration of tacrolimus (systemic). Avoid combination.
Cyclosporine (systemic): Tacrolimus (systemic) may enhance the nephrotoxic effect of cyclosporine (systemic). Cyclosporine (systemic) may enhance the nephrotoxic effect of tacrolimus (systemic). Tacrolimus (systemic) may increase the serum concentration of cyclosporine (systemic). Cyclosporine (systemic) may increase the serum concentration of tacrolimus (systemic). Avoid combination.
CYP3A4 inducers (moderate): CYP3A4 Inducers (moderate) may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
CYP3A4 inducers (strong): CYP3A4 inducers (strong) may increase the metabolism of CYP3A4 substrates.
Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consider therapy modification.
CYP3A4 inhibitors (moderate): CYP3A4 inhibitors (moderate) may decrease the metabolism of CYP3A4 substrates. Monitor therapy.
CYP3A4 inhibitors (strong): CYP3A4 inhibitors (strong) may increase the serum concentration of tacrolimus (systemic).
Management: Monitor clinical tacrolimus response closely and frequently monitor tacrolimus serum concentrations with concurrent use of any strong CYP3A4 inhibitor. Tacrolimus dose reductions and/or prolongation of the dosing interval will likely be required. Consider therapy modification.
Dabigatran etexilate: P-glycoprotein/ABCB1 inhibitors may increase serum concentrations of the active metabolite(s) of dabigatran etexilate.
Management: Dabigatran dose reductions may be needed. Specific recommendations vary. Refer to full monograph or dabigatran labeling. Consider therapy modification.
Dabrafenib: Dabrafenib may decrease the serum concentration of CYP3A4 substrates.
Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification.
Danazol: Danazol may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Dasatinib: Dasatinib may increase the serum concentration of CYP3A4 substrates. Monitor therapy.
Deferasirox: Deferasirox may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Deferiprone: Myelosuppressive agents may enhance the neutropenic effect of deferiprone. Avoid combination.
Denosumab: Denosumab may enhance the adverse/toxic effect of immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy.
Dipyrone: Dipyrone may enhance the adverse/toxic effect of myelosuppressive agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased. Avoid combination.
Doxorubicin (conventional): P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of doxorubicin (conventional).
Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification.
Dronedarone: Tacrolimus (systemic) may enhance the QTc-prolonging effect of dronedarone. Dronedarone may increase the serum concentration of tacrolimus (systemic).
Management: Monitor for increased serum tacrolimus concentrations, tacrolimus toxicity, and QTc interval prolongation if combined with dronedarone. Tacrolimus dose adjustments may be needed.
Consider therapy modification.
Echinacea: Echinacea may diminish the therapeutic effect of immunosuppressants. Consider therapy modification.
Edoxaban: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of edoxaban.
Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification.
Efavirenz: Efavirenz may decrease the serum concentration of tacrolimus (systemic).
Management: Closely monitor tacrolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of tacrolimus may be required. Consider therapy modification.
Efonidipine: Efonidipine may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Enzalutamide: Enzalutamide may decrease the serum concentration of tacrolimus (systemic). Avoid combination.
Eplerenone: Eplerenone may enhance the hyperkalemic effect of tacrolimus (systemic). Avoid combination.
Ertapenem: Ertapenem may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Erythromycin (systemic): Erythromycin (systemic) may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Everolimus: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of everolimus.
Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification.
Fenofibrate and derivatives: Tacrolimus (systemic) may enhance the nephrotoxic effect of fenofibrate and derivatives. Monitor therapy.
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of fingolimod.
Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (e.g., infections). Consider therapy modification.
Fluconazole: Fluconazole may increase the serum concentration of tacrolimus (systemic).
Management: Monitor tacrolimus concentrations closely and adjust oral tacrolimus dose as necessary when concomitantly administered with fluconazole. Reduced doses of tacrolimus will likely be required. Consider therapy modification.
Fosaprepitant: Fosaprepitant may increase the serum concentration of CYP3A4 substrates. Monitor therapy.
Foscarnet: Foscarnet may enhance the nephrotoxic effect of tacrolimus (systemic). Avoid combination.
Fosphenytoin: Fosphenytoin may decrease the serum concentration of tacrolimus (systemic). Tacrolimus (systemic) may increase the serum concentration of fosphenytoin. Monitor therapy.
Fusidic acid (systemic): Fusidic acid (systemic) may increase the serum concentration of CYP3A4 substrates. Avoid combination.
Grapefruit juice: Grapefruit juice may decrease the metabolism of tacrolimus (systemic). Avoid combination.
Grazoprevir: Grazoprevir may increase the serum concentration of tacrolimus (systemic).
Monitor therapy.
Highest risk QTc-prolonging agents: QTc-prolonging agents (indeterminate risk and risk modifying) may enhance the QTc-prolonging effect of highest risk QTc-prolonging agents.
Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification.
Idelalisib: Idelalisib may increase the serum concentration of CYP3A4 substrates. Avoid combination.
Itraconazole: ltraconazole may increase the serum concentration of tacrolimus (systemic).
Management: Monitor tacrolimus concentrations closely and adjust dose as necessary when concomitantly administered with itraconazole. Tacrolimus dose reductions will likely be required. The magnitude of this interaction may be greater in older patients. Consider therapy modification
Ivacaftor: Ivacaftor may increase the serum concentration of CYP3A4 substrates. Monitor therapy.
Ketoconazole (systemic): Ketoconazole (systemic) may increase the serum concentration of tacrolimus (systemic).
Management: Tacrolimus dose adjustment may be required when taken with ketoconazole due to elevated plasma concentrations of tacrolimus. Monitor tacrolimus concentrations and clinical response closely. Consider therapy modification.
Ledipasvir: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of ledipasvir. Monitor therapy.
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification.
Levofloxacin (systemic): Levofloxacin (systemic) may enhance the QTc-prolonging effect of tacrolimus (systemic). Levofloxacin (systemic) may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Luliconazole: Luliconazole may increase the serum concentration of CYP3A4 substrates. Monitor therapy.
Mifepristone: Mifepristone may enhance the QTc-prolonging effect of tacrolimus (systemic). Mifepristone may increase the serum concentration of tacrolimus (systemic).
Management: Avoid tacrolimus during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. Avoid combination.
Mitotane: Mitotane may decrease the serum concentration of CYP3A4 substrates.
Management: Doses of CYP3AA substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification.
Moderate risk QTc-prolonging agents: QTc-prolonging agents (indeterminate risk and risk modifying) may enhance the QTc prolonging effect of moderate risk QTc-prolonging agents. Monitor therapy.
Naloxegol: P-glycoprotein/ABCB 1 inhibitors may increase the serum concentration of naloxegol. Monitor therapy.
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination.
Nelfinavir: Nelfinavir may increase the serum concentration of tacrolimus (systemic). Avoid combination.
Netupitant: Netupitant may increase the serum concentration of CYP3A4 substrates. Monitor therapy.
Nivolumab: Immunosuppressants may diminish the therapeutic effect of nivolumab. Consider therapy modification.
Nonsteroidal anti-inflammatory agents (NSAIDs): Nonsteroidal anti-inflammatory agents (NSAIDs) may enhance the nephrotoxic effect of tacrolimus (systemic). Monitor therapy.
Ombitasvir, paritaprevir, and ritonavir: Ombitasvir, paritaprevir, and ritonavir may increase the serum concentration of tacrolimus (systemic).
Management: Do not administer tacrolimus on the day the ombitasvir/paritaprevir/ritonavir product is initiated. Beginning the day after initiation, restart tacrolimus at a reduced dose. Typical tacrolimus dose is 0.5 mg every 7 days. Consider therapy modification.
Ombitasvir, paritaprevir, ritonavir, and dasabuvir: Ombitasvir, paritaprevir, ritonavir, and dasabuvir may increase the serum concentration of tacrolimus (systemic).
Management: Do not administer tacrolimus on the day the ombitasvir/paritaprevir/ritonavir/dasabuvir product is initiated. Beginning the day after initiation, restart tacrolimus at a reduced dose. Typical tacrolimus dose is 0.5 mg every 7 days. Consider therapy modification.
Osimertinib: Osimertinib may increase the serum concentration of CYP3A4 substrates. Osimertinib may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Palbociclib: Palbociclib may increase the serum concentration of CYP3A4 substrates. Monitor therapy.
Pazopanib: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of pazopanib. Avoid combination.
P-glycoprotein/ABCB1 inducers: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of P-glycoprotein/ABCB1 substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy.
P-glycoprotein/ABCB1 inhibitors: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy.
P-glycoprotein/ABCB1 substrates: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy.
Phenytoin: Phenytoin may decrease the serum concentration of tacrolimus (systemic). Tacrolimus (systemic) may increase the serum concentration of phenytoin. Monitor therapy.
Pimecrolimus: Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants. Avoid combination.
Posaconazole: Posaconazole may increase the serum concentration of tacrolimus (systemic).
Management: Reduce tacrolimus dose to approximately one third of original dose when starting posaconazole. Tacrolimus blood concentrations should be monitored closely during and at discontinuation of posaconazole. Consider therapy modification.
Potassium-sparing diuretics: Potassium-sparing diuretics may enhance the hyperkalemic effect of tacrolimus (systemic). Avoid combination.
Protease inhibitors (Pls): Protease inhibitors may decrease the metabolism of tacrolimus (systemic). Consider therapy modification.
Proton pump inhibitors (PPIs): Proton pump inhibitors may increase the serum concentration of tacrolimus (systemic).
Management: Tacrolimus dose adjustment may be required. Rabeprazole, pantoprazole, or selected H₂-receptor antagonists (i.e., ranitidine or famotidine) may be less likely to interact. Genetic testing may predict patients at highest risk.
Exceptions: Pantoprazole. Consider therapy modification.
Prucalopride: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of prucalopride. Monitor therapy.
Ranolazine: Ranolazine may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Rifamycin derivatives: Rifamycin derivatives may decrease the serum concentration of tacrolimus (systemic).
Management: Consider alternatives when possible. If these combination are used, monitor for reduced tacrolimus concentrations/effects following rifamycin initiation/dose increase, or increased concentrations/effects following rifamycin discontinuation/dose decrease. Consider therapy modification.
Rifaximin: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of rifaximin. Monitor therapy.
Ritonavir: Ritonavir may increase the serum concentration of tacrolimus (systemic).
Management: Tacrolimus dose reductions may be needed with concurrent ritonavir. Monitor tacrolimus concentrations closely to determine dose; doses of tacrolimus 0.5 mg to 1 mg every week may be adequate. Consider therapy modification.
Roflumilast: Roflumilast may enhance the immunosuppressive effect of immunosuppressants. Consider therapy modification.
Schisandra: Schisandra may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Sevelamer: Sevelamer may decrease the serum concentration of tacrolimus (systemic). Monitor therapy.
Silodosin: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of silodosin. Avoid combination.
Siltuximab: Siltuximab may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of sipuleucel-T. Monitor therapy.
Sirolimus: Tacrolimus (systemic) may enhance the adverse/toxic effect of sirolimus. Sirolimus may enhance the adverse/toxic effect of tacrolimus (systemic). Sirolimus may decrease the serum concentration of tacrolimus (systemic). Avoid combination.
St John's Wort: St John's Wort may decrease the serum concentration of tacrolimus (systemic). Consider therapy modification.
Stiripentol: Stiripentol may increase the serum concentration of CYP3A4 substrates.
Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity.
Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification.
Tacrolimus (topical): Tacrolimus (topical) may enhance the adverse/toxic effect of immunosuppressants. Avoid combination.
Telaprevir: Telaprevir may increase the serum concentration of tacrolimus (systemic).
Management: Significant tacrolimus dose reductions are likely to be required if used with telaprevir. Concurrent use should be performed with great caution and close monitoring of both tacrolimus concentrations and clinical response. Consider therapy modification.
Temsirolimus: Tacrolimus (systemic) may enhance the adverse/toxic effect of temsirolimus. Temsirolimus may enhance the adverse/toxic effect of tacrolimus (systemic). Temsirolimus may decrease the serum concentration of tacrolimus (systemic). Avoid combination.
Tocilizumab: Tocilizumab may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of tofacitinib.
Management: Concurrent use with antirheumatic doses of methotrexate or non-biologic disease modifying antirheumatic drugs (DMARDSs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination.
Tofisopam: Tofisopam may increase the serum concentration of tacrolimus (systemic). Monitor therapy.
Topotecan: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of topotecan. Avoid combination.
Trastuzumab: Trastuzumab may enhance the neutropenic effect of immunosuppressants. Monitor therapy.
Vaccines (inactivated): Immunosuppressants may diminish the therapeutic effect of vaccines (inactivated).
Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification.
Vaccines (live): Immunosuppressants may enhance the adverse/toxic effect of vaccines (live).
Immunosuppressants may diminish the therapeutic effect of vaccines (live).
Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination.
Venetoclax: P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of venetoclax.
Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification.
Vincristine (liposomal): P-glycoprotein/ABCB1 inhibitors may increase the serum concentration of vincristine (liposomal). Avoid combination.
Voriconazole: Voriconazole may increase the serum concentration of tacrolimus (systemic).
Management: When starting voriconazole in patients already receiving tacrolimus, reduce tacrolimus dose to one-third of the original dose. Monitor tacrolimus blood levels closely. Consider therapy modification.
Drug/Food interactions: Food decreases rate and extent of absorption. High-fat meals have most pronounced effect (37% decrease in AUC and 77% decrease in maximum serum concentration (C_max)). Grapefruit juice, a CYP3A4 inhibitor, may increase serum level and/or toxicity of tacrolimus.
Management: Administer with or without food, but be consistent. Avoid concurrent use of grapefruit juice.