indication

For use after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It was first approved by the FDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, and limb transplants. It has also been used in a topical preparation in the treatment of severe atopic dermatitis.

pharmacology

Tacrolimus is a macrolide antibiotic. It acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription. Although this activity is similar to cyclosporine studies have shown that the incidence of acute rejection is reduced by tacrolimus use over cyclosporine. Tacrolimus has also been shown to be effective in the topical treatment of eczema, particularly atopic eczema. It suppresses inflammation in a similar way to steroids, but is not as powerful. An important dermatological advantage of tacrolimus is that it can be used directly on the face; topical steroids cannot be used on the face, as they thin the skin dramatically there. On other parts of the body, topical steroid are generally a better treatment.

mechanism of action

The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines. Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-, all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to downregulate the expression of FceRI on Langerhans cells.

toxicity

Side effects can be severe and include blurred vision, liver and kidney problems (it is nephrotoxic), seizures, tremors, hypertension, hypomagnesemia, diabetes mellitus, hyperkalemia, itching, insomnia, confusion. LD₅₀=134-194 mg/kg (rat).

biotransformation

Hepatic, extensive, primarily by CYP3A4. The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus. In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.

absorption

20% bioavailability; less after eating food rich in fat

half life

11.3 hours (range from 3.5 to 40.6 hours)

route of elimination

In man, less than 1% of the dose administered is excreted unchanged in urine. Fecal elimination accounted for 92.6±30.7%, urinary elimination accounted for 2.3±1.1%.

drug interactions

Abarelix: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Amikacin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Amikacin. Use caution during concomitant therapy.

Amiodarone: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Amitriptyline: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Amoxapine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Amphotericin B: Additive renal impairment may occur during concomitant therapy with Amphotericin B. Use caution during concomitant therapy.

Amprenavir: The protease inhibitor, Amprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Amprenavir therapy is initiated, discontinued or altered.

Apomorphine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Apramycin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Apramycin. Use caution during concomitant therapy.

Arsenic trioxide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Atazanavir: The protease inhibitor, Atazanavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Atazanavir therapy is initiated, discontinued or altered.

Bleomycin: Tacrolimus (Topical) may enhance the adverse/toxic effect of Immunosuppressants. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.

Bromocriptine: Bromocriptine may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Bromocriptine therapy is initiated, discontinued or altered.

Carbamazepine: Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.

Carboplatin: Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as carboplatin. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.

Carmustine: Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as carmustine. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.

Caspofungin: Caspofungin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Caspofungin therapy is initiated, discontinued or altered.

Chlorambucil: Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants sucb as chlorambucil. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.

Chloramphenicol: Chloramphenicol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Chloramphenicol therapy is initiated, discontinued or altered.

Chlorpromazine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Cimetidine: Cimetidine may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Cimetidine therapy is initiated, discontinued or altered.

Cisapride: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Cisapride may also increase the concentration of Tacrolimus in the blood.

Cisplatin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Cisplatin. Use caution during concomitant therapy.

Cladribine: Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as tacrolimus. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.

Clarithromycin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The macrolide antibiotic, Clarithromycin, may also increase the blood concentration of Tacrolimus.

Clofarabine: Tacrolimus (topical) may enhance the adverse/toxic effect of immunosuppressants such as clofarabine. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.

Clomipramine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Clotrimazole: The antifungal, Clotrimazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Clotrimazole therapy is initiated, discontinued or altered.

Conivaptan: The strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Conivaptan is initiated, discontinued or dose changed.

Cyclosporine: Additive renal impairment may occur during concomitant therapy with cyclosporine. Combination therapy should be avoided.

Danazol: Danazol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Danazol therapy is initiated, discontinued or altered.

Darunavir: The protease inhibitor, Darunavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Darunavir therapy is initiated, discontinued or altered.

Dasatinib: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Delavirdine: The strong CYP3A4 inhibitor, Delavirdine, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Delavirdine is initiated, discontinued or dose changed.

Desipramine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Diltiazem: Diltiazem may increase the serum concentration of tacrolimus by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tacrolimus if diltiazem therapy is initiated, discontinued or dose changed.

Disopyramide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Dofetilide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Dolasetron: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Domperidone: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Doxepin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Droperidol: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Erythromycin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The macrolide antibiotic, erythromycin, may also increase the blood concentration of tacrolimus.

Ethinyl Estradiol: Ethinyl estradiol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ethinyl estradiol therapy is initiated, discontinued or altered.

Felodipine: Felodipine increases tacrolimus levels

Flecainide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Fluconazole: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The antifungal, fluconazole, may also increase serum concentrations of tacrolimus.

Fluoxetine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Flupenthixol: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Fosamprenavir: The protease inhibitor, Fosamprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Fosamprenavir therapy is initiated, discontinued or altered.

Foscarnet: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Fosphenytoin: The hydantoin decreases the effect of tacrolimus

Gatifloxacin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Gentamicin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Gentamicin. Use caution during concomitant therapy.

Halofantrine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Haloperidol: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Ibutilide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Imatinib: The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Imatinib is initiated, discontinued or dose changed.

Imipramine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Indapamide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Indinavir: The protease inhibitor, Indinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Indinavir therapy is initiated, discontinued or altered.

Isoniazid: The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Isoniazid is initiated, discontinued or dose changed.

Isradipine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Itraconazole: The antifungal, Itraconazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Itraconazole therapy is initiated, discontinued or altered.

Ketoconazole: The antifungal, Ketoconazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ketoconzole therapy is initiated, discontinued or altered.

Lapatinib: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Levofloxacin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Lopinavir: The protease inhibitor, Lopinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Lopinavir therapy is initiated, discontinued or altered.

Loxapine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Maprotiline: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Mefloquine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Mesoridazine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Methadone: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Methylprednisolone: Methylprednisone may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Methylprednisone therapy is initiated, discontinued or altered.

Metoclopramide: Metoclopramide may increase the concentration of Tacrolimus in the blood. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Metoclopramide therapy is initiated, discontinued or altered.

Metronidazole: Metronidazole increases the levels/toxicity of tacrolimus

Mibefradil: The calcium channel blocker, Mibefradil, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Mibefradil therapy is initiated, discontinued or altered.

Miconazole: The strong CYP3A4 inhibitor, Miconazole, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Miconazole is initiated, discontinued or dose changed.

Moxifloxacin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Mycophenolate mofetil: Tacrolimus may increase the plasma concentration of Mycophenolic acid. Monitor and adjust the dose of Mycophenolate mofetil to the therapeutic range.

Natalizumab: Tacrolimus may increase the toxic/adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.

Nefazodone: Nefazodone may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nefazodone therapy is initiated, discontinued or altered.

Nelfinavir: The protease inhibitor, Nelfinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nelfinavir therapy is initiated, discontinued or altered.

Neomycin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Neomycin. Use caution during concomitant therapy.

Netilmicin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Netilmicin. Use caution during concomitant therapy.

Nicardipine: The calcium channel blocker, Nicardipine, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nicardipine therapy is initiated, discontinued or altered.

Nifedipine: The calcium channel blocker, Nifedipine, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nifedipine therapy is initiated, discontinued or altered.

Nilotinib: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Norfloxacin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Nortriptyline: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Octreotide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Omeprazole: Omeprazole may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Omeprazole therapy is initiated, discontinued or altered.

Pentamidine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Perflutren: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Phenobarbital: Phenobarbital may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenobarbital therapy is initiated, discontinued or altered.

Phenytoin: Phenytoin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenytoin therapy is initiated, discontinued or altered.

Pimozide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Posaconazole: The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Posaconazole is initiated, discontinued or dose changed.

Probucol: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Procainamide: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Propafenone: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Protriptyline: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Quetiapine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Quinidine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Quinidine, a strong CYP3A4 inhibitor, may also increase the serum concentration of Tacrolimus by inhibiting its metabolism and clearance.

Quinupristin: This combination presents an increased risk of toxicity

Ranolazine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Rifabutin: Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.

Rifampin: Rifampin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Rifampin therapy is initiated, discontinued or altered.

Risperidone: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Ritonavir: The protease inhibitor, Ritonavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ritonavir therapy is initiated, discontinued or altered.

Saquinavir: The protease inhibitor, Saquinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Saquinavir therapy is initiated, discontinued or altered.

Sirolimus: Sirolimus may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Sirolimus therapy is initiated, discontinued or altered.

Sotalol: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Sparfloxacin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

St. John's Wort: St. John's Wort may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if St. John's Wort therapy is initiated, discontinued or altered.

Streptomycin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Streptomycin. Use caution during concomitant therapy.

Sunitinib: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Telithromycin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Telithromycin, a strong CYP3A4 inhibitor, may also increase the serum concentration of Tacrolimus by inhibiting its metabolism and clearance.

Temsirolimus: Temsirolimus may decrease the blood concentration of Tacrolimus. Concomitant therapy may increase the adverse/toxic effects of both agents. Concomitant therapy should be avoided.

Tetrabenazine: May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.

Thioridazine: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Thiothixene: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Tipranavir: Tipranavir may decrease the metabolism and clearance of Tacrolimus. Dose adjustments may be required. Monitor for Tacrolimus efficacy and toxicity during concomitant therapy.

Tobramycin: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Tobramycin. Use caution during concomitant therapy.

Topotecan: The p-glycoprotein inhibitor, Tacrolimus, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Trimipramine: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Troleandomycin: The macrolide antibiotic, Troleandomycin, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Troleandomycin therapy is initiated, discontinued or altered.

Verapamil: The calcium channel blocker, Verapamil, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Verapamil therapy is initiated, discontinued or altered.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tacrolimus by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of tacrolimus if voriconazole is initiated, discontinued or dose changed.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).