Patients should be informed that tacrolimus  can cause diabetes mellitus and should be advised of the need to see their physician if they develop frequent urination, increased thirst or hunger.

As with other immunosuppressive agents, owing to the potential risk of malignant skin changes, exposure to sunlight and ultraviolet (UV) light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

Laboratory Tests
Serum creatinine, potassium, and fasting glucose should be assessed regularly. Routine monitoring of metabolic and hematologic systems should be performed as clinically warranted.

Drug Interactions
Due to the potential for additive or synergistic impairment of renal function, care should be taken when administering tacrolimus with drugs that may be associated with renal dysfunction. These include, but are not limited to, aminoglycosides, amphotericin B, and cisplatin. Initial clinical experience with the co-administration of tacrolimus and cyclosporine resulted in additive/synergistic nephrotoxicity. Patients switched from cyclosporine to tacrolimus should receive the first tacrolimus  dose no sooner than 24 hours after the last cyclosporine dose. Dosing may be further delayed in the presence of elevated cyclosporine levels.

Drugs that May Alter Tacrolimus Concentrations
Since tacrolimus is metabolized mainly by the CYP3A enzyme systems, substances known to inhibit these enzymes may decrease the metabolism or increase bioavailability of tacrolimus as indicated by increased whole blood or plasma concentrations. Drugs known to induce these enzyme systems may result in an increased metabolism of tacrolimus or decreased bioavailability as indicated by decreased whole blood or plasma concentrations. Monitoring of blood concentrations and appropriate dosage adjustments are essential when such drugs are used concomitantly.

a Drugs That May Increase Tacrolimus Blood Concentrations

Calcium  Antifungal Macrolide 
Channel Blockers  Agents  Antibiotics 
diltiazem clotrimazole clarithromycin
nicardipine fluconazole erythromycin
nifedipine itraconazole troleandomycin
verapamil ketoconazoleb   
  voriconazole  
  Gastrointestinal   Other   
Prokinetic Agents  Drugs   
cisapride bromocriptine  
metoclopramide chloramphenicol  
  cimetidine  
  cyclosporine  
  danazol  
  ethinyl estradiol  
  methylprednisolone  
  lansoprazolec   
  omeprazole  
  protease  inhibitors  
  nefazodone  
  magnesium-aluminum-hydroxide  

a) This table is not all inclusive.

b) In a study of 6 normal volunteers, a significant increase in tacrolimus oral bioavailability (14±5% vs. 30±8%) was observed with concomitant ketoconazole administration (200 mg). The apparent oral clearance of tacrolimus during ketoconazole administration was significantly decreased compared to tacrolimus alone (0.430±0.129 L/hr/kg vs. 0.148±0.043 L/hr/kg). Overall, IV clearance of tacrolimus was no