3S-[3R*[E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*]]
-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5, 19-dihydroxy
-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy
-4,10,12,18-tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,1-c] [1,4] oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, monohydrate

Absorption
In healthy volunteers, as well as kidney and liver transplant patients, tacrolimus C max ranged from approximately 19.2 to 68.5 ng/mL, T max ranged from 1.5 to 3 h, AUC ranged from 203 to 3,300 ng•h/mL, t ½ ranged from 11.7 to 34.8 h, and bioavailability ranged from approximately 17% to 22%.

Food effects
The rate and extent of absorption were greatest under fasted conditions. The presence and composition of food decreased the rate and extent of absorption. The effect was most pronounced with a high-fat meal. Mean AUC and C max were decreased 37% and 77%, respectively. T max was lengthened 5-fold. A high-carbohydrate meal decreased mean AUC and mean C max 28% and 65%, respectively.

Distribution
Tacrolimus Vd is about 0.85 to 1.94 L/kg. Protein binding is about 99%, mainly to albumin and alpha-1 acid glycoprotein.

Metabolism
Tacrolimus is extensively metabolized by the mixed function oxidation system, primarily the CYP-450 system (CYP3A). The major metabolite identified is 13-demethyl tacrolimus.

Elimination
Cl is about 0.04 to 0.083 L/h/kg. Less than 1% of an administered dose is excreted unchanged in the urine. The t ½ is approximately 31.9 to 48.1 h (PO and IV).

Special Populations
Hepatic Function Impairment
The mean Cl was substantially lower and t ½ prolonged in patients with severe hepatic function impairment.

Children
Children younger than 12 yr of age need higher doses than adults to achieve similar trough concentrations.

Antifungal agents (eg, clotrimazole, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole), bromocriptine, calcium channel blockers (eg, diltiazem, felodipine, nicardipine, nifedipine, verapamil), chloramphenicol, cimetidine, cisapride, cyclosporine, danazol, ethinyl estradiol, fosphenytoin, lansoprazole, macrolide antibiotics (eg, clarithromycin, erythromycin, troleandomycin), magnesium-aluminum hydroxide, methylprednisolone, metoclopramide, metronidazole, nefazodone, omeprazole, protease inhibitors (eg, indinavir, ritonavir, saquinavir), telithromycin, theophylline
Tacrolimus blood concentrations may be elevated, increasing the risk of toxicity.

Carbamazepine, caspofungin, phenobarbital, phenytoin, prednisolone, prednisone, rifabutin, rifampin, sirolimus, St. John's wort
Tacrolimus blood concentrations may be reduced, increasing the risk of transplant rejection.

Cyclosporine
Additive nephrotoxicity.

CYP3A4 inhibitors (eg, cimetidine, erythromycin, ketoconazole)
Use with caution during topical administration.

Ethanol
Risk of facial flushing may be increased with topical tacrolimus.

Hydantoins (eg, phenytoin)
Tacrolimus plasma levels may be reduced, while hydantoin concentrations may be increased.

Mycophenolate mofetil, sildenafil, simvastatin
Plasma levels may be elevated by tacrolimus, increasing the risk of adverse reactions.

Vaccination (eg, BCG, measles, mumps, oral polio, rubella, TY 21a typhoid, yellow fever)
Vaccination may be less effective. Avoid use of live vaccines.

Ziprasidone
Risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased. Coadministration is contraindicated.