red closely and dosage adjustments should be considered. Some evidence suggests that lower doses should be used in these patients [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
Overdosage
Limited overdosage experience is available. Acute overdosages of up to 30 times the intended dose have been reported. Almost all cases have been asymptomatic and all patients recovered with no sequelae. Acute overdosage was sometimes followed by adverse reactions consistent with those listed in Adverse Reactions (6) (including tremors, abnormal renal function, hypertension, and peripheral edema); in one case of acute overdosage, transient urticaria and lethargy were observed. Based on the poor aqueous solubility and extensive erythrocyte and plasma protein binding, it is anticipated that Tacrolimus is not dialyzable to any significant extent; there is no experience with charcoal hemoperfusion. The oral use of activated charcoal has been reported in treating acute overdoses, but experience has not been sufficient to warrant recommending its use. General supportive measures and treatment of specific symptoms should be followed in all cases of overdosage.
In acute oral and IV toxicity studies, mortalities were seen at or above the following doses: in adult rats, 52 times the recommended human oral dose; in immature rats, 16 times the recommended oral dose; and in adult rats, 16 times the recommended human IV dose (all based on body surface area corrections).
Tacrolimus Description
Tacrolimus USP is available for oral administration as capsules containing the equivalent of 0.5 mg, 1 mg or 5 mg of anhydrous Tacrolimus. Inactive ingredients include croscarmellose sodium, lactose monohydrate and magnesium stearate. The 0.5 mg capsule shell contains gelatin, iron oxide red, iron oxide yellow and titanium dioxide, the 1 mg capsule shell contains gelatin and titanium dioxide and the 5 mg capsule shell contains gelatin, iron oxide red, iron oxide black, and titanium dioxide.
Tacrolimus USP, previously known as FK506, is the active ingredient in Tacrolimus capsules USP. Tacrolimus USP is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. Chemically, Tacrolimus USP is designated as [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.
The chemical structure of Tacrolimus is:
Tacrolimus USP has an empirical formula of C44H69NO12•H2O and a formula weight of 822.03. Tacrolimus USP appears as white to off white granular powder. It is practically insoluble in water, freely soluble in methanol, ethanol, acetone, ehyl acetate, chloroform.
Tacrolimus Capsules meets USP Organic Impurities Test Procedure 2.
Tacrolimus - Clinical Pharmacology
Mechanism of Action
Tacrolimus inhibits T-lymphocyte activation, although the exact mechanism of action is not known. Experimental evidence suggests that Tacrolimus binds 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 inhibited. This effect may prevent th
