Tacrolimus

CLINICAL USE

Immunosuppressive agent:Prophylaxis and treatment of acute rejection in liver, heart and kidney transplantationTreatment of moderate to severe atopic eczema

DOSE IN NORMAL RENAL FUNCTION

Oral:Liver transplantation: 100–200 mcg/kg/day in 2 divided dosesKidney transplantation: 150–300 mcg/kg/ day in 2 divided dosesHeart transplantation: 75 mcg/kg/day in 2 divided dosesIV:Liver transplantation: 10–50 mcg/kg as a continuous 24 hour infusion, starting 6 hours post surgeryKidney transplantation: 50–100 mcg/kg as a continuous 24 hour infusion, starting within 24 hours of surgeryHeart transplantation:

10 to 20 &nbsp &nbsp : mcg/kg as a continuous 24 hour infusion

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :822

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :>98

%Excreted unchanged in urine &nbsp &nbsp : <1

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :1300 litres

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :12–16/Probably unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Dose as in normal renal function

10 to 20 &nbsp &nbsp : Dose as in normal renal function

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in normal renal function

HDF/high flux &nbsp :Unknown dialysability. Dose as in normal renal function

CAV/VVHD &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Ciclosporin: may increase the half-life of ciclosporin and exacerbate any toxic effects. The two should not be prescribed concomitantly. Care should be taken when converting from ciclosporin to tacrolimusTacrolimus levels increased by: atazanavir, basiliximab, bromocriptine, caspofungin, chloramphenicol, cimetidine, cortisone, danazol, dapsone, diltiazem, ergotamine, ethinyloestradiol, gestodene, grapefruit juice, imidazole and triazole antifungals, lidocaine, felodipine, lansoprazole, possibly levofloxacin, macrolides, midazolam, nelfinavir, nicardipine, nifedipine, omeprazole, pantoprazole, quinidine, quinupristin/dalfopristin, ritonavir, saquinavir, tamoxifen, telithromycin, theophylline, verapamil and voriconazoleTacrolimus levels decreased by: carbamazepine, caspofungin, isoniazid, phenobarbital, phenytoin (phenytoin levels possibly increased), rifampicin and St John’s wortIncreased nephrotoxicity with: aciclovir, aminoglycosides, amphotericin, co-trimoxazole, ganciclovir, NSAIDs and vancomycin
Increased risk of hyperkalaemia with: potassium-sparing-diuretics and potassium salts

Clotrimazole: more than doubles the bioavailability of tacrolimus (US-based researchers report that concomitant clotrimazole substantially increases the relative oral bioavailability of tacrolimus in renal transplant recipients.

ADMINISTRATION

Reconstition

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Route

IV, oral, topical

Rate of Administration

Continuous infusion over 24 hours

Comments

Dilute in glucose 5% or sodium chloride 0.9% to a concentration of 4–100 micrograms/mL, i.e. 5 mg in 50–1000 mL
Incompatible with PVC.
Add to either glucose 5% in polyethylene or glass containers or to sodium chloride 0.9% in polyethylene containersContains polyethoxylated castor oil which has been associated with anaphylaxis

OTHER INFORMATION

When converting from oral to IV, give one fifth of the total daily dose over 24 hours and monitor levels
Also available as a 0.03% and 0.1% ointment for eczema and anal Crohn’s diseaseApproximate whole blood ranges: Initially: liver: 5–10 ng/mL, renal: —8–15 ng/mL . Maintenance: 5–15 ng/mL —.

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