Tacrolimus

Indications

Tacrolimus is used for: Prophylaxis of rejection in kidney, liver & cardiac graft transplant

Adult Dose

Oral Prophylaxis of rejection in kidney graft transplant Adult: Initially, 0.2-0.3 mg/kg/day in 2 divided doses every 12 hr. Begin oral dose within 24 hr of transplant. Prophylaxis of rejection in liver graft transplant Adult: Initially, 0.1-0.2 mg/kg/day in 2 divided doses every 12 hr. Start treatment 12 hr after transplantation. Fistulising Crohn's disease Adult: 200 mcg/kg/day in 2 divided doses for 10 wk. Prophylaxis of cardiac graft rejection Adult: With or without antibody induction: Starting within 5 days of transplantation but no earlier than 6 hr after transplantation. 75 mcg/kg daily in 2 divided doses. Hepatic impairment: Severe impairment (Child-Pugh score of ?10): Use lower dosages and close monitoring of blood concentrations needed.

Child Dose

Oral Prophylaxis of rejection in liver graft transplant Child: Initially, 0.15-0.20 mg/kg/day in 2 divided doses every 12 hr. Begin no sooner than 6 hr after transplant.

Renal Dose

Renal impairment: Dose reduction needed.

Administration

Should be taken on an empty stomach. Take on an empty stomach at least 1 hr before or 2-3 hr after meals. Avoid grapefruit & grapefruit juice.

Contra Indications

Hypersensitivity, lactation.

Precautions

Monitoring of blood trough serum concentrations to prevent organ rejection and to reduce drug-related toxicity. Topical: Used with caution on the face or neck, large areas of the body (not >50% of the total BSA), or areas of broken skin. Infections at the treatment site should be cleared prior to therapy. Delay use in patients with unknown cause of lymphadenopathy or acute infectious mononucleosis till resolution. Use in patients with Netherton's syndrome is not recommended. Pregnancy.

Pregnancy-Lactation

Interactions

Increased nephrotoxicity with ciclosporin, aminoglycosides, amphotericin B, cisplatin, NSAIDs, vancomycin, co-trimoxazole, aciclovir, ganciclovir. Increased risk of hyperkalemia with potassium-sparing diuretics. Increased plasma concentrations and toxicity with azole antifungals, calcium-channel blockers, cimetidine, danazol, HIV-protease inhibitors, macrolide antibacterials and metoclopramide. Antacids, rifampin, rifabutin, casofungin, phenytoin, phenobarbital and carbamazepine decrease tacrolimus plasma concentrations. Concurrent admin of sirolimus and tacrolimus decrease levels of both.

Adverse Effects

Side effects of Tacrolimus : Systemic: Tremor, headache, paraesthesias, nausea and diarrhoea, hypertension, blood dyscrasias, leucocytosis, impaired renal function, serum electrolyte disturbances, infectious complications. Mood changes, sleep disturbances, confusion, dizziness, tinnitus, visual disturbances convulsions, alterations in glucose metabolism, ECG changes, tachycardia, myocardial hypertrophy, constipation, dyspepsia and GI haemorrhage; dyspnoea, asthma, pleural effusions; alopoecia, hirsutism, skin rash and pruritus; myalgia, spasm, leg cramps, peripheral oedema, liver dysfunction and coagulation disorders. Topical: Burning, stinging, soreness, pruritus, skin disorders, headache and flu-like symptoms. Increased incidence of malignancy. Potentially Fatal: Nephrotoxicity, neurotoxicity and anaphylactic reaction.

Mechanism of Action

Tacrolimus inhibits T-lymphocyte activation, although the exact mechanism of action unclear. Tacrolimus bind to cytosolic receptors known as immunophilins (i.e., cyclophilin and FK binding protein-12 [FKBP-12], respectively), forming complexes that inhibit the production of cytokines via the calcineurin pathway. Inhibition of calcineurin activity inhibits early activation of T-cells (ie.immunosuppresion results).