logo image

Tacrolimus information from DrugsUpdate  

See Available Brands of Tacrolimus in India

P - Caution when used during pregnancy
L - Contraindicated in Lactation
FI - Food *

Tacrolimus is an immunosuppressive drug whose main use is after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection. It reduces T-cell and interleukin-2 (IL-2) activity. It is also used in a topical preparation in the treatment of severe atopic dermatitis (eczema), severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.

Pharmacodynamics

Pharmacokinetics

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).

Absorption
Incomplete and variable. Food decreased rate and extent of tacrolimus absorption.

Distribution
99% bound to plasma protein, mainly to albumin and alpha-1-acid glycoprotein, and has a high level of association with erythrocytes.

Metabolism
Extensively metabolized by cytochrome P-450 system (CYP3A).

Tacrolimus Indications / Tacrolimus Uses

Information Not Available

Tacrolimus Adverse Reactions / Tacrolimus Side Effects

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.

Precautions

Hypertension is a common adverse effect of Tacrolimus therapy. Mild or moderate hypertension is more frequently reported than severe hypertension. Antihypertensive therapy may be required; the control of blood pressure can be accomplished with any of the common antihypertensive agents. Since Tacrolimus may cause hyperkalemia, potassium-sparing diuretics should be avoided. While calcium-channel blocking agents can be effective in treating Tacrolimus-associated hypertension, care should be taken since interference with Tacrolimus metabolism may require a dosage reduction.

Special 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.

Other Drug 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.

Other Interactions

Food Interaction


Food decreases rate and extent of absorption. Grapefruit and pomelo juice may increase the serum levels. St John's wort may decrease serum levels.

Dosage

Oral
Prevention 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.
Renal impairment: Dose reduction needed.
Hepatic impairment: Severe impairment (Child-Pugh score of ≥10): Use lower dosages and close monitoring of blood concentrations needed.

Oral
Prevention 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.
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 impairment: Dose reduction needed.
Hepatic impairment: Severe impairment (Child-Pugh score of ≥10): Use lower dosages and close monitoring of blood concentrations needed.

Oral
Fistulising Crohn's disease
Adult: 200 mcg/kg/day in 2 divided doses for 10 wk.
Renal impairment: Dose reduction needed.
Hepatic impairment: Severe impairment (Child-Pugh score of ≥10): Use lower dosages and close monitoring of blood concentrations needed.

Oral
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.

Intravenous

Prevention of rejection in kidney graft transplant
Adult: Initially, 0.05-0.1 mg/kg/day as a continuous infusion over 24 hr. Start within 24 hr of transplantation for up to a max of 7 days, then transfer to oral treatment.
Renal impairment: Dose reduction needed.
Hepatic impairment: Severe impairment (Child-Pugh score of ≥10): Use lower dosages and close monitoring of blood concentrations needed.

Intravenous
Prevention of rejection in liver graft transplant
Adult: Initially, 10-50 mcg/kg/day as a continuous infusion over 24 hr. Start treatment 12 hr after transplantation and continue for up to a max of 7 days. Transfer to oral therapy as soon as patient is able to tolerate; 1st oral dose should be given 8-12 hr after stopping infusion.
Child: Initially, 0.03-0.05 mg/kg/day as a continuous infusion over 24hr. Begin no sooner than 6 hr post-transplant, starting at the lower end of the dosage range. Continue until the oral medication can be tolerated. Oral therapy should start 8-12hr after IV infusion discontinued.
Renal impairment: Dose reduction needed.
Hepatic impairment: Severe impairment (Child-Pugh score of ≥10): Use lower dosages and close monitoring of blood concentrations needed.

Intravenous
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. 10–20 mcg/kg daily via infusion over 24 hr, for up to a max of 7 days. Transfer to oral therapy as soon as patient is able to tolerate; 1st oral dose to be given 8-12 hr after stopping infusion.

Topical/Cutaneous
Atopic dermatitis
Adult: >15 yr: Apply thinly 0.03% or 0.1% ointment to affected area bid. Rub in gently and completely. For short-term and intermittent use only. If no improvement after 6 wk, re-confirm diagnosis.
Child: 2-15 yr: Apply thinly 0.03% oint to affected area bid. Rub in gently and completely. For short-term and intermittent use only.

Reconstitution
Dilute concentrate with 0.9% sodium chloride or 5% dextrose injection to a concentration of 4–20 mcg/ml. Diluted solution may be stored in polyethylene or glass containers for up to 24 hr. Diluted infusion solution must not be stored in a PVC container due to reduced stability and potential for extraction of phthalates.

Incompatibility

Do not use plasticized polyvinyl chloride (PVC) container as stability of the solution is decreased and polyoxyl 60 hydrogenated castor oil contained in the formulation may leach phthalates from PVC containers. Tacrolimus injection should not be mixed or co-infused with solutions of pH 9 or greater due to chemical instability in alkaline media.

Food(before/after)

Should be taken on an empty stomach. (Take on an empty stomach at least 1 hr before or 2-3 hr after meals.)

List of Contraindications

Tacrolimus and Pregnancy

Caution when used during pregnancy.


Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Tacrolimus and Lactation

Contraindicated in lactation

Tacrolimus and Children

Children generally require higher doses to maintain trough tacrolimus levels similar to adults (oral and IV). Safety and efficacy not established in children younger than 2 yr of age (topical).

Tacrolimus and Geriatic

Information Not Available

Tacrolimus and Other Contraindications

Hypersensitivity, lactation.

Storage

Topical/Cutaneous


Store at 15-30°C.

Lab interference

Topical/Cutaneous


Store at 15-30°C.

© 2011-2018 DrugsUpdate.com. Disclaimer | Site Map

Feedback