tacrolimus - definition of tacrolimus in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia.

tacrolimus /tac·ro·li·mus/ (tak″ro-li´mus) a macrolide immunosuppressant having actions similar to those of cyclosporine; used to prevent rejection of organ transplants; also used topically to treat moderate to severe atopic dermatitis.

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An immunosuppressive drug produced by the actinomycete Streptomyces tsukubaensis, used in combination with corticosteroids to prevent rejection of organ transplants.

tacrolimus,

an immunosuppressive drug that modifies biologic response.

indications This drug is prescribed to suppress the immune system after transplantation of the liver or other organs and can be applied topically for the treatment of dermatitis unresponsive to other medications.

contraindications This drug should not be given to patients with allergy to tacrolimus or those receiving potassium-sparing diuretics, cycloSPORINE, or other immunosuppressive agents, with the exception of adrenal corticosteroids.

adverse effects The side effects most often reported include tremor, headache, diarrhea, hypertension, nausea, renal dysfunction, hyperglycemia, and increased risk of infection.

tacrolimus (FK506),

n brand name: Prograf;
drug class: immunosuppressant;
action: inhibits T-lymphocyte activation leading to immunosuppression;
use: prophylaxis of organ rejection in patients receiving allogenic liver transplants.

tacrolimus

an immunosuppressive agent derived from Streptomyces tsukabaensis. It selectively binds FK-binding proteins and the complex inhibits calcineurin.

immunosuppressants

Drugs that prevent or reduce the immune response. They are used in the treatment of a variety of severe inflammations such as uveitis, scleritis, keratoconjunctivitis sicca, Behçet's syndrome, sympathetic ophthalmia, and to prevent corneal graft rejection. They include the corticosteroids (e.g. prednisolone), ciclosporin (cyclosporine), tacrolimus, and cytotoxic agents (e.g. azathioprine, chlorambucil, cyclophosphamide, methotrexate). It must be noted that immunosuppressants render the patient more susceptible to infection because immunity is reduced.

tacrolimus Warning - Hazardous drug!

Prograf

Pharmacologic class: Macrolide

Therapeutic class: Immunosuppressant

Pregnancy risk category C

FDA Boxed Warning

• Immunosuppression may increase patient's susceptibility to infection and lymphoma development. Give under supervision of physician experienced in immunosuppressive therapy and management of organ transplant patients, in facility with adequate diagnostic and treatment resources. Physician responsible for maintenance therapy should have complete information needed for patient follow-up.

Action

Unknown. Thought to inhibit T-lymphocyte activation.

Availability

Capsules: 0.5 mg, 1 mg, 5 mg

Injection: 5 mg/ml

Topical ointment: 0.03%, 0.1%

⊘Indications and dosages

➣ Prevention of organ rejection in patients with allogeneic liver transplants

Adults: Initially, 0.1 to 0.15 mg/kg/day P.O. in two divided doses q 12 hours. Alternatively, 0.03 to 0.05 mg/kg/day by continuous I.V. infusion.

Children: 0.15 to 0.2 mg/kg/day P.O. in two divided doses q 12 hours. Alternatively, 0.03 to 0.05 mg/kg/day by continuous I.V. infusion.

➣ Prevention of organ rejection in patients with allogeneic kidney transplants

Adults: Initially, 0.2 mg/kg/day P.O. in two divided doses q 12 hours. Alternatively, 0.03 to 0.05 mg/kg/day by continuous I.V. infusion.

➣ Prevention of heart transplant rejection

Adults: Initially, 0.075 mg/kg/day P.O. q 12 hours in two divided doses.

➣ Moderate to severe atopic dermatitis

Adults: 0.03% or 0.1% ointment applied b.i.d. to affected area, continued 1 week after dermatitis symptoms resolve

Children ages 2 and older: 0.03% ointment applied b.i.d. to affected area, continued 1 week after dermatitis symptoms resolve

Dosage adjustment

• Hepatic or renal impairment

Contraindications

• Hypersensitivity to drug or its components (including castor oil derivatives)

Precautions

Use cautiously in:
• severe hepatic disease, renal impairment, diabetes mellitus, hypertension, hyperkalemia, hyperuricemia, lymphoma
• pregnant or breastfeeding patients
• children younger than age 12 (age 2 for ointment use).

Administration

• Give oral form without food.
• Give I.V. doses by infusion only.
• Start therapy within 24 hours of kidney transplantation and no earlier than 6 hours after liver or heart transplantation. Switch to oral dosing as soon as tolerable, starting 8 to 12 hours after I.V. dosing ends.
☞ Before giving I.V., ensure that epinephrine 1:1,000 and oxygen are at hand in case of emergency.
• For I.V. use, dilute in normal saline solution or dextrose 5% in water to a concentration of 0.004 to 0.02 mg/ml. Give by infusion only.
• After applying ointment, don't place occlusive dressing or wrapping over affected area.

Route	Onset	Peak	Duration
P.O.	Unknown	1.5-3.5 hr	Unknown
I.V.	Rapid	1-2 hr	Unknown
Ointment	Unknown	Unknown	Unknown

Adverse reactions

CNS: tremor, headache, insomnia, paresthesia, delirium, asthenia, coma

CV: hypertension, peripheral edema

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, ascites, anorexia

GU: hematuria, proteinuria, urinary tract infection, albuminuria, abnormal renal function, oliguria, renal failure

Hematologic: anemia, leukocytosis, thrombocytopenia

Metabolic: hyperglycemia, hypomagnesemia, hypokalemia, hyperkalemia

Musculoskeletal: back pain

Respiratory: dyspnea, pleural effusion, atelectasis

Skin: burning (with ointment), rash, flushing, pruritus, alopecia

Other: pain, fever, chills, anaphylaxis

Interactions

Drug-drug. Bromocriptine, chloramphenicol, cimetidine, clarithromycin, clotrimazole, cyclosporine, danazol, diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, methylprednisolone, metoclopramide, metronidazole, nicardipine, omeprazole, protease inhibitors, verapamil: increased tacrolimus blood level

Cyclosporine: increased risk of nephrotoxicity

CYP450 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin): decreased tacrolimus metabolism

Immunosuppressants (except adrenocorticoids): immunologic oversuppression

Live-virus vaccines: interference with immune response to vaccine

Mycophenolate mofetil: increased mycophenolate blood level

Nephrotoxic drugs (such as aminoglycosides, amphotericin B, cisplatin, cyclosporine): additive or synergistic effects

Drug-diagnostic tests. Blood urea nitrogen, creatinine, glucose: increased levels

Hemoglobin, magnesium, platelets, white blood cells: decreased levels

Liver function tests: abnormal values

Potassium: increased or decreased level

Drug-food. Any food: inhibited drug absorption

Grapefruit juice: increased drug blood level

Drug-herbs. Astragalus, echinacea, melatonin: decreased immunosuppression

St. John's wort: decreased tacrolimus blood level

Patient monitoring

☞ Once I.V. infusion starts, watch closely for signs and symptoms of anaphylaxis.
• Monitor cardiac, liver, and kidney function test results. Watch for signs and symptoms of cardiovascular disorder, nephrotoxicity, and hepatic dysfunction.
• Assess neurologic status for evidence of neurotoxicity.
• Monitor potassium level closely. Stay alert for signs and symptoms of hyperkalemia.
• Monitor blood glucose. Watch for indications of hyperglycemia.
• Evaluate respiratory status regularly.

Patient teaching

☞ Teach patient to recognize and immediately report serious adverse reactions.
• Tell patient to take oral doses without food.
• Tell diabetic patient to expect increased blood glucose level, which may warrant further antidiabetic therapy. Advise him to monitor glucose level carefully.
• Instruct patient not to place occlusive dressings or wrappings over affected area after applying ointment. Tell him to use drug for 1 week after dermatitis symptoms resolve.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

tacrolimus

FK506, Prograf Immunology An immunosuppressant that inhibits IL-2 synthesis and binding; it is similar to, and synergistic with, cyclosporine, up to 50-fold more immunosuppressive than cyclosporine; it is used in BM, kidney, liver, lung, and other transplants Adverse effects Neurotoxicity–tremor, seizures, white matter disease, headache, nausea, paresthesias of hands, feet, insomnia; nephrotoxicity, hyperglycemia, hirsutism, paresthesia, ↑ lipids, ↑ K+, HUS, ↓ Mg2+. Cf Cyclosporine.