Tacrolimus

A to Z Drug Facts

  Action Suppresses cell-mediated immune reactions and some humoral immunity, but exact mechanism is not known.

  Indications

PO and IV: Prophylaxis of organ rejection in patients receiving allogenic liver or kidney transplants. Used in conjunction with adrenal corticosteroids.

Topical: Atopic dermatitis.

Prophylaxis of rejection for patients receiving kidney, bone marrow, cardiac, pancreas, pancreatic island cell, and small bowel transplantation.

  Contraindications Hypersensitivity to polyoxyl 60 hydrogenated castor oil, which is present in the injection.

  Route/Dosage

Prophylaxis of Organ Rejection Liver Transplants:

Adults: PO 0.1 to 0.15 mg/kg/day in 2 divided daily doses q 12 hr no sooner than 6 hr after transplantation. IV 0.03 to 0.05 mg/kg/day as continuous infusion.

Children: PO 0.15 to 0.2 mg/kg/day in 2 divided daily doses q 12 hr. IV 0.03 to 0.05 mg/kg/day as continuous infusion.

Prophylaxis of Organ Rejection Kidney Transplants:

Adults: PO 0.2 mg/kg/day in 2 divided daily doses q 12 hr, starting within 24 hr of transplantation but delayed until renal function is recovered (eg, serum creatinine of 4 mg/dL or less). Black patients may require higher doses to achieve comparable blood concentration.

Topical Dermatits:

Adults: Topical Apply thin layer of 0.03% and 0.1% to affected skin areas bid and rub in gently and completely; continue for 1 wk after clearing of atopic dermatitis.

Children at least 2 yr: Topical Apply thin layer of 0.03% to affected skin areas bid and rub in gently and completely; continue for 1 wk after clearing of atopic dermatitis.

  Interactions

Azole antifungal agents (eg, fluconazole, ketoconazole), calcium channel blockers (eg, diltiazem, nifedipine), clotrimazole, macrolide antibiotics (eg, erythromycin):

Tacrolimus plasma levels may be elevated, increasing the risk of toxicity.

Cyclosporine: Additive nephrotoxicity.

Hydantoins (eg, phenytoin): Tacrolimus plasma levels may be reduced, while hydantoin concentrations may be increased.

Mycophenolate mofetil: Plasma levels of mycophenolate mofetil may be elevated.

Rifamycins (eg, rifampin, St. John's wort): Tacrolimus plasma levels may be reduced, increasing the risk of rejection.

  Lab Test Interferences None well documented.

  Adverse Reactions

CARDIOVASCULAR: Hypertension; edema; peripheral edema, angina pectoris, arrhythmia, cerebrovascular accident, palpitations, peripheral vascular disorder, vasodilation (topical). CNS: Headache; insomnia; anxiety; paresthesia; tremor, weakness, abnormal dreams, agitation, confusion (oral and IV); depression, dizziness, migraine, neuritis (topical). DERMATOLOGIC: Rash; pruritus; burning sensation, erythema, infection, herpes simplex, eczema herpetibum, pustular rash, folliculitis, uticaria, maculopapular rash, fungal dermatitis, acne, sunburn, skin disorder, vesiculobullous rash, skin tingling, dry skin, benign skin neoplasm, contact dermatitis, eczema, exfoliative dermatitis, alopesia, cellutitis, ecchymosis, skin discoloration, sweating, furunculosis (topical). EENT: Abnormal vision, tinnitus (oral and IV); pharyngitis, rhinitis, sinusitis, otitis media, conjunctivitis, laryngitis, ear pain, eye disorder, eye pain, taste perversion (topical). GI: Diarrhea; nausea; constipation; anorexia; vomiting; abdominal pain; dyspepsia, gastroenteritis, gastritis (topical). GU: Renal dysfunction, UTI, oliguria (oral and IV); dysmenorrhea, increased creatinine, unintended pregnancy, vaginal moniliasis (topical). HEMATOLOGIC: Leukocytosis; anemia, thrombocytopenia (oral and IV); leukopenia (topical). HEPATIC: Abnormal LFTs; bilirubinemia (topical). METABOLIC: Hyperglycemia; hyperkalemia, hypomagnesemia, hyperuricemia (oral and IV); hypoglycemia (topical). RESPIRATORY: Dyspnea; pleural effusion, atelectasis (oral and IV); Increased cough, asthma, bronchitis, pneumonia, hypoxia, lung disorder (topical). OTHER: Fever; pain; back pain; ascites (oral and IV); flu-like symptoms, allergic reaction, infection, accidental injury, lack of drug effect, lymphadenopathy, face edema, hyperesthesia, varicella zoster/herpes zoster, asthenia, periodontal abscess, myalgia, cyst, arthralgia, arthritis, anaphylactoid reaction, angioedema, breast pain, cheilitis, chills, dehydration, epistaxis, exacerbation of untreated area, hernia, malaise, neck pain, photosensitivity (topical).

  Precautions

Pregnancy: Category C. Lactation: Excreted in breast milk. Avoid nursing. CHILDREN: Children generally require higher doses to maintain trough tacrolimus levels similar to adults (oral and IV). Safety and efficacy not established in children at least 2 yr (topical). Anaphylactic reactions: May occur with IV injection. Hepatic disease: May require reduced doses. Renal function impairment: May require reduced doses; monitor closely. Hyperglycemia: Frequently occurs with tacrolimus; may require treatment.

  Administration/Storage

• Dilute IV form of the medication prior to use with 0.9% Normal Saline or 5% Dextrose Injection to a concentration between 0.004 mg/mL and 0.02 mg/mL.
• Diluted solution must be stored in glass or polyethylene containers for up to 24 hr after mixing. Storage in PVC containers reduces stability.
• Do not use solutions that contain particulate matter or are discolored.
• The initial IV or oral dose of this medication should be no sooner than 6 hr after transplantation.
• Switch patients to the oral form of the medication as soon as possible.
• When converting from IV to oral dosage form, the first oral dose should be no sooner than 8 to 12 hr after discontinuation of IV administration.
• Oral medication is most effective on an empty stomach.
• Do not use this medication simultaneously with cyclosporine. Discontinue cyclosporine at least 24 hr before administering this drug.
• Diluted IV solution may be stored at controlled room temperature.
• Store capsules at room temperature.

  Assessment/Interventions

• Obtain patient history. Note hypersensitivity to other antirejection drugs such as cyclosporine and polyoxyethylated castor oil.
• Obtain baseline laboratory tests, including BUN, creatinine, lipid levels, potassium, WBC with differential and CBC. Perform and evaluate these tests periodically during treatment.
• Assess for preexisting hypertension, particularly in children.
• Assess for any signs of infection, bleeding, or bruising.
• Remain with patient for the first 30 min of the initial IV administration of this medication and assess for symptoms of anaphylactic reaction. Assess frequently during all IV administrations.
• Maintain medical asepsis and eliminate any potential sources of environmental contamination.
• Monitor patient and lab tests for evidence of organ rejection.

  Patient/Family Education

• Warn patient not to alter the dose or discontinue the medication without consulting the health care provider.
• Instruct patient to check with health care provider before taking any OTC or prescription medications, or receiving any vaccinations.
• Patient should report any serious side effects to the health care provider.
• Inform patient of the need for frequent laboratory tests to assess the effectiveness of the treatment regimen and the need to keep appointments.
• Direct patient to avoid contact with others who may have any type of infection.
• Direct patient to take the medication 30 min before or 2 hr after meals. If the medication causes GI upset, take with a full glass of water. May be taken with food, but is less effective.
• Advise patient to minimize or avoid exposure to natural or artificial sunlight while using tacrolimus ointment.
• Instruct patient to be sure skin is completely dry before applying tacrlimus ointment after a shower or bath.
• Instruct patient not to use tacrolimus with occlusive dressings.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts