Tacrolimus
(FK506)
Tacrolimus (Prograf)
FK506 (Prograf)
Tacrolimus
(tah- KROH-lih-mus)
Pregnancy Category: C Prograf (Rx)

Classification: Immunosuppressive drug

Action/Kinetics: Produced by Streptomyces tsukubaensis. Mechanism of action is not known but it inhibits T-lymphocyte formation leading to immunosuppression. Absorption from the GI tract is variable. t 1/2, terminal elimination: 11.7 hr in liver transplant clients and 21.2 hr in healthy volunteers. Food decreases both the absorption and bioavailability of tacrolimus. Significantly bound to proteins and erythrocytes; extensively metabolized by the liver and excreted through the urine.

Uses: Prophylaxis of organ rejection in allogeneic liver transplants and kidney transplants; usually used with corticosteroids. Investigational: Transplants of bone marrow, heart, pancreas, pancreatic island cells, and small bowel. Treatment of autoimmune disease and severe recalcitrant psoriasis.

Contraindications: Hypersensitivity to tacrolimus or HCO-60 polyoxyl 60 hydrogenated castor oil (vehicle used for the injection). Lactation. Concomitant use with cyclosporine.

Special Concerns: Increased risk of developing lymphomas and other malignancies (especially of the skin).

Side Effects: CNS: Headache, tremor, insomnia, paresthesia, seizures, coma delirium, abnormal dreams, anxiety, agitation, confusion, depression, dizziness, emotional lability, hallucinations, hypertonia, incoordination, myoclonus nervousness, psychosis, somnolence, abnormal thinking. Neurotoxicity: Changes in motor function, mental status, and sensory function; tremor, headache. GI: Diarrhea, nausea, constipation, abnormal LFT, anorexia, vomiting, dyspepsia, dysphasia, flatulence, GI hemorrhage, GI perforation ileus, increased appetite, oral moniliasis. Hepatic: Hepatitis, cholangitis, cholestatic jaundice, jaundice, liver damage. CV: Hypertension, chest pain, abnormal ECG, hemorrhage hypotension, tachycardia. Hematologic: Anemia, thrombocytopenia, leukocytosis, coagulation disorder, ecchymosis, hypochromic anemia, leukopenia, decreased prothrombin. GU: Abnormal kidney function, nephrotoxicity, UTI, oliguria, hematuria, kidney failure. Metabolic: Hyperkalemia, hypokalemia, hyperglycemia, hypomagnesemia, acidosis, alkalosis, hyperlipemia, hyperphosphatemia, hyperuricemia, hypocalcemia, hypophosphatemia, hyponatremia, hypoproteinemia, bilirubinemia. Respiratory: Pleural effusion, atelectasis, dyspnea, asthma, bronchitis, increased cough, pulmonary edema, pharyngitis, pneumonia, lung disorder, respiratory disorder, rhinitis, sinusitis, alteration in voice. Musculoskeletal: Arthralgia, leg cramps, myalgia, myasthenia, osteoporosis, generalized spasm. Dermatologic: Pruritus, rash, alopecia, herpes simplex, sweating, skin disorder, herpes simplex. Miscellaneous: Hypersensitivity reactions (including anaphylaxis), increased incidence of malignancies, lymphoma, diabetes mellitus, pain, fever, asthenia, back pain, ascites, peripheral edema, abdominal pain, enlarged abdomen, abscess, chills, hernia, photosensitivity, peritonitis, abnormal healing.

Laboratory Test Alterations: Alkaline phosphatase, AST, ALT.

Drug Interactions: Aminoglycosides / Additive or synergistic impairment of renal function Amphotericin B / Additive or synergistic impairment of renal function Antifungal drugs / Tacrolimus blood levels Bromocriptine / Tacrolimus blood levels Calcium channel blocking drugs / Tacrolimus blood levels Carbamazepine / Tacrolimus blood levels Chloramphenicol / Tacrolimus blood levels Cimetidine / Tacrolimus blood levels Cisplatin / Additive or synergistic impairment of renal function Clarithromycin / Tacrolimus blood levels Cyclosporine / Additive or synergistic nephrotoxicity; also, tacrolimus blood levels Danazol / Tacrolimus blood levels Diltiazem / Tacrolimus blood levels Echinacea / Do not give with tacrolimus Erythromycin / Tacrolimus blood levels Methylprednisolone / Tacrolimus blood levels Metoclopramide / Tacrolimus blood levels Nefazodone / Possible tacrolimus toxicity Phenobarbital / Tacrolimus blood levels Phenytoin / Tacrolimus blood levels Rifamycin / Tacrolimus blood levels Vaccines / Effectiveness of vaccines

How Supplied: Capsule: 1 mg, 5 mg; Injection: 5 mg/ml

Dosage
?IV Infusion Only Immunosuppression.
Initial: 0.05-0.1 mg/kg/day as a continuous IV infusion. Early in the period following transplantation, concomitant adrenal corticosteroid use is recommended.
?Capsules Immunosuppression.
Initial: 0.15-0.3 mg/kg/day administered in two divided doses q 12 hr. Maintenance: Titrate dose based on clinical assessment of rejection and tolerability. Lower doses may suffice for maintenance therapy.