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tacrolimus (oral, IV)(ta-kroe-li-mus) ,
Pregnancy Category: C
Prevention of organ rejection in patients who have undergone allogenic liver, kidney, or heart transplantation (used concurrently with corticosteroids).
Inhibits T-lymphocyte activation.
Prevention of transplanted organ rejection.
Absorption: Absorption following oral administration is erratic and incomplete (5–67%).
Distribution: Crosses the placenta and enters breast milk.
Protein Binding: 99%.
Metabolism and Excretion: 99% metabolized by the liver; <1% excreted unchanged in the urine.
Half-life: Liver transplant patients—11.7 hr; healthy volunteers—21.2 hr.
Time/action profile (immunosuppression)
|PO||rapid||1.3–3.2 hr†||12 hr|
Contraindicated in: Hypersensitivity to tacrolimus or to castor oil (a component in the injection). Lactation: Breastfeeding should be avoided.
Use Cautiously in: Renal or hepatic impairment (dose ↓ may be required; if oliguria occurs, wait 48 hr before initiating tacrolimus).Concurrent use with cyclosporine should be avoided.Exposure to sunlight/UV light (may ↑ risk of malignant skin changes). Obstetric: Hyperkalemia and renal impairment may occur in the newborn; use only if benefit to mother justifies risk to the fetus.
Adverse Reactions/Side Effects
Central nervous system
- seizures (life-threatening)
- dizziness (most frequent)
- headache (most frequent)
- insomnia (most frequent)
- tremor (most frequent)
- abnormal dreams
- emotional lability
Ear, Eye, Nose, Throat
- abnormal vision
- cough (most frequent)
- pleural effusion (most frequent)
- pulmonary edema
- hypertension (most frequent)
- peripheral edema (most frequent)
- QTc interval prolongation
- GI bleeding (life-threatening)
- abdominal pain (most frequent)
- anorexia (most frequent)
- ascites (most frequent)
- constipation (most frequent)
- diarrhea (most frequent)
- dyspepsia (most frequent)
- ↑ liver enzymes (most frequent)
- nausea (most frequent)
- vomiting (most frequent)
- cholestatic jaundice
- ↑ appetite
- oral thrush
- nephrotoxicity (most frequent)
- urinary tract infection (most frequent)
- pruritus (most frequent)
- rash (most frequent)
- herpes simplex
- hyperglycemia (most frequent)
Fluid and Electrolyte
- hyperkalemia (most frequent)
- hyperlipidemia (most frequent)
- hypokalemia (most frequent)
- hypomagnesemia (most frequent)
- hypophosphatemia (most frequent)
- metabolic acidosis
- metabolic alkalosis
- anemia (most frequent)
- leukocytosis (most frequent)
- leukopenia (most frequent)
- thrombocytopenia (most frequent)
- coagulation defects
- pure red cell aplasia
- arthralgia (most frequent)
- leg cramps
- muscle spasm
- paresthesia (most frequent)
- allergic reactions including anaphylaxis (life-threatening)
- fever (most frequent)
- generalized pain (most frequent)
- abnormal healing
- risk of lymphoma/skin cancer
Drug-Drug interactionRisk of nephrotoxicity is ↑ by concurrent use of aminoglycosides, amphotericin B, cisplatin, or cyclosporine (allow 24 hr to pass after stopping cyclosporine before starting tacrolimus).Concurrent use of potassium-sparing diuretics, ACE inhibitors, or angiotensin II receptor antagonists ↑ risk of hyperkalemia.The following drugs ↑ tacrolimus blood levels: azoleantifungals, bromocriptine, calcium channel blockers, chloramphenicol, cimetidine, clarithromycin, cyclosporine, danazol, erythromycin, lansoprazole, magnesium/aluminum hydroxidemethylprednisolone, omeprazole, nefazodone, metoclopramide, protease inhibitors, and voriconazole.Phenobarbital, phenytoin, caspofungin, sirolimuscarbamazepine, and rifamycins may ↓ tacrolimus blood levels.Vaccinations may be less effective if given concurrently with tacrolimus (avoid use of live-virus vaccines). Concomitant use with astragalus, echinacea, and melatonin may interfere with immunosuppression.St. John's wort may ↓ tacrolimus blood levels.Food ↓ the rate and extent of GI absorption.Grapefruit juice ↑ absorption.
Route/DosageBecause of the potential risk for anaphylaxis, the IV route of administration of tacrolimus should be reserved for those patients unable to take the drug orally.Kidney Transplantation
Oral (Adults) Initial dose—0.2 mg/kg/day in 2 divided doses; titrate to achieve recommended blood concentration.
Oral (Children) 0.15–0.4 mg/kg/day in 2 divided doses.
Intravenous (Adults) Initial dose—0.03–0.1 mg/kg/day as a continuous infusion; titrate to achieve recommended blood concentration.
Intravenous (Children) 0.03–0.15 mg/kg/day.Liver Transplantation
Oral (Adults) Initial dose—0.1–0.15 mg/kg/day in 2 divided doses; titrate to achieve recommended blood concentration.
Oral (Children) Initial dose—0.15–0.2 mg/kg/day in 2 divided doses; titrate to achieve recommended blood concentration.
Intravenous (Adults and Children) Same as for kidney transplant.Heart Transplanatation
Oral (Adults) Initial dose—0.075 mg/kg/day in 2 divided doses; titrate to achieve recommended blood concentration.
Intravenous (Adults) Initial dose—0.01 mg/kg/day as a continuous infusion; titrate to achieve recommended blood concentration.
Availability (generic available)
Capsules: 0.5 mg, 1 mg, 5 mg
Injection: 5 mg/mL
- Prevention of Organ Rejection: Monitor blood pressure closely during therapy. Hypertension is a common complication of tacrolimus therapy and should be treated.
- Observe patients receiving IV tacrolimus for the development of anaphylaxis (rash, pruritus, laryngeal edema, wheezing) for at least 30 min and frequently thereafter. If signs develop, stop infusion and initiate treatment.
- Lab Test Considerations: Tacrolimus blood level monitoring may be helpful in the evaluation of rejection and toxicity, dose adjustments, and assessment of compliance. For liver transplantation, most patients are stable when tacrolimus trough whole blood concentrations are maintained between 5–20 ng/mL. For kidney transplantation, during the first 3 mo, most patients maintained tacrolimus whole blood concentrations between 7–20 ng/mL and then between 5–15 ng/mL through 1 yr. For heart transplantation, from wk 1 to 3 mo, most patients maintained tacrolimus trough whole blood concentrations between 8–20 ng/mL and then between 6–18 ng/mL from 3–18 mo post-transplant.
- Monitor serum creatinine, potassium, and glucose closely. ↑ serum creatinine and ↓ urine output may indicate nephrotoxicity. May also cause insulin-dependent post-transplant diabetes mellitus (incidence is higher in African American and Hispanic patients).
- May also cause hyperuricemia, hypokalemia, hyperkalemia, hypomagnesemia, metabolic acidosis, metabolic alkalosis, hyperlipidemia, hyperphosphatemia, hypophosphatemia, hypocalcemia, and hyponatremia.
- Monitor CBC. May cause anemia, leukocytosis, and thrombocytopenia.
Potential Nursing DiagnosesRisk for infection (Adverse Reactions)
- Do not confuse Prograf with Prozac.
- Therapy should be provided by clinicians and in facilities experienced in transplant management.
- Therapy with tacrolimus should be started no sooner than 6 hr post-transplantation. Concurrent therapy with corticosteroids is recommended in the early postoperative period.
- Tacrolimus should not be used concomitantly with cyclosporine. Tacrolimus or cyclosporine should be discontinued at least 24 hr before starting the other.
- Oral therapy is preferred because of the risk of anaphylactic reactions with IV tacrolimus. IV therapy should be replaced with oral therapy as soon as possible.
- Adults should be started at the lower end of the dose range. Pediatric: Children require higher doses to maintain blood trough concentrations of tacrolimus similar to adults.
- Oral: Oral doses can be initiated 8–12 hr after discontinuation of IV doses. Maybe taken with or without food, but with or without food should be consistent, 12 hrs apart, at the same time each day.
- Continuous Infusion: Dilute in 0.9% NaCl or D5W for a concentration of 0.004–0.02 mg/mL prior to use. May be stored in polyethylene or glass containers for 24 hr following dilution. Do not store in PVC containers.
- Rate: Administer daily dose as a continuous infusion over 24 hr.
- Y-Site Compatibility: alemtuzumab, alfentanil, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, amphotericin B colloidal, amphotericin B lipid complex, amphotericin liposome,. anidulafungin., argatroban, atracurium, azithromycin, aztreonam, benztropine, bivalirudin, bleomycin, bumetanide, buprenorphine, busulfan, butorphanol, calcium acetate, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine,. ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone sodium phosphate, dexmedetomidate, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doripenem, doxacurium, doxorubicin, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, epirubicin, ertapenem, erythromycin lactobionate, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, foscarnet, fosphenytoin, gemcitabine,. gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hetastarch, hydralazine, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, leucovorin, levofloxacin, levorphanol, lidocaine, linezolid, lorazepam, magnesioum sulfate, mannitol, mechlorethamine, meperidine, meropenem, mesna, metaraminol, methotrexate, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, micafungin, midazolam, milrinone, mitoxantrone, morphine, multivitamins, mycophenolate, nafcilin, nalbuphine, naloxone, nesiritide, nicardipine,.norepinephrine, nitroglycerin, nitroprussidenorepinephrine, oxtreotide, ondansetron, oxacillin, oxytocin, paclitaxel, palosetron, pamidronate, pamcuronium, pemetrexed, penicillin G potassium, pentamidine, pentazocine, perphenazine, phentolamine, phenylephrine,. piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, streptozocin, succinylcholine, sufentanil, teniposide, theophylline, thiotepa, ticarcillin/clavulactam, tigecycline, tirofiban, tobramycin, tolazoline, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, verapamil, vinCRIStine, vinorelbine, voriconazole, zidovudine, zolendronic acid
- Y-Site Incompatibility: acyclovir, allopruinol, azathioprine, cefepeme, dantrolene, diazepam, diazoxide, esomeprezole, folic acid, ganciclovir, iron sucrose, levothyroxine, omeprazole, phenytoin, thiopental
- Instruct patient to take tacrolimus at the same time each day, as directed. Do not skip or double up on missed doses. Do not discontinue medication without advice of health care professional. Advise patient to read the Medication Guide prior to starting and with each Rx renewal; new information may be available.
- Reinforce the need for lifelong therapy to prevent transplant rejection. Review symptoms of rejection for transplanted organ and stress need to notify health care professional immediately if they occur.
- Advise patient to avoid grapefruit or grapefruit juice and eating raw oysters or other shellfish; make sure they are fully cooked before eating.
- Advise patient to wear protective clothing and sunscreen to avoid photosensitivity reactions.
- Instruct patient to avoid exposure to chicken pox, measles, mumps, and rubella. If exposed, see health care professional for prophylactic therapy.
- Advise patient of the risk of taking tacrolimus during pregnancy.
- Inform patient of the risk of lymphoma with tacrolimus therapy.
- Emphasize the importance of repeated lab tests during tacrolimus therapy.
- Prevention of transplanted liver, kidney, or heart rejection.
A trademark for the drug tacrolimus.
a trademark for an immunosuppressive drug (tacrolimus).