Tacrolimus is an immunosuppressive agent used for prophylaxis of organ rejection post-transplant. Tacrolimus use is in combination with one or, most commonly, two other immunosuppressive medications. It has an application as an agent for as prevention or treatment for certain autoimmune diseases.
In solid organ transplantation, it serves as the treatment of organ rejection in kidney, liver, and heart allogeneic transplants. There is also an off-label indication for the prevention of rejection in lung transplant patients.
Other off-label indications include:
Tacrolimus indications also include topical use in moderate to severe atopic dermatitis, as well as other off-label dermatologic disease states.
Tacrolimus is a calcineurin inhibitor (CNI). It inhibits T-cell proliferation by binding to FK506 binding protein (FKBP).
Tacrolimus can administration can be by oral, sublingual, topical, or intravenous (IV) route. Oral tacrolimus is available in immediate-release (IR) and extended-release (ER: XR and XL) formulations. The various formulations have different pharmacokinetic parameters and are not interchangeable. Doses should be titrated to target trough concentrations.
Prevention of Post-Organ Transplant Rejection (Adult Dosing):
Heart Transplant: In combination with an antimetabolite
Kidney Transplant: Use in combination with an antimetabolite agent
Tacrolimus can be administered with or without food but may occur with food in the presence of GI intolerance. IR doses should be 12 hours apart. Dose rounding should be to a whole number that is feasible with the available strengths. For example, IR tacrolimus comes in 0.5 mg, 1mg, and 5 mg strengths.
Infection may be secondary to immunosuppression and highlights the importance of reducing target doses with careful monitoring to balance the risk of rejection.
Contraindications to tacrolimus include:
Tacrolimus is a narrow therapeutic index drug. Therapeutic monitoring of tacrolimus in transplant patients is a valuable tool in adjusting drug levels. Since tacrolimus use is typically in combination with other immunosuppressants, target levels usually decrease as post-transplant time increases to minimize Calcineurin Inhibitor mediated nephrotoxicity and adverse effects. Whole blood concentrations should be used, drawn typically within 30 minutes before the next dose. Therapeutic levels range from 5 to 20 mcg/mL, though 5 to 15 mcg/mL is often employed to alleviate toxicity while preventing rejection.
Additional monitoring parameters include renal function, hepatic function, serum electrolytes (Mg, Phos, K), glucose, and blood pressure. Parameters should initially be measured two to three times a week post-operatively, gradually decreasing as time passes, achieving target levels, and patient stabilization.
Following are recommendations for tacrolimus level ranges per British Columbia Transplant Guidelines (http://www.transplant.bc.ca/health-professionals/transplant-clinical-guidelines). However, target levels vary by institution, induction protocols, and patient needs.
Adult and Kidney and Kidney/Pancreas Transplant:
Adult Liver Transplant:
Adult Heart Transplant:
Adult Lung Transplant:
Due to tacrolimus' pathway of metabolism, many drug-drug interactions exist. If starting medications that inhibit or induce the metabolism of tacrolimus, added monitoring is suggested to prevent a supra or sub-therapeutic level.
Tacrolimus toxicity commonly presents as acute renal failure. Close monitoring of serum creatinine, GFR, and urine output is necessary for patients on tacrolimus.
Toxicity may also present as the development of adverse effects such as tremors, electrolyte disturbances, headaches, and increased in SCr.
No antidote exists currently to counter toxicity. Hemodialysis does not remove tacrolimus.
Management of post-transplant patients is multidisciplinary. A combination of the skills and knowledge of each profession contributes to the successful longevity of the transplanted organ, as well as a higher quality of life for the patient. As per the CMS guidelines, a multidisciplinary team for transplant must include the following disciplines at the minimum:
Awareness of all aspects of the transplant journey, education, and support are at the core of graft longevity. Patients must receive instruction on not only the medical aspects of the transplant, but the financial needs, necessary dietary changes, and effects of the medication. This area is where specialty nursing can play a significant role and counsel the patient appropriately.
Post-transplant, the patient is closely followed by the team, both inpatient and outpatient. Nursing again will be performing the initial dosing of tacrolimus, and of course, they should coordinate with the pharmacy staff regarding proper dosing and administrator. The pharmacy will also perform medication reconciliation, both initially, and as the overall drug regimen changes, to preclude drug interactions. Nursing will also be in the best position to monitor for adverse effects, and report these promptly to the physician in charge of the case. Collaborative, interprofessional evaluations by nursing, medical, and pharmacy of patient's state of health and being, as well as the medication efficacy and adverse effects, allow for thorough vigilance through the eyes and expertise of various professionals. [Level V]
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