From the Guidelines
Tacrolimus should be administered at a dose of 0.05 mg/kg intravenously or 0.15 mg/kg orally twice per day for the treatment of steroid-refractory aGVHD, with careful monitoring of renal function and adjustment of trough levels to minimize toxicity 1.
Key Considerations
- The initial dose of tacrolimus may vary based on individual factors and transplant type, but target trough concentrations should be maintained between 4-8 ng/ml to balance efficacy and toxicity 1.
- Combination regimens with other immunosuppressive agents, such as MMF or AZA, may be used to allow for lower tacrolimus trough levels and preserve renal function 1.
- Basiliximab induction with delayed introduction of tacrolimus is recommended in patients at risk of post-transplant renal dysfunction 1.
- Regular monitoring of kidney function, blood pressure, and electrolytes is essential to minimize the risk of nephrotoxicity, neurotoxicity, and other common side effects.
Administration and Formulations
- Oral tacrolimus should be taken consistently with or without food to maintain stable blood levels, typically twice daily at 12-hour intervals.
- Tacrolimus is available as immediate-release capsules (Prograf), extended-release formulations (Envarsus XR, Astagraf XL), and oral suspension, which are not interchangeable without medical supervision.
- Topical tacrolimus (Protopic) should be applied as a thin layer to affected skin areas once or twice daily.
Special Considerations
- Patients with a history of recurrent or de novo non-melanoma skin cancer may benefit from an mTORi-based immunosuppression regimen 1.
- Screening for preformed DSAs should be performed in recipients at risk of humoral sensitization, and monitoring for de novo DSAs may be recommended to identify patients at risk of subclinical rejection 1.
From the FDA Drug Label
Tacrolimus, previously known as FK506, is the active ingredient in Tacrolimus capsules, USP Tacrolimus is a calcineurin-inhibitor immunosuppressant produced by Streptomyces tsukubaensis Tacrolimus has an empirical formula of C44H69NO12•H2O and a formula weight of 822. 03. The preparation of Tacrolimus is as a calcineurin-inhibitor immunosuppressant, available for oral administration as capsules containing the equivalent of 0.5 mg, 1 mg, or 5 mg of anhydrous tacrolimus USP.
- The inactive ingredients include:
- croscarmellose sodium
- hypromellose
- lactose monohydrate
- magnesium stearate
- The capsule shell contains:
- gelatin
- sodium lauryl sulfate (SLS)
- titanium dioxide
- iron oxide (yellow or red) 2
From the Research
Tacrolimus Preparation
- Tacrolimus is an immunosuppressive drug that requires careful dosing and monitoring to achieve optimal therapeutic levels 3, 4, 5, 6, 7
- The drug has a narrow therapeutic window, and its metabolism can be affected by various factors, including concomitant medications and genetic variations 3, 7
- Therapeutic drug monitoring is essential to adjust the dosage and minimize the risk of adverse effects or suboptimal immunosuppression 3, 4, 5, 7
Dosing Considerations
- The initial intravenous dose of tacrolimus can be adjusted to achieve target levels, with a recommended starting dose of 0.017 mg/kg/day 3
- Oral tacrolimus can be initiated with a 3.1:1 conversion ratio from intravenous dosing 3
- The area under the curve (AUC) is a more accurate predictor of tacrolimus exposure than trough concentrations, but AUC monitoring may not be feasible in all clinical settings 5
- Individualized C0 targets can be estimated using the AUC/C0 ratio to guide dosing adjustments 5
Clinical Outcomes
- Tacrolimus has been shown to be effective in preventing rejection and improving renal function in transplant patients 4, 6
- However, the drug can also have nephrotoxic effects, particularly at higher doses or with prolonged use 4
- Close monitoring of renal function and tacrolimus levels is necessary to minimize the risk of adverse effects and optimize clinical outcomes 3, 4, 5, 7