Version June 2024
| Drug | Suggested dose | |
| Glucocorticoids | ||
| Methylprednisolone, prednisone*¶ | Day 0 (intraoperatively) | Methylprednisolone 7 mg/kg (maximum 500 mg) IV once |
| Days 1 to 3 | Prednisone 1 mg/kg (maximum 80 mg) orally once dailyΔ | |
| Days 4 to 7 | Prednisone 20 mg orally once daily | |
| Days 8 to 14 | Prednisone 15 mg orally once daily | |
| Days 15 to 21 | Prednisone 10 mg orally once daily | |
| Day 22 and beyond | Prednisone 5 mg orally once daily | |
| Calcineurin inhibitors◊ | ||
| Tacrolimus | Oral◊ | |
| Intermediate-release tacrolimus capsules (Prograf) | ||
Starting dose:
Sublingual: To convert from oral immediate-release to sublingual, initiate sublingual treatment in a 1:1 ratio (mg:mg) using previously established total daily dose of immediate-release tacrolimus and titrate to target trough concentrations (NOTE: initial ratios of oral immediate-release to sublingual vary by center; eg, some centers reduce dose by 50% when converting). May administer by opening capsule(s) and applying contents under the tongue every 12 hours; adjust dose to target trough concentrations[2,3]. Refer to Lexicomp monograph for specifics including handling precautions and administration. Nasogastric tube: May administer contents of immediate-release capsules mixed in water or a compounded oral suspension via feeding tube in a 1:1 (mg:mg) ratio using previously established dosing. Avoid the use of polyvinylchloride (PVC) materials (eg, cups, tubing) as adsorption of drug to PVC may reduce tacrolimus bioavailability[10]. Readjust dose according to target trough concentrations. | ||
| Extended-release tacrolimus capsules (Astagraf XL, Advagraf) | ||
| NOTE: The initial dosing of extended-release tacrolimus listed here is based on manufacturer's labeling for use in combination with glucocorticoids and mycophenolate; initial doses are titrated to target trough concentrations. Many centers prefer to initiate tacrolimus using the intermediate-release formulation due to simpler dose titration and use lower initial doses with rATG induction; refer to UpToDate contributors' regimen above. May thereafter convert to the extended-release formulation. Starting dose (manufacturer's label):[5,6]
To convert from IV to extended-release (Astagraf XL): Administer the first oral extended-release dose 8 to 12 hours after discontinuation of IV tacrolimus. To convert from immediate-release to extended-release (Astagraf XL, Advagraf): Initiate extended-release treatment in a 1:1 ratio (mg:mg) using previously established total daily dose of immediate-release tacrolimus[4-6]. Administer once daily in the morning. Readjust dose according to target trough concentrations. | ||
| Extended-release tacrolimus tablets (Envarsus XR) | ||
| NOTE: The initial dosing of extended-release tacrolimus listed here is based on manufacturer's labeling for use in combination with glucocorticoids and mycophenolate with basiliximab induction; initial doses are titrated to target trough concentrations. Many centers prefer to initiate tacrolimus using the intermediate-release formulation due to simpler dose titration and use lower initial doses with rATG induction; refer to UpToDate contributors' regimen above. May thereafter convert to the extended-release formulation. Starting dose (manufacturer's label):[7]
To convert from IV to extended-release (Envarsus XR): Administer the first oral extended-release dose 8 to 12 hours after discontinuation of IV tacrolimus. To convert from immediate-release to extended-release (Envarsus XR): Initiate extended-release treatment with a once-daily dose that is 70 to 80% of the total daily dose of immediate-release tacrolimus[7]. | ||
| Intravenous◊ | ||
| IV (Prograf) | ||
Starting dose (manufacturer's label):[1]
NOTE: Due to risk of anaphylaxis, kidney toxicity, and neurotoxicity associated with use of IV formulation, oral or sublingual administration is highly preferred. To convert from immediate-release oral to IV: Administer one-fifth (⅕th) to one-third (⅓rd) of the total daily oral dose as a continuous infusion over 24 hours. To convert from IV to immediate-release oral capsules: Administer the first oral immediate-release dose 8 to 12 hours after discontinuation of IV tacrolimus. | ||
| Cyclosporine (modified)◊ | Starting dose: 4 to 10 mg/kg/day orally in two divided doses in combination with glucocorticoid and mycophenolate; titrate to target trough concentrations. Some centers initiate with non-weight-based dosing (eg, 50 to 100 mg orally twice daily). To convert from oral to IV: Administer one-third (⅓rd) of the total daily oral dose as a single dose over 2 to 6 hours. Many centers administer as two divided doses (ie, each infused over 2 to 6 hours, given every 12 hours) or as a 24-hour continuous infusion. | |
| Antimetabolites | ||
| Mycophenolate mofetil (MMF) | Starting dose: 500 mg to 1 g orally twice daily. IV and oral doses of MMF are equivalent. | |
| Enteric-coated mycophenolate sodium (EC-MPS) | Starting dose: 360 to 720 mg orally twice daily. Tablets must be swallowed whole. NOTE: MMF and EC-MPS are not equivalent. 250 mg of MMF is equivalent to 180 mg of EC-MPS; as an example, to convert from MMF 1000 mg twice daily, switch to EC-MPS 720 mg orally twice daily. | |
| Azathioprine | Starting dose: 1.5 mg/kg (range: 1 to 2 mg/kg) orally once daily as part of a combination regimen. Refer to UpToDate for role of TPMT activity testing. IV and oral doses of azathioprine are equivalent. | |
| mTOR inhibitors | ||
| Sirolimus | Conversion from calcineurin inhibitor for calcineurin inhibitor minimization or avoidance:
| |
| Everolimus | Conversion from calcineurin inhibitor for calcineurin inhibitor minimization or avoidance:
| |
| Costimulatory blockers | ||
| Belatacept | Conversion from calcineurin inhibitor:[8,9]
NOTE: Taper calcineurin inhibitor dose slowly over 1 month (100% of calcineurin inhibitor dose on day 1, 40 to 60% of calcineurin inhibitor dose on day 15, 20 to 30% of calcineurin inhibitor dose on day 22, discontinue on day 29 and beyond). Protocols for conversion to belatacept may vary among centers, and belatacept dose intensity may be individualized (eg, according to time since transplantation). | |
This table is for use in conjunction with UpToDate content on maintenance immunosuppressive therapy in adult kidney transplantation. Kidney transplant recipients typically receive a combination regimen consisting of a calcineurin inhibitor (usually tacrolimus), an antimetabolite (usually mycophenolate), and a glucocorticoid. For approach to regimen selection, determining initial dose, and dose adjustments, refer to UpToDate clinical topics and Lexicomp monographs.
Important note: Immunosuppressant medications have a narrow therapeutic margin and are subject to high significance drug interactions. Drug therapy should be managed by transplant specialists with expertise in therapeutic drug monitoring, and doses should be adjusted based on measurement of immunosuppressant concentrations, particularly when drug therapy is initiated or altered. If there are any concerns about the safety of a given medication or supplement, they should be discussed with the patient's transplant team prior to initiation.IV: intravenous; mTOR: mammalian (mechanistic) target of rapamycin; rATG: rabbit antithymocyte globulin; TPMT: thiopurine S-methyltransferase enzyme.
* Glucocorticoid regimens vary among transplant centers, and there is no consensus on the optimal dose or maintenance schedule following kidney transplantation. The use of long-term glucocorticoids as part of a maintenance immunosuppressive regimen also varies from center to center and patient to patient. Some centers continue maintenance glucocorticoids indefinitely, while some centers may choose to use long-term glucocorticoids in patients who are receiving a second transplant, who have a high panel of reactive antibody (PRA), or who have an immunologic cause for chronic kidney disease requiring glucocorticoids. Other centers may choose to withdraw glucocorticoids early after transplant (within weeks to months) in patients at low to moderate risk for rejection to minimize toxicity and decrease overall immunosuppression.
¶ This suggested glucocorticoid dosing regimen may require modification if the patient develops acute rejection in the early posttransplant period. Refer to UpToDate content on the modification of maintenance immunosuppression in kidney transplant recipients who develop acute rejection for further details.
Δ In patients who are unable to take oral medications in the immediate postoperative setting, intravenous methylprednisolone 1 mg/kg (maximum dose 80 mg) once daily can be used to in place of oral prednisone.
◊ Most centers initiate calcineurin inhibitor therapy just prior to or within the first 24 hours of transplantation. Initial doses are typically at the lower end of the dose range and titrated to target drug concentrations by the patient's transplant team based upon frequent (eg, daily) monitoring of levels. Do not substitute different tacrolimus or cyclosporine formulations without close drug level monitoring and supervision by the patient's transplant team.آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
