Tacrolimus (Systemic)

Name: Tacrolimus (Systemic)

Brand Names U.S.

  • Astagraf XL
  • Envarsus XR
  • Hecoria [DSC]
  • Prograf

Pharmacologic Category

  • Calcineurin Inhibitor
  • Immunosuppressant Agent

Special Populations Hepatic Function Impairment

The mean clearance was substantially lower in patients with severe hepatic impairment.

Special Populations Race

Cmax is lower, Tmax is prolonged, and bioavailability is increased in kidney transplant patients who are black.

Off Label Uses

Graft-versus-host disease (prevention/treatment)

Data from a retrospective study in patients, including pediatric patients, converted from cyclosporine to tacrolimus for resistant acute graft-versus-host disease (GVHD) suggests that the use of tacrolimus (systemic) may be beneficial for the prevention and treatment of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation [Furlong 2000]. Additionally, another retrospective study in pediatric allogeneic marrow transplantation demonstrated that tacrolimus was well-tolerated in pediatric patients undergoing allogeneic marrow transplantation. Clinical experience also suggests the utility of tacrolimus (systemic) in this setting [Przepiorka 1999], [Uberti 1999]. Additional data may be necessary to further define the role of tacrolimus in this condition.

Immunosuppression (maintenance) after lung transplant

Data from a number of clinical trials evaluating the use of tacrolimus in lung transplant support the use of tacrolimus in this setting. Results of a meta-analysis of trials comparing tacrolimus to cyclosporine for primary immunosuppression in lung transplant recipients suggest that while there was no difference in survival or rejection, tacrolimus may be superior to cyclosporine with regard to incidence of bronchiolitis obliterans syndrome (BOS), lymphocytic bronchitis, treatment withdrawal, and arterial hypertension; however, tacrolimus may be inferior with regard to the development of diabetes. The International Society for Heart and Lung Transplantation (ISHLT) registry data indicate that tacrolimus is the most frequently used calcineurin inhibitor for maintenance immunosuppression after lung transplant. Based on an ISHLT clinical practice guideline for the diagnosis and management of BOS, switching to tacrolimus is suggested if cyclosporine-treated patients develop BOS as described by multiple case series.

Intestinal transplant

Based on recommendations from experts and clinical experience in intestinal transplantation, tacrolimus is recommended as the calcineurin inhibitor of choice for prevention of rejection after intestinal transplant [Abu-Elmagd 2009a], [Abu-Elmagd 2009b], [Horslen 2006]. Specific dosing recommendations cannot be made due to insufficient evidence. Additional data may be necessary to further define the role of tacrolimus in intestinal transplant.

Rheumatoid arthritis (refractory)

Data from a randomized, double-blind, multicenter study in patients with disease-modifying antirheumatic drug (DMARD) refractory rheumatoid arthritis supports the use of tacrolimus monotherapy in the treatment of this condition [Yocum 2003]. The use of tacrolimus using a lower dose in addition to methotrexate in patients who do not respond adequately to methotrexate has also been evaluated[Lee 2016]. Additional trials may be necessary to further define the role of tacrolimus in the treatment of this condition.


Results from controlled and noncontrolled studies demonstrate that tacrolimus is generally effective in treating uveitis. However, limited prospective studies or controlled clinical trials have been performed. Further data are needed to establish the efficacy, safety, optimal dosage, and length of tacrolimus therapy for the treatment of uveitis in adults. An expert review panel recommends tacrolimus as third-line therapy for the treatment of uveitis in adults.

Dosing Geriatric

Refer to adult dosing. Use with caution; begin at the low end of dosing range.

Dietary Considerations

Capsule: Administer immediate release with or without food; be consistent with timing and composition of meals, food decreases bioavailability. Administer extended release on an empty stomach 1 hour before or 2 hours after a meal. Avoid grapefruit and grapefruit juice. Avoid alcohol.

ALERT U.S. Boxed Warning

Malignancies and serious infection:

Increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections and the possible development of malignancies such as lymphoma and skin cancer may result from immunosuppression and may lead to hospitalization or death.

Experienced physician:

Only health care providers experienced in immunosuppressive therapy and management of organ transplant patients should prescribe tacrolimus. Manage patients receiving the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources. The health care provider responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

Mortality in liver transplantation (Astagraf XL):

Increased mortality in female transplant patients with Astagraf XL. Astagraf XL is not approved for use in liver transplantation.