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tacrolimus (Envarsus PA / Envarsus / Envarsus XR)

✓ Approved

Paladin Labs, Inc. · FKBP1A · Small Molecule

What is tacrolimus?

tacrolimus is a small molecule developed by Paladin Labs, Inc.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesEnvarsus PA, Envarsus, Envarsus XR
CompanyPaladin Labs, Inc.
Drug ClassSmall Molecule
Molecular TargetFKBP1A
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Paladin Labs, Inc.

Mechanism of Action

Molecular Targets

tacrolimus acts on 1 molecular target:

FKBP1AFKBP prolyl isomerase 1A (FKBP-12, FKBP12)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

tacrolimus is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Immune system disordersSolid organ transplant rejection✓ Approved

Related Research Articles

PubMedFrontiers in immunology2026-10-22

Phenotypic shift from active class IV lupus nephritis to lupus podocytopathy: a case report highlighting the treatment-altering role of repeat kidney biopsy.

Wang Zhifa Z, Deng Jinxiu J, Shen Jinfeng J, Jiang Hui H et al.

The underlying pathophysiological mechanisms of proteinuria relapse in lupus nephritis (LN) patients during immunological remission are complex, often involving non-immune complex-mediated podocyte injury. We report a 21-year-old male with class IV LN and thrombotic microangiopathy (TMA). After multi-target induction and maintenance therapy, the patient achieved complete clinical remission. During subsequent follow-up, he developed progressive nephrotic-range proteinuria while maintaining serological remission (persistently negative autoantibodies and normal complement levels). Intensification of conventional immunosuppressants was ineffective. A repeat kidney biopsy revealed significant resolution of immune complex deposits but prominent focal segmental glomerulosclerosis (FSGS)-like changes with extensive podocyte foot process effacement. The regimen was adjusted to a podocyte-targeted therapy centered on tacrolimus, resulting in a rapid and sustained reduction in proteinuria. This case suggests that in the clinico-serological dissociation phase of LN, repeat kidney biopsy is of significant clinical value for identifying pathological phenotypic shifts, avoiding excessive immunosuppression, and guiding precision medicine.

PMID 42903163
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PubMedFrontiers in immunology2026-10-22

Case Report: Acute liver failure in systemic lupus erythematosus with autoimmune hepatitis-primary biliary cholangitis overlap: a belimumab-containing regimen and longitudinal follow-up.

Zhang Lina L, Zhang Tong T, Zhang Jing J, Wang Xiuhong X et al.

Severe autoimmune liver injury as the first manifestation of systemic lupus erythematosus (SLE) is rare, and concomitant autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap is uncommon. B-cell-activating factor (BAFF) provides a biological rationale for adjunctive therapy, although clinical evidence remains limited. A 72-year-old woman presented with 4 weeks of fatigue and anorexia and developed coagulopathy (international normalized ratio [INR] 1.8), ascites, and hepatic encephalopathy. Autoimmune testing showed antinuclear antibody 1:1280, high-titer anti-double-stranded DNA antibodies with hypocomplementemia, immunoglobulin G (IgG) 30.0 g/L, and antimitochondrial antibody positivity. Hepatitis B surface antigen, hepatitis C antibody, hepatitis E antibody, and Epstein-Barr virus and cytomegalovirus DNA tests were negative. Liver biopsy 42 days after corticosteroid initiation demonstrated interface hepatitis, destructive small-bile-duct injury, plasma cell-rich inflammation, and Batts-Ludwig stage 2 fibrosis without cirrhosis, supporting a clinicopathologic diagnosis of AIH-PBC overlap. Previously unrecognized chronic autoimmune liver disease could not be excluded. Prednisolone was started at 50 mg/day, followed 10 days later by intravenous belimumab, with concomitant ursodeoxycholic acid. Tacrolimus was added during maintenance. By 10 October 2025, liver biochemistry had improved, IgG was 9.42 g/L, and prednisolone had been reduced to 2.5 mg/day. Liver stiffness decreased from 21.5 to 9.7 kPa. Sustained biochemical improvement occurred during a belimumab-containing multidrug regimen. This observation does not establish the independent efficacy of belimumab or histological regression of fibrosis.

PMID 42903101
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PubMedThe Journal of the Association of Physicians of India2026-10-22

Risk Factors and Emerging Therapies for Immune Checkpoint Inhibitor-related Myocarditis: A Narrative Review.

Kalluri Ujjvala U, Subair Maazen Naduthra MN

Immune checkpoint inhibitors (ICIs) represent a groundbreaking development in immunotherapy, offering significant promise in the treatment of various malignancies previously considered incurable. However, despite their potential benefits, the increasing use of ICIs is associated with a spectrum of immune-related adverse events (irAEs). Myocarditis is a rare and potentially underestimated complication that represents the highest mortality rate among irAEs. The review aims to evaluate the current understanding of ICI-myocarditis (ICI-M) through providing a detailed overview of diagnostic challenges, screening strategies, and, in particular, the risk factors and evolving treatment agents beyond corticosteroids. A comprehensive literature review was conducted on PubMed, analyzing data from relevant clinical studies, case reports, preclinical models, and expert consensus guidelines. In addition, data from one ongoing clinical trial (ATRIUM trial) not yet indexed in PubMed were included to reflect emerging therapeutic developments. Despite the low incidence of ICI-M (0.06%-1%), which is likely underestimated, the mortality rate is the highest among irAEs; the most identifiable risk factors include combination therapy with ICI agents (anti-PD1 and anti-CTLA-4), preexisting cardiovascular and autoimmune diseases, use of ICIs alongside other anticancer treatments, certain tumor types, older age, and female sex. Diagnosis of the condition is faced with challenges such as nonspecific clinical features and often requires multimodal evaluation including biomarkers, imaging, and biopsy. High-dose corticosteroids remain the first-line treatment; however, steroid-refractory cases are increasingly reported. Promising second-line options include mycophenolate mofetil, antithymocyte globulin, abatacept, and tacrolimus; however, there is a lack of prospective data to support their efficacy. Studies conducted on various preclinical models highlight potential therapeutic targets such as CXCR3. ICI-M poses a significant challenge in cardio-oncology practice due to its underestimation, high mortality rate, and lack of robust clinical data evaluating standardized screening protocols and second-line treatment measures. Although several second-line agents show promise, the evidence supporting their usage is largely on the basis of expert consensus and case reports, hence representing a strong need for prospective studies offering direct comparisons. Likewise, preclinical studies show great promise in identifying the pathophysiology and potential therapeutic targets for ICI-M; however, translational studies are necessary to validate these findings.

PMID 42902674
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PubMedClinical transplantation and research2026-10-20

Sirolimus-based immunosuppression and reported rejection or death in heart transplant recipients using the U.S. Food and Drug Administration Adverse Event Reporting System.

Ogura Toru T, Shiraishi Chihiro C, Urawa Aiko A

Sirolimus, although not approved for heart transplant recipients (HTRs), is frequently prescribed off-label for mitigating calcineurin inhibitor-related toxicity and promoting graft survival. However, its adverse event profile and real-world outcome associations within specific immunosuppressive combinations remain unclear. This retrospective pharmacovigilance study utilized data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). To minimize confounding by concomitant medication, paired comparisons were restricted to regimens differing only by sirolimus use. Reporting odds ratios (RORs) and adjusted RORs (aRORs), controlling for demographic and geographic variables, were calculated for the composite outcome of transplant rejection or death. Each sirolimus-containing regimen was compared with its corresponding nonsirolimus reference. The sirolimus plus tacrolimus regimen showed lower disproportional reporting of transplant rejection or death than the tacrolimus regimen (ROR, 0.532 [95% CI, 0.284-0.994], P=0.048; aROR, 0.419 [95% CI, 0.218-0.804], P=0.009). In other tacrolimus-based regimens (tacrolimus plus mycophenolic acid, tacrolimus plus prednisone, and tacrolimus plus mycophenolic acid plus prednisone), sirolimus addition consistently showed RORs and aRORs <1.000, indicating a similar but nonsignificant trend toward lower reporting of transplant rejection or death. This FAERS-based analysis suggested an association between sirolimus-containing regimens and lower disproportional reporting of transplant rejection or death among HTRs. These findings should be interpreted as hypothesis-generating, as spontaneous reporting data are susceptible to confounding and cannot establish causality. Prospective studies with detailed clinical data are needed to determine whether this association persists after adequate confounding control.

PMID 42897907
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PubMedBMC nephrology2026-10-20

External evaluation of population pharmacokinetic models for tacrolimus in kidney transplant recipients: implications for model-informed precision dosing.

Raju Arun Prasath AP, Naithani Priyanka P, Kenwar Deepesh D, Singh Sarbpreet S et al.

Tacrolimus, a primary immunosuppressant in kidney transplantation, exhibits variable pharmacokinetics. While model-informed precision dosing (MIPD) using population pharmacokinetic (PopPK) models improve dosing accuracy, models developed in specific populations lack applicability in other populations. We aimed to evaluate the predictive performance of published models integrated in clinical decision support systems (CDSS) in Indian adult renal transplant recipients. Predictive performance of four published PopPK models were evaluated using an independent dataset of 120 trough concentrations from 60 adult renal transplant recipients. Models were assessed using prediction based and simulation-based diagnostics. Maximum a posteriori (MAP) Bayesian prediction was also used to evaluate the model performance. A priori predictions (PRED) for all four models demonstrated systematic underprediction, with relative mean prediction error (rME) ranging from - 25.0% to -64.0%, failing clinical acceptability thresholds. However, integrating patient-specific data via MAP Bayesian estimation corrected this bias and improved precision. Notably, all models achieved higher accuracy and precision, with more than 60% of individual predictions falling within [Formula: see text] ([Formula: see text]) of the observed values. Additionally, scaling down the clearance parameter by 30% mitigated the systematic bias observed in the initial a priori predictions. Published PopPK models exhibited significant systematic bias when applied to Indian renal transplant recipients, posing a substantial risk of overdosing if used without adjustment for initial dose selection. However, these models adapted using MAP Bayesian approach or scaling of clearance parameter demonstrate better predictive performance in this cohort, suggesting they can guide proactive precision dosing in the Indian cohort. Prospective studies evaluating the target attainment and clinical outcomes are required to establish their clinical applicability.

PMID 42897489
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PubMedFrontiers in immunology2026-10-20

Effect of immunosuppressive drugs on glucose-stimulated insulin secretion: concentration-response studies in dynamic perifusion assays.

Chuang Sung-Ting ST, Watts Brandon B, Alcazar Oscar O, Buchwald Peter P

Immunosuppressive drugs, which are required to maintain graft function in transplant recipients, are associated with many unavoidable side effects including posttransplant diabetes mellitus (PTDM) that involves both peripheral insulin resistance and impairment of insulin secretion. To characterize in detail the concentration-dependency of the effect of well-known immunosuppressive drugs on glucose-stimulated insulin secretion (GSIS), we performed dynamic perifusion studies with human pancreatic islets. The effect on the time-profile of GSIS has been assessed over a wide concentration range for several clinically relevant immunomodulatory therapies, including small-molecule drugs (cyclosporine, sirolimus, tacrolimus, prednisolone acetate, and loteprednol etabonate) and biologics (abatacept and anti-CD40L), plus a prospective β-cell proliferation-inducing agent (harmine). While biologics showed no significant detrimental effects after one-day treatment even at relatively high concentrations (5 µM), all small-molecule drugs inhibited insulin secretion in a concentration-dependent manner, although glucocorticoids showed a distinct response pattern. Calcineurin and mTOR inhibitors preserved GSIS within their therapeutic ranges but progressively distorted its time-profile at higher concentrations and completely suppressed secretion at the highest levels, where they were also cytotoxic. Cyclosporine exhibited the least, only about 35-fold, separation between its therapeutic target (C targ) and half-maximal GSIS inhibitory (IC50) concentrations. Glucocorticoids did not alter the shape of the time-profile but inhibited overall insulin secretion even at therapeutic levels without affecting islet viability. Their inhibitory effect only increased slowly with concentration and did not follow a classic sigmoid pattern that has unity Hill slope. These findings establish quantitative benchmarks for immunosuppressant-induced β-cell toxicity and provide a framework for optimizing immunosuppressive regimens to reduce the risk of PTDM.

PMID 42898311
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