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Tacrolimus is a brand name for Tacrolimus. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Tacrolimus extended-release capsules is indicated for the prophylaxis of organ rejection in kidney transplant patients in combination with other immunosuppressants in adult patients who can swallow capsules intact [see Clinical Studies ( 14.1 ), ( 14.2 )] . Pediatric use information is approved…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Capsules must be taken whole. 1 ) Take consistently every morning at the same time on an empty stomach at least 1 hour before a meal or at least 2 hours after a meal. 1 ) Avoid eating grapefruit or drinking grapefruit juice or alcohol.
1 ) African-American patients and patients with severe hepatic impairment may require dosing adjustments. 3 ) Frequent monitoring of trough concentrations is recommended. 4 ) For complete dosing information, see Full Prescribing Information.
1 Important Administration Instructions Tacrolimus extended-release capsules should not be used without the supervision by a physician with experience in immunosuppressive therapy. Tacrolimus extended-release capsules is not interchangeable or substitutable for tacrolimus extended-release tablets, tacrolimus immediate-release capsules or tacrolimus for oral suspension.
Under or overexposure to tacrolimus may result in graft rejection or other serious adverse reactions. 4 )]. Advise patients to swallow tacrolimus extended-release capsules whole with liquid; patients must not chew, divide, or crush the capsules.
3 )]. , for a missed 8:00 AM dose, a dose may be taken by 10:00 PM). Beyond the 14-hour time frame, the patient should wait until the usual scheduled time the following morning to take the next regular daily dose. Instruct the patient not to double the next dose.
2 )]. 4 )] . 2 Dosage Recommendations for Kidney Transplant Patients Table 1 includes the recommended starting tacrolimus extended-release capsules dosages and whole blood trough concentration ranges; the observed trough concentrations are shown in another section of the Full Prescribing Information [see Clinical Studies ( 14 )] .
11 )] . 's ASTAGRAF XL (tacrolimus extended-release capsules). 's marketing exclusivity rights, this drug product is not labeled with that information. 3 ) and Clinical Studies ( 14 )] . 3 )]. 3 )]. 3 )] , or after a change in renal or hepatic function.
When interpreting measured concentrations, consider that the time to achieve tacrolimus steady state is approximately 7 days after initiating or changing the tacrolimus extended-release capsules dose. , immunoassays or high performance liquid chromatography with tandem mass spectrometric detection (HPLC/MS/MS)].
14) ] The most common adverse reactions (≥ 30%) are: diarrhea, constipation, nausea, peripheral edema, tremor and anemia. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact eVenus Pharmaceutical Laboratories, Inc. gov/medwatch . 1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In addition, the clinical trials were not designed to establish comparative differences across study arms with regards to the adverse reactions discussed below. S. 1 )] . S. 2 )] . In Study 1, the proportion of patients who discontinued treatment due to adverse reactions was 9% and 11% in the tacrolimus extended-release capsules and tacrolimus immediate-release treatment groups, respectively, through 12 months of treatment.
The most common adverse reactions leading to discontinuation in tacrolimus extended-release capsules-treated patients were related to infections or renal/urinary disorders. Infections The overall incidence of infections, serious infections, and infections with identified etiology reported in patients treated with the tacrolimus extended-release capsules or tacrolimus immediate-release product in Study 1 are shown in Table 2 .
Table 2:
Percentage of Patients with Infections in Study 1 Study 1 was not designed to support comparative claims of tacrolimus extended-release capsules compared to tacrolimus immediate-release product for the adverse reactions reported in this table.
5 )] .
Table 3:
Percentage of Patients with NODAT Through One Year Post-Kidney Transplant in Study 1 Study 1 was not designed to support comparative claims of tacrolimus extended-release capsules compared to tacrolimus immediate-release product for the adverse reactions reported in this table.
5 WARNINGS AND PRECAUTIONS Not Interchangeable with Other Tacrolimus Products-Medication Errors: Instruct patients or caregivers to recognize the appearance of tacrolimus extended-release capsules. 4 ) New onset diabetes after transplant: Monitor blood glucose.
5 ) Nephrotoxicity (acute and/or chronic): May occur due to tacrolimus extended-release capsules, drug interactions, concomitant nephrotoxic drugs. Monitor renal function; consider dosage reduction. 6 ) Neurotoxicity: Including risk of posterior reversible encephalopathy syndrome (PRES), monitor for neurologic abnormalities; reduce dosage or discontinue tacrolimus extended-release capsules.
7 ) Hyperkalemia: Risk may be increased with other agents associated with hyperkalemia; monitor serum potassium levels. 8 ) Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. 9 ) QT prolongation: Consider obtaining electrocardiograms and monitoring electrolytes in patients at high risk.
11 ) Immunizations: Avoid live vaccines. 12 ) Pure red cell aplasia: Consider discontinuation of tacrolimus extended-release capsules. 13 ) Thrombotic Microangiopathy, Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura: May occur, especially in patients with infections and certain concomitant medications.
1 Lymphoma and Other Malignancies Immunosuppressants, including tacrolimus extended-release capsules, increase the risk of developing lymphomas and other malignancies, particularly of the skin . The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.
Examine patients for skin changes and advise to avoid or limit exposure to sunlight and UV light by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor. Post-transplant lymphoproliferative disorder (PTLD), associated with Epstein-Barr Virus (EBV), has been reported in immunosuppressed organ transplant patients.
2 )] . Known hypersensitivity to tacrolimus. ( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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The immunosuppressive activity of tacrolimus is mainly due to the parent drug rather than to its metabolites. Immunoassays may react with metabolites as well as the parent drug. Therefore, whole blood tacrolimus trough concentrations obtained with immunoassays may be numerically higher than concentrations obtained with an assay using HPLC/MS/MS.
Comparison of the whole blood tacrolimus trough concentrations of patients to those described in the prescribing information and other published literature must be made with knowledge of the assay method(s) employed.
8 )] . Common Adverse Reactions The most common (≥ 30%) adverse reactions observed with tacrolimus extended-release capsules in Study 1 were: diarrhea, constipation, nausea, peripheral edema, tremor, and anemia. The incidence of adverse reactions that occurred in ≥ 15% of tacrolimus extended-release capsules-treated patients compared to tacrolimus immediate-release product through one year of treatment in Study 1 is shown by treatment groups in Table 4 .
Table 4:
Adverse Reactions (≥ 15%) in Kidney Transplant Patients Through One Year Post-Transplant in Study 1 Study 1 was not designed to support comparative claims of tacrolimus extended-release capsules compared to tacrolimus immediate-release for the adverse reactions reported in this table.
's ASTAGRAF XL (tacrolimus extended-release capsules). 's marketing exclusivity rights, this drug product is not labeled with that information. S. S. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
7 )] , coma, status epilepticus, quadriplegia, flaccid paralysis, hemiparesis, aphasia, syncope, carpal tunnel syndrome, nerve compression, mutism, dysarthria, somnolence Psychiatric Disorders: Mental status changes Renal and Urinary Disorders: Hemorrhagic cystitis, hematuria, urinary retention, urinary incontinence Respiratory, Thoracic and Mediastinal Disorders: Interstitial lung disease, pulmonary hypertension, lung infiltration, rhinitis allergic, hiccups Skin and Subcutaneous Tissue Disorders: Hyperpigmentation, photosensitivity Vascular Disorders: Hemorrhage
The risk of PTLD appears greatest in patients who are EBV seronegative, a population which includes many young children. Monitor EBV serology during treatment. 2 Serious Infections Immunosuppressants, including tacrolimus extended-release capsules, increase the risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections.
These infections may lead to serious, including fatal, outcomes.
Serious viral infections reported include:
Polyomavirus-associated nephropathy (especially due to BK virus infection) JC virus-associated progressive multifocal leukoencephalopathy (PML) Cytomegalovirus (CMV) infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor are at highest risk of CMV viremia and CMV disease.
2 )] . 3 Increased Mortality in Female Liver Transplant Patients In a clinical trial of 471 liver transplant patients randomized to tacrolimus extended-release capsules or tacrolimus immediate-release product, mortality at 12 months was 10% higher among the 76 female patients (18%) treated with tacrolimus extended-release capsules compared to the 64 female patients (8%) treated with tacrolimus immediate-release product.
Tacrolimus extended-release capsules is not approved for the prophylaxis of organ rejection in patients who received a liver transplant. S. This led to serious adverse reactions, including graft rejection, or other adverse reactions due to under- or over-exposure to tacrolimus.
Tacrolimus extended-release capsules is not interchangeable or substitutable for tacrolimus extended-release tablets, tacrolimus immediate-release capsules or tacrolimus for oral suspension. Changes between tacrolimus immediate-release and extended-release dosage forms must occur under physician supervision.
Instruct patients and caregivers to recognize the appearance of tacrolimus extended-release capsules [see Dosage Forms and Strengths ( 3 )] and to confirm with the healthcare provider if a different product is dispensed or if dosing instructions have changed.
5 New Onset Diabetes After Transplant Tacrolimus extended-release capsules caused new onset diabetes after transplant (NODAT) in kidney transplant patients, which may be reversible in some patients. African-American and Hispanic kidney transplant patients are at an increased risk.
8 )] . 6 Nephrotoxicity due to Tacrolimus Extended-Release Capsules and Drug Interactions Tacrolimus extended-release capsules, like other calcineurin-inhibitors, can cause acute or chronic nephrotoxicity in transplant patients due to its vasoconstrictive effect on renal vasculature, toxic tubulopathy and tubular-interstitial effects.
Acute renal impairment associated with tacrolimus toxicity can result in high serum creatinine, hyperkalemia, decreased secretion of urea and hyperuricemia, and is usually reversible. In patients with elevated serum creatinine and tacrolimus whole blood trough concentrations greater than the recommended range, consider dosage reduction or temporary interruption of tacrolimus administration.
, aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). 2 )]. 7 Neurotoxicity Tacrolimus extended-release capsules may cause a spectrum of neurotoxicities. 2 )] . As symptoms may be associated with tacrolimus whole blood trough concentrations at or above the recommended range, monitor for neurologic symptoms and consider dosage reduction or discontinuation of tacrolimus extended-release capsules if neurotoxicity occurs.
8 Hyperkalemia Mild to severe hyperkalemia, which may require treatment, has been reported with tacrolimus including tacrolimus extended-release capsules. 1 )] . Monitor serum potassium levels periodically during treatment. 1 )] . 8 )] .
2 )] . 10 Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection.
11 )] . 2 )] . A rapid, sharp rise in tacrolimus levels has been reported after co-administration with a strong CYP3A4 inhibitor, clarithromycin, despite an initial reduction of tacrolimus dose. 2) ] . 11 QT Prolongation Tacrolimus extended-release capsules may prolong the QT/QTc interval and cause Torsades de pointes .
Avoid tacrolimus extended-release capsules in patients with congenital long QT syndrome. , hypokalemia, hypocalcemia, or hypomagnesemia). 2 )] . 12 Immunizations Whenever possible, administer the complete complement of vaccines before transplantation and treatment with tacrolimus extended-release capsules.
, intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines). Inactivated vaccines noted to be safe for administration after transplantation may not be sufficiently immunogenic during treatment with tacrolimus extended-release capsules.
13 Pure Red Cell Aplasia Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus. All of these patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease, or concomitant medications associated with PRCA.
A mechanism for tacrolimus-induced PRCA has not been elucidated. If PRCA is diagnosed, consider discontinuation of tacrolimus extended-release capsules. 14 Thrombotic Microangiopathy (TMA) Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura Cases of thrombotic microangiopathy (TMA), including hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), have been reported in patients treated with tacrolimus extended-release capsules TMA may have a multifactorial etiology.
Risk factors for TMA that can occur in transplant patients include, for example, severe infections, graft-versus-host disease (GVHD), Human Leukocyte Antigen (HLA) mismatch, the use of calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors.
These risk factors may, either alone or combined, contribute to the risk of TMA. In patients with signs and symptoms of TMA, consider tacrolimus as a risk factor. Concurrent use of tacrolimus and mTOR inhibitors may contribute to the risk of TMA.
15 Cannabidiol Drug Interactions When cannabidiol and tacrolimus extended-release capsules are co-administered, closely monitor for an increase in tacrolimus blood levels and for adverse reactions suggestive of tacrolimus toxicity.
3) ] .