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Be sure to stop by Booth 501 to speak with
us and learn more about the control, consistency, convenience, and confidence
that ENVARSUS XR has been offering for 10 years and counting.
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As we reflect on a decade of making a difference, we’re excited to continue
helping patients navigate common post-transplant pitfalls—together.
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Best regards,
The ENVARSUS XR Brand Team
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Please see Important Safety Information below and full
Prescribing Information, including Boxed Warning, and updated Warnings and
Precautions.
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ENVARSUS XR was first approved by the FDA on July
10, 2015.
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INDICATIONS AND USAGE
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ENVARSUS XR is indicated for the prophylaxis of organ rejection in de novo
kidney transplant patients in combination with other immunosuppressants.
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ENVARSUS XR is also indicated for the prophylaxis of organ rejection in kidney
transplant patients converted from tacrolimus immediate-release formulations in
combination with other immunosuppressants.
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IMPORTANT SAFETY INFORMATION
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WARNING: MALIGNANCIES AND SERIOUS INFECTIONS
Increased risk for developing serious infections and malignancies with ENVARSUS
XR or other immunosuppressants that may lead to hospitalization or death
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CONTRAINDICATIONS
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ENVARSUS XR is contraindicated in patients with known hypersensitivity to
tacrolimus or to any of the ingredients in ENVARSUS XR.
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WARNINGS AND PRECAUTIONS
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Lymphoma and Other Malignancies: Immunosuppressants, including ENVARSUS
XR, increase the risk of developing lymphomas and other malignancies,
particularly of the skin. Post-transplant lymphoproliferative disorder (PTLD),
associated with Epstein-Barr Virus (EBV), has been reported in immunosuppressed
organ transplant patients.
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Serious Infections: Immunosuppressants, including ENVARSUS XR, increase
the risk of developing bacterial, viral, fungal, and protozoal infections,
including opportunistic infections. These infections may lead to serious,
including fatal, outcomes.
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Not Interchangeable with Other Tacrolimus Products – Medication Errors:
Medication errors, including substitution and dispensing errors, between
tacrolimus capsules and tacrolimus extended-release capsules were reported
outside the U.S. in some cases leading to adverse reactions. ENVARSUS XR is not
interchangeable or substitutable with tacrolimus extended-release capsules,
tacrolimus capsules or tacrolimus for oral suspension.
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New Onset Diabetes after Transplant: ENVARSUS XR 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.
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Nephrotoxicity due to ENVARSUS XR and Drug Interactions: ENVARSUS XR,
like other calcineurin-inhibitors, can cause acute or chronic nephrotoxicity. 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. The risk for nephrotoxicity
may increase when ENVARSUS XR is concomitantly administered with CYP3A
inhibitors (by increasing tacrolimus whole blood concentrations) or drugs
associated with nephrotoxicity. When tacrolimus is used concurrently with CYP3A
inhibitors or other known nephrotoxic drugs, monitor renal function and
tacrolimus blood concentrations, and adjust dose of both tacrolimus and/or
concomitant medications during concurrent use.
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Neurotoxicity: ENVARSUS XR may cause a spectrum of neurotoxicities. The
most severe neurotoxicities include posterior reversible encephalopathy syndrome
(PRES), delirium, seizure, and coma; others include tremors, paresthesias,
headache, mental status changes, and changes in motor and sensory functions.
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Hyperkalemia: Mild to severe hyperkalemia, which may require treatment,
has been reported with tacrolimus including ENVARSUS XR. Concomitant use of
agents associated with hyperkalemia may increase the risk for hyperkalemia.
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Hypertension: Hypertension is a common adverse reaction of ENVARSUS XR
therapy and may require antihypertensive therapy.
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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. In contrast, the
concomitant use of strong CYP3A inhibitors may decrease the metabolism of
tacrolimus, leading to higher whole blood trough concentrations and greater risk
of serious adverse reactions. Therefore, adjust ENVARSUS XR dose and monitor
tacrolimus whole blood trough concentrations when co-administering ENVARSUS XR
with strong CYP3A inhibitors or strong CYP3A inducers. A rapid, sharp rise in
tacrolimus levels has been reported after co-administration with strong CYP3A4
inhibitors despite an initial reduction of tacrolimus dose. Early and frequent
monitoring of tacrolimus whole blood trough levels is recommended.
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QT Prolongation: ENVARSUS XR may prolong the QT/QTc interval and cause
Torsade de pointes. Avoid ENVARSUS XR in patients with congenital long QT
syndrome. Consider obtaining electrocardiograms and monitoring electrolytes
periodically during treatment in patients with congestive heart failure,
bradyarrhythmias, those taking certain antiarrhythmic medications or other
products that lead to QT prolongation, and those with electrolyte disturbances.
When co-administering ENVARSUS XR with other substrates and/or inhibitors of
CYP3A, especially those that also have the potential to prolong the QT interval,
a reduction in ENVARSUS XR dosage, monitoring of tacrolimus whole blood
concentrations, and monitoring for QT prolongation is recommended.
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Immunizations: Whenever possible, administer the complete complement of
vaccines before transplantation and treatment with ENVARSUS XR. Avoid the use of
live attenuated vaccines during treatment with ENVARSUS XR. Inactivated vaccines
noted to be safe for administration after transplantation may not be
sufficiently immunogenic during treatment with ENVARSUS XR.
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Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been
reported in patients treated with tacrolimus. If PRCA is diagnosed, consider
discontinuation of ENVARSUS XR.
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Cannabidiol Drug Interactions: When cannabidiol and ENVARSUS XR are
co-administered, closely monitor for an increase in tacrolimus blood levels and
for adverse reactions suggestive of tacrolimus toxicity. A dose reduction of
ENVARSUS XR should be considered as needed when ENVARSUS XR is co-administered
with cannabidiol.
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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 ENVARSUS XR.
Transplant patients may have other risk factors which contribute to the risk of
TMA. In patients with signs and symptoms of TMA, consider ENVARSUS XR as a risk
factor. Concurrent use of ENVARSUS XR and mammalian target of rapamycin (mTOR)
inhibitors may contribute to the risk of TMA.
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ADVERSE REACTIONS
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De Novo kidney transplant patients: Most common adverse reactions (incidence
≥15%) reported with ENVARSUS XR are diarrhea, anemia, urinary tract infection,
hypertension, tremor, constipation, diabetes mellitus, peripheral edema,
hyperkalemia and headache.
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Conversion of kidney transplant patients from immediate-release tacrolimus: Most
common adverse reactions (incidence ≥10%) reported with ENVARSUS XR include:
diarrhea and blood creatinine increased.
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USE IN SPECIFIC POPULATIONS
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Pregnancy: Based on postmarketing surveillance, registry and animal data
may cause fetal harm. Advise pregnant women of the potential risk to the fetus.
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Nursing Mothers: Tacrolimus is present in human milk. Discontinue drug or
nursing, taking into account the importance of drug to the mother.
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Females and Males of Reproductive Potential: Advise female and male
patients of reproductive potential to speak with their healthcare provider on
family planning options including appropriate contraception prior to starting
treatment with ENVARSUS XR. Based on animal studies, ENVARSUS XR may affect
fertility in males and females.
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Pediatric Use: The safety and efficacy of ENVARSUS XR in pediatric
patients have not been established.
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Geriatric Use: Clinical studies of ENVARSUS XR did not include sufficient
numbers of patients aged 65 and over to determine whether they respond
differently from younger patients.
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Renal Impairment: Frequent monitoring of renal function is recommended.
Lower doses may be required.
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Hepatic Impairment: Frequent monitoring of tacrolimus trough
concentrations is recommended. With greater tacrolimus whole blood trough
concentrations in patients with severe hepatic impairment, there is a greater
risk of adverse reactions and dosage reduction is recommended.
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Race: African-American patients may require higher doses to attain
comparable trough concentrations compared to Caucasian patients.
African-American and Hispanic kidney transplant patients are at an increased
risk for new onset diabetes after transplant. Monitor blood glucose
concentrations and treat appropriately.
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To report SUSPECTED ADVERSE REACTIONS, contact Veloxis Pharmaceuticals, Inc. at
1-844-VELOXIS (835-6947) or
FDA at 1-800-FDA-1088 or visit
www.fda.gov/medwatch.
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Please see full
Prescribing Information, including Boxed Warning, and updated Warnings and
Precautions.
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References: 1. ENVARSUS XR [package insert]. Cary, NC: Veloxis
Pharmaceuticals, Inc.; 4/2024. 2. Combined Symphony Health, 867, 3PL
data, 10/2024. 3. Data on File. Veloxis Pharmaceuticals, Inc.; 2024.
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