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It’s easy to learn about the unique benefits of ENVARSUS XR by joining these webinars or watching the videos.
Immunosuppression in "Rapid Metabolizers" of Tacrolimus
A rapid metabolizer is defined as an expressor of the CYP3A5*1 gene variant. They have increased CYP3A5 activity, which leads to increased metabolism of tacrolimus. Patients with this gene variant require a 1.5–2.0 times higher dose of immediate-release tacrolimus
(IR-Tac), which may lead to higher tacrolimus peaks. Unlike IR-Tac, the PK of ENVARSUS XR is not impacted by genotype.
Tarek Alhamad, MD, MS, FACP, FASN
St. Louis, MO
- Review the challenges in achieving consistent therapeutic levels of tacrolimus
- Introduce the impact of specific genetic mutations of the CYP3A5 allele
- Discuss the clinical implications for rapid metabolizers of tacrolimus and treatment
- Review ASERTAA trial, which examined the effects of rapid tacrolimus metabolism in African-Americans
- Discuss the clinical utilization of ENVARSUS XR (tacrolimus extended-release tablets)
Length: 27 minutes
A Transplant Coordinator's Perspective on ENVARSUS XR
Discover a seasoned transplant coordinator's approach to ENVARSUS XR. The prerecorded webinar includes conversion steps, patient case studies and financial support programs for ENVARSUS XR.
Andrea Markwardt, RN, CCTN, MSN
Kidney and Pancreas Transplant Coordinator
St. Louis, MO
- The impact of specific genetic mutations of the CYP3A5 allele
- Clinical implications for rapid metabolizers of tacrolimus and treatment considerations
- How to utilize ENVARSUS XR in clinical practice
- Financial support options for patients
Length: 32 minutes
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ENVARSUS XR Overview Video
ENVARSUS XR is a one-of-a-kind formulation of tacrolimus supported by extensive clinical data. Examine the potential benefits for your patients.
Slide 1: Intro Screen - ENVARSUS XR is a unique formulation of tacrolimus developed by Veloxis pharmaceuticals.
Slide 2: Please see boxed warning regarding malignancies and serious infections as well as additional full Important Safety Information at the end of the video.
Slide 3: Tacrolimus, the mainstay of immunosuppression, has a narrow therapeutic window and highly variable pharmacokinetics. This poses challenges to achieving the optimal level of immunosuppression for each patient.
Prolonging the time the drug is within the therapeutic window may be important to avoid supratherapeutic and subtherapeutic drug exposure. One of the challenges in achieving and maintaining the desired therapeutic exposure of tacrolimus is poor bioavailability which can also make it difficult to achieve the target trough level and overall drug exposure.
Sometimes, the desired target trough can be achieved by giving a higher dose. However, administering a higher dose to some patients can result in a significantly higher peak concentration, sometimes well above the maximum therapeutic concentration.
Likewise, dose reductions necessary to address overexposure and its potential complications can lower trough, and therefore total exposure, below the desired level, placing the patient at risk for rejection.
Slide 4: ENVARSUS XR is a unique, once-daily formulation of tacrolimus designed to provide a controlled release over 24 hours through the entire GI tract.
Slide 5: ENVARSUS XR demonstrates a smooth pharmacokinetic profile across all patient types, allowing for stable tacrolimus exposure over 24 hours.
Slide 6: While IR Tacrolimus is absorbed almost entirely in the proximal GI tract, ENVARSUS XR is designed for dissolution and absorption over a broad area of the GI tract.
Slide 7: This allows ENVARSUS XR to maintain whole blood concentrations within the narrow therapeutic window while overcoming some of the limitations of other tacrolimus formulations.
In a robust three-period crossover study, ENVARSUS XR, achieved target trough levels with a significantly lower peak versus Prograf or Astagraf XL.
Slide 8: The Pharmacokinetics of Envarsus XR have been evaluated in multiple patient types, including rapid metabolizers.
Slide 9: Rapid metabolizers of tacrolimus are carriers of the CYP3A5*1 allele, and though the prevalence of the gene varies by race, race, as a phenotype, is not a sufficient predictor of metabolizer status.
Slide 10: Regardless of race, in fact, 1 in 3 kidney transplant recipients may be a rapid metabolizer of tacrolimus, and may be at risk of underimmunosuppression.
Slide 11: Studies have shown that Rapid Metabolizers require 1.5 to 2 times higher doses of tacrolimus to achieve target trough levels.
The DeKAF study found that despite 60% higher doses of immediate release tacrolimus, trough levels were more likely to be below target in African-American patients.
The ASERTAA study examined the impact of Immediate Release tacrolimus and ENVARSUS XR in the rapid metabolizer population.
Slide 12: In the ASERTAA Study, patients were genotyped to determine metabolizer status. Non-expressors of the CYP3A5*1 genotype demonstrated an IR-Tacrolimus pharmacokinetic profile consistent with previous studies.
In this study, rapid metabolizers required a 61% higher dose of IR-Tacrolimus to achieve the required target trough. This resulted in an increase in the peak concentration, with a 34% higher average Cmax in rapid metabolizers than in nonexpressors.
Slide 13: Compare this with the pharmacokinetics of patients when converted to ENVARSUS XR. Nonexpressors demonstrated the smooth ENVARSUS XR pharmacokinetic curve that is consistent with other published literature. Most interesting, perhaps, is that ENVARSUS XR demonstrated the same pharmacokinetic profile in rapid metabolizers. The peak concentrations were not different in rapid metabolizers and nonexpressors.
And in both groups ENVARSUS XR significantly reduced the peak experienced versus IR-tacrolimus; in the rapid metabolizer group, conversion to ENVARSUS XR resulted in a 34% reduction in Cmax compared to IR-tacrolimus.
Slide 14: Patients can be switched to ENVARSUS XR with confidence.
Slide 15: ENVARSUS XR is unique. It has been designated an orphan drug by the FDA, and there are no substitutes or generic equivalents available.
Veloxis supported a robust clinical development program to bring ENVARSUS XR to market, studying the drug in more than sixteen hundred patients.
Slide 16: The body of evidence for ENVARSUS XR is clear, with robust safety and efficacy data. Patients can be switched to ENVARSUS XR with confidence, without sacrificing efficacy.
In a large multicenter, multinational Phase 3 study, there were no significant differences in outcomes between Prograf and once-daily ENVARSUS XR. Renal function was maintained and there were no acute rejection episodes in the first 30 days post-conversion.
Slide 17: ENVARSUS XR delivers its unique pharmacokinetics while maintaining the expected safety profile. In the same Phase 3 study, there were no significant differences between ENVARSUS XR and Prograf for predefined clinically significant laboratory measures, opportunistic infection, malignancies or NODAT.
Slide 18: A majority of the kidney transplant centers in the US have identified patients for whom they prescribed ENVARSUS XR. ENVARSUS XR delivers a controlled, smooth release with once-daily dosing, resulting in a 30% lower peak on average compared with IR-tacrolimus.
There are many options for immunosuppression, so it is important to consider adjusting the immunosuppression regimen of patients who are unable to maintain adequate drug doses, requiring excessively high drug levels, or experiencing side effects.
Veloxis Ambassador Video
Watch three patients tell their transplant journey and experience on ENVARSUS XR.