ENVARSUS® PA is NOT interchangeable or substitutable on an equal dose-by-dose basis with other existing tacrolimus-containing products (immediate- or extended-release capsules).
Inadvertent, unintentional, or unsupervised switching of immediate- or extended-release formulations of tacrolimus is unsafe. This can lead to graft rejection or increased incidence of adverse reactions, including under- or over-exposure to tacrolimus. Alterations in formulation or regimen should only take place under the close supervision of a transplant specialist.2
Inadvertent switching warning
Health Canada has released a Dear Healthcare Professional Letter on inadvertent switching between different tacrolimus oral formulations, which could lead to graft rejection and other adverse reactions, titled ‟Tacrolimus and the Risk of Graft Rejection due to Medication Errors: Inadvertent Switching between Different Oral Formulations.”
To learn more, please consult the complete letter here.
ENVARSUS® PA patient wallet card
An ENVARSUS® PA patient card is available to help minimize the risk of medication errors as a result of inadvertent substitution with other tacrolimus products.
To order some cards for your patients, please contact us at 1-888-867-7426 or medinfo.paladin@endo.com
ENVARSUS® PA tablets are available in the following strengths:
0.75 mg
1 mg
4 mg
Dosing considerations for ENVARSUS® PA2
Monitoring
This therapy requires careful monitoring by adequately qualified and equipped personnel. This medicinal product should only be prescribed, and changes in immunosuppressive therapy be initiated, by physicians experienced in immunosuppressive therapy and the management of transplant patients.
Substitution
Inadvertent, unintentional, or unsupervised switching of immediate- or extended-release formulations of tacrolimus is unsafe. This can lead to graft rejection or increased incidence of adverse reactions, including under- or over-exposure to tacrolimus. Alterations in formulation or regimen should only take place under the close supervision of a transplant specialist.
Cyclosporine
Tacrolimus should not be used simultaneously with cyclosporine.
Patients to be converted from cyclosporine to tacrolimus should receive the first tacrolimus dose no sooner than 24 hours after the last cyclosporine dose. Dosing may be further delayed in the presence of elevated cyclosporine levels.
Patients to be converted from tacrolimus to cyclosporine should receive the first cyclosporine dose no sooner than 24 hours after the last ENVARSUS® PA dose. Dosing may be further delayed in the presence of elevated tacrolimus levels.
After conversion, trough levels must be monitored for dose adjustments to achieve desired trough levels of cyclosporine or tacrolimus.
Therapeutic drug monitoring
Following conversion to any alternative formulation, therapeutic drug monitoring must be performed and dose adjustments made to ensure that whole blood trough levels of tacrolimus are maintained.
Due to intersubject variability following dosing with tacrolimus, individualization of the dosing regimen is necessary for optimal therapy.
Therapeutic drug monitoring is recommended for all patients receiving tacrolimus.
Ethnic origin
It should be noted that Black African American patients may require a higher dose to achieve the targeted trough levels.
Administration
ENVARSUS® PA should be taken in a consistent manner, each day at the same time, preferably in the morning. It is recommended to take ENVARSUS® PA either at least one hour before a meal or two hours after a meal. Patients converting from immediate-release (IR) tacrolimus formulations who routinely took their medication with meals should continue to do so.
To avoid inadvertent substitution or other errors, be sure to write ENVARSUS® PA on your patient’s prescription.
ENVARSUS® PA administration instructions2
Once-daily oral formulation of tacrolimus
The tablets should be swallowed whole (patients should not chew, divide, or crush the tablets) with fluid (preferably water) immediately after removal from the container.
Patients should avoid eating grapefruit or drinking grapefruit juice or alcohol when taking ENVARSUS® PA.
A missed dose should be taken as soon as possible on the same day. A double dose should not be taken on the next day.
ENVARSUS® PA should be taken in a consistent manner, each day at the same time, preferably in the morning.
It is recommended that ENVARSUS® PA be taken at least one hour before a meal or two hours after a meal. High-fat meals should be avoided.
Patients converting from IR tacrolimus formulations who routinely took their medication with meals should continue to do so.
Several cases of accidental overdose have been reported with tacrolimus. Symptoms have included tremor; headache; nausea and vomiting; infections; urticaria; lethargy; and increases in blood urea nitrogen, serum creatinine, and alanine aminotransferase levels.
No specific antidote to tacrolimus therapy is available. If an overdose occurs, general supportive measures and symptomatic treatment should be conducted. It is anticipated that tacrolimus will not be dialysable.
In isolated patients with very high plasma levels, hemofiltration or diafiltration have been effective in reducing toxic concentrations. In cases of oral intoxication, gastric lavage and/or the use of adsorbents (such as activated charcoal) may be helpful if used shortly after intake.
Please see the Product Monograph for complete dosing and administration information.