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ENVARSUS PA is a brand name for Tacrolimus, supplied as a tablet (extended-release). The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ENVARSUS PA (tacrolimus prolonged-release tablets) is indicated in adult patients for: • the prophylaxis of organ rejection in allogenic kidney or liver transplant in combination with other immunosuppressants. 1.1 Pediatrics Pediatrics (<18 years of age): No data are available to Health Canada; therefore, Health…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations • ENVARSUS PA is a once-a-day oral formulation of tacrolimus. ENVARSUS PA therapy requires careful monitoring by adequately qualified and equipped personnel. This medicinal Serious Warnings and Precautions • ENVARSUS PA, as other immunosuppressants, can increase the risk for developing serious infections and malignancies that may lead to hospitalization or death (see 7 WARNINGS AND PRECAUTIONS, Carcinogenesis and Immune) • Only physicians experienced in immunosuppressive therapy and management of organ transplant should prescribe ENVARSUS PA.
Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient and should be consulted if a patient is converted to an alternative formulation so that therapeutic drug monitoring can be instituted.
ENVARSUS® PA (tacrolimus prolonged-release tablets) Page 5 of 41 product should only be prescribed, and changes in immunosuppressive therapy be initiated, by physicians experienced in immunosuppressive therapy and the management of transplant patients.
• 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. • Tacrolimus should not be used simultaneously with cyclosporine. • 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. • It should be noted that Black African American patients may require a higher dose to achieve the targeted trough levels.
• 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 1 hour before a meal or 2 hours after a meal. Patients converting from immediate-release tacrolimus formulations who routinely took their medication with meals should continue to do so.
1 Adverse Reaction Overview The most common adverse reactions reported with tacrolimus were: diarrhea, urinary tract infection, anemia, hypertension, constipation. 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. ENVARSUS® PA (tacrolimus prolonged-release tablets) Page 13 of 41 Kidney An integrated analysis of three clinical studies (two phase 3 studies [3001 and 3002] and one phase 2 study [2017]) in both de novo and stable kidney transplant recipients allowed for comparison of safety information (ENVARSUS PA versus tacrolimus immediate-release formulation).
In the mITT analysis set (n=924) of the pooled studies, 460 patients were in the ENVARSUS PA group and 464 patients were in the immediate-release formulation group (Table 4). 1%) TEAE: treatment emergent adverse event. 0. Treatment-emergent was defined as any AE that started after the first dose and within 30 days after the final dose of study drug.
4%) patients, respectively. 5%) AEs with fatal outcome in kidney transplant patients receiving ENVARSUS PA in the pooled phase 2 and 3 studies, regardless of the causality assessment. 2%). Liver An integrated analysis of two (2) Phase 2 studies in both de novo and stable liver transplant recipients allowed for comparison of safety information (ENVARSUS PA versus immediate- release formulation).
Of the 117 patients randomized in the pooled studies, 88 patients were in the ENVARSUS PA group and 29 were in the immediate-release formulation group. 4% of patients. 1 Clinical Trial Adverse Reactions – Pediatrics No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.
, General 05/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ...........................................................................................
2 TABLE OF CONTENTS ............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................
4 1 INDICATIONS .............................................................................................................. 1 Pediatrics...................................................................................................................
2 Geriatrics ................................................................................................................... 4 2 CONTRAINDICATIONS.................................................................................................
4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 4 4 DOSAGE AND ADMINISTRATION................................................................................. 1 Dosing Considerations ..............................................................................................
2 Recommended Dose and Dosage Adjustment ......................................................... 4 Administration .......................................................................................................... 5 Missed Dose ..............................................................................................................
7 5 OVERDOSAGE............................................................................................................. 7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 7 7 WARNINGS AND PRECAUTIONS ..................................................................................
ENVARSUS PA is contraindicated in patients: • who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTH, COMPOSITION and PACKAGING.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Tacrolimus in Canada.
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2 Recommended Dose and Dosage Adjustment Prophylaxis of de novo kidney and liver transplant rejection Table 1 provides the initial once daily oral dosage and subsequent dosing of ENVARSUS PA to maintain tacrolimus whole blood trough concentration for de novo kidney transplant patients or de novo liver transplant patients.
The initial dose of ENVARSUS PA should be administered within 24 hours of kidney transplantation surgery or liver transplantation surgery. Dosing should be titrated to maintain the whole blood trough concentration levels based on clinical assessment for rejection and tolerability.
13 mg/kg/day Day 1-60: 5-20 ng/mL Month 3-12: 5-15 ng/mL ENVARSUS PA should be concomitantly used with corticosteroids and/or mycophenolic acids (mycophenolate mofetil, mycophenolic acid sodium) or azathioprine, as appropriate. Antibody ENVARSUS® PA (tacrolimus prolonged-release tablets) Page 6 of 41 induction should be used in de novo transplant patients according to standard practice of the transplant centre.
Conversion from tacrolimus immediate-release formulations to ENVARSUS PA ENVARSUS PA is not interchangeable or substitutable on an equal dose by dose basis with other existing tacrolimus containing medicinal products (immediate-release or extended-release).
7 mg total daily dose basis. Tacrolimus trough levels should be measured prior to the conversion and within a week after the conversion. Dose adjustments should be made to ensure that similar whole blood trough concentration is maintained after the conversion (Table 2).
Clinical studies with ENVARSUS PA showed that Black African American patients may require a higher dose of ENVARSUS PA to achieve the desired tacrolimus trough levels. 85 mg has been used in clinical trials for Black African American patients (Table 2).
85 mg ENVARSUS PA Conversion from Cyclosporine to tacrolimus or vice versa 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 have to be monitored for dose adjustments to achieve desired trough levels of cyclosporine or tacrolimus. No adequate and well-controlled studies have been conducted for the conversion from cyclosporine to ENVARSUS PA or vice-versa.
4 Administration ENVARSUS PA is a […]
3 Less Common Clinical Trial Adverse Reactions The following adverse reactions were also reported in clinical studies of solid organ transplant recipients who were treated with ENVARSUS PA at a frequency of ≥ 1% to < 15%.
Blood and lymphatic system disorders:
Febrile neutropenia, hyperbilirubinemia, iron deficiency anemia, leukocytosis, leukopenia, neutropenia, polycythemia, thrombocytopenia Cardiac disorders: Angina pectoris, atrial fibrillation, cardiac murmur, chest discomfort, chest pain, myocardial infarction, palpitations, supraventricular extrasystoles, tachycardia Ear and labyrinth disorders: Deafness unilateral, ear pain, hearing impaired, tinnitus Endocrine disorders: Dysfunctional uterine bleeding, hyperparathyroidism Eye disorders: Eye inflammation, glaucoma, lacrimation increased Gastrointestinal disorders: Abdominal abscess, abdominal discomfort, abdominal distension, abdominal hernia, abdominal pain, abdominal pain lower, abdominal pain upper, anorectal discomfort, cytomegalovirus enteritis, dry mouth, dyspepsia, flatulence, gastroenteritis, gastroesophageal reflux disease, gastroesophageal reflux disorder, hiccups, inguinal hernia, mouth ulceration, nausea, oral candidiasis, oesophageal candidiasis, oropharyngeal pain, rectal hemorrhage, small intestinal obstruction, toothache, vomiting ENVARSUS® PA (tacrolimus prolonged-release tablets) Page 15 of 41 General disorders and administration site conditions: Asthenia, chills, fatigue, generalised oedema, impaired healing, irritability, lethargy, malaise, night sweats, oedema, oedema peripheral, pain, pyrexia, secretion discharge Hepatobiliary disorders: Ascites, bile duct stenosis, biliary dilatation, biliary drainage, biliary tract disorder, cholestasis, hypertransaminasemia, hypoalbuminemia, jaundice Immune system disorders: Allergic bronchitis, seasonal allergy, swelling face Infections and infestations: Aspergillosis, bacteremia, BK virus infection, body tinea, candidiasis, cellulitis, cytomegalovirus infection, cytomegalovirus syndrome, cytomegalovirus viremia, device related infection, enterococcal infection, […]
1 Special Populations ................................................................................................. 1 Pregnant Women ................................................................................................
2 Breast-feeding ..................................................................................................... 3 Pediatrics .............................................................................................................
4 Geriatrics ............................................................................................................. 12 8 ADVERSE REACTIONS................................................................................................
1 Adverse Reaction Overview .................................................................................... 2 Clinical Trial Adverse Reactions .............................................................................. 1 Clinical Trial Adverse Reactions – Pediatrics ...........................................................
3 Less Common Clinical Trial Adverse Reactions ....................................................... 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data..............................................................................................................
5 Post-Market Adverse Reactions.............................................................................. 17 9 DRUG INTERACTIONS ............................................................................................... 2 Drug Interactions Overview ....................................................................................
3 Drug-Behavioural Interactions ................................................................................ 4 Drug-Drug Interactions ........................................................................................... 5 Drug-Food Interactions ...........................................................................................
6 Drug-Herb Interactions ........................................................................................... 7 Drug-Laboratory Test Interactions.......................................................................... 22 10 CLINICAL PHARMACOLOGY .......................................................................................
1 Mechanism of Action .......................................................................................... 2 Pharmacodynamics ............................................................................................. 3 Pharmacokinetics ................................................................................................
22 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 25 12 SPECIAL HANDLING INSTRUCTIONS........................................................................... 25 PART II: SCIENTIFIC INFORMATION ......................................................................................
26 13 PHARMACEUTICAL INFORMATION ........................................................................... 26 14 CLINICAL TRIALS .......................................................................................................
1 Clinical Trials by Indication .................................................................................. 27 15 MICROBIOLOGY .......................................................................................................
31 16 NON-CLINICAL TOXICOLOGY ..................................................................................... 31 PATIENT MEDICATION INFORMATION ................................................................................. 34 […]