Invokana® (Canagliflozin), Invokamet® (Canagliflozin/Metformin) and Invokamet XR (Canagliflozin/Metformin Extended-Release) – Label Updates

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Invokana® (canagliflozin), Invokamet® (canagliflozin/metformin) and Invokamet XR (canagliflozin/metformin extended-release) – Label updates • On August 18, 2020, the FDA approved updates to the drug labels for Invokana (canagliflozin), Invokamet (canagliflozin/metformin) and Invokamet XR (canagliflozin/metformin extended-release) regarding the removal of the boxed warning for lower limb amputation and the removal of the albuminuria condition for continued dosing of patients whose estimated glomerular filtration rate (eGFR) falls between 30 and less than 45 mL/min/1.73 m2. • Invokana, Invokamet (canagliflozin/metformin), and Invokamet XR (canagliflozin/metformin extended-release) are indicated for the following: — As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus — To reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease — To reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day • Invokana, Invokamet and Invokamet XR are not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. • Invokana is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m2. Invokana is likely to be ineffective in this setting based upon its mechanism of action. • Invokamet and Invokamet XR carry a boxed warning for lactic acidosis. • Refer to the drug labels for dosage recommendations based on eGFR. optumrx.com OptumRx® specializes in the delivery, clinical management and affordability of prescription medications and consumer health products. We are an Optum® company — a leading provider of integrated health services. Learn more at optum.com. All Optum® trademarks and logos are owned by Optum, Inc. All other brand or product names are trademarks or registered marks of their respective owners. This document contains information that is considered proprietary to OptumRx and should not be reproduced without the express written consent of OptumRx. RxNews® is published by the OptumRx Clinical Services Department. ©2020 Optum, Inc. All rights reserved. .

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Think Medicines!
Think Issue 13 August 2016 MHRA Drug Safety SGLT2 inhibitors: updated advice on the risk of diabetic Medicines!Updates can be found ketoacidosis (DKA) at the following link. The MHRA are advising health care professionals to test for raised ketones in patients with ketoacidosis symptoms, who are taking SGLT2 inhibitors even if New higher strength Humalog® plasma glucose levels are near-normal. SGLT2 inhibitors include: Canagliflozin, 200 units/ml KwikPen™ Dapagliflozin and Empagliflozin. Serious, life-threatening, and fatal cases of In order to minimize medication DKA have been reported in patients taking an SGLT2 inhibitor. In several cases, errors. blood glucose levels were only moderately elevated (e.g. <14mmol/L) Insulin lispro 200 units/ml representing an atypical presentation for DKA, which could delay diagnosis and solution for injection should treatment. ONLY be administered using the Advice for health Care Professionals: Humalog 200 units/ml pre-filled Inform patients of the signs of diabetic ketoacidosis (DKA) and advise them to pen (KwikPen). seek immediate medical advice if they develop any of these symptoms (e.g. When switching from one rapid weight loss, feeling sick or being sick, stomach pain, fast and deep Humalog strength to another, breathing, sleepiness, a sweet smell to the breath, a sweet or metallic taste in the dose does not need to be the mouth, or a different odour to urine or sweat). converted. Unnecessary dose Discuss the risk factors of DKA with patients. conversion may lead to under/ Discontinue treatment with the SGLT2 inhibitor immediately if DKA is over dosing and resultant hyper/ suspected or diagnosed.
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IHS PROVIDER September 2017
September 2017 Volume 42 Number 9 Indian Health Service National Pharmacy and Therapeutics Committee SGLT-2 inhibitors (Update) NPTC Formulary Brief August Meeting 2017 Background: The FDA has currently approved three SGLT-2 inhibitors, two of which have completed FDA-mandated cardiovascular outcomes trials. Last year, in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG), empagliflozin not only reduced cardiovascular events, but also mortality.1 This year, the Canagliflozin Cardiovascular Assessment Study (CANVAS) demonstrated equivocal cardiovascular benefits, no mortality benefit, and significant harms in those receiving canagliflozin.2 The DECLARE-TIMI 58 cardiovascular study of dapagliflozin will be completed in April 2019 (ClinicalTrials.gov Identifier: NCT01730534). Uncertainty remains regarding the current data, long- term benefits and harms, and differentiation among SGLT-2 inhibitors. Following a review of SGLT2 inhibitors at the August 2017 NPTC meeting on their cardiovascular outcomes, net benefit and place in therapy, no modifications were made to the National Core Formulary (NCF). Discussion: EMPA-REG enrolled 7,020 patients with Type 2 diabetes mellitus (T2DM) and HgbA1c values between 7.0-10.0%. All patients had established cardiovascular disease (CVD) and were observed for a median duration of 3.1 years. Empagliflozin reduced the primary outcome of cardiovascular (CV) death, nonfatal myocardial infarction (MI), or nonfatal cardiovascular accident (CVA) by 6.5 events per 1000 patient-years (pt-yrs). Mortality decreased by 9.2 events per 1000 pt-yrs, primarily driven by a reduction in CV mortality of 7.8 events per 1000 pt-yrs. Heart failure hospitalization decreased by 5.1 events per 1000 pt-yrs.
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Step Therapy
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Ertugliflozin 5Mg, 15Mg Film-Coated Tablet (Steglatro®) Merck Sharp & Dohme
1 www.scottishmedicines.org.uk SMC2102 ertugliflozin 5mg, 15mg film-coated tablet (Steglatro®) Merck Sharp & Dohme 7 December 2018 The Scottish Medicines Consortium (SMC) has completed its assessment of the above product and advises NHS Boards and Area Drug and Therapeutic Committees (ADTCs) on its use in NHSScotland. The advice is summarised as follows: ADVICE: following a full submission ertugliflozin (Steglatro®) is accepted for restricted use within NHSScotland. Indication under review: in adults aged 18 years and older with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control: As monotherapy in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications. In addition to other medicinal products for the treatment of diabetes. SMC restriction: ertugliflozin is accepted for use as monotherapy and as add-on therapy. When used as monotherapy it is restricted to patients who would otherwise receive a dipeptidyl peptidase-4 inhibitor and in whom a sulphonylurea or pioglitazone is not appropriate. Ertugliflozin was superior to placebo in lowering HbA1c in adults with type 2 diabetes mellitus in phase III studies in monotherapy, dual therapy and triple therapy settings. Chairman Scottish Medicines Consortium Published 14 January 2019 1 Indication In adults aged 18 years and older with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control: As monotherapy in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications. In addition to other medicinal products for the treatment of diabetes.1 Dosing Information The recommended starting dose is 5mg orally once daily which can, if tolerated, be increased to 15mg once daily if additional glycaemic control is needed.
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ANTI-HYPERGLYCEMIC DIABETES AGENTS in T2DM: Color Outcomes Comparison Summary Table
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Cost-Effectiveness of Empagliflozin Versus Canagliflozin, Dapagliflozin
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The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates
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The Combination of Canagliflozin with a Half-Dose of Glimepiride
Harada et al. Int J Diabetes Clin Res 2016, 3:065 Volume 3 | Issue 3 International Journal of ISSN: 2377-3634 Diabetes and Clinical Research Original Article: Open Access The Combination of Canagliflozin with a Half-Dose of Glimepiride Improves Glycemic Control and Blood Glucose Perturbation without Increasing the Risk of Hypoglycemia and Ketosis Mayuko Harada, Yasuhisa Abe, Yuki Maeda, Michiko Kajikawa, and Mitsuru Hashiramoto* Division of Diabetes and Endocrinology, Yodogawa Christian Hospital, Japan *Corresponding author: Mitsuru Hashiramoto, MD, PhD, Division of Diabetes and Endocrinology, Yodogawa Christian Hospital, 1-7-50 Kuni-Jima, Higashi-Yodogawa-Ku, Osaka 533-0024, Japan, Tel: +81-6-6322-2259, Fax: +81-6-6-6320-6308, E-mail: [email protected] Abstract Introduction Aim: To evaluate the efficacy and safety of administering The application of sulfonylurea (SU) remains one of the most canagliflozin to Japanese type 2 diabetes mellitus (T2DM) patients popular approaches in pharmacological therapy for type 2 diabetes and reducing the dosage of their existing regimen of sulfonylurea mellitus (T2DM) patients because SU exerts potent stimulatory (SU) by half. effects on insulin secretion from pancreatic β cells and is relatively Methods: Seventeen Japanese T2DM patients on antidiabetes inexpensive and well tolerated. Hypoglycemia, however, is a major medication (SU) completed this 12-week prospective single-arm safety concern that is associated with the use of SUs, because it open-label study. First, the dose of SU was reduced by half and impairs a patient's quality of life and can become life threatening a concomitant administration of canagliflozin (100 mg/day) was initiated.
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Canagliflozin: a Novel Agent for the Treatment of Type 2 Diabetes Mellitus Correspondence Course Program Number: 0171-9999-13-072-H01-P 1
CE Canagliﬂozin: A Novel Agent for the Treatment of Type 2 Diabetes Mellitus By Marquita D. Bradshaw, Pharm.D., BCACP and Rikki L. Tonet, Pharm.D. Candidate 2014 Objectives INTRODUCTION • Describe the pathophysiological defects in Type 2 T2DM is one of the four clinical classes of diabetes Diabetes Mellitus (T2DM) incorporated in the omi- identified which results from a progressive insulin nous octet secretory defect on the background of insulin re- • Describe the mechanism of action of canagliflozin sistance.2 Signs and symptoms of T2DM include • Identify the potential place in therapy of cana- polyuria, polydipsia, and polyphagia which may not gliflozin be overt. Often patients with T2DM are not diag- • Summarize patient counseling points when dispens- nosed until complications appear; therefore resulting ing canagliflozin in subsequent reduction in quality of life if diabetes • Identify available strengths of canagliflozin (Phar- remains uncontrolled. macy technicians***) Approximately 25.8 million children and adults in Conflict of interest statement: There is no conflict the United States are living with diabetes, including 7 of interest involved in writing this article or in the million who are currently undiagnosed.3 This equates subject matter of this article. to 8.3% of the population in the United States. In 2010, South Carolina had the fifth highest prevalence Abstract: Several oral and injectable agents are of diabetes in the nation.4 The prevalence of diabetes available for the treatment of Type 2 Diabetes Melli- in South Carolina is presently 9.6% and has increased tus (T2DM). A recent consensus statement published more rapidly than the national rate.4 by the American Diabetes Association emphasizes a patient-centered approach.1 Canagliflozin belongs Previously it was thought that a triumvirate was to a novel therapeutic class.
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INVOKAMET (Canagliflozin and Metformin Hydrochloride)
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