Jardiance (Page 6 of 7)
14.2 Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease
The effect of JARDIANCE on cardiovascular risk in adult patients with type 2 diabetes and established, stable, atherosclerotic cardiovascular disease was evaluated in the EMPA-REG OUTCOME study, a multicenter, multi-national, randomized, double-blind parallel group trial. The study compared the risk of experiencing a major adverse cardiovascular event (MACE) between JARDIANCE and placebo when these were added to and used concomitantly with standard of care treatments for diabetes and atherosclerotic cardiovascular disease. Coadministered antidiabetic medications were to be kept stable for the first 12 weeks of the trial. Thereafter, antidiabetic and atherosclerotic therapies could be adjusted, at the discretion of investigators, to ensure participants were treated according to the standard care for these diseases.
A total of 7020 patients were treated (JARDIANCE 10 mg = 2345; JARDIANCE 25 mg = 2342; placebo = 2333) and followed for a median of 3.1 years. Approximately 72% of the study population was Caucasian, 22% was Asian, and 5% was Black. The mean age was 63 years and approximately 72% were male.
All patients in the study had inadequately controlled type 2 diabetes mellitus at baseline (HbA1c greater than or equal to 7%). The mean HbA1c at baseline was 8.1% and 57% of participants had had diabetes for more than 10 years. Approximately 31%, 22% and 20% reported a past history of neuropathy, retinopathy and nephropathy to investigators respectively and the mean eGFR was 74 mL/min/1.73 m2. At baseline, patients were treated with one (~30%) or more (~70%) antidiabetic medications including metformin (74%), insulin (48%), and sulfonylurea (43%).
All patients had established atherosclerotic cardiovascular disease at baseline including one (82%) or more (18%) of the following; a documented history of coronary artery disease (76%), stroke (23%) or peripheral artery disease (21%). At baseline, the mean systolic blood pressure was 136 mmHg, the mean diastolic blood pressure was 76 mmHg, the mean LDL was 86 mg/dL, the mean HDL was 44 mg/dL, and the mean urinary albumin to creatinine ratio (UACR) was 175 mg/g. At baseline, approximately 81% of patients were treated with renin angiotensin system inhibitors, 65% with beta-blockers, 43% with diuretics, 77% with statins, and 86% with antiplatelet agents (mostly aspirin).
The primary endpoint in EMPA-REG OUTCOME was the time to first occurrence of a Major Adverse Cardiac Event (MACE). A major adverse cardiac event was defined as occurrence of either a cardiovascular death or a nonfatal myocardial infarction (MI) or a nonfatal stroke. The statistical analysis plan had pre-specified that the 10 and 25 mg doses would be combined. A Cox proportional hazards model was used to test for non-inferiority against the pre-specified risk margin of 1.3 for the hazard ratio of MACE and superiority on MACE if non-inferiority was demonstrated. Type-1 error was controlled across multiples tests using a hierarchical testing strategy.
JARDIANCE significantly reduced the risk of first occurrence of primary composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (HR: 0.86; 95% CI 0.74, 0.99). The treatment effect was due to a significant reduction in the risk of cardiovascular death in subjects randomized to empagliflozin (HR: 0.62; 95% CI 0.49, 0.77), with no change in the risk of non-fatal myocardial infarction or non-fatal stroke (see Table 13 and Figure 5 and 6). Results for the 10 mg and 25 mg empagliflozin doses were consistent with results for the combined dose groups.
a Treated set (patients who had received at least one dose of study drug)b p−value for superiority (2−sided) 0.04c Total number of events | |||
Placebo N=2333 | JARDIANCE N=4687 | Hazard ratio vs placebo (95% CI) | |
Composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke (time to first occurrence)b | 282 (12.1%) | 490 (10.5%) | 0.86 (0.74, 0.99) |
Non-fatal myocardial infarctionc | 121 (5.2%) | 213 (4.5%) | 0.87 (0.70, 1.09) |
Non-fatal strokec | 60 (2.6%) | 150 (3.2%) | 1.24 (0.92, 1.67) |
Cardiovascular deathc | 137 (5.9%) | 172 (3.7%) | 0.62 (0.49, 0.77) |
The efficacy of JARDIANCE on cardiovascular death was generally consistent across major demographic and disease subgroups.
Vital status was obtained for 99.2% of subjects in the trial. A total of 463 deaths were recorded during the EMPA-REG OUTCOME trial. Most of these deaths were categorized as cardiovascular deaths. The non-cardiovascular deaths were only a small proportion of deaths, and were balanced between the treatment groups (2.1% in patients treated with JARDIANCE, and 2.4% of patients treated with placebo).
16 HOW SUPPLIED/STORAGE AND HANDLING
JARDIANCE tablets are available in 10 mg and 25 mg strengths as follows:
10 mg tablets:
pale yellow, round, biconvex and bevel-edged, film-coated tablets
debossed with “S 10” on one side and the Boehringer Ingelheim company
symbol on the other side.
Bottles of 30 (NDC 0597-0152-30)
Bottles of 90 (NDC 0597-0152-90)
Cartons containing 3
blister cards of 10 tablets each (3 x 10) (NDC 0597-0152-37), institutional
pack.
25 mg tablets: pale yellow, oval, biconvex film-coated tablets, debossed with “S
25” on one side and the Boehringer Ingelheim company symbol on the
other side.
Bottles of 30 (NDC 0597-0153-30)
Bottles of 90 (NDC 0597-0153-90)
Cartons containing 3
blister cards of 10 tablets each (3 x 10) (NDC 0597-0153-37), institutional
pack.
Dispense in a well-closed container as defined in the USP.
Storage
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Instructions
Instruct patients to read the Patient Information before starting
JARDIANCE therapy and to reread it each time the prescription is renewed.
Instruct patients to inform their doctor or pharmacist if they develop
any unusual symptom, or if any known symptom persists or worsens.
Inform patients of the potential risks and benefits of JARDIANCE and of alternative modes of therapy. Also inform patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and HbA1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications. Advise patients to seek medical advice promptly during periods of stress such as fever, trauma, infection, or surgery, as medication requirements may change.
Instruct patients to take JARDIANCE only as prescribed. If a dose is missed, it should be taken as soon as the patient remembers. Advise patients not to double their next dose.
Inform patients that the most common adverse reactions associated with the use of JARDIANCE are urinary tract infections and mycotic genital infections.
Advise pregnant women, and females of reproductive potential of the potential risk to a fetus with treatment with JARDIANCE [see Use in Specific Populations (8.1)]. Instruct females of reproductive potential to report pregnancies to their physicians as soon as possible.
Advise women that breastfeeding is not recommended during treatment with JARDIANCE [see Use in Specific Populations (8.2)].
Hypotension
Inform patients that hypotension may occur with JARDIANCE and advise
them to contact their healthcare provider if they experience such
symptoms [see Warnings and Precautions (5.1)]. Inform patients that dehydration may increase
the risk for hypotension, and to have adequate fluid intake.
Ketoacidosis
Inform patients that ketoacidosis is a serious life-threatening
condition. Cases of ketoacidosis have been reported during use of
JARDIANCE. Instruct patients to check ketones (when possible) if symptoms
consistent with ketoacidosis occur even if blood glucose is not elevated.
If symptoms of ketoacidosis (including nausea, vomiting, abdominal
pain, tiredness, and labored breathing) occur, instruct patients to
discontinue JARDIANCE and seek medical advice immediately [see Warnings and Precautions (5.2)].
Acute Kidney Injury
Inform patients that acute
kidney injury has been reported during use of JARDIANCE. Advise patients
to seek medical advice immediately if they have reduced oral intake
(such as due to acute illness or fasting) or increased fluid losses
(such as due to vomiting, diarrhea, or excessive heat exposure), as
it may be appropriate to temporarily discontinue JARDIANCE use in
those settings [see Warnings and Precautions (5.3)].
Serious Urinary Tract Infections
Inform patients of the potential for urinary tract infections,
which may be serious. Provide them with information on the symptoms
of urinary tract infections. Advise them to seek medical advice if
such symptoms occur [see Warnings and Precautions (5.4) ].
Genital Mycotic Infections
in Females (e.g., Vulvovaginitis)
Inform female
patients that vaginal yeast infections may occur and provide them
with information on the signs and symptoms of vaginal yeast infections.
Advise them of treatment options and when to seek medical advice [see Warnings and Precautions (5.6)].
Genital Mycotic Infections in Males (e.g., Balanitis or Balanoposthitis)
Inform male patients that yeast infection of penis (e.g.,
balanitis or balanoposthitis) may occur, especially in uncircumcised
males and patients with chronic and recurrent infections. Provide
them with information on the signs and symptoms of balanitis and balanoposthitis
(rash or redness of the glans or foreskin of the penis). Advise them
of treatment options and when to seek medical advice [see
Warnings and Precautions (5.6)].
Hypersensitivity
Reactions
Inform patients that serious hypersensitivity
reactions, such as urticaria and angioedema, have been reported with
JARDIANCE. Advise patients to report immediately any skin reaction
or angioedema, and to discontinue drug until they have consulted prescribing
physician [see Warnings and Precautions (5.7)].
Laboratory Tests
Inform patients that renal function should be assessed prior to
initiation of JARDIANCE and monitored periodically thereafter.
Inform patients that elevated glucose in urinalysis is expected when taking JARDIANCE.
Inform patients that response to all diabetic therapies should be monitored by periodic measurements of blood glucose and HbA1c levels, with a goal of decreasing these levels toward the normal range. Hemoglobin A1c monitoring is especially useful for evaluating long-term glycemic control.
Distributed by:
Boehringer Ingelheim
Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Marketed by:
Boehringer
Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
and
Eli Lilly and Company
Indianapolis, IN
46285 USA
Licensed
from:
Boehringer Ingelheim International GmbH, Ingelheim,
Germany
Boehringer Ingelheim Pharmaceuticals, Inc. either owns or uses the Jardiance® and EMPA-REG OUTCOME® trademarks under license.
The other trademarks referenced are owned by third parties not affiliated with Boehringer Ingelheim Pharmaceuticals, Inc.
Copyright © 2017 Boehringer Ingelheim International GmbHALL RIGHTS RESERVED
This Patient Information has been approved by the U.S. Food and Drug Administration. | Revised: December 2017 | ||||
PATIENT INFORMATIONJARDIANCE® (jar DEE ans)(empagliflozin)Tablets | |||||
What is the
most important information I should know about JARDIANCE? JARDIANCE can cause serious side effects, including:
| |||||
What is JARDIANCE?
| |||||
Who should
not take JARDIANCE? Do not take JARDIANCE if you:
| |||||
What should
I tell my doctor before using JARDIANCE? Before you take JARDIANCE, tell your doctor if you:
Especially tell your doctor if you take:
| |||||
How should
I take JARDIANCE?
| |||||
What are the possible
side effects of JARDIANCE? JARDIANCE may cause serious side effects, including:
| |||||
|
| ||||
If you get any of
these symptoms during treatment with JARDIANCE, if possible, check
for ketones in your urine, even if your blood
sugar is less than 250 mg/dL.
| |||||
|
|
|
| ||
| |||||
How should I store JARDIANCE? Store JARDIANCE at room temperature 68°F to 77°F (20°C to 25°C). | |||||
General information about the safe and effective use of JARDIANCE. Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use JARDIANCE for a condition for which it is not prescribed. Do not give JARDIANCE to other people, even if they have the same symptoms you have. It may harm them.This Patient Information summarizes the most important information about JARDIANCE. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about JARDIANCE that is written for health professionals.For more information about JARDIANCE, go to www.jardiance.com, scan the code below, or call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or (TTY) 1-800-459-9906. | |||||
What are the ingredients in JARDIANCE? Active Ingredient: empagliflozinInactive Ingredients: lactose monohydrate, microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide and magnesium stearate. In addition, the film coating contains the following inactive ingredients: hypromellose, titanium dioxide, talc, polyethylene glycol, and yellow ferric oxide. | |||||
Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc.; Ridgefield, CT 06877 USAMarketed by: Boehringer Ingelheim Pharmaceuticals, Inc.; Ridgefield, CT 06877 USA and Eli Lilly and Company, Indianapolis, IN 46285 USALicensed from: Boehringer Ingelheim International GmbH, Ingelheim, GermanyBoehringer Ingelheim Pharmaceuticals, Inc. either owns or uses the Jardiance® and EMPA-REG OUTCOME® trademarks under license.The other trademarks referenced are owned by third parties not affiliated with Boehringer Ingelheim Pharmaceuticals, Inc.Copyright © 2017 Boehringer Ingelheim International GmbHALL RIGHTS RESERVEDIT5728RL112017 |
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.