设为首页 加入收藏

TOP

JARDIANCE® (empagliflozin) tablets, for oral use
2014-10-06 19:00:08 来源: 作者: 【 】 浏览:1107次 评论:0

JARDIANCE (empagliflozin) tablet, film coated
[Boehringer Ingelheim Pharmaceuticals, Inc.]  
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use JARDIANCE safely and effectively. See full prescribing information for JARDIANCE.

JARDIANCE® (empagliflozin) tablets, for oral use
Initial U.S. Approval: 2014
INDICATIONS AND USAGE
JARDIANCE is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1.1)
Limitation of Use:

Not for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis (1.1)
 
DOSAGE AND ADMINISTRATION
The recommended dose of JARDIANCE is 10 mg once daily, taken in the morning, with or without food (2.1)
Dose may be increased to 25 mg once daily (2.1)
Assess renal function before initiating JARDIANCE. Do not initiate JARDIANCE if eGFR is below 45 mL/min/1.73 m2 (2.2)
Discontinue JARDIANCE if eGFR falls persistently below 45 mL/min/1.73 m2 (2.2)
DOSAGE FORMS AND STRENGTHS
Tablets: 10 mg, 25 mg (3)
CONTRAINDICATIONS
History of serious hypersensitivity reaction to JARDIANCE (4)
Severe renal impairment, end-stage renal disease, or dialysis (4)
WARNINGS AND PRECAUTIONS
Hypotension: Before initiating JARDIANCE assess and correct volume status in patients with renal impairment, the elderly, in patients with low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms during therapy. (5.1)
Impairment in renal function: Monitor renal function during therapy. More frequent monitoring is recommended in patients with eGFR below 60 mL/min/1.73 m2 (5.2)
Hypoglycemia: Consider lowering the dose of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating JARDIANCE (5.3)
Genital mycotic infections: Monitor and treat as appropriate (5.4)
Urinary tract infections: Monitor and treat as appropriate (5.5)
Increased LDL-C: Monitor and treat as appropriate (5.6)
Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JARDIANCE (5.7)
ADVERSE REACTIONS
The most common adverse reactions associated with JARDIANCE (5% or greater incidence) were urinary tract infections and female genital mycotic infections (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or 1-800-459-9906 TTY, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
Pregnancy: No adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefits justifies the potential risk to the fetus. (8.1)
Nursing mothers: Discontinue JARDIANCE or discontinue nursing (8.3)
Geriatric patients: Higher incidence of adverse reactions related to volume depletion and reduced renal function (5.1, 5.2, 8.5)
Patients with renal impairment: Higher incidence of adverse reactions related to reduced renal function (2.2, 5.2, 8.6)
 
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 8/2014
 

Back to Highlights and Tabs
FULL PRESCRIBING INFORMATION: CONTENTS*
1  INDICATIONS AND USAGE
1.1 Limitation of Use
2  DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
2.2 Patients with Renal Impairment
3  DOSAGE FORMS AND STRENGTHS
4  CONTRAINDICATIONS
5  WARNINGS AND PRECAUTIONS
5.1 Hypotension
5.2 Impairment in Renal Function
5.3 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues
5.4 Genital Mycotic Infections
5.5 Urinary Tract Infections
5.6 Increased Low-Density Lipoprotein Cholesterol (LDL-C)
5.7 Macrovascular Outcomes
6  ADVERSE REACTIONS
6.1 Clinical Trials Experience
7  DRUG INTERACTIONS
7.1 Diuretics
7.2 Insulin or Insulin Secretagogues
7.3 Positive Urine Glucose Test
7.4 Interference with 1,5-anhydroglucitol (1,5-AG) Assay
8  USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10  OVERDOSAGE
11  DESCRIPTION
12  CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13  NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14  CLINICAL STUDIES
14.1 Monotherapy
14.2 Combination Therapy
14.3 Renal Impairment
16  HOW SUPPLIED/STORAGE AND HANDLING
17  PATIENT COUNSELING INFORMATION
*
Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION
 

1  INDICATIONS AND USAGE

JARDIANCE is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [see Clinical Studies (14)].

 

1.1 Limitation of Use

JARDIANCE is not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

 

2  DOSAGE AND ADMINISTRATION

 

2.1 Recommended Dosage

The recommended dose of JARDIANCE is 10 mg once daily in the morning, taken with or without food. In patients tolerating JARDIANCE, the dose may be increased to 25 mg [see Clinical Studies (14)].

In patients with volume depletion, correcting this condition prior to initiation of JARDIANCE is recommended [see Warnings and Precautions (5.1), Use in Specific Populations (8.5), and Patient Counseling Information (17)].

 

2.2 Patients with Renal Impairment

Assessment of renal function is recommended prior to initiation of JARDIANCE and periodically thereafter.

JARDIANCE should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m2.

No dose adjustment is needed in patients with an eGFR greater than or equal to 45 mL/min/1.73 m2.

JARDIANCE should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m2[see Warnings and Precautions (5.1, 5.2), and Use in Specific Populations (8.6)]

 

3  DOSAGE FORMS AND STRENGTHS

  • JARDIANCE (empagliflozin) 10 mg tablets are 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.
  • JARDIANCE (empagliflozin) 25 mg tablets are pale yellow, oval, biconvex, film-coated tablets debossed with “S 25” on one side and the Boehringer Ingelheim company symbol on the other side.

 

4  CONTRAINDICATIONS

  • History of serious hypersensitivity to JARDIANCE.
  • Severe renal impairment, end-stage renal disease, or dialysis [see Use in Specific Populations (8.6)].

 

5  WARNINGS AND PRECAUTIONS

 

5.1 Hypotension

JARDIANCE causes intravascular volume contraction. Symptomatic hypotension may occur after initiating JARDIANCE [see Adverse Reactions (6.1)] particularly in patients with renal impairment, the elderly, in patients with low systolic blood pressure, and in patients on diuretics. Before initiating JARDIANCE, assess for volume contraction and correct volume status if indicated. Monitor for signs and symptoms of hypotension after initiating therapy and increase monitoring in clinical situations where volume contraction is expected [see Use in Specific Populations (8.5)].

 

5.2 Impairment in Renal Function

JARDIANCE increases serum creatinine and decreases eGFR [see Adverse Reactions (6.1)]. The risk of impaired renal function with JARDIANCE is increased in elderly patients and patients with moderate renal impairment. More frequent monitoring of renal function is recommended in these patients [see Use in Specific Populations (8.5, 8.6)]. Renal function should be eva luated prior to initiating JARDIANCE and periodically thereafter.

 

5.3 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues

Insulin and insulin secretagogues are known to cause hypoglycemia. The risk of hypoglycemia is increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin [see Adverse Reactions (6.1)]. Therefore, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with JARDIANCE.

 

5.4 Genital Mycotic Infections

JARDIANCE increases the risk for genital mycotic infections [see Adverse Reactions (6.1)]. Patients with a history of chronic or recurrent genital mycotic infections were more likely to develop mycotic genital infections. Monitor and treat as appropriate.

 

5.5 Urinary Tract Infections

JARDIANCE increases the risk for urinary tract infections [see Adverse Reactions (6.1)]. Monitor and treat as appropriate.

 

5.6 Increased Low-Density Lipoprotein Cholesterol (LDL-C)

Increases in LDL-C can occur with JARDIANCE [see Adverse Reactions (6.1)]. Monitor and treat as appropriate.

 

5.7 Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JARDIANCE or any other antidiabetic drug.

 

6  ADVERSE REACTIONS

The following important adverse reactions are described below and elsewhere in the labeling:

  • Hypotension [see Warnings and Precautions (5.1)]
  • Impairment in Renal Function [see Warnings and Precautions (5.2)]
  • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.3)]
  • Genital Mycotic Infections [see Warnings and Precautions (5.4)]
  • Urinary Tract Infections [see Warnings and Precautions (5.5)]
  • Increased Low-Density Lipoprotein Cholesterol (LDL-C) [see Warnings and Precautions (5.6)]

 

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pool of Placebo-Controlled Trials eva luating JARDIANCE 10 and 25 mg
The data in Table 1 are derived from a pool of four 24-week placebo-controlled trials and 18-week data from a placebo-controlled trial with insulin. JARDIANCE was used as monotherapy in one trial and as add-on therapy in four trials [see Clinical Studies (14)].

These data reflect exposure of 1976 patients to JARDIANCE with a mean exposure duration of approximately 23 weeks. Patients received placebo (N=995), JARDIANCE 10 mg (N=999), or JARDIANCE 25 mg (N=977) once daily. The mean age of the population was 56 years and 3% were older than 75 years of age. More than half (55%) of the population was male; 46% were White, 50% were Asian, and 3% were Black or African American. At baseline, 57% of the population had diabetes more than 5 years and had a mean hemoglobin A1c (HbA1c) of 8%. Established microvascular complications of diabetes at baseline included diabetic nephropathy (7%), retinopathy (8%), or neuropathy (16%). Baseline renal function was normal or mildly impaired in 91% of patients and moderately impaired in 9% of patients (mean eGFR 86.8 mL/min/1.73 m2).

Table 1 shows common adverse reactions (excluding hypoglycemia) associated with the use of JARDIANCE. The adverse reactions were not present at baseline, occurred more commonly on JARDIANCE than on placebo and occurred in greater than or equal to 2% of patients treated with JARDIANCE 10 mg or JARDIANCE 25 mg.

Table 1 Adverse Reactions Reported in ≥2% of Patients Treated with JARDIANCE and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of JARDIANCE Monotherapy or Combination Therapy
aPredefined adverse event grouping, including, but not limited to, urinary tract infection, asymptomatic bacteriuria, cystitis
bFemale genital mycotic infections include the following adverse reactions: vulvovaginal mycotic infection, vaginal infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, genital infection fungal, genitourinary tract infection, vulvovaginitis, cervicitis, urogenital infection fungal, vaginitis bacterial. Percentages calculated with the number of female subjects in each group as denominator: placebo (N=481), JARDIANCE 10 mg (N=443), JARDIANCE 25 mg (N=420).
cPredefined adverse event grouping, including, but not limited to, polyuria, pollakiuria, and nocturia
dMale genital mycotic infections include the following adverse reactions: balanoposthitis, balanitis, genital infections fungal, genitourinary tract infection, balanitis candida, scrotal abscess, penile infection. Percentages calculated with the number of male subjects in each group as denominator: placebo (N=514), JARDIANCE 10 mg (N=556), JARDIANCE 25 mg (N=557).
  Number (%) of Patients
Placebo
N=995
JARDIANCE 10 mg
N=999
JARDIANCE 25 mg
N=977
Urinary tract infectiona 7.6% 9.3% 7.6%
Female genital mycotic infectionsb 1.5% 5.4% 6.4%
Upper respiratory tract infection 3.8% 3.1% 4.0%
Increased urinationc 1.0% 3.4% 3.2%
Dyslipidemia 3.4% 3.9% 2.9%
Arthralgia 2.2% 2.4% 2.3%
Male genital mycotic infectionsd 0.4% 3.1% 1.6%
Nausea 1.4% 2.3% 1.1%

Thirst (including polydipsia) was reported in 0%, 1.7%, and 1.5% for placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively.

Volume Depletion
JARDIANCE causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion. In the pool of five placebo-controlled clinical trials, adverse reactions related to volume depletion (e.g., blood pressure (ambulatory) decreased, blood pressure systolic decreased, dehydration, hypotension, hypovolemia, orthostatic hypotension, and syncope) were reported by 0.3%, 0.5%, and 0.3% of patients treated with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg respectively. JARDIANCE may increase the risk of hypotension in patients at risk for volume contraction [see Warnings and Precautions (5.1) and Use in Specific Populations (8.5, 8.6)].

Increased Urination
In the pool five placebo-controlled clinical trials, adverse reactions of increased urination (e.g., polyuria, pollakiuria, and nocturia) occurred more frequently on JARDIANCE than on placebo (see Table 1). Specifically, nocturia was reported by 0.4%, 0.3%, and 0.8% of patients treated with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively.

Impairment in Renal Function
Use of JARDIANCE was associated with increases in serum creatinine and decreases in eGFR (see Table 2). Patients with moderate renal impairment at baseline had larger mean changes. [see Warnings and Precautions (5.2) and Use in Specific Populations (8.5, 8.6)].

Table 2 Changes from Baseline in Serum Creatinine and eGFR in the Pool of Four 24-week Placebo-Controlled Studies and Renal Impairment Study
aSubset of patients from renal impairment study with eGFR 30 to less than 60 mL/min/1.73 m2
  Pool of 24-Week Placebo-Controlled Studies
Placebo JARDIANCE 10 mg JARDIANCE 25 mg
Baseline N 825 830 822
Creatinine (mg/dL) 0.84 0.85 0.85
eGFR (mL/min/1.73 m2) 87.3 87.1 87.8
Week 12 Change N 771 797 783
Creatinine (mg/dL) 0.00 0.02 0.01
eGFR (mL/min/1.73 m2) -0.3 -1.3 -1.4
Week 24 Change N 708 769 754
Creatinine (mg/dL) 0.00 0.01 0.01
eGFR (mL/min/1.73 m2) -0.3 -0.6 -1.4
  Moderate Renal Impairmenta
Placebo   JARDIANCE 25 mg
Baseline N 187 -- 187
Creatinine (mg/dL) 1.49 -- 1.46
eGFR (mL/min/1.73 m2) 44.3 -- 45.4
Week 12 Change N 176 -- 179
Creatinine (mg/dL) 0.01 -- 0.12
eGFR (mL/min/1.73 m2) 0.1 -- -3.8
Week 24 Change N 170 -- 171
Creatinine (mg/dL) 0.01 -- 0.10
eGFR (mL/min/1.73 m2) 0.2 -- -3.2
Week 52 Change N 164 -- 162
Creatinine (mg/dL) 0.02 -- 0.11
eGFR (mL/min/1.73 m2) -0.3 -- -2.8

Hypoglycemia
The incidence of hypoglycemia by study is shown in Table 3. The incidence of hypoglycemia increased when JARDIANCE was administered with insulin or sulfonylurea [see Warnings and Precautions (5.3)].

Table 3 Incidence of Overalla and Severeb Hypoglycemic Events in Controlled Clinical Studies
aOverall hypoglycemic events: plasma or capillary glucose of less than or equal to 70 mg/dL
bSevere hypoglycemic events: requiring assistance regardless of blood glucose
cInsulin dose could not be adjusted during the initial 18 week treatment period
Monotherapy
(24 weeks)
Placebo
(n=229)
JARDIANCE 10 mg
(n=224)
JARDIANCE 25 mg
(n=223)
Overall (%) 0.4% 0.4% 0.4%
Severe (%) 0% 0% 0%
In Combination with
Metformin
(24 weeks)
Placebo + Metformin
(n=206)
JARDIANCE 10 mg + Metformin
(n=217)
JARDIANCE 25 mg + Metformin
(n=214)
Overall (%) 0.5% 1.8% 1.4%
Severe (%) 0% 0% 0%
In Combination with
Metformin + Sulfonylurea
(24 weeks)
Placebo
(n=225)
JARDIANCE 10 mg + Metformin + Sulfonylurea
(n=224)
JARDIANCE 25 mg + Metformin + Sulfonylurea
(n=217)
Overall (%) 8.4% 16.1% 11.5%
Severe (%) 0% 0% 0%
In Combination with
Pioglitazone +/- Metformin
(24 weeks)
Placebo
(n=165)
JARDIANCE 10 mg + Pioglitazone +/- Metformin
(n=165)
JARDIANCE 25 mg + Pioglitazone +/- Metformin
(n=168)
Overall (%) 1.8% 1.2% 2.4%
Severe (%) 0% 0% 0%
In Combination with Insulin
(18 weeksc)
Placebo
(n=170)
JARDIANCE 10 mg
(n=169)
JARDIANCE 25 mg
(n=155)
Overall (%) 20.6% 19.5% 28.4%
Severe (%) 0% 0% 1.3%

Genital Mycotic Infections
In the pool five placebo-controlled clinical trials, the incidence of genital mycotic infections (e.g., vaginal mycotic infection, vaginal infection, genital infection fungal, vulvovaginal candidiasis, and vulvitis) was increased in patients treated with JARDIANCE compared to placebo, occurring in 0.9%, 4.1%. and 3.7% of patients randomized to placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively. Discontinuation from study due to genital infection occurred in 0% of placebo-treated patients and 0.2% of patients treated with either JARD

以下是“全球医药”详细资料
Tags: 责任编辑:admin
】【打印繁体】【投稿】【收藏】 【推荐】【举报】【评论】 【关闭】 【返回顶部
分享到QQ空间
分享到: 
上一篇Voraxaze(glucarpidase) 下一篇STELARA(ustekinumab)injection, ..

相关栏目

最新文章

图片主题

热门文章

推荐文章

相关文章

广告位