达格列净片 FARXIGA (dapagliflozin) FDA药品说明书翻译

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FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE 适应症和用途

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

本药用于配合饮食控制和运动改善2型糖尿病患者的血糖控制。

1.1 Limitation of Use 使用限制

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

本药不适用于1型糖尿病或糖尿病酮症酸中毒患者。

2 DOSAGE AND ADMINISTRATION 用法用量

2.1 Recommended Dosing 推荐剂量

The recommended starting dose of FARXIGA is 5 mg once daily, taken in the morning, with or without food. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose can be increased to 10 mg once daily.

推荐起始剂量为一次5mg，一日1次，早晨服用，可与或不与食物同服。对本药一次5mg，一日1次剂量耐受且须更多血糖扩指着，可增至一次10mg，一日1次。

In patients with volume depletion, correcting this condition prior to initiation of FARXIGA is recommended [see Warnings and Precautions (5.1), Use in Specific Populations (8.5, 8.6), and Patient Counseling Information (17)].

血容量减少患者，推荐用药前应先纠正血容量减少。

2.2 Patients with Renal Impairment 肾功能不全时剂量

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

建议在开始使用本药前及使用期间定期评估肾功能。

FARXIGA should not be initiated in patients with an eGFR less than 60 mL/min/1.73 m2. 肾小球滤过率＜60ml/(min/1.73m2)患者不得开始用药。

No dose adjustment is needed in patients with mild renal impairment (eGFR of 60 mL/min/1.73 m2 or greater).

轻度肾功能损害者[肾小球滤过率≥60ml/(min/1.73m2)]无需调整剂量。 FARXIGA should be discontinued when eGFR is persistently less than 60 mL/min/1.73 m2[see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)].

肾小球滤过率持续＜60ml/(min/1.73m2)时应停药。

3 DOSAGE FORMS AND STRENGTHS 剂型和规格

FARXIGA 5 mg tablets are yellow, biconvex, round, film-coated tablets with “5” engraved on

one side and “1427” engraved on the other side.

FARXIGA 10 mg tablets are yellow, biconvex, diamond-shaped, film-coated tablets with “10”

engraved on one side and “1428” engraved on the other side.

达格列净片 (1)5mg。(2)10mg。

4 CONTRAINDICATIONS 禁忌症

History of a serious hypersensitivity reaction to FARXIGA [see Adverse Reactions (6.1)]. Severe renal impairment, end-stage renal disease (ESRD), or patients on dialysis [see Use in

Specific Populations (8.6)].

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1.对本药有严重过敏史者。

2.重度肾功能损害、晚期肾病患者。

3.透析患者。

5 WARNINGS AND PRECAUTIONS 警告和注意事项

5.1 Hypotension 低血压

FARXIGA causes intravascular volume contraction. Symptomatic hypotension can occur after initiating FARXIGA [see Adverse Reactions (6.1)] particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics. Before initiating FARXIGA in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms of hypotension after initiating therapy. 本药可引起血管收缩，开始用药后可出现症状性低血压。尤其肾功能损害者[(肾小球滤过率＜60ml/(min/1.73m2)]、老年患者、使用髓袢利尿药的患者。以上患者开始使用本药前应先评估并纠正血容量状况。用药后应监测低血压迹象和症状。

5.2 Impairment in Renal Function 肾功能损害

FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Adverse reactions related to renal function can occur after initiating FARXIGA [see Adverse Reactions (6.1)]. Renal function should be evaluated prior to initiation of FARXIGA and monitored periodically thereafter

本药可增加血清肌酸酐并降低肾小球滤过率。老年患者和肾功能损害者对此类作用更为敏感。用药后可能出现与肾功能相关的不良反应，开始使用本药前及使用期间应定期评估肾功能。

5.3 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues 低血糖(与胰岛素和胰岛素促泌剂合用时)

Insulin and insulin secretagogues are known to cause hypoglycemia. FARXIGA can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue [see Adverse Reactions (6.1)]. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when these agents are used in combination with FARXIGA. 已知胰岛素和胰岛素促泌剂可引起低血糖。本药与以上两种药物合用时发生低血糖的风险增加。合用时可能需降低胰岛素或胰岛素促泌剂的剂量，以降低低血糖风险。

5.4 Genital Mycotic Infections 生殖器霉菌感染

FARXIGA increases the risk of genital mycotic infections. Patients with a history of genital mycotic infections were more likely to develop genital mycotic infections [see Adverse Reactions (6.1)]. Monitor and treat appropriately.

本药增加发生生殖器霉菌感染的风险。有生殖器霉菌感染病史的患者更易出现。应进行适当的监测和治疗。

5.5 Increases in Low-Density Lipoprotein Cholesterol (LDL-C) 低密度脂蛋白(LDL-C)升高 Increases in LDL-C occur with FARXIGA [see Adverse Reactions (6.1)]. Monitor LDL-C and treat per standard of care after initiating FARXIGA.

本药可使LDL-C升高，开始用药后应监测LDL-C并进行标准治疗。

5.6 Bladder Cancer 膀胱癌

Across 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 10/6045

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patients (0.17%) treated with FARXIGA and 1/3512 patient (0.03%) treated with placebo/comparator. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were 4 cases with FARXIGA and no cases with placebo/comparator. Bladder cancer risk factors and hematuria (a potential indicator of preexisting tumors) were balanced between treatment arms at baseline. There were too few cases to determine whether the emergence of these events is related to FARXIGA.

22项临床试验中，有0.17%(10/6045)使用本药和0.03%(1/3512)使用安慰剂患者出现新近诊断的膀胱癌的报道。排除诊断为膀胱癌时用药不足一年的患者，有4例使用本药患者出现膀胱癌(使用安慰剂患者0例)。开始用药时在治疗组中评估膀胱癌风险因素和血尿(已存在肿瘤的潜在指标)，评估人数过少无法确定膀胱癌是否与本药相关。

There are insufficient data to determine whether FARXIGA has an effect on pre-existing bladder tumors. Consequently, FARXIGA should not be used in patients with active bladder cancer. In patients with prior history of bladder cancer, the benefits of glycemic control versus unknown risks for cancer recurrence with FARXIGA should be considered.

尚无充分的数据确定本药对已存在的膀胱癌是否有作用。故活动期膀胱癌患者不得用药。有膀胱癌病史者，用药时应权衡血糖控制与复发的未知风险。

5.7 Macrovascular Outcomes 大血管病变

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

尚无本药或其他任一抗糖尿病药降低大血管病变风险的临床试验证据。

6 ADVERSE REACTIONS 不良反应

The following important adverse reactions are described below and elsewhere in the labeling: 下列重要不良反应已在说明书其他章节讨论：

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)]

Increases in Low-Density Lipoprotein Cholesterol (LDL-C) [see Warnings and Precautions

(5.5)]

Bladder Cancer [see Warnings and Precautions (5.6)]

低血压、肾功能损害、低血糖(与胰岛素和胰岛素促泌剂合用时)、生殖器霉菌感染、LDL-C升高、膀胱癌。

6.1 Clinical Trials Experience 临床试验经验

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 clinical practice.

由于临床试验是在各种不同条件下进行的，观察到的不良反应发生率不能直接与其他临床试验中的发生率相比较，可能也不能反应临床实践中观察到的发生率。

Pool of 12 Placebo-Controlled Studies for FARXIGA 5 and 10 mg

12项本药5mg、10mg安慰剂对照试验合并数据

The data in Table 1 is derived from 12 placebo-controlled studies ranging from 12 to 24 weeks. In 4 studies FARXIGA was used as monotherapy, and in 8 studies FARXIGA was used as add-on to

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background antidiabetic therapy or as combination therapy with metformin [see Clinical Studies

(14)].

表1中的数据来源于12项安慰剂对照试验，试验时长12-24周。其中4项为本药单药治疗，另外8项为本药加入标准糖尿病治疗方案或与二甲双胍合用。

These data reflect exposure of 2338 patients to FARXIGA with a mean exposure duration of 21 weeks. Patients received placebo (N=1393), FARXIGA 5 mg (N=1145), or FARXIGA 10 mg (N=1193) once daily. The mean age of the population was 55 years and 2% were older than 75 years of age. Fifty percent (50%) of the population were male; 81% were White, 14% were Asian, and 3% were Black or African American. At baseline, the population had diabetes for an average of 6 years, had a mean hemoglobin A1c (HbA1c) of 8.3%, and 21% had established microvascular complications of diabetes. Baseline renal function was normal or mildly impaired in 92% of patients and moderately impaired in 8% of patients (mean eGFR 86 mL/min/1.73 m2).

试验数据中，2338名患者接受本药治疗，平均暴露时间为21周。其中安慰剂组1393名患者、本药5mg组1145名患者、本药10mg组1193名患者，患者均接受一日1次用药。受试者平均年龄55岁，其中2%＞75岁。50%为男性，81%为白种人，14%为亚洲人，3%为黑人或非暨美国人。基线水平，受试者患病平均年数为6年，糖化血红蛋白(HbA1c)平均值为8.3%，其中21%受试者出现糖尿病微血管并发症。92%受试者肾功能正常或出现轻度肾功能损害，8%受试者出现中度肾功能损害，平均肾小球滤过率为86ml/(min/1.73m2)。

Table 1 shows common adverse reactions associated with the use of FARXIGA. These adverse reactions were not present at baseline, occurred more commonly on FARXIGA than on placebo, and occurred in at least 2% of patients treated with either FARXIGA 5 mg or FARXIGA 10 mg.

本药的常见不良反应见表1。这些不良反应并不是在基线时出现，本药较安慰剂更为常见发生程度，在本药5mg或10mg组中发生率≥2%。

Table 1: Adverse Reactions in Placebo-Controlled Studies Reported in ≥2% of Patients Treated with FARXIGA 表1 安慰剂对照试验中本药发生率≥2%的不良反应

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reported for females: vulvovaginal mycotic infection, vaginal infection, vulvovaginal candidiasis, vulvovaginitis, genital infection, genital candidiasis, fungal genital infection, vulvitis, genitourinary tract infection, vulval abscess, and vaginitis bacterial. (N for females: Placebo=677, FARXIGA 5 mg=581, FARXIGA 10 mg=598).

* 女性生殖器霉菌感染包括以下不良反应(按发生率排序)：外阴阴道霉菌感染、阴道感染、外阴阴道念珠菌病、外阴阴道炎、生殖感染、生殖器念珠菌病、生殖器真菌感染、外阴炎、泌尿生殖道感染、外阴脓肿、细菌性阴道炎。

Urinary tract infections include the following adverse reactions, listed in order of frequency reported: urinary tract infection, cystitis, Escherichia urinary tract infection, genitourinary tract infection, pyelonephritis, trigonitis, urethritis, kidney infection, and prostatitis.

尿道感染包括以下不良反应(按发生率排序)：尿道感染、膀胱炎、大肠埃希菌型尿路感染、泌尿生殖道感染、肾盂肾炎、膀胱三角炎、尿道炎、肾脏感染、前列腺炎。

Increased urination includes the following adverse reactions, listed in order of frequency reported: pollakiuria, polyuria, and urine output increased.

排尿增加包括以下不良反应(按发生率排序)：尿频、多尿、尿量增加。

§ Genital mycotic infections include the following adverse reactions, listed in order of frequency reported for males: balanitis, fungal genital infection, balanitis candida, genital candidiasis, genital infection male, penile infection, balanoposthitis, balanoposthitis infective, genital infection, posthitis. (N for males: Placebo=716, FARXIGA 5 mg=564, FARXIGA 10 mg=595). § 男性生殖器霉菌感染包括以下不良反应(按发生率排序)：龟头炎、生殖器真菌感染、龟头念珠菌病、生殖器念珠菌病、男性生殖器感染、阴茎感染、龟头包皮炎、感染性龟头包皮炎、生殖感染、包皮炎。

Pool of 13 Placebo-Controlled Studies for FARXIGA 10 mg

13项本药10mg安慰剂对照试验合并数据

The safety and tolerability of FARXIGA 10 mg was also evaluated in a larger placebo-controlled study pool. This pool combined 13 placebo-controlled studies, including 3 monotherapy studies, 9 add-on to background antidiabetic therapy studies, and an initial combination with metformin study. Across these 13 studies, 2360 patients were treated once daily with FARXIGA 10 mg for a mean duration of exposure of 22 weeks. The mean age of the population was 59 years and 4% were older than 75 years. Fifty-eight percent (58%) of the population were male; 84% were White, 9% were Asian, and 3% were Black or African American. At baseline, the population had diabetes for an average of 9 years, had a mean HbA1c of 8.2%, and 30% had established microvascular disease. Baseline renal function was normal or mildly impaired in 88% of patients and moderately impaired in 11% of patients (mean eGFR 82 mL/min/1.73 m2).

本药10mg的安全性和耐受性在一项大型安慰剂对照合并研究中进行评估。这项合并对照研究包括13项临床试验，其中3项为本药单药治疗，另外9项为本药加入标准糖尿病治疗方案或用药初期与二甲双胍合用。试验数据中，2360名患者接受本药10mg治疗，一日1次，患者平均暴露时间为22周。受试者平均年龄59岁，其中4%＞75岁。58%为男性，84%为白种人，9%为亚洲人，3%为黑人或非暨美国人。基线水平，受试者患病平均年数为9年，HbA1c平均值为8.2%，其中30%受试者出现糖尿病微血管并发症。88%受试者肾功能正常或出现轻度肾功能损害，11%受试者出现中度肾功能损害，平均肾小球滤过率为82ml/(min/1.73m2)。

Volume Depletion 血容量不足

FARXIGA causes an osmotic diuresis, which may lead to reductions in intravascular volume. Adverse reactions related to volume depletion (including reports of dehydration, hypovolemia,

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orthostatic hypotension, or hypotension) are shown in Table 2 for the 12-study and 13-study, short-term, placebo-controlled pools [see Warnings and Precautions (5.1)].

本药可引起渗透性利尿，降低血容量。12项和13项短期、安慰剂对照合并数据中与血容量不足(包括脱水、血容量减少、直立性低血压、低血压的报道)相关的不良反应见表2。

Table 2: Adverse Reactions of Volume Depletion* in Clinical Studies with FARXIGA 表2 本药临床试验中血容量不足的不良反应

hypotension.

* 血容量不足包括脱水、血容量减少、直立性低血压、低血压的报道。

Impairment of Renal Function 肾功能损害

Use of FARXIGA was associated with increases in serum creatinine and decreases in eGFR (see Table 3). In patients with normal or mildly impaired renal function at baseline, serum creatinine and eGFR returned to baseline values at Week 24. Renal-related adverse reactions, including renal failure and blood creatinine increase, were more frequent in patients treated with FARXIGA (see Table 4). Elderly patients and patients with impaired renal function were more susceptible to these adverse reactions (see Table 4). Sustained decreases in eGFR were seen in patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2). 本药可增加血清肌酸酐并降低肾小球滤过率(见表3)。基线肾功能正常或轻度肾功能损害者，用药24周后血清肌酸酐和肾小球滤过率水平回至基线值。使用本药患者出现与肾相关的不良反应(包括肾衰竭和血清肌酸酐升高)频率更高(见表4)。老年患者和肾功能损害者对此类作用更为敏感(见表4)。中度肾功能损害者[肾小球滤过率＞30ml/(min/1.73m2)，＜60ml/(min/1.73m2)]曾出现持续的肾小球滤过率降低。

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Table 3: Changes in Serum Creatinine and eGFR Associated with FARXIGA in the Pool of 12 Placebo-Controlled Studies and Moderate Renal Impairment Study

表3 本药12周临床试验中和中度肾功能损害试验中血清肌酸酐、肾小球滤过率改变

表3复制出来样式太乱，鉴于内容较简单，故直接截图了。

Table 4: Proportion of Patients with at Least One Renal Impairment-Related Adverse Reaction 表4 至少有一项肾功能损害相关不良反应的患者比例

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* 患者来源于12项安慰剂对照试验的长期扩展。

Subset of patients from the pool of 13 placebo-controlled studies with long-term extensions. 患者来源于13项安慰剂对照试验的长期扩展。

The safety of FARXIGA was evaluated in a study of patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2) [see Clinical Studies (14)]. In this study 13 patients experienced bone fractures for treatment durations up to 104 weeks. No fractures occurred in the placebo group, 5 occurred in the FARXIGA 5 mg group, and 8 occurred in the FARXIGA 10 mg group. Eight of these 13 fractures were in patients who had a baseline eGFR of 30 to 45 mL/min/1.73 m2. Eleven of the 13 fractures were reported within the first 52 weeks. There was no apparent pattern with respect to the anatomic site of fracture.

本药的安全性通过一项在中度肾功能损害者[肾小球滤过率＞30ml/(min/1.73m2)，＜60ml/(min/1.73m2)]中的试验评估。在这项试验中，13名患者用药104周期间出现骨折，安慰剂组未出现骨折。出现骨折的13名患者中：5名为本药5mg组，8名为本药10mg组；8名为基

线肾小球滤过率30-45ml/(min/1.73m2)；11名用药52周内出现骨折。骨折的位置无固定模式。

Hypoglycemia 低血糖

The frequency of hypoglycemia by study [see Clinical Studies (14)] is shown in Table 5. Hypoglycemia was more frequent when FARXIGA was added to sulfonylurea or insulin [see Warnings and Precautions (5.3)].

试验中低血糖的发生率见表5，本药与磺酰脲或胰岛素合用时候更易发生低血糖。

Table 5: Incidence of Major* and Minor Hypoglycemia in Placebo-Controlled Studies 表5 安慰剂对照试验中低血压的主要和小幅度发生率

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表5复制出来样式太乱，鉴于内容较简单，故直接截图了。

* Major episodes of hypoglycemia were defined as symptomatic episodes requiring external (third party) assistance due to severe impairment in consciousness or behavior with a capillary or plasma glucose value <54 mg/dL and prompt recovery after glucose or glucagon administration. * 低血糖主要发作定义为出现意识或行为严重损害(伴毛细血管或血浆葡萄糖值＜54mg/dl)后需外界(第三方)协助的有症状发作，发作在使用葡萄糖或胰高血糖素后迅速恢复。 Minor episodes of hypoglycemia were defined as either a symptomatic episode with a capillary or plasma glucose measurement <63 mg/dL regardless of need for external assistance, or an asymptomatic capillary or plasma glucose measurement <63 mg/dL that does not qualify as a major episode.

低血糖小幅度发作定义为伴毛细血管或血浆葡萄糖值＜63mg/dl无需外界协助的有症状发作，或伴毛细血管或血浆葡萄糖值＜63mg/dl未评价为主要发作的无症状发作。

OAD = oral antidiabetic therapy OAD=口服抗糖尿病药疗法

Genital Mycotic Infections 生殖器霉菌感染

Genital mycotic infections were more frequent with FARXIGA treatment. Genital mycotic infections were reported in 0.9% of patients on placebo, 5.7% on FARXIGA 5 mg, and 4.8% on FARXIGA 10 mg, in the 12-study placebo-controlled pool. Discontinuation from study due to genital infection occurred in 0% of placebo-treated patients and 0.2% of patients treated with FARXIGA 10 mg. Infections were more frequently reported in females than in males (see Table 1). The most frequently reported genital mycotic infections were vulvovaginal mycotic infections in females and balanitis in males. Patients with a history of genital mycotic infections were more likely

to have a genital mycotic infection during the study than those with no prior history (10.0%, 23.1%,

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and 25.0% versus 0.8%, 5.9%, and 5.0% on placebo, FARXIGA 5 mg, and FARXIGA 10 mg, respectively).

使用本药患者更易出现生殖器霉菌感染。在12项安慰剂对照试验的已有报道中，出现生殖器霉菌感染患者比例，安慰剂组为0.9%、本药5mg组为5.7%、本药10mg组为4.8%。由于生殖器霉菌感染停药患者比例，安慰剂组为0%、本药10mg组为0.2%。报道中女性感染较男性感染更为常见(见表1)，最为常见的生殖器霉菌感染为女性外阴阴道霉菌感染、男性龟头炎。试验中有生殖器霉菌感染病史的患者更易出现感染。

Hypersensitivity Reactions 过敏反应

Hypersensitivity reactions (e.g., angioedema, urticaria, hypersensitivity) were reported with FARXIGA treatment. Across the clinical program, serious anaphylactic reactions and severe cutaneous adverse reactions and angioedema were reported in 0.2% of comparator-treated patients and 0.3% of FARXIGA-treated patients. If hypersensitivity reactions occur,

discontinue use of FARXIGA; treat per standard of care and monitor until signs and symptoms resolve.

使用本药治疗有出现过敏反应(如血管神经性水肿、过敏)的报道。临床研究中，出现严重过敏反应、严重皮肤不良反应、血管神经水肿患者的比例，对照组为0.2%、使用本药组为0.3%。如出现过敏反应，应停药并进行对症治疗及监测，直至迹象和症状解决。

Laboratory Tests 实验室测试

Increase in Hematocrit 血细胞比容升高

In the pool of 13 placebo-controlled studies, increases from baseline in mean hematocrit values were observed in FARXIGA-treated patients starting at Week 1 and continuing up to Week 16, when the maximum mean difference from baseline was observed. At Week 24, the mean changes from baseline in hematocrit were 0.33% in the placebo group and 2.30% in the FARXIGA 10 mg group. By Week 24, hematocrit values >55% were reported in 0.4% of placebo-treated patients and

1.3% of FARXIGA 10 mg–treated patients.

13项安慰剂对照试验合并数据显示，患者用药1周后出现血细胞比容平均值较基线水平升高且继续持续升高。第16周时血细胞比容平均值较基线差异最大。第24周时，血细胞比容平均值较基线的变化，安慰剂组为-0.33%、本药10mg组为2.30%。截至第24周，血细胞比容＞55%的患者比例，安慰剂组为0.4%、本药10mg组为1.3%。

Increase in Serum Inorganic Phosphorus 血清无机磷升高

In the pool of 13 placebo-controlled studies, increases from baseline in mean serum phosphorus levels were reported at Week 24 in FARXIGA-treated patients compared with placebo-treated patients (mean increase of 0.13 versus 0.04 mg/dL, respectively). Higher proportions of patients with marked laboratory abnormalities of hyperphosphatemia (≥5.6 mg/dL for age 17-65 years or ≥5.1 mg/dL for age ≥66 years) were reported on FARXIGA at Week 24 (0.9% versus 1.7% for placebo and FARXIGA 10 mg, respectively).

13项安慰剂对照试验合并数据显示，与使用安慰剂相比，患者用药24周后出现血清无机磷平均值较基线水平升高(安慰剂组为-0.04mg/dl，本药为0.13mg/dl)。用药24周后，使用本药患者出现高磷血症(实验室检测数据17-65岁者≥5.6mg/dl，≥66岁者≥5.1mg/dl)患者比例更高(安慰剂组为0.9%、本药10mg组为1.7%)。

Increase in Low-Density Lipoprotein Cholesterol LDL-C升高

In the pool of 13 placebo-controlled studies, changes from baseline in mean lipid values were reported in FARXIGA-treated patients compared to placebo-treated patients. Mean percent changes from baseline at Week 24, were 0.0% versus 2.5% for total cholesterol and 1.0% versus 2.9% for LDL cholesterol, in the placebo and FARXIGA 10 mg groups, respectively.

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13项安慰剂对照试验合并数据显示，与使用安慰剂相比，使用本药患者出现LDL-C较基线水平升高。第24时，LDL-C平均变化值，安慰剂组总胆固醇为0.0%、低密度脂蛋白胆固醇为-1.0%，本药10mg组总胆固醇为2.5%、低密度脂蛋白胆固醇为2.9%。

8 USE IN SPECIFIC POPULATIONS 特殊人群用药

8.1 Pregnancy 妊娠期妇女

Pregnancy Category C 妊娠分级：C级

There are no adequate and well-controlled studies of FARXIGA in pregnant women. Based on results of reproductive and developmental toxicity studies in animals, dapagliflozin may affect renal development and maturation. In a juvenile rat study, increased incidence and/or severity of renal pelvic and tubular dilatations were evident at the lowest tested dose which was

approximately 15 times clinical exposure from a 10 mg dose.

尚未在妊娠期妇女中进行充分、严格的对照试验，基于动物生殖毒性试验结果，本药可能影响肾脏的发育和成熟。在一项大鼠幼崽研究中，给予最低测试剂量(约为人类临床暴露量10mg的15倍)可出现明显的肾盂炎和食道扩张发生率增加和(或)加重。

These outcomes occurred with drug exposures during periods of animal development that correlate with the late second and third trimesters of human pregnancy. During pregnancy, consider appropriate alternative therapies, especially during the second and third trimesters. FARXIGA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In a juvenile toxicity study, when dapagliflozin was dosed directly to young rats from postnatal day (PND) 21 until PND 90 at doses of 1, 15, or 75 mg/kg/day, increased kidney weights and renal pelvic and tubular dilatations were reported at all levels. Exposure at the lowest tested dose was 15 times the maximum clinical dose, based on AUC. The renal pelvic and tubular dilatations observed in juvenile animals did not fully reverse within the approximate 1-month recovery period.

这些在动物发育期间使用药物暴露量出现的结果，与人类妊娠中期、妊娠晚期相关。妊娠期间，应采取替代疗法，尤其妊娠中期、妊娠晚期。本药仅在利大于弊的情况下方可用于妊娠期妇女。在一项大鼠幼崽毒性研究中，给予本药剂量为一日1mg/kg、15mg/kg、75mg/kg(于出生后21-90日期间)，所有剂量组出现肾脏重量增加、肾盂炎、食道扩张。给予的最低测试剂量以曲线下面积(AUC)计，约为人类最大临床暴露量的15倍。在幼崽中出现的肾盂炎、食管扩张并未在1个月恢复期间完全恢复。

In a prenatal and postnatal development study, maternal rats were dosed from gestation day 6 through lactation day 21 at doses of 1, 15, or 75 mg/kg/day, and pups were indirectly exposed in utero and throughout lactation. Increased incidence or severity of renal pelvic dilatation was observed in adult offspring of treated dams at 75 mg/kg/day (maternal and pup dapagliflozin exposures were 1415 times and 137 times, respectively, the human values at the clinical dose). Dose-related reductions in pup body weights were observed at doses ≥1 mg/kg/day (approximately ≥19 times the clinical dose). No adverse effects on developmental endpoints were noted at 1 mg/kg/day, or approximately 19 times the clinical dose.

在一项大鼠出生前和出生后发育研究中，妊娠大鼠从妊娠第6日到哺乳第21日，给予本药剂量为一日1mg/kg、15mg/kg、75mg/kg，幼崽在子宫内及哺乳期间间接暴露于本药。使用每日75mg/kg组(妊娠大鼠暴露量相当于人类治疗暴露量的1415倍，幼崽暴露量相当于人类治疗暴露量的137倍)中，成年后代出现肾盂炎和食道扩张发生率增加或加重。所有组(约为临床剂量≥19倍)中幼崽出现与剂量相关的体重降低。每日1mg/kg组(约为临床剂量的19倍)中，未见发育相关不良反应。

In embryo-fetal development studies in rats and rabbits, dapagliflozin was administered for

intervals coinciding with the first trimester period of organogenesis in humans. No developmental

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toxicities were observed in rabbits at any dose tested. In rats, dapagliflozin was neither

embryolethal nor teratogenic at doses up to 75 mg/kg/day or 1441 times the maximum clinical dose of 10 mg. At higher doses in rats, malformations of blood vessels, ribs, vertebra, manubria, and skeletal variations in fetuses at ≥150 mg/kg or 2344 times the 10 mg clinical dose were observed

在一项大鼠、家兔胚胎-胎仔发育研究中，间隔给予本药以保持与人类妊娠前期器官形成期一致。家兔任一剂量组未见生殖毒性。大鼠给予本药剂量达一日75mg/kg(相当于最大临床暴露量10mg的1441倍)时未见致畸作用。大鼠使用更高剂量(≥150mg/kg，相当于临床剂量10mg的2344倍)时出现血管、肋骨、椎骨、胸骨柄畸形，以及胎仔骨骼变化。

8.3 Nursing Mothers 哺乳期妇女

It is not known whether FARXIGA is excreted in human milk. Dapagliflozin is excreted in rat milk reaching levels 0.49 times that found in maternal plasma. Data in juvenile rats directly exposed to dapagliflozin showed risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from FARXIGA, a decision should be made whether to discontinue nursing or to discontinue FARXIGA, taking into account the importance of the drug to the mother.

本药是否随人类乳汁排泄尚不明确。本药可随大鼠乳汁排泄(为母体浓度的0.49倍)。直接暴露于本药后的大鼠幼崽，可见肾脏发育风险(肾盂炎和食道扩张)。由于人类肾脏发育在母体子宫内以及出生后2年(需哺乳)，可能有药物暴露对人类肾脏发育有风险。由于许多药物都可随人类乳汁排泄，且本药哺乳时造成严重不良反应的可能性，哺乳期妇女用药应权衡利弊，应考虑停药或停止哺乳。

8.4 Pediatric Use 儿童用药

Safety and effectiveness of FARXIGA in pediatric patients under 18 years of age have not been established.

18岁以下儿童使用本药的安全性和有效性尚不明确。

8.5 Geriatric Use 老人用药

No FARXIGA dosage change is recommended based on age. A total of 1424 (24%) of the 5936 FARXIGA-treated patients were 65 years and older and 207 (3.5%) patients were 75 years and older in a pool of 21 double-blind, controlled, clinical safety and efficacy studies of FARXIGA. After controlling for level of renal function (eGFR), efficacy was similar for patients under age 65 years and those 65 years and older. In patients ≥65 years of age, a higher proportion of patients treated with FARXIGA had adverse reactions related to volume depletion and renal impairment or failure compared to patients treated with placebo [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

尚无根据年龄调整用药剂量的推荐。21项双盲、对照、临床安全性和有效性临床试验的合并数据显示，使用本药的5936名患者中，1424名(24%)年龄≥65岁，207名(3.5%)年龄≥75岁。调整肾功能水平(肌酐清除率)后，65岁以上患者与65岁以下患者疗效相似。在年龄≥65岁患者中，因血容量不足和肾功能损害或肾衰竭出现不良反应的患者比例较安慰剂组高。

8.6 Renal Impairment 肾功能损害

The safety and efficacy of FARXIGA were evaluated in a study that included patients with

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moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2). Compared to placebo-treated patients, patients with moderate renal impairment treated with FARXIGA did not have improvement in glycemic control [see Clinical Studies (14.7)] and had more renal-related adverse reactions and more bone fractures [see Dosage and Administration (2.2), Warnings and Precautions (5.2), and Adverse Reactions (6.1)]; therefore, FARXIGA should not be initiated in this population.

本药安全性和有效性评价研究包括中度肾功能损害者[肾小球滤过率≥30ml/(min/1.73m2)，＜60ml/(min/1.73m2)]。与安慰剂组相比，中度肾功能损害者用药后未改善血糖控制，且肾脏相关的不良反应和骨折更多，故中度肾功能损害者不得使用本药。

Based on its mechanism of action, FARXIGA is not expected to be effective in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2) or ESRD [see Contraindications (4)]. 基于作用机制，本药对重度肾功能损害者[肾小球滤过率＜30ml/(min/1.73m2)]应无作用。

8.7 Hepatic Impairment 肝功能损害

No dose adjustment is recommended for patients with mild, moderate, or severe hepatic impairment. However, the benefit-risk for the use of dapagliflozin in patients with severe hepatic impairment should be individually assessed since the safety and efficacy of dapagliflozin have not been specifically studied in this population [see Clinical Pharmacology (12.3)].

尚无轻至重度肝功能损害者用药剂量调整的推荐。但考虑到此类患者用药的安全性和有效性尚不明确，重度肝功能损害者如需用药应单独评估。

10 OVERDOSAGE 药物过量

There were no reports of overdose during the clinical development program for FARXIGA. In the event of an overdose, contact the Poison Control Center. It is also reasonable to employ supportive measures, as dictated by the patient’s clinical status. The removal of dapagliflozin by hemodialysis has not been studied.

本药临床研究中尚无药物过量的报道。如出现过量，联系中毒防治中心。可根据患者口述的临床状态进行支持治疗。尚无本药血液透析的研究。

12 CLINICAL PHARMACOLOGY 临床药理学

12.1 Mechanism of Action 作用机制

Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. 钠-葡萄糖2型转运体（SGLT2）主要负责重新吸收肾小管内的葡萄糖。本药为SGLT2抑制药，通过抑制SGLT2可减少葡萄糖的重吸收，降低葡萄糖肾阈，以此增加尿糖的排泄。

12.2 Pharmacodynamics 药效学

General 一般情况

Increases in the amount of glucose excreted in the urine were observed in healthy subjects and in patients with type 2 diabetes mellitus following the administration of dapagliflozin (see Figure 1). Dapagliflozin dose of 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of approximately 70 grams of glucose in the urine per day at Week 12. A near maximum glucose excretion was observed at the dapagliflozin daily dose of 20 mg. This urinary glucose excretion with dapagliflozin also results in increases in urinary volume [see Adverse

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Reactions (6.1)].

健康受试者和糖尿病患者用药后可见尿液葡萄糖排出量增加(见图1)。糖尿病患者连续12周使用本药一日10mg剂量，第12周时，可见尿液中的葡萄糖排出量约为70g。使用本药一日20mg剂量可观察到接近最高值的葡萄糖排泄量。尿液葡萄糖排出量的增加也增加了尿量。

Figure 1: Scatter Plot and Fitted Line of Change from Baseline in 24-Hour Urinary Glucose Amount versus Dapagliflozin Dose in Healthy Subjects and Subjects with Type 2 Diabetes Mellitus (T2DM) (Semi-Log Plot) 图1 本药用于健康受试者和2型糖尿病患者从基线到24小时内尿液葡萄糖总量变化散点图和拟和线

Cardiac Electrophysiology 心脏电生理学

Dapagliflozin was not associated with clinically meaningful prolongation of QTc interval at daily doses up to 150 mg (15 times the recommended maximum dose) in a study of healthy subjects. In addition, no clinically meaningful effect on QTc interval was observed following single doses of up to 500 mg (50 times the recommended maximum dose) of dapagliflozin in healthy subjects.

在健康受试者的研究中，本药一日剂量达150mg(推荐最大剂量的15倍)，未见临床有意义的QT间期延长。另外，单次剂量达500mg(推荐最大剂量的50倍)，亦未见临床有意义的对QT间期的影响。

12.3 Pharmacokinetics 药动学

Absorption 吸收

Following oral administration of dapagliflozin, the maximum plasma concentration (C max ) is usually attained within 2 hours under fasting state. The C max and AUC values increase dose

proportionally with increase in dapagliflozin dose in the therapeutic dose range. The absolute oral

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bioavailability of dapagliflozin following the administration of a 10 mg dose is 78%. Administration of dapagliflozin with a high-fat meal decreases its Cmax by up to 50% and prolongs T max by approximately 1 hour, but does not alter AUC as compared with the fasted

state. These changes are not considered to be clinically meaningful and dapagliflozin can be administered with or without food.

空腹状态下，本药常于口服2小时内达血药峰浓度(Cmax)。Cmax和曲线下面积(AUC)在治疗剂量范围内随剂量增加而成比例增加。口服本药10mg，绝对生物利用度为78%。本药与高脂肪餐同时服用，Cmax可降低50%，Tmax(达峰时间)推迟约1小时，但与空腹状态相比，未改变AUC值。这些改变未见临床意义，本药可与或不与食物同服。

Distribution 分布

Dapagliflozin is approximately 91% protein bound. Protein binding is not altered in patients with renal or hepatic impairment.

本药蛋白结合率约为91%，肾功能或肝功能损害者的蛋白结合率未见改变。

Metabolism 代谢

The metabolism of dapagliflozin is primarily mediated by UGT1A9; CYP-mediated metabolism is a minor clearance pathway in humans. Dapagliflozin is extensively metabolized, primarily to yield dapagliflozin 3-O-glucuronide, which is an inactive metabolite. Dapagliflozin 3-Oglucuronide accounted for 61% of a 50 mg [14C]-dapagliflozin dose and is the predominant drug-related component in human plasma.

本药主要随尿苷二磷酸葡萄糖醛酸转移酶1A(UGT1A9)代谢，在人类中细胞色素P450(CYP酶)诱导的代谢为小部分清除通路。本药主要代谢为达格列净3-氧-葡萄苷酸(非活性代谢物)，达

是人类血浆中主要的与药物相关格列净3-氧-葡萄苷酸可降低 [14C]达格列净50mg剂量的61%，

的组分。

Elimination 消除

Dapagliflozin and related metabolites are primarily eliminated via the renal pathway. Following a single 50 mg dose of [14C]-dapagliflozin, 75% and 21% total radioactivity is excreted in urine and feces, respectively. In urine, less than 2% of the dose is excreted as parent drug. In feces,

approximately 15% of the dose is excreted as parent drug. The mean plasma terminal half-life (t½) for dapagliflozin is approximately 12.9 hours following a single oral dose of FARXIGA 10 mg. 本药及其代谢物主要经肾脏消除，单次给予[14C]达格列净50mg剂量，随尿液和粪便排泄量分别为75%和21%。尿液排出物中，有2%为药物本体形式；粪便排出物中，约15%为药物本体形式。单次口服本药10mg剂量，平均血浆消除半衰期约为12.9小时。

Specific Populations 特殊人群

Renal Impairment 肾功能损害者

At steady state (20 mg once-daily dapagliflozin for 7 days), patients with type 2 diabetes with mild, moderate, or severe renal impairment (as determined by eGFR) had geometric mean systemic exposures of dapagliflozin that were 45%, 2.04-fold, and 3.03-fold higher, respectively, as compared to patients with type 2 diabetes with normal renal function. Higher systemic exposure of dapagliflozin in patients with type 2 diabetes mellitus with renal impairment did not result in a correspondingly higher 24-hour urinary glucose excretion. The steady-state 24-hour urinary glucose excretion in patients with type 2 diabetes and mild, moderate, and severe renal impairment was 42%, 80%, and 90% lower, respectively, than patients with type 2 diabetes with normal renal function. The impact of hemodialysis on dapagliflozin exposure is not known. [See Dosage and

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Administration (2.2), Warnings and Precautions (5.2), Use in Specific Populations (8.6), and Clinical Studies (14.7).]

稳态下(连续7日使用本药一次20mg，一日1次)，与正常肾功能的2型糖尿病患者相比，伴轻度、中度、重度肾功能损害(以肾小球滤过率决定)的2型糖尿病患者几何学上的平均系统暴露量分别为其45%、2.04倍、3.03倍。伴肾功能损害的2型糖尿病患者更高的系统暴露量，并未相应的增加24小时尿葡萄糖排泄率，与正常肾功能的2型糖尿病患者相比，伴轻度、中度、重度肾功能损害的2型糖尿病患者24小时尿葡萄糖排泄率分别为其42%、80%、90%。血液透析对本药暴露量的影响尚不明确。

Hepatic Impairment 肝功能损害者

In subjects with mild and moderate hepatic impairment (Child-Pugh classes A and B), mean Cmax and AUC of dapagliflozin were up to 12% and 36% higher, respectively, as compared to healthy matched control subjects following single-dose administration of 10 mg dapagliflozin. These differences were not considered to be clinically meaningful. In patients with severe hepatic impairment (Child-Pugh class C), mean C max and AUC of dapagliflozin were up to 40% and 67% higher, respectively, as compared to healthy matched controls [see Use in Specific

Populations (8.7)].

与对照组受试者相比，轻度、中度肝功能损害(Child-Pugh分级A、B)的受试者，单次给予10mg本药后平均Cmax和AUC分别增加12%和36%。这些变化未被认定有临床意义。重度肝功能损害(Child-Pugh分级C)的受试者平均Cmax和AUC分别增加40%和67%。

Effects of Age, Gender, Race, and Body Weight on Pharmacokinetics 年龄、性别、种族、体重对药物动力学的影响

Based on a population pharmacokinetic analysis, age, gender, race, and body weight do not have a clinically meaningful effect on the pharmacokinetics of dapagliflozin and thus, no dose adjustment is recommended.

基于人群药物动力学的分析，年龄、性别、种族、体重对本药的药物动力学无临床意义影响，故无需调整剂量。

Pediatric 儿童

Pharmacokinetics in the pediatric population has not been studied.

尚无儿童药物动力学的研究。

Drug Interactions 药物相互作用

In Vitro Assessment of Drug Interactions 体外评估

In in vitro studies, dapagliflozin and dapagliflozin 3-O-glucuronide neither inhibited CYP 1A2, 2C9, 2C19, 2D6, or 3A4, nor induced CYP 1A2, 2B6, or 3A4. Dapagliflozin is a weak substrate of the P-glycoprotein (P-gp) active transporter, and dapagliflozin 3-O-glucuronide is a substrate for the OAT3 active transporter. Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters. Overall, dapagliflozin is unlikely to affect the pharmacokinetics of concurrently administered medications that are P-gp, OCT2, OAT1, or OAT3 substrates.

体外试验中，本药及其代谢物并未抑制CYP 1A2、CYP 2C9、CYP 2C19、CYP 2D6、CYP 3A4，也未诱导CYP 1A2、CYP 2B6、CYP 3A4。本药为弱效P-糖蛋白(P-gp)活性转运体底物，其代谢物为有机阴离子转运载体(OAT)3活性底物。本药及其代谢物并未有意义的抑制P-gp OCT2、P-gp OCT1、P-gp OCT3，故本药与P-gp OCT2、P-gp OCT1、P-gp OCT3底物药物合

定期提供最近FDA说明书翻译,纯手工翻译。

用时，不影响其药物动力学。

Effects of Other Drugs on Dapagliflozin 其他药物对本药的影响

Table 6 shows the effect of coadministered drugs on the pharmacokinetics of dapagliflozin. No dose adjustments are recommended for dapagliflozin.

本药与其他药物合用的药物动力学作用见表6，合用时无需调整本药剂量。

Table 6: Effects of Coadministered Drugs on Dapagliflozin Systemic Exposure

表6 与药物合用时对本药系统暴露量的影响

AUC = AUC(INF) for drugs given as single dose and AUC = AUC(TAU) for drugs given in multiple doses. AUC(INF)为单次给药，AUC(TAU)为多次给药

= no change (geometric mean ratio of test:reference within 0.80 to 1.25);无变化

↓ or ↑ = parameter was lower or higher, respectively, with coadministration compared to dapagliflozin administered alone (geometric mean ratio of test:reference was lower than 0.80 or higher than 1.25). 与单用药物相比，合用时参数较高或较低

Effects of Dapagliflozin on Other Drugs 本药对其他药物的影响

Table 7 shows the effect of dapagliflozin on other coadministered drugs. Dapagliflozin did not

定期提供最近FDA说明书翻译,纯手工翻译。

meaningfully affect the pharmacokinetics of the coadministered drugs.

合用时本药对其他药物的影响见表7，本药对与其合用的药物的药物动力学无有意义的影响。

Table 7: Effects of Dapagliflozin on the Systemic Exposures of Coadministered Drugs 表7 本药对其他药物系统暴露量的影响

AUC = AUC(INF) for drugs given as single dose and AUC = AUC(TAU) for drugs given in multiple doses. AUC(INF)为单次给药，AUC(TAU)为多次给药

= no change (geometric mean ratio of test:reference within 0.80 to 1.25); 无变化

↓ or ↑ = parameter was lower or higher, respectively, with coadministration compared to

dapagliflozin administered alone (geometric mean ratio of test:reference was lower than 0.80 or higher than 1.25). 与单用药物相比，合用时参数较高或较低

13 NONCLINICAL TOXICOLOGY 非临床毒性

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 致癌、致突变、生育力损害

Dapagliflozin did not induce tumors in either mice or rats at any of the doses evaluated in 2-year carcinogenicity studies. Oral doses in mice consisted of 5, 15, and 40 mg/kg/day in males and 2, 10,

定期提供最近FDA说明书翻译,纯手工翻译。

and 20 mg/kg/day in females, and oral doses in rats were 0.5, 2, and 10 mg/kg/day for both males and females. The highest doses evaluated in mice were approximately 72 times (males) and 105 times (females) the clinical dose of 10 mg per day based on AUC exposure. In rats, the highest dose was approximately 131 times (males) and 186 times (females) the clinical dose of 10 mg per day based on AUC exposure.

为期2年的致癌性研究中，小鼠和大鼠任何剂量未见本药可诱导肿瘤。口服剂量为：①雄性小鼠，一日5mg/kg、15mg/kg、40mg/kg；一日40mg/kg剂量以AUC计，约为人类临床10mg剂量的72倍。②雌性小鼠，一日2mg/kg、10mg/kg、20mg/kg；一日20mg/kg剂量以AUC计，约为人类临床10mg剂量的105倍。③雄性、雌性大鼠，一日0.5mg/kg、2mg/kg、10mg/kg；一日10mg/kg剂量以AUC计，约为人类临床10mg剂量的131倍(雄性)和186倍(雌性)。 Dapagliflozin was negative in the Ames mutagenicity assay and was positive in a series of in

vitro clastogenicity assays in the presence of S9 activation and at concentrations ≥100 μg/mL. Dapagliflozin was negative for clastogenicity in a series of in vivo studies evaluating micronuclei or DNA repair in rats at exposure multiples >2100 times the clinical dose.

本药Ames试验、大鼠体内骨髓微核试验、大鼠体内DNA修复试验结果为阴性，体外一系列染色体畸形试验结果为阳性。

There was no carcinogenicity or mutagenicity signal in animal studies, suggesting that dapagliflozin does not represent a genotoxic risk to humans.

动物试验中未见致畸或诱导突变作用，本药对人类无遗传毒性。

Dapagliflozin had no effects on mating, fertility, or early embryonic development in treated male or female rats at exposure multiples ≤1708 times and 998 times the maximum recommended human dose in males and females, respectively.

雄性大鼠使用本药剂量达人类最大推荐剂量≤1708倍、雌性大鼠≤998倍时未见对交配、生育、早期胚胎发育有影响。

16 HOW SUPPLIED/STORAGE AND HANDLING 如何供应/储存/处理 How Supplied FARXIGA (dapagliflozin) tablets have markings on both sides and are available in the strengths and packages listed in Table 14

Table 14: FARXIGA Tablet Presentations

Tablet Film-Coated Tablet Markings Package Size NDC Code Strength Tablet

Color/Shape

yellow, “5” engraved on one Bottles of 30 Bottles of 0003-1427-11 5 mg

biconvex, round 0003-1427-12

engraved on the other 0003-1427-13

side Cartons of 100 0003-1427-14

yellow, “10” engraved on one Bottles of 30 Bottles of 0003-1428-11 10 mg

biconvex, 0003-1428-12

diamond-shaped engraved on the other 0003-1428-13

side Cartons of 100 0003-1428-14

描绘的地方不翻译了，么用。

Storage and Handling 储存

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C

(59°F and 86°F) [see USP Controlled Room Temperature].

于20-25℃(15-30℃)保存。

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