DAPAGLIFLOZIN 5 MG TAB 30
Generic: DAPAGLIFLOZIN
DAPAGLIFLOZIN 5 MG TAB 30
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Identification
DAPAGLIFLOZIN
DAPAGLIFLOZIN
Prasco Laboratories
HUMAN PRESCRIPTION DRUG
Administration
TABLET, FILM COATED
ORAL
NDA202293
Active Ingredients
| Ingredient | Strength |
|---|---|
| DAPAGLIFLOZIN PROPANEDIOL | 5 mg/1 |
Pharmacological Class
Data sourced from openFDA / DailyMed. For full prescribing information, consult the drug label.
Wholesale compliance resources
Drug Resources
Clinical Drug Information
Indications & Usage
1 INDICATIONS AND USAGE DAPAGLIFLOZIN TABLETS are indicated: • To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression. • To reduce the risk of CV death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established CV disease or multiple CV risk factors. • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. Limitations of Use • DAPAGLIFLOZIN TABLETS are not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see Warnings and Precautions (5.1) ] . • DAPAGLIFLOZIN TABLETS are not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m 2 . DAPAGLIFLOZIN TABLETS are likely to be ineffective in this setting based upon its mechanism of action. • DAPAGLIFLOZIN TABLETS are not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. DAPAGLIFLOZIN TABLETS are not expected to be effective in these populations. DAPAGLIFLOZIN TABLETS, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, are indicated: • To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular (CV) death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression. (1) • To reduce the risk of CV death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. (1) • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established CV disease or multiple CV risk factors. (1) • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. (1) Limitations of use: • Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. (1) • Not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m 2 . DAPAGLIFLOZIN TABLETS are likely to be ineffective in this setting based upon its mechanism of action. (1) • Not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for the treatment of kidney disease. DAPAGLIFLOZIN TABLETS are not expected to be effective in these populations. (1)
Dosage & Administration
2 DOSAGE AND ADMINISTRATION • Assess renal function prior to initiation and then as clinically indicated. Assess volume status and correct volume depletion before initiating. (2.1) • To improve glycemic control, the recommended starting dosage is 5 mg orally once daily. Dosage can be increased to 10 mg orally once daily for additional glycemic control. (2.2) • For all other indications, the recommended dosage is 10 mg orally once daily. (2.3) • See full prescribing information for dosage recommendations in patients with renal impairment. ( 2.2 , 2.3 ) • Withhold DAPAGLIFLOZIN TABLETS for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. (2.4) 2.1 Testing Prior to Initiation of DAPAGLIFLOZIN TABLETS • Assess renal function prior to initiation of DAPAGLIFLOZIN TABLETS and then as clinically indicated [see Warnings and Precautions (5.2) ]. • Assess volume status. In patients with volume depletion, correct this condition before initiating DAPAGLIFLOZIN TABLETS [see Warnings and Precautions (5.2) and Use in Specific Populations (8.5 , 8.6) ] . 2.2 Recommended Dosage for Glycemic Control in Adults and Pediatric Patients Aged 10 Years and Older with Type 2 Diabetes Mellitus In adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, the recommended starting dosage of DAPAGLIFLOZIN TABLETS is 5 mg orally once daily to improve glycemic control. For additional glycemic control, the dosage can be increased to 10 mg orally once daily. For Adult and Pediatric Patients with Type 2 Diabetes Mellitus and Renal Impairment: • The recommended dosage for DAPAGLIFLOZIN TABLETS in patients with an eGFR greater than or equal to 45 mL/min/1.73 m 2 is the same as the recommended dosage in patients with normal renal function. • DAPAGLIFLOZIN TABLETS are not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m 2 . DAPAGLIFLOZIN TABLETS are likely to be ineffective to improve glycemic control in this setting based upon its mechanism of action. 2.3 Recommended Dosage for Other Indications in Adults The recommended dosage of DAPAGLIFLOZIN TABLETS is 10 mg orally once daily in adults for the following indications: • To reduce the risk of sustained eGFR decline, end stage kidney disease (ESKD), CV death, and hospitalization for heart failure (hHF) in patients with chronic kidney disease at risk of progression. • To reduce the risk of CV death, hHF, and urgent heart failure visit in patients with heart failure. • To reduce the risk of hHF in patients with type 2 diabetes mellitus and either established CV disease or multiple CV risk factors. For Adults with Renal Impairment Receiving DAPAGLIFLOZIN TABLETS for Indications Other than Glycemic Control: • The recommended dosage of DAPAGLIFLOZIN TABLETS in patients with an eGFR greater than or equal to 25 mL/min/1.73 m 2 is the same as the recommended dosage in patients with normal renal function. • Initiation with DAPAGLIFLOZIN TABLETS is not recommended in patients with an eGFR less than 25 mL/min/1.73 m 2 . • If the eGFR falls below 25 mL/min/1.73 m 2 while receiving treatment with DAPAGLIFLOZIN TABLETS, patients may continue DAPAGLIFLOZIN TABLETS 10 mg orally once daily to reduce the risk of eGFR decline, ESKD, CV death and hHF. 2.4 Temporary Interruption for Surgery Withhold DAPAGLIFLOZIN TABLETS for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume DAPAGLIFLOZIN TABLETS when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ]. 2.5 Recommendations Regarding Missed Dose • If a dose is missed, instruct patients to take the dose as soon as possible. • Advise patients not to double up the next dose.
Adverse Reactions
6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: • Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions (5.1) ] • Volume Depletion [see Warnings and Precautions (5.2) ] • Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.3) ] • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.4) ] • Most common adverse reactions (5% or greater incidence) were female genital mycotic infections, nasopharyngitis, and urinary tract infections. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 clinical practice. Dapagliflozin has been evaluated in clinical trials in adult and pediatric patients aged 10 years and older with type 2 diabetes mellitus, in adult patients with heart failure, and in adult patients with chronic kidney disease. The overall safety profile of dapagliflozin was consistent across the studied indications. No new adverse reactions were identified in the DAPA-HF and DELIVER heart failure trials, or in the DAPA-CKD trial in patients with chronic kidney disease. Severe hypoglycemia and diabetic ketoacidosis (DKA) were observed only in patients with diabetes mellitus. Clinical Trials for Glycemic Control in Adult Patients with Type 2 Diabetes Mellitus Pool of 12 Placebo-Controlled Adult Trials for Dapagliflozin 5 and 10 mg for Glycemic Control The data in Table 1 is derived from 12 glycemic control placebo-controlled trials in adult patients with type 2 diabetes mellitus ranging from 12 to 24 weeks. In 4 trials dapagliflozin was used as monotherapy, and in 8 trials dapagliflozin was used as add-on to background antidiabetic therapy or as combination therapy with metformin [see Clinical Studies (14.1) ]. These data reflect exposure of 2338 adult patients to dapagliflozin with a mean exposure duration of 21 weeks. Patients received placebo (N=1393), dapagliflozin 5 mg (N=1145), or dapagliflozin 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 m 2 ). Table 1 shows common adverse reactions in adults associated with the use of dapagliflozin. These adverse reactions were not present at baseline, occurred more commonly on dapagliflozin than on placebo, and occurred in at least 2% of patients treated with either dapagliflozin 5 mg or dapagliflozin 10 mg. Table 1: Adverse Reactions in Placebo-Controlled Trials of Glycemic Control Reported in ≥2% of Adults Treated with Dapagliflozin Adverse Reaction % of Patients Pool of 12 Placebo-Controlled Trials Placebo N=1393 Dapagliflozin 5 mg N=1145 Dapagliflozin 10 mg N=1193 Female genital mycotic infections Genital mycotic infections include the following adverse reactions, listed in order of frequency 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, dapagliflozin 5 mg=581, dapagliflozin 10 mg=598). 1.5 8.4 6.9 Nasopharyngitis 6.2 6.6 6.3 Urinary tract infections 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. 3.7 5.7 4.3 Back pain 3.2 3.1 4.2 Increased urination Increased urination includes the following adverse reactions, listed in order of frequency reported: pollakiuria, polyuria, and urine output increased. 1.7 2.9 3.8 Male genital mycotic infections 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, and posthitis. (N for males: Placebo=716, dapagliflozin 5 mg=564, dapagliflozin 10 mg=595). 0.3 2.8 2.7 Nausea 2.4 2.8 2.5 Influenza 2.3 2.7 2.3 Dyslipidemia 1.5 2.1 2.5 Constipation 1.5 2.2 1.9 Discomfort with urination 0.7 1.6 2.1 Pain in extremity 1.4 2.0 1.7 Pool of 13 Placebo-Controlled Adult Trials for Dapagliflozin 10 mg for Glycemic Control Dapagliflozin 10 mg was also evaluated in a larger glycemic control placebo-controlled trial pool in adult patients with type 2 diabetes mellitus. This pool combined 13 placebo-controlled trials, including 3 monotherapy trials, 9 add-on to background antidiabetic therapy trials, and an initial combination with metformin trial. Across these 13 trials, 2360 patients were treated once daily with dapagliflozin 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 m 2 ). Other Adverse Reactions in Adult Patients with Type 2 Diabetes Mellitus Volume Depletion Dapagliflozin causes an osmotic diuresis, which may lead to a reduction in intravascular volume. Adverse reactions related to volume depletion (including reports of dehydration, hypovolemia, orthostatic hypotension, or hypotension) in adult patients with type 2 diabetes mellitus for the 12 trial and 13 trial, short term, placebo controlled pools and for the DECLARE trial are shown in Table 2 [see Warnings and Precautions (5.2) ]. Table 2: Adverse Reactions Related to Volume Depletion Volume depletion includes reports of dehydration, hypovolemia, orthostatic hypotension, or hypotension. in Clinical Trials in Adults with Type 2 Diabetes Mellitus with Dapagliflozin Pool of 12 Placebo-Controlled Trials Pool of 13 Placebo-Controlled Trials DECLARE Trial Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg Placebo Dapagliflozin 10 mg Placebo Dapagliflozin 10 mg Overall population N (%) N=1393 5 (0.4%) N=1145 7 (0.6%) N=1193 9 (0.8%) N=2295 17 (0.7%) N=2360 27 (1.1%) N=8569 207 (2.4%) N=8574 213 (2.5%) Patient Subgroup n (%) Patients on loop diuretics n=55 1 (1.8%) n=40 0 n=31 3 (9.7%) n=267 4 (1.5%) n=236 6 (2.5%) n=934 57 (6.1%) n=866 57 (6.6%) Patients with moderate renal impairment with eGFR ≥30 and 55% were reported in 0.4% of placebo-treated patients and 1.3% of dapagliflozin 10 mg-treated patients. Increase in Low-Density Lipoprotein Cholesterol In the pool of 13 placebo-controlled trials of glycemic control, changes from baseline in mean lipid values were reported in dapagliflozin-treated adult 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 dapagliflozin 10 mg groups, respectively. In the DECLARE trial [see Clinical Studies (14.3) ] , mean changes from baseline after 4 years were 0.4 mg/dL versus 4.1 mg/dL for total cholesterol, and -2.5 mg/dL versus -4.4 mg/dL for LDL cholesterol, in dapagliflozin-treated and the placebo groups, respectively. Decrease in Serum Bicarbonate In a trial of concomitant therapy of dapagliflozin 10 mg with exenatide extended-release (on a background of metformin) in adults, four patients (1.7%) on concomitant therapy had a serum bicarbonate value of less than or equal to 13 mEq/L compared to one each (0.4%) in the dapagliflozin and exenatide-extended release treatment groups [see Warnings and Precautions (5.1) ]. Clinical Trial in Pediatric Patients with Type 2 Diabetes Mellitus The dapagliflozin safety profile observed in a 26-week placebo-controlled clinical trial with a 26-week extension in 157 pediatric patients aged 10 years and older with type 2 diabetes mellitus was similar to that observed in adults [see Clinical Studies (14.2) ]. 6.2 Postmarketing Experience Additional adverse reactions have been identified during post-approval use of dapagliflozin. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections: Necrotizing fasciitis of the perineum (Fournier’s Gangrene), urosepsis and pyelonephritis Metabolism and Nutrition Disorders: Ketoacidosis Renal and Urinary Disorders: Acute kidney injury Skin and Subcutaneous Tissue Disorders: Rash
Information for Patients
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, inform them that using DAPAGLIFLOZIN TABLETS can increase their risk of life-threatening diabetic ketoacidosis. For all other patients, inform them that DAPAGLIFLOZIN TABLETS can cause potentially fatal ketoacidosis and that type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are risk factors. Educate all patients on precipitating factors (such as insulin dose reduction or missed insulin doses, infection, reduced caloric intake, ketogenic diet, surgery, dehydration, and alcohol abuse) and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing). Inform patients that blood glucose may be normal even in the presence of ketoacidosis. Advise patients that they may be asked to monitor ketones. If symptoms of ketoacidosis occur, instruct patients to discontinue DAPAGLIFLOZIN TABLETS and seek medical attention immediately [see Warnings and Precautions (5.1) ] . Volume Depletion Inform patients that symptomatic hypotension may occur with DAPAGLIFLOZIN TABLETS and advise them to contact their healthcare provider if they experience such symptoms [see Warnings and Precautions (5.2) ] . Inform patients that dehydration may increase the risk for hypotension, and to have adequate fluid intake. Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections Counsel patients that genitourinary infections may occur when taking DAPAGLIFLOZIN TABLETS and may become serious. Educate patients on the symptoms and advise them to seek medical advice if symptoms occur. Specifically, advise patients to promptly seek medical attention if they develop pain or tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, along with a fever above 100.4°F or malaise [see Warnings and Precautions (5.3) ] . Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Inform patients that the incidence of hypoglycemia may increase when DAPAGLIFLOZIN TABLETS are added to an insulin secretagogue (e.g., sulfonylurea) and/or insulin. Educate patients on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.4) ] . Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions (e.g., urticaria, anaphylactic reactions, and angioedema) have been reported with dapagliflozin. Advise patients to immediately report any signs or symptoms suggesting allergic reaction or angioedema, and to take no more of the drug until they have consulted prescribing physicians. Pregnancy Advise pregnant patients of the potential risk to a fetus with treatment with DAPAGLIFLOZIN TABLETS. Instruct patients to immediately inform their healthcare provider if pregnant or planning to become pregnant [see Use in Specific Populations (8.1) ] . Lactation Advise patients that use of DAPAGLIFLOZIN TABLETS is not recommended while breastfeeding [see Use in Specific Populations (8.2) ]. Laboratory Tests Due to its mechanism of action, patients taking DAPAGLIFLOZIN TABLETS will test positive for glucose in their urine. Missed Dose Instruct patients to take DAPAGLIFLOZIN TABLETS only as prescribed. If a dose is missed, it should be taken as soon as possible. Advise patients not to double their next dose [see Dosage and Administration (2.5) ]. Distributed by: Prasco Laboratories Mason, OH 45040 USA
Clinical data sourced from openFDA drug labeling. For complete prescribing information, consult the full drug label.