Dapagliflozin and metformin hydrochloride
Tablet, Film Coated, Extended Release · Oral
• Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by non-specific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1) ] .
• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast,…
Uses
Dapagliflozin and Metformin HCl extended-release tablets are a combination of dapagliflozin and metformin hydrochloride (HCl) extended-release, indicated 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. Dapagliflozin, when used as a component of Dapagliflozin and Metformin HCl extended-release tablets, is indicated in adults with type 2 diabetes mellitus to reduce the risk of:
• Sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in patients with chronic kidney disease at risk of progression.
• Cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in patients with heart failure.
• Hospitalization for heart failure in patients with type 2 diabetes mellitus and either established cardiovascular disease (CVD) or multiple cardiovascular (CV) risk factors. Limitations of Use
• Dapagliflozin and Metformin HCl extended-release tablets are not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see Warnings and Precautions (5.2) ].
• Because of the metformin HCl component, the use of Dapagliflozin and Metformin HCl extended-release tablets are limited to patients with type 2 diabetes mellitus for all indications.
• Dapagliflozin and Metformin HCl extended-release 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 and Metformin HCl extended-release tablets are not expected to be effective in these populations. Dapagliflozin and Metformin HCl extended-release tablets are a combination of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and metformin hydrochloride (HCl), a biguanide, indicated 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) Dapagliflozin when used as a component of Dapagliflozin and Metformin HCl extended-release tablets is indicated in adults with type 2 diabetes mellitus to reduce the risk of:
• Sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in patients with chronic kidney disease at risk of progression. (1)
• Cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in patients with heart failure. (1)
• Hospitalization for heart failure in patients with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors. (1) Limitations of use :
• Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. (1)
• Because of the metformin HCI component, the use of Dapagliflozin and Metformin HCl extended-release tablets are limited to patients with type 2 diabetes mellitus for all indications. (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 and Metformin HCl extended-release tablets are not expected to be effective in these populations. (1)
Dosage and administration
• Assess renal function prior to initiating and then as clinically indicated. ( 2.1 )
• Assess volume status and correct volume depletion before initiating. ( 2.1 )
• Individualize the starting dosage based on the patient’s current treatment. ( 2.3 )
• Administer orally once daily in the morning with food. ( 2.2 )
• To improve glycemic control, for patients aged 10 years and older not already taking dapagliflozin, the recommended starting dosage for dapagliflozin is 5 mg once daily. ( 2.3 )
• For indications in adults related to heart failure and chronic kidney disease the recommended dosage of dapagliflozin is 10 mg once daily. ( 2.3 )
• Do not exceed a daily dosage of 10 mg dapagliflozin/2,000 mg metformin HCl extended-release. ( 2.3 )
• See Full Prescribing Information for dosage recommendations in patients with renal impairment. ( 2.4 )
• Dapagliflozin and Metformin HCl extended-release tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures. ( 2.5 )
• Withhold Dapagliflozin and Metformin HCl extended-release tablets for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. ( 2.6 ) 2.1 Testing Prior to Initiation of Dapagliflozin and Metformin HCl Extended-Release Tablets
• Assess renal function prior to initiating Dapagliflozin and Metformin HCl extended-release tablets and then as clinically indicated [see Warnings and Precautions ( 5.1 , 5.3 )] .
• Assess volume status. In patients with volume depletion, correct this condition before initiating Dapagliflozin and Metformin HCl extended-release tablets [see Warnings and Precautions (5.3) and Use in Specific Populations (8.5 , 8.6)]. 2.2 Recommended Administration
• Take Dapagliflozin and Metformin HCl extended-release tablets orally once daily in the morning with food.
• Swallow Dapagliflozin and Metformin HCl extended-release tablets whole and never crush, cut, or chew. 2.3 Recommended Dosage
• Individualize the starting dosage of Dapagliflozin and Metformin HCl extended-release tablets based upon the patient’s current regimen. Patients taking an evening dosage of metformin HCl extended-release should skip their last dose before starting Dapagliflozin and Metformin HCl extended-release tablets.
• To improve glycemic control in adults and pediatric patients aged 10 years and older not already taking: ∘ Dapagliflozin: the recommended starting dosage of dapagliflozin in Dapagliflozin and Metformin HCl extended-release tablets is 5 mg orally once daily. ∘ Metformin HCl extended-release: the recommended starting dosage of metformin HCl extended release in Dapagliflozin and Metformin HCl extended-release tablets is 500 mg orally once daily.
• For Dapagliflozin and Metformin HCl extended-release tablets indications in adults related to heart failure and chronic kidney disease, the recommended dosage of dapagliflozin in Dapagliflozin and Metformin HCl extended-release tablets is 10 mg orally once daily.
• For all Dapagliflozin and Metformin HCl extended-release tablets indications, the dosage may be adjusted based on effectiveness and tolerability. The maximum recommended daily dosage of dapagliflozin is 10 mg and 2,000 mg of metformin HCl extended-release, with gradual dosage escalation to reduce gastrointestinal adverse reactions with metformin HCl [see Adverse Reactions (6.1) ]. 2.4 Recommended Dosage in Patients with Renal Impairment
• The recommended dosage of Dapagliflozin and Metformin HCl extended-release tablets in patients with an estimated glomerular filtration rate (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.
• Initiation of Dapagliflozin and Metformin HCl extended-release tablets is not recommended in patients with an eGFR between 30 and 45 mL/min/1.73 m 2 . Assess the benefit and risk of continuing therapy if eGFR falls persistently below this level. ∘ Dapagliflozin is likely to be ineffective to improve glycemic control in patients with eGFR less than 45 mL/min/1.73 m 2 . ∘ Metformin HCl initiation is not recommended for patients with eGFR less than 45 mL/min/1.73 m 2 .
• Dapagliflozin and Metformin HCl extended-release tablets are contraindicated in patients with an eGFR below 30 mL/min/1.73 m 2 and end-stage renal disease due to the metformin HCl component [see Contraindications (4) , Warnings and Precautions (5.1 , 5.2) , and Use in Specific Populations (8.6) ]. 2.5 Discontinuation for Iodinated Contrast Imaging Procedures Discontinue Dapagliflozin and Metformin HCl extended-release tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR less than 60 mL/min/1.73 m 2 , in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart Dapagliflozin and Metformin HCl extended-release tablets if renal function is stable [see Warnings and Precautions (5.1) ] . 2.6 Temporary Interruption for Surgery Withhold Dapagliflozin and Metformin HCl extended-release tablets for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume Dapagliflozin and Metformin HCl extended-release tablets when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ] .
Dosage forms and strengths
Dapagliflozin and Metformin HCl extended-release tablets are available as follows: Table 1: Dosage Forms and Strengths for Dapagliflozin and Metformin HCl Extended-Release Tablets Dapagliflozin Strength Metformin HCl Strength Color/Shape Tablet Markings 5 mg 1,000 mg pink to dark pink, biconvex, oval-shaped, and film-coated tablet "1071" and "5/1000" debossed on one side and plain on the reverse side 10 mg 1,000 mg yellow to dark yellow, biconvex, oval-shaped, and film-coated tablet "1073" and "10/1000" debossed on one side and plain on the reverse side
• 5 mg dapagliflozin/1,000 mg metformin HCl extended-release (3)
• 10 mg dapagliflozin/1,000 mg metformin HCl extended-release (3)
Contraindications
Dapagliflozin and Metformin HCl extended-release tablets are contraindicated in patients with:
• Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) or end-stage renal disease [see Warnings and Precautions (5.1) ] .
• History of a serious hypersensitivity reaction to dapagliflozin, metformin HCl, or any of the excipients in Dapagliflozin and Metformin HCl extended-release tablets. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported with dapagliflozin [see Adverse Reactions (6.1) ] .
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin [see Warnings and Precautions (5.1) and Warnings and Precautions (5.2) ] .
• Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) or end-stage renal disease. ( 4 )
• History of serious hypersensitivity to dapagliflozin, metformin HCl, or any of the excipients in Dapagliflozin and Metformin HCl extended-release tablets. ( 4 )
• Metabolic acidosis, including diabetic ketoacidosis. ( 4 )
Warnings and precautions
• Lactic Acidosis : See boxed warning. ( 5.1 )
• Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue Dapagliflozin and Metformin HCl extended-release tablets if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. (5.2)
• Volume Depletion: Before initiating Dapagliflozin and Metformin HCl extended-release tablets, assess and correct volume status in the elderly, patients with renal impairment or low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms during therapy. (5.3 )
• Urosepsis and Pyelonephritis : Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated. (5.4)
• Hypoglycemia : Consider a lower dosage of insulin or an insulin secretagogue to reduce the risk of hypoglycemia when used concomitantly with Dapagliflozin and Metformin HCl extended-release tablets. (5.5)
• Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Serious, life-threatening cases have occurred in both females and males. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment. (5.6)
• Vitamin B 12 Deficiency : Metformin may lower vitamin B 12 levels. Measure hematological parameters annually. ( 5.7 )
• Genital Mycotic Infections : Monitor and treat if indicated. (5.8) 5.1 Lactic Acidosis There have been post-marketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by non-specific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of Dapagliflozin and Metformin HCl extended-release tablets. In Dapagliflozin and Metformin HCl extended-release tablets-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin HCl is dialyzable, with a clearance of up to 170 mL/min under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery. Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur, instruct them to discontinue Dapagliflozin and Metformin HCl extended-release tablets and report these symptoms to their healthcare provider. For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: Renal Impairment : The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient’s renal function include [see Dosage and Administration (2.1 , 2.4 ) and Clinical Pharmacology (12.3) ] :
• Before initiating Dapagliflozin and Metformin HCl extended-release tablets, obtain an estimated glomerular filtration rate (eGFR).
• Dapagliflozin and Metformin HCl extended-release tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Contraindications (4) ] .
• Obtain an eGFR at least annually in all patients taking Dapagliflozin and Metformin HCl extended-release tablets. In patients at increased risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. Drug Interactions: The concomitant use of Dapagliflozin and Metformin HCl extended-release tablets with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance or increase metformin accumulation (e.g., cationic drugs) [see Drug Interactions (7) ] . Therefore, consider more frequent monitoring of patients. Age 65 or Greater: The risk of metformin-associated lactic acidosis increases with the patient’s age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. Assess renal function more frequently in elderly patients [see Use in Specific Populations (8.5) ] . Radiological Studies with Contrast: Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis. Stop Dapagliflozin and Metformin HCl extended-release tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure, and restart Dapagliflozin and Metformin HCl extended-release tablets if renal function is stable.
Side effects
The following important adverse reactions are described below and elsewhere in the labeling:
• Lactic Acidosis [see Boxed Warning and Warnings and Precautions (5.1) ]
• Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions (5.2) ]
• Volume Depletion [see Warnings and Precautions (5.3) ]
• Urosepsis and Pyelonephritis [see Warnings and Precautions (5.4) ]
• Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions (5.5) ]
• Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) [see Warnings and Precautions (5.6) ]
• Vitamin B 12 Concentrations [see Warnings and Precautions (5.7) ]
• Genital Mycotic Infections [see Warnings and Precautions (5.8) ]
• Adverse reactions reported in >5% of patients treated with Dapagliflozin and Metformin HCl extended-release tablets were female genital mycotic infection, nasopharyngitis, urinary tract infection, diarrhea, and headache. (6.1)
• Adverse reactions reported in >5% of patients treated with metformin extended-release are: diarrhea and nausea/vomiting. (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. Clinical Trials with Metformin HCl Extended-Release in Adults with Type 2 Diabetes Mellitus In placebo-controlled monotherapy trials of metformin HCl extended-release, diarrhea and nausea/vomiting were reported in >5% of metformin-treated patients and more commonly than in placebo-treated patients (9.6% versus 2.6% for diarrhea and 6.5% versus 1.5% for nausea/vomiting). Diarrhea led to discontinuation of study medication in 0.6% of the patients treated with metformin HCl extended-release. Clinical Trials with Dapagliflozin in Adults Dapagliflozin Dapagliflozin has been evaluated in clinical trials in adult and pediatric patients 10 years of age 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, DELIVER and DAPA-CKD trials. Pools of Placebo-Controlled Clinical Trials for Glycemic Control in Adults Pool of 8 Placebo-Controlled Adult Trials for Dapagliflozin and Metformin HCl for Glycemic Control Data from a prespecified pool of adult patients from 8 short-term, placebo-controlled trials of dapagliflozin coadministered with metformin HCl immediate- or extended-release was used to evaluate safety. This pool included several add-on trials (metformin HCl alone and in combination with a dipeptidyl peptidase-4 [DPP4] inhibitor and metformin HCl, or insulin and metformin HCl, 2 initial combination with metformin HCl trials, and 2 trials of patients with CVD and type 2 diabetes mellitus who received their usual treatment [with metformin HCl as background therapy]). For trials that included background therapy with and without metformin HCl, only patients who received metformin HCl were included in the 8-trial placebo-controlled pool. Across these 8 trials, 983 patients were treated once daily with dapagliflozin 10 mg and metformin HCl, and 1185 were treated with placebo and metformin HCl. These 8 trials provide a mean duration of exposure of 23 weeks. The mean age of the population was 57 years and 2% were older than 75 years. Fifty-four percent (54%) of the population was male; 88% White, 6% Asian, and 3% Black or African American. At baseline, the population had diabetes for an average of 8 years, mean hemoglobin A1c (HbA1c) was 8.4%, and renal function was normal or mildly impaired in 90% of patients and moderately impaired in 10% of patients. The overall incidence of adverse events for the 8-trial, short-term, placebo-controlled pool in adult patients treated with dapagliflozin 10 mg and metformin HCl was 60.3% compared to 58.2% for the placebo and metformin HCl group. Discontinuation of therapy due to adverse events in patients who received dapagliflozin 10 mg and metformin HCl was 4% compared to 3.3% for the placebo and metformin HCl group. The most commonly reported events leading to discontinuation and reported in at least 3 patients treated with dapagliflozin 10 mg and metformin HCl were renal impairment (0.7%), increased blood creatinine (0.2%), decreased renal creatinine clearance (0.2%), and urinary tract infection (0.2%). Table 2 shows common adverse reactions in adults associated with the use of dapagliflozin and metformin HCl. These adverse reactions were not present at baseline, occurred more commonly on dapagliflozin and metformin HCl than on placebo, and occurred in at least 2% of patients treated with either dapagliflozin 5 mg or dapagliflozin 10 mg. Table 2: Adverse Reactions in Placebo-Controlled Trials Reported in ≥2% of Adult Patients Treated with Dapagliflozin and Metformin HCl Adverse Reaction % of Patients Pool of 8 Placebo-Controlled Trials Placebo and Metformin HCl N=1185 Dapagliflozin 5 mg and Metformin HCl N=410 Dapagliflozin 10 mg and Metformin HCl N=983 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, genital infection, vulvovaginitis, fungal genital infection, vulvovaginal candidiasis, vulval abscess, genital candidiasis, and vaginitis bacterial. (N for females: Placebo and metformin HCl=534, dapagliflozin 5 mg and metformin HCl=223, dapagliflozin 10 mg and metformin HCl=430).
Drug interactions
Table 6: Clinically Relevant Interactions with Dapagliflozin and Metformin HCl Extended-Release Tablets Carbonic Anhydrase Inhibitors Clinical Impact Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with Dapagliflozin and Metformin HCl extended-release tablets may increase the risk for lactic acidosis. Intervention Consider more frequent monitoring of these patients. Drugs that Reduce Metformin Clearance Clinical Impact Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors, such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3) ] . Intervention Consider the benefits and risks of concomitant use. Alcohol Clinical Impact Alcohol is known to potentiate the effect of metformin on lactate metabolism. Intervention Warn patients against excessive alcohol intake while receiving Dapagliflozin and Metformin HCl extended-release tablets. Insulin or Insulin Secretagogues Clinical Impact The risk of hypoglycemia may be increased when Dapagliflozin and Metformin HCl extended-release tablets are used concomitantly with insulin or insulin secretagogues (e.g., sulfonylurea) [see Warnings and Precautions (5.5) ]. Intervention Concomitant use may require lower doses of insulin or the insulin secretagogue to reduce the risk of hypoglycemia. Drugs Affecting Glycemic Control Clinical Impact Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These medications include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. Intervention When such drugs are administered to a patient receiving Dapagliflozin and Metformin HCl extended-release tablets, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving Dapagliflozin and Metformin HCl extended-release tablets, observe the patient closely for hypoglycemia. Lithium Clinical Impact Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention Monitor serum lithium concentration more frequently during Dapagliflozin and Metformin HCl extended-release tablets initiation and dosage changes. Positive Urine Glucose Test Clinical Impact SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Intervention Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control. Interference with 1,5-anhydroglucitol (1,5-AG) Assay Clinical Impact Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Intervention Monitoring glycemic control with 1,5-AG assay is not recommended. Use alternative methods to monitor glycemic control.
• Carbonic anhydrase inhibitors: May increase risk of lactic acidosis. Consider more frequent monitoring. (7)
• Drugs that reduce metformin clearance: May increase risk of lactic acidosis. Consider benefits and risks of concomitant use. (7)
• See full prescribing information for additional drug interactions and information on interference of Dapagliflozin and Metformin HCl extended-release tablets with laboratory tests. (7)
Use in specific populations
• Pregnancy: Advise females of the potential risk to a fetus, especially during the second and third trimesters. (8.1)
• Lactation: Not recommended when breastfeeding. (8.2)
• Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. (8.3)
• Geriatrics: Higher incidence of adverse reactions related to hypotension. Assess renal function more frequently. ( 8.5 , 8.6 )
• Renal Impairment: Higher incidence of adverse reactions related to volume depletion. ( 8.6 )
• Hepatic Impairment: Avoid use in patients with hepatic impairment. (8.7) 8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects, Dapagliflozin and Metformin HCl extended-release tablets are not recommended during the second and third trimesters of pregnancy. Limited data with Dapagliflozin and Metformin HCl extended-release tablets or dapagliflozin in pregnant women are not sufficient to determine drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk (see Data ) . There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . In animal studies, adverse renal pelvic and tubule dilatations, that were not fully reversible, were observed in rats when dapagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at all doses tested; the lowest of which provided an exposure 15-times the 10 mg clinical dose (see Data ) . The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a HbA1c greater than 7% and has been reported to be as high as 20 to 25% in women with HbA1c greater than 10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Human Data Published data from post-marketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Dapagliflozin Dapagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 1, 15, or 75 mg/kg/day, increased kidney weights and increased the incidence of renal pelvic and tubular dilatations at all dose levels. Exposure at the lowest dose tested was 15-times the 10 mg clinical dose (based on AUC). The renal pelvic and tubular dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. In a prenatal and postnatal development study, dapagliflozin was administered to maternal rats 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 21-day-old pups 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 10 mg clinical dose, based on AUC). Dose-related reductions in pup body weights were observed at greater or equal to 29-times the 10 mg clinical dose (based on AUC). No adverse effects on developmental endpoints were noted at 1 mg/kg/day (19-times the 10 mg clinical dose, based on AUC). These outcomes occurred with drug exposure during periods of renal development in rats that corresponds to the late second and third trimester of human development. In embryofetal development studies in rats and rabbits, dapagliflozin was administered throughout organogenesis, corresponding to the first trimester of human pregnancy. In rats, dapagliflozin was neither embryolethal nor teratogenic at doses up to 75 mg/kg/day (1441-times the 10 mg clinical dose, based on AUC). Dose-related effects on the rat fetus (structural abnormalities and reduced body weight) occurred only at higher dosages, equal to or greater than 150 mg/kg (more than 2344-times the 10 mg clinical dose, based on AUC), which were associated with maternal toxicity. No developmental toxicities were observed in rabbits at doses up to 180 mg/kg/day (1191-times the 10 mg clinical dose, based on AUC). Metformin HCl Metformin HCl did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits up to 600 mg/kg/day during the period of organogenesis. This represents an exposure of about 2- and 6-times a 2,000 mg clinical dose based on body surface area (mg/m 2 ) for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin. 8.2 Lactation Risk Summary There is no information regarding the presence of Dapagliflozin and Metformin HCl extended-release tablets or dapagliflozin in human milk, the effects on the breastfed infant, or the effects on milk production. Limited published studies report that metformin is present in human milk (see Data ) .
Pregnancy
8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects, Dapagliflozin and Metformin HCl extended-release tablets are not recommended during the second and third trimesters of pregnancy. Limited data with Dapagliflozin and Metformin HCl extended-release tablets or dapagliflozin in pregnant women are not sufficient to determine drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk (see Data ) . There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . In animal studies, adverse renal pelvic and tubule dilatations, that were not fully reversible, were observed in rats when dapagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at all doses tested; the lowest of which provided an exposure 15-times the 10 mg clinical dose (see Data ) . The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a HbA1c greater than 7% and has been reported to be as high as 20 to 25% in women with HbA1c greater than 10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Human Data Published data from post-marketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Dapagliflozin Dapagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 1, 15, or 75 mg/kg/day, increased kidney weights and increased the incidence of renal pelvic and tubular dilatations at all dose levels. Exposure at the lowest dose tested was 15-times the 10 mg clinical dose (based on AUC). The renal pelvic and tubular dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. In a prenatal and postnatal development study, dapagliflozin was administered to maternal rats 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 21-day-old pups 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 10 mg clinical dose, based on AUC). Dose-related reductions in pup body weights were observed at greater or equal to 29-times the 10 mg clinical dose (based on AUC). No adverse effects on developmental endpoints were noted at 1 mg/kg/day (19-times the 10 mg clinical dose, based on AUC). These outcomes occurred with drug exposure during periods of renal development in rats that corresponds to the late second and third trimester of human development. In embryofetal development studies in rats and rabbits, dapagliflozin was administered throughout organogenesis, corresponding to the first trimester of human pregnancy. In rats, dapagliflozin was neither embryolethal nor teratogenic at doses up to 75 mg/kg/day (1441-times the 10 mg clinical dose, based on AUC). Dose-related effects on the rat fetus (structural abnormalities and reduced body weight) occurred only at higher dosages, equal to or greater than 150 mg/kg (more than 2344-times the 10 mg clinical dose, based on AUC), which were associated with maternal toxicity. No developmental toxicities were observed in rabbits at doses up to 180 mg/kg/day (1191-times the 10 mg clinical dose, based on AUC). Metformin HCl Metformin HCl did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits up to 600 mg/kg/day during the period of organogenesis. This represents an exposure of about 2- and 6-times a 2,000 mg clinical dose based on body surface area (mg/m 2 ) for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Dapagliflozin and Metformin HCl extended-release tablets as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients aged 10 years and older. Use of Dapagliflozin and Metformin HCl extended-release tablets for this indication is supported by a 26-week placebo-controlled trial of dapagliflozin with a 26-week extension in 157 pediatric patients aged 10 to 17 years with type 2 diabetes mellitus, pediatric pharmacokinetic data, and trials in adults with type 2 diabetes mellitus [see Clinical Pharmacology (12.3) and Clinical Studies (14.1 , 14.2) ] . The safety profile observed in the placebo-controlled trial of dapagliflozin in pediatric patients with type 2 diabetes mellitus was similar to that observed in adults [see Adverse Reactions (6.1) ] . The use of Dapagliflozin and Metformin HCl extended-release tablets for this indication is also supported by evidence from adequate and well-controlled trials of metformin HCl immediate-release tablets in adults with additional data from a controlled clinical trial using metformin HCl immediate-release tablets in pediatric patients 10 to 16 years old with type 2 diabetes mellitus, and pharmacokinetic data with metformin HCl extended-release tablets in adults [see Clinical Pharmacology (12.3) and Clinical Studies (14.1 , 14.2)] . In the clinical trial with pediatric patients receiving metformin HCl immediate-release tablets, adverse reactions with metformin HCl immediate-release tablets were similar to those described in adults [see Adverse Reactions (6.1) ] . The safety and effectiveness of Dapagliflozin and Metformin HCl extended-release tablets for glycemic control in patients with type 2 diabetes mellitus have not been established in pediatric patients less than 10 years of age. The safety and effectiveness of Dapagliflozin and Metformin HCl extended-release tablets have not been established in pediatric patients to reduce the risk of [see Indications and Usage (1) ] :
• sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in patients with chronic kidney disease at risk of progression.
• cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in patients with heart failure.
• hospitalization for heart failure in patients with type 2 diabetes mellitus and either established cardiovascular disease (CVD) or multiple cardiovascular (CV) risk factors.
Geriatric use
8.5 Geriatric Use Dapagliflozin and Metformin HCl extended-release tablets No Dapagliflozin and Metformin HCl extended-release tablets dosage change is recommended based on age. More frequent assessment of renal function is recommended in elderly patients. Dapagliflozin A total of 1424 (24%) of the 5936 dapagliflozin-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 trials assessing the efficacy of dapagliflozin in improving glycemic control. 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 dapagliflozin for glycemic control had adverse reactions of hypotension [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ] . In the DAPA-HF, DELIVER and DAPA-CKD trials, safety and efficacy were similar for patients aged 65 years and younger and those older than 65 in both the overall population and in the patients with type 2 diabetes mellitus. In the DAPA-HF trial, 2714 (57%) out of 4744 patients with heart failure with reduced ejection fraction (HFrEF) were older than 65 years. Out of 2139 patients with HFrEF and type 2 diabetes mellitus, 1211 (57%) were older than 65 years. In the DELIVER trial, 4759 (76%) out of 6263 patients with heart failure (LVEF >40%) were older than 65 years. Out of 2806 patients with LVEF >40% and type 2 diabetes mellitus, 2072 (74%) were older than 65 years. In the DAPA-CKD trial, 1818 (42%) out of 4304 patients with chronic kidney disease were older than 65 years. Out of 2906 patients with chronic kidney disease and type 2 diabetes mellitus, 1399 (48%) were older than 65 years. Metformin HCl Controlled clinical trials of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently than younger patients. In general, dosage selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [see Warnings and Precautions (5.1) ] .
Overdosage
Dapagliflozin In the event of an overdose, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. The removal of dapagliflozin by hemodialysis has not been studied. Metformin HCl Overdose of metformin HCl has occurred, including ingestion of amounts >50 grams. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1) ] . Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.
Description
Dapagliflozin and Metformin HCl extended-release tablets contain: dapagliflozin, a SGLT2 inhibitor, and metformin HCl, a biguanide. Dapagliflozin Dapagliflozin is described chemically as D-glucitol, 1,5-anhydro-1- C -[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, (1S)-, compounded with (2S)-1,2-propanediol, hydrate (1:1:1). The empirical formula is C 21 H 25 ClO 6
• C 3 H 8 O 2
• H 2 O and the formula weight is 502.98. The structural formula is: Dapagliflozin chemical structure Metformin HCl Metformin HCl ( N,N -dimethylimidodicarbonimidic diamide HCl) is a white to off-white crystalline compound with a molecular formula of C 4 H 11 N 5
• HCl and a molecular weight of 165.63. Metformin HCl is freely soluble in water, slightly soluble in alcohol, and is practically insoluble in acetone, ether, and chloroform. The pK a of metformin is 12.4. The pH of a 1% aqueous solution of metformin HCl is 6.68. The structural formula is: Metformin hydrochloride chemical structure Dapagliflozin and Metformin HCl extended-release tablets Dapagliflozin and Metformin HCl extended-release tablets are available for oral administration as tablets containing the equivalent of 5 mg dapagliflozin as dapagliflozin propanediol and 1,000 mg metformin HCl which is equivalent to 779.86 mg metformin base (Dapagliflozin and Metformin HCl extended-release tablets 5 mg/1,000 mg), or the equivalent of 10 mg dapagliflozin as dapagliflozin propanediol and 1,000 mg metformin HCl which is equivalent to 779.86 mg metformin base (Dapagliflozin and Metformin HCl extended-release tablets 10 mg/1,000 mg). Each film-coated tablet of Dapagliflozin and Metformin HCl extended-release tablets contains the following inactive ingredients: anhydrous lactose, carboxymethylcellulose sodium, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, and silicon dioxide. The film coatings contain the following inactive ingredients: iron oxides, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
Mechanism of action
12.1 Mechanism of Action Dapagliflozin 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 thereby promotes urinary glucose excretion. Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure which is believed to be mediated by increased tubuloglomerular feedback. Metformin HCl Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.
How supplied
How Supplied Dapagliflozin and Metformin HCl extended-release tablets have markings on one side, are plain on the reverse side, and are available in the strengths and packages listed in Table 21. Table 21: Dapagliflozin and Metformin HCl Extended-Release Tablets Presentations Tablet Strength Film-Coated Tablet Color/Shape Tablet Markings Pack Size NDC Code 5 mg/ 1,000 mg pink to dark pink, biconvex, oval-shaped "1071" and "5/1000" debossed on one side and plain on the reverse side Bottle of 60 66993-361-60 10 mg/ 1,000 mg yellow to dark yellow, biconvex, oval-shaped "1073" and "10/1000" debossed on one side and plain on the reverse side Bottle of 30 66993-362-30 Storage and Handling 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].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Lactic Acidosis Inform patients of the risks of lactic acidosis due to the metformin component and its symptoms and conditions that predispose to its development [see Warnings and Precautions (5.1) ] . Advise patients to discontinue Dapagliflozin and Metformin HCl extended-release tablets immediately and to promptly notify their healthcare provider if unexplained hyperventilation, myalgia, malaise, unusual somnolence, dizziness, slow or irregular heartbeat, sensation of feeling cold (especially in the extremities), or other non-specific symptoms occur. Gastrointestinal symptoms are common during initiation of metformin treatment and may occur during initiation of Dapagliflozin and Metformin HCl extended-release tablets therapy; however, inform patients to consult their physician if they develop unexplained symptoms. Although gastrointestinal symptoms that occur after stabilization are unlikely to be drug related, such an occurrence of symptoms should be evaluated to determine if it may be due to lactic acidosis or other serious disease. Counsel patients against excessive alcohol intake while receiving Dapagliflozin and Metformin HCl extended-release tablets [see Warnings and Precautions (5.1) ] . Inform patients about the importance of regular testing of renal function and hematological parameters when receiving treatment with Dapagliflozin and Metformin HCl extended-release tablets [see Contraindications (4) and Warnings and Precautions (5.1) ]. Instruct patients to inform their healthcare provider that they are taking Dapagliflozin and Metformin HCl extended-release tablets prior to any surgical or radiological procedure, as temporary discontinuation of Dapagliflozin and Metformin HCl extended-release tablets may be required until renal function has been confirmed to be normal [see Warnings and Precautions (5.1) ] . Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis Inform patients that Dapagliflozin and Metformin HCl extended-release 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 and Metformin HCl extended-release tablets and seek medical attention immediately [see Warnings and Precautions (5.2) ] . Volume Depletion Inform patients that symptomatic hypotension may occur with Dapagliflozin and Metformin HCl extended-release tablets and advise them to contact their healthcare provider if they experience such symptoms [see Warnings and Precautions (5.3) ] . Inform patients that dehydration may increase the risk for hypotension, and to have adequate fluid intake. 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 promptly if such symptoms occur [see Warnings and Precautions (5.4) ] . Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues Inform patients that the incidence of hypoglycemia may increase when Dapagliflozin and Metformin HCl extended-release 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 (5.5) ] . Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) Inform patients that necrotizing infections of the perineum (Fournier’s Gangrene) have occurred with dapagliflozin, a component of Dapagliflozin and Metformin HCl extended-release tablets. Counsel 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 (5.6) ] . 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 (5.8) ] . Genital Mycotic Infections in Males (e.g., Balanitis or Balanoposthitis) Inform male patients that yeast infections of the penis (e.g., balanitis or balanoposthitis) may occur, especially in patients with prior history. 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 (5.8) ] . Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions (e.g., urticaria, anaphylactic reactions, and angioedema) have been reported with the components of Dapagliflozin and Metformin HCl extended-release tablets. 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 and Metformin HCl extended-release tablets. Instruct patients to immediately inform their healthcare provider if pregnant or planning to become pregnant [see Use in Specific Populations (8.1) ] .
Label text from the FDA structured product label by Prasco Laboratories (revised Dec 20, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Metformin Hydrochloride in 28 products
- Dapagliflozin in 26 products
- Dapagliflozin Propanediol in 2 products
Dapagliflozin and metformin hydrochloride NDC products (28)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 67877-622 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Ascend Laboratories, LLC | ANDA |
| 67877-621 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Ascend Laboratories, LLC | ANDA |
| 67877-620 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Ascend Laboratories, LLC | ANDA |
| 67877-619 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Ascend Laboratories, LLC | ANDA |
| 59651-154 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 59651-155 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 59651-156 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 59651-157 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 84677-022 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 84677-021 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 84677-020 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 70748-104 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 70748-103 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 70748-102 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 70748-101 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 33342-406 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Extended Release | Macleods Pharmaceuticals Limited | ANDA |
| 33342-407 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Extended Release | Macleods Pharmaceuticals Limited | ANDA |
| 33342-408 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Extended Release | Macleods Pharmaceuticals Limited | ANDA |
| 33342-409 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Extended Release | Macleods Pharmaceuticals Limited | ANDA |
| 72205-434 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-435 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-436 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-437 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Novadoz Pharmaceuticals LLC | ANDA |
| 63304-026 | Dapagliflozin 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 63304-027 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 500 mg/1 Tablet, Film Coated, Extended Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 63304-028 | Dapagliflozin 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 66993-362 | Dapagliflozin Propanediol 10 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Prasco Laboratories | NDA AUTHORIZED GENERIC |
| 66993-361 | Dapagliflozin Propanediol 5 mg/1; Metformin Hydrochloride 1000 mg/1 Tablet, Film Coated, Extended Release | Prasco Laboratories | NDA AUTHORIZED GENERIC |
Frequently asked questions
What is Dapagliflozin and metformin hydrochloride used for?
Dapagliflozin and Metformin HCl extended-release tablets are a combination of dapagliflozin and metformin hydrochloride (HCl) extended-release, indicated 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. Dapagliflozin, when used as a component of Dapagliflozin and Metformin HCl extended-release…
What are the side effects of Dapagliflozin and metformin hydrochloride?
The following important adverse reactions are described below and elsewhere in the labeling: • Lactic Acidosis [see Boxed Warning and Warnings and Precautions (5.1) ] • Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions (5.2) ] • Volume Depletion [see Warnings and Precautions (5.3) ] • Urosepsis and Pyelonephritis [see Warnings and… See the full label for the complete list.
Who makes Dapagliflozin and metformin hydrochloride?
Dapagliflozin and metformin hydrochloride is listed by 8 labelers in the FDA NDC directory, including Ascend Laboratories, LLC, Aurobindo Pharma Limited, Golden State Medical Supply, Inc., Lupin Pharmaceuticals, Inc..