DAPAGLIFLOZIN AND SAXAGLIPTIN 10 mg; 5 mg Tablet, Film Coated, 90-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Sodium-Glucose Cotransporter 2 Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Dapagliflozin is used to lower blood sugar in people with type 2 diabetes (condition in which blood sugar is too high because the body does not make or use insulin normally). to reduce the risk of being hospitalized for heart failure in certain adults with type 2 diabetes to reduce the risk of being hospitalized for heart failure and death in adults with heart failure to reduce the risk of worsening of kidney disease, being hospitalized for heart failure, and death in certain adults with kidney disease Dapagliflozin is in a class of medications called sodium-glucose co-transporter 2 (SG...
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 4ELV7Z65AP
Stearic acid is a fatty acid derived from plant or animal sources. It acts as a binder and lubricant in tablets and capsules, helping them hold together and flow smoothly during manufacturing.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
13 inactive ingredients listed in the exact product block matched to this NDC.
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| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Dapagliflozin And Saxagliptin 10 mg/1; 5 mgthis 72205-0438-02 | Novadoz | 90 tablets | — | AB | FDA listed | — |
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This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72205-0438-01 | 30 TABLET, FILM COATED in 1 BOTTLE (72205-438-01) | 2026-04-09 | Active |
| 72205-0438-02 You're viewing this | 90 TABLET, FILM COATED in 1 BOTTLE (72205-438-02) | 2026-04-09 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Dapagliflozin and saxagliptin tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Dapagliflozin and saxagliptin tablets are not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [ see WARNINGS AND PRECAUTIONS (5.1) ]. Dapagliflozin and saxagliptin tablets is a combination of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor and saxagliptin a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults 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 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Assess renal function before initiation of therapy and periodically thereafter. ( 2.1 ) Take orally, once daily in the morning with or without food. ( 2.2 ) For patients not already taking dapagliflozin, the recommended starting dose of dapagliflozin and saxagliptin tablets is a 5 mg dapagliflozin/5 mg saxagliptin tablet once daily.
( 2.2 ) In patients tolerating 5 mg dapagliflozin and 5 mg saxagliptin once daily who require additional glycemic control, the dapagliflozin and saxagliptin tablets dose can be increased to 10 mg dapagliflozin/5 mg saxagliptin tablet once daily. ( 2.2 ) Swallow tablet whole. Do not crush, cut or chew.
( 2.2 ) Withhold dapagliflozin and saxagliptin for at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. ( 2.5 )
2.1Prior to Initiation of Dapagliflozin and Saxagliptin Tablets Assess renal function prior to initiation of dapagliflozin and saxagliptin tablets therapy and periodically thereafter [see WARNINGS AND PRECAUTIONS (5.4) ] . Assess volume status. In patients with volume depletion, correct this condition before initiating of dapagliflozin and saxagliptin tablets [see WARNINGS AND PRECAUTIONS (5.4) and USE IN SPECIFIC POPULATIONS (8.5 , 8.6 )] .
2.2Dosage For patients not already taking dapagliflozin, the recommended starting dose of dapagliflozin and saxagliptin tablets is a 5 mg dapagliflozin/5 mg saxagliptin tablet taken orally once daily in the morning with or without food. In patients tolerating 5 mg dapagliflozin and 5 mg saxagliptin once daily who require additional glycemic control, the dapagliflozin and saxagliptin tablets dose can be increased to 10 mg dapagliflozin/5 mg saxagliptin tablet once daily in the morning with or without food. Swallow whole.
Do not crush, cut or chew dapagliflozin and saxagliptin tablets.
2.3Patients with Renal Impairment No dose adjustment is needed in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 45 mL/min/1.73 m2. Dapagliflozin and saxagliptin tablets are contraindicated in patients with an eGFR less than 45 mL/min/1.73 m2 [see CONTRAINDICATIONS (4) and USE IN SPECIFIC POPULATIONS (8.6) ].
2.4Use with Strong CYP3A4/5 Inhibitors Do not coadminister dapagliflozin and saxagliptin tablets with strong cytochrome P450 3A4/5 inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin) [ see DRUG INTERACTIONS (7)].
2.5Temporary Interruption for Surgery Withhold dapagliflozin and saxagliptin tablets for at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. Resume dapagliflozin and saxagliptin tablets when the patient is clinically stable and has resumed oral intake [see WARNINGS AND PRECAUTIONS (5.1) and CLINICAL PHARMACOLOGY (12.2) ] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Dapagliflozin and saxagliptin tablets are available as follows: Table 1: Dosage Forms and Strengths for Dapagliflozin and saxagliptin Dapagliflozin Strength Saxagliptin Strength Color / Shape Tablet Markings 10 mg 5 mg Light brown to brown, biconvex, round, film-coated tablet Debossed with "MS" on one side and "4" on other side. Tablets: 10 mg dapagliflozin/5 mg saxagliptin ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Dapagliflozin and saxagliptin is contraindicated in patients with: History of a serious hypersensitivity reactions to dapagliflozin or to saxagliptin, including anaphylactic reaction, angioedema or exfoliative skin conditions [ see WARNINGS AND PRECAUTIONS (5.8) and ADVERSE REACTIONS (6.2)]. Moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m 2 ), end-stage renal disease (ESRD), or patients on dialysis [ see USE IN SPECIFIC POPULATIONS (8.6)]. History of a serious hypersensitivity reaction to dapagliflozin or to saxagliptin.
( 4 ) Moderate to severe renal impairment (eGFR <45 mL/min/1.73 m 2 ), end-stage renal disease, or patients on dialysis. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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 saxagliptin if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting.
( 5.1 ) Pancreatitis: If pancreatitis is suspected, promptly discontinue dapagliflozin and saxagliptin. ( 5.2 ) Heart Failure: Consider risks and benefits of dapagliflozin and saxagliptin in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms.
( 5.3 ) Volume Depletion: Before initiating dapagliflozin and saxagliptin, assess volume status and renal function in the elderly, patients with renal impairment or low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms during therapy. ( 5.4 ) Urosepsis and Pyelonephritis: Evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated.
( 5.5 ) Hypoglycemia: Consider lowering the dose of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating dapagliflozin and saxagliptin. ( 5.6 ) 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. ( 5.7 ) Hypersensitivity Reactions : There have been postmarketing reports of serious hypersensitivity reactions in patients treated with saxagliptin, such as anaphylaxis, angioedema, and exfoliative skin conditions. Promptly discontinue dapagliflozin and saxagliptin, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes.
( 5.8 ) Genital Mycotic Infections: Monitor and treat if indicated. ( 5.9 ) Arthralgia: Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue drug if appropriate.
( 5.10 ) Bullous Pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue dapagliflozin and saxagliptin.
( 5.11 )
5.1Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, dapagliflozin, a component of dapagliflozin and saxagliptin, significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium-glucose cotransporter 2 (SGLT2) inhibitors compared to patients who received placebo.
Dapagliflozin and saxagliptin is not indicated for glycemic control in patients with type 1 diabetes mellitus. Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including dapagliflozin.
Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following important adverse reactions are described below or elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see WARNINGS AND PRECAUTIONS (5.1) ] Pancreatitis [see WARNINGS AND PRECAUTIONS (5.2) ] Heart Failure [see WARNINGS AND PRECAUTIONS (5.3) ] Volume Depletion [see WARNINGS AND PRECAUTIONS (5.4) ] Urosepsis and Pyelonephritis [see WARNINGS AND PRECAUTIONS (5.5) ] Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues [see WARNINGS AND PRECAUTIONS (5.6) ] Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) [see WARNINGS AND PRECAUTIONS (5.7) ] Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS (5.8) ] Genital Mycotic Infections [see WARNINGS AND PRECAUTIONS (5.9) ] Severe and Disabling Arthralgia [see WARNINGS AND PRECAUTIONS (5.10) ] Bullous Pemphigoid [see WARNINGS AND PRECAUTIONS (5.11) ] Adverse reactions reported in ≥5% of subjects treated with dapagliflozin and saxagliptin were: upper respiratory tract infection, urinary tract infection, and dyslipidemia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of combined use of 10 mg dapagliflozin and 5 mg saxagliptin has been evaluated in adult subjects with type 2 diabetes mellitus in a pooled safety analysis of three phase 3 active/placebo-controlled clinical trials with a median exposure of 51 weeks.
The pooled safety analysis included a total of 1169 adults: 492 patients in the combination of saxagliptin and dapagliflozin plus metformin group, 341 patients in the dapagliflozin plus metformin group, 336 patients in the saxagliptin plus metformin group.The mean age of these subjects was 54 years, 0.8% were 75 years or older and 53.7% were female. The population was 80.9% White, 8.3% Black or African American, 3.7% Asian, and 6.6% Other race. At baseline the population had diabetes for an average of 7.5 years and a mean HbA1c of 8.4%.
The mean eGFR at baseline was 94.4 mL/min/1.73 m 2 . The common adverse reactions were based on the pooled analyses of these studies as shown in Table 2. Table 2: Adverse Reactions Reported in ≥2% of Subjects Treated with 10 mg Dapagliflozin and 5 mg Saxagliptin plus Metformin (≥1,500 mg) Adverse Reaction Preferred Term* Frequency % Upper respiratory tract infection *
13.6 Urinary tract infection *
5.7 Dyslipidemia *
5.1 Headache
4.3 Diarrhea
3.7 Back pain
3.3 Genital infection *
3.0Arthralgia 2.4 * Adverse reactions that are medically related were grouped to a single preferred term. Additionally, adverse reactions reported in <5% and ≥2% from the dapagliflozin development program and ≥1% more frequently compared to placebo included increased urination and discomfort with urination. Hypoglycemia In the pooled analysis, the incidences of hypoglycemia (defined as a blood glucose <54 mg/dL regardless of the presence or absence of symptoms) and severe hypoglycemia (event requiring assistance due to neuroglycopenia, characterized by altered mental and/or physical status) was 1% and 0.2%, respectively.
Genital Mycotic Infections Genital mycotic infections were reported in 15 subjects (3%) treated with dapagliflozin and saxagliptin. Reported adverse reactions by frequency included vulvovaginal mycotic infection, balanoposthitis, genital fungal infection, vaginal infection, and vulvovaginitis. The majority of subjects (84.2%) who experienced genital infection adverse reactions were females.
Urinary Tract Infections Urinary tract infections were reported in 28 subjects (5.7%) treated with dapagliflozin and saxagliptin. Reported ad…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 3 : Clinically Relevant Interactions with Dapagliflozin and Saxagliptin Strong Inhibitors of CYP3A4/5 Enzymes Clinical Impact Ketoconazole significantly increased saxagliptin exposure. Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). Intervention Do not coadminister dapagliflozin and saxagliptin with strong cytochrome P450 3A4/5 inhibitors [see DOSAGE AND ADMINISTRATION (2.4) and CLINICAL PHARMACOLOGY (12.3) ] .
Insulin or Insulin Secretagogues Clinical Impact The risk of hypoglycemia may be increased when dapagliflozin and saxagliptin is used concomitantly with insulin or insulin secretagogues (e.g., sulfonylurea) [see WARNINGS AND PRECUATIONS (5.6) ] . Intervention Concomitant use may require lower doses of insulin or the insulin secretagogue to reduce the risk of 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 saxagliptin 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. Strong CYP3A4/5 Inhibitors (e.g., Ketoconazole): Do not coadminister dapagliflozin and saxagliptin with strong cytochrome P450 3A4/5 inhibitors. ( 7 ) See full prescribing information for additional drug interactions and information on interference of dapagliflozin and saxagliptin with laboratory tests.
( 7 )
👥 Use in Specific Populations ▾
8 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 ) Geriatrics: Higher incidence of adverse reactions related to hypotension. ( 8.5 ) Renal Impairment: Higher incidence of adverse reactions related to volume depletion. ( 8.6 )
8.1Pregnancy Risk Summary Based on animal data showing adverse renal effects from dapagliflozin, dapagliflozin and saxagliptin is not recommended during the second and third trimesters of pregnancy. The limited available data with dapagliflozin and saxagliptin or its components (dapagliflozin and saxagliptin) in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. 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 tubular dilatations, that were not fully reversible, were observed in rats when dapagliflozin (a component of dapagliflozin and saxagliptin) 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). No adverse developmental effects were observed when saxagliptin was administered to pregnant rats and rabbits ( see Data).
The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an HbA1c greater than 7% and has been reported to be as high as 20 to 25% in women with an 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 embryo-fetal 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 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 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 pup 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 than 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 embryo-fetal development studies in rats and rabbits, dapagliflozin was administered to throughout organogenesis, corresponding to the first trimester of human pregnancy. In rats, dapagliflozin was neither embryolethal nor teratogenic at…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on animal data showing adverse renal effects from dapagliflozin, dapagliflozin and saxagliptin is not recommended during the second and third trimesters of pregnancy. The limited available data with dapagliflozin and saxagliptin or its components (dapagliflozin and saxagliptin) in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. 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 tubular dilatations, that were not fully reversible, were observed in rats when dapagliflozin (a component of dapagliflozin and saxagliptin) 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). No adverse developmental effects were observed when saxagliptin was administered to pregnant rats and rabbits ( see Data).
The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an HbA1c greater than 7% and has been reported to be as high as 20 to 25% in women with an 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 embryo-fetal 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 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 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 pup 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 than 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 embryo-fetal development studies in rats and rabbits, dapagliflozin was administered to 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 ob…
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of dapagliflozin and saxagliptin in pediatric patients under 18 years of age have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Because elderly patients are more likely to have decreased renal function, care should be taken when using dapagliflozin and saxagliptin in the elderly based on renal function [see DOSAGE AND ADMINISTRATION (2.3) ] . 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 studies assessing the efficacy of dapagliflozin in improving glycemic control. After controlling for level of renal function (eGFR), in clinical studies with dapagliflozin, efficacy was similar for patients under age 65 years and those 65 years and older.
In patients 65 years and older, a higher proportion of patients treated with dapagliflozin had adverse reactions of hypotension [see WARNINGS AND PRECAUTIONS (5.4)]. Saxagliptin In the seven double-blind, controlled clinical safety and efficacy trials of saxagliptin, a total of 4751 (42.0%) of the 11,301 patients randomized to saxagliptin were 65 years and over, and 1210 (10.7%) were 75 years and over. No overall differences in safety or effectiveness were observed between subjects ≥65 years old and younger subjects.
While this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE In the event of an overdose, contact the Poison Control Center. Appropriate supportive treatment should be initiated as dictated by the patient’s clinical status. The removal of dapagliflozin by hemodialysis has not been studied. Saxagliptin and its major metabolite can be removed by hemodialysis (23% of dose over 4 hours).
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
Saxagliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production.
In patients with type 2 diabetes mellitus, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Saxagliptin is a competitive DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.
12.2Pharmacodynamics Dapagliflozin 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. Dapagliflozin dose of 5 or 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 REACTIONS (6.1) ]. After discontinuation of dapagliflozin, on average, the elevation in urinary glucose excretion approaches baseline by about 3 days from discontinuation for the 10 mg dose. 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) Saxagliptin In patients with type 2 diabetes mellitus, administration of saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period.
After an oral glucose load or a meal, this DPP-4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased glucose-dependent insulin secretion from pancreatic beta cells. The rise in insulin and decrease in glucagon were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal. Cardiac Electrophysiology Dapagliflozin 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 daily dose) of dapagliflozin in healthy subjects. Saxagliptin In a randomized, double-blind, placebo-controlled, 4-way crossover, active comparator study using moxifloxacin in 40 healthy subjects, saxagliptin was not associated with clinically meaningful prolongation of the QTc interval or heart rate at daily doses up to 40 mg (8 times the recommended maximum daily dose). fig-1
12.3Pharmacokinetics Overall, the pharmacokinetics of dapagliflozin and saxagliptin were not affected in a clinically relevant manner when administered as dapagliflozin and saxagliptin. Saxagliptin The pharmacokinetics of saxagliptin and its active metabolite, 5-hydroxy saxagliptin, were similar in healthy subjects and in patients with type 2 diabetes me…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
Saxagliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production.
In patients with type 2 diabetes mellitus, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Saxagliptin is a competitive DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Dapagliflozin and saxagliptin tablets are available in packages as listed: Table 11: Dapagliflozin and saxagliptin Tablet Presentations Tablet Strength Film-Coated Tablet Color / Shape Tablet Markings Pack Size NDC Code 10mg dapagliflozin/ 5 mg saxagliptin Light brown to brown, biconvex, round Debossed with "MS" on one side and "4" on other side. Bottles of 30 Bottles of 90 72205-438-01 72205-438-02 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Dapagliflozin and saxagliptin tablets for oral use contain dapagliflozin and saxagliptin. Dapagliflozin is an active inhibitor of sodium-glucose cotransporter 2 (SGLT2). It is described chemically as (1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl] phenyl]-D-glucitol with an molecular formula as C 21 H 25 ClO 6 and the molecular weight of 408.88.The structural formula is: Saxagliptin is an active inhibitor of the dipeptidyl-peptidase-4 (DPP-4) enzyme.
It is isolated in the dihydrate form chemically known as (1 S , 3 S , 5 S )-2-((2 S )-2-amino-2-(3-hydroxyadamantan-1-yl) acetyl)-2-azabicyclo [3.1.0] hexane-3-carbonitrile hydrochloride dihydrate. The molecular formula is C 18 H 25 N 3 O 2 .HCl.2H 2 O and the molecular weight is 387.90. The structural formula is : Dapagliflozin and saxagliptin tablet is available as film-coated tablet: • 10 mg dapagliflozin / 5 mg saxagliptin.
Each tablet contains 10 mg dapagliflozin and 5 mg saxagliptin (equivalent to 5.58 mg saxagliptin hydrochloride). Each tablet also contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, sodium lauryl sulphate, stearic acid, iron oxide yellow, iron oxide red, polyvinyl alcohol, polyethylene glycol, talc and titanium dioxide. dapa-saxa-dapagliflozin-structure dapa-saxa-saxagliptin-stucture.
💬 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 Inform patients that dapagliflozin and saxagliptin 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 saxagliptin and seek medical attention immediately [see WARNINGS AND PRECAUTIONS (5.1) ] .
Pancreatitis Inform patients that acute pancreatitis has been reported during postmarketing use of saxagliptin. Inform patients that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Instruct patients to promptly discontinue dapagliflozin and saxagliptin and contact their healthcare provider if persistent severe abdominal pain occurs [see WARNINGS AND PRECAUTIONS (5.2) ].
Heart Failure Inform patients of the signs and symptoms of heart failure. Instruct patients to contact their healthcare provider as soon as possible if they experience symptoms of heart failure, including increasing shortness of breath, rapid increase in weight or swelling of the feet [see WARNINGS AND PRECAUTIONS (5.3) ]. Volume Depletion Inform patients that symptomatic hypotension may occur with dapagliflozin and saxagliptin and advise them to contact their healthcare provider if they experience such symptoms.
Inform patients that dehydration may increase the risk for hypotension, and to have adequate fluid intake [see WARNINGS AND PRECAUTIONS (5.4) ]. Serious Urinary Tract Infections Inform patients of the potential for urinary tract infections, which may be serious. Inform them of the symptoms of urinary tract infections and advise them to seek medical advice if such symptoms occur [ see WARNINGS AND PRECAUTIONS (5.5) ].
Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues Inform patients that the incidence of hypoglycemia may increase when dapagliflozin and saxagliptin is added to an insulin secretagogue (e.g., sulfonylurea) and/or insulin. Educate patients on the signs and symptoms of hypoglycemia [see WARNINGS AND PRECAUTIONS (5.6) ]. 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 saxagliptin .
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 (5.7) ]. Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, and exfoliative skin conditions) have been reported with dapagliflozin and saxagliptin, components of dapagliflozin and saxagliptin. Symptoms of these allergic reactions include: rash, skin flaking or peeling, urticaria, swelling of the skin, or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing.
Advise patients to immediately report any signs or symptoms suggesting allergic reaction, angioedema or exfoliative skin conditions, and stop taking dapagliflozin and saxagliptin and seek medical advice promptly [see WARNINGS…