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Dapagliflozin Propanediol

Class: Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
Chemical Name: (1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-d-glucitol,
Molecular Formula: C21H25ClO6
CAS Number: 461432-26-8
Brands: Farxiga

Introduction

Antidiabetic agent; sodium-glucose cotransporter 2 (SGLT2) inhibitor.1

Uses for Dapagliflozin Propanediol

Diabetes Mellitus

Used as monotherapy as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.1 2 3 15 32 34

Used in combination with other antidiabetic agents (e.g., metformin and/or a sulfonylurea, a peroxisome proliferator-activated receptorγ [PPARγ] agonist [thiazolidinedione], a dipeptidyl peptidase-4 [DPP-4] inhibitor) or insulin as an adjunct to diet and exercise in patients with type 2 diabetes mellitus who have not achieved adequate glycemic control.1 4 5 6 7 8 9 10 12 13 16

Not indicated for type 1 diabetes mellitus or treatment of diabetic ketoacidosis.1

Dapagliflozin Propanediol Dosage and Administration

Administration

Oral Administration

Administer once daily in the morning, with or without food.1

If a dose is missed, take missed dose as soon as it is remembered followed by resumption of regular schedule.1 If missed dose is not remembered until the time of the next dose, skip missed dose and resume regular schedule.1 Do not double dose to replace a missed dose.1

Dosage

Dosage of dapagliflozin propanediol is expressed in terms of dapagliflozin.1

Adults

Diabetes Mellitus
Oral

Initially, 5 mg once daily.1

If well tolerated, increase dosage to 10 mg once daily in patients who require additional glycemic control.1

Special Populations

Hepatic Impairment

Mild, moderate or severe hepatic impairment: No dosage adjustment necessary.1

Renal Impairment

Mild renal impairment (eGFR ≥60 mL/minute per 1.73 m2): No dosage adjustment necessary.1

Moderate renal impairment: Do not initiate if eGFR <60 mL/minute per 1.73 m2.1 (See Renal Impairment under Cautions.) Continued use of dapagliflozin not recommended in patients with an eGFR persistently between 30 and <60 mL/minute per 1.73 m2.1

Severe renal impairment (eGFR <30 mL/minute per 1.73 m2): Contraindicated.1

Geriatric Patients

No dosage adjustment necessary based solely on age.1

Gender

Dosage adjustment based on gender not necessary.1

Race

Dosage adjustment based on race not necessary.1

Body Weight

Dosage adjustment based on body weight not necessary.1

Cautions for Dapagliflozin Propanediol

Contraindications

  • History of serious hypersensitivity reaction to dapagliflozin.1

  • Severe renal impairment (eGFR <30 mL/minute per 1.73 m2), end-stage renal disease, or on dialysis.1

Warnings/Precautions

Ketoacidosis

Ketoacidosis (e.g., diabetic ketoacidosis, ketoacidosis, ketosis) requiring hospitalization reported with SGLT2 inhibitors; may occur without markedly elevated blood glucose concentrations (e.g., <250 mg/dL).1 39 40 41 42 50

Evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing signs or symptoms of acidosis regardless of the patient's blood glucose concentration; discontinue SGLT2 inhibitor and initiate appropriate treatment to correct acidosis if confirmed.1 39 40 50 (See Advice to Patients.)

Prior to initiating dapagliflozin therapy, consider factors that may predispose patients to ketoacidosis (e.g., pancreatic insulin deficiency, reduced caloric intake, alcohol abuse).1 50

Consider temporarily discontinuing SGLT2 inhibitor in patients with clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).1 50

Some clinicians suggest monitoring of urine and/or plasma ketone levels if patients feel unwell, regardless of ambient glucose concentrations.40 42

Hypotension

May cause intravascular volume contraction.1 Symptomatic hypotension can occur, particularly in patients with impaired renal function (eGFR <60 mL/minute per 1.73 m2), geriatric patients, or patients receiving loop diuretics.1 (See Specific Drugs under Interactions.) Assess and correct intravascular volume status prior to initiating dapagliflozin in such patients.1

Monitor patients for signs and symptoms of hypotension after initiating therapy.1

Renal Effects

Causes intravascular volume contraction and can cause renal impairment.1 51

May increase Scr concentration and decrease eGFR; geriatric patients and patients with impaired renal function may be more susceptible to these changes.1 Adverse reactions related to renal function can occur following initiation of the drug.1

Prior to initiating dapagliflozin therapy, consider factors that may predispose patients to acute kidney injury, such as hypovolemia, chronic renal insufficiency, heart failure, and concomitant medications (e.g., diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIAs).1 51

Consider temporarily discontinuing dapagliflozin in any setting of reduced oral intake (e.g., acute illness, fasting) or fluid losses (e.g., GI illness, excessive heat exposure).1 51

Evaluate renal function prior to initiation of dapagliflozin and monitor periodically thereafter.1 Discontinue dapagliflozin and initiate appropriate treatment if kidney injury occurs.1 51

Concomitant Therapy with Hypoglycemic Agents

When adding dapagliflozin to therapy with an insulin secretagogue (e.g., a sulfonylurea) or insulin, consider reducing dosage of the concomitant insulin secretagogue or insulin to reduce the risk of hypoglycemia.1 (See Specific Drugs under Interactions)

Genital Mycotic Infections

Possible increased risk of genital mycotic infections in males (e.g., balanitis) and females (e.g., vulvovaginal mycotic infection).1 11 37 Patients with a history of genital mycotic infections were more likely to develop such infections.1 37

Monitor patients for genital mycotic infections and institute appropriate treatment if these infections occur.1

Urosepsis and Pyelonephritis

May increase the risk of serious urinary tract infections (e.g., urosepsis, pyelonephritis requiring hospitalization).1 50

Prior to initiating dapagliflozin therapy, consider patient factors that may predispose to serious urinary tract infections (e.g., history of difficulty urinating; infection of the bladder, kidneys, or urinary tract).50

Monitor patients for urinary tract infections and initiate treatment if indicated.1 50

Risk of Bone Fracture

Increased risk of bone fracture, along with dose-related decreases in bone mineral density in older adults, observed in patients receiving another SGLT2 inhibitor (canagliflozin).43 Bone fractures observed more frequently than with placebo in patients with moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m2) receiving dapagliflozin, usually within 52 weeks of initiating therapy.1 FDA continuing to evaluate bone fracture risk with SGLT2 inhibitors.43

Effects on Lipoproteins

Increases in LDL-cholesterol can occur.1 Monitor serum LDL-cholesterol concentrations and treat such lipid elevations according to the standard of care.1

Bladder Cancer

Newly diagnosed cases of bladder cancer reported in clinical studies.1 10 Too few cases to determine whether the emergence of these events is related to dapagliflozin; insufficient data to determine whether dapagliflozin has an effect on pre-existing bladder tumors. 1

Do not use dapagliflozin in patients with active bladder cancer.1 Consider benefits of glycemic control versus unknown risks for cancer recurrence.1

Macrovascular Outcomes

Evidence of macrovascular risk reduction with dapagliflozin or any other antidiabetic agent has not been conclusively demonstrated in clinical trials.1

Sensitivity Reactions

Hypersensitivity reactions (e.g., angioedema, urticaria, hypersensitivity), some serious, reported.1 If a hypersensitivity reaction occurs, discontinue dapagliflozin, institute appropriate treatment, and monitor patients until signs and symptoms resolve.1

Specific Populations

Pregnancy

Category C.1

No adequate and well-controlled studies of dapagliflozin in pregnant women.1

Studies in animals indicate that dapagliflozin use during pregnancy may affect renal development and maturation.1

Consider alternative therapies in pregnant women, especially during the second and third trimesters.1 Use during pregnancy only if potential benefit justifies the potential risk to the fetus.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1

Geriatric Use

Efficacy similar in patients <65 years of age and those ≥65 years of age after controlling for renal function (eGFR).1 Such patients more likely to experience adverse effects related to volume depletion and renal impairment or failure.1

Hepatic Impairment

No dosage adjustment necessary for patients with mild, moderate, or severe hepatic impairment.1 Assess benefits versus risks in patients with severe hepatic impairment; safety and efficacy not established in such patients.1 22

Renal Impairment

Patients with moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m2) receiving dapagliflozin had no overall improvement in glycemic control and had higher rates of renal-related adverse reactions and more bone fractures than placebo recipients; do not initiate in such patients.1 35

Not expected to be effective in patients with severe renal impairment (eGFR <30 mL/minute per 1.73 m2) or end-stage renal disease; contraindicated in such patients.1

Impact of hemodialysis on dapagliflozin exposure is not known; contraindicated in patients on dialysis.1

Assess renal function prior to initiation of therapy and periodically thereafter.1

Common Adverse Effects

Female genital mycotic infection,1 2 3 4 6 7 8 nasopharyngitis,1 2 3 5 6 7 8 urinary tract infection,1 2 3 4 5 6 8 33 back pain,1 5 8 increased urination,1 male genital mycotic infection,1 2 3 4 7 nausea,1 4 dyslipidemia,1 4 8 constipation,1 discomfort with urination,1 pain in extremity.1 8

Interactions for Dapagliflozin Propanediol

Metabolism principally mediated by uridine diphosphate-glucuronosyltransferase (UGT) isoenzyme 1A9.1 20

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Did not inhibit CYP-450 isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 or 3A4 in vitro.1 19 Did not induce CYP isoenzymes 1A2, 2B6, or 3A4 in vitro.1 19

Drugs Affected by Organic Anion Transporter

Dapagliflozin 3-O-glucuronide, inactive metabolite of dapagliflozin, is a substrate of organic anion transport (OAT) 3.1 Dapagliflozin and dapagliflozin 3-O-glucuronide did not meaningfully inhibit OAT1 or OAT3 active transporters; pharmacokinetic interactions unlikely with OAT1 or OAT3 substrates.1

Drugs Affected by Organic Cation Transporter

Did not meaningfully inhibit organic cation transporter (OCT) 2; pharmacokinetic interactions unlikely with substrates of OCT2.1

Drugs Affected by P-glycoprotein Transport

Weak P-glycoprotein substrate; did not meaningfully inhibit P-glycoprotein.1 19 20 Unlikely to affect pharmacokinetics of concurrently administered P-glycoprotein substrates.1

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Antidiabetic agents

Risk of hypoglycemia increased when used concomitantly with insulin secretagogue (e.g,, sulfonylurea) or insulin1

Reduced dosage of insulin or insulin secretagogue may be required to reduce the risk of hypoglycemia1

Bumetanide

Increased bumetanide AUC and peak plasma concentration1 (see also Diuretics entry in this table)

No dosage adjustment necessary1

Digoxin

No clinically meaningful effect on digoxin AUC or peak plasma concentration1 20 26

No adjustment of digoxin dosage necessary1

Diuretics

Possible increased incidence of symptomatic hypotension1

Assess and correct intravascular volume prior to dapagliflozin initiation; monitor for signs and symptoms of hypotension after initiating therapy1

Glimepiride

Increased glimepiride AUC1 20

No dosage adjustment necessary1 25

Hydrochlorothiazide

No clinically important effect on pharmacokinetics of either drug1 20 (see also Diuretics entry in this table)

No dosage adjustment necessary1

Mefenamic acid

Increased dapagliflozin peak plasma concentration and AUC1 20 24

No adjustment of dapagliflozin dosage necessary.24

Metformin

No clinically meaningful effect on pharmacokinetics of either drug 1 20 25

No dosage adjustment necessary1 25

Pioglitazone

Decreased pioglitazone peak plasma concentration1 20

No dosage adjustment necessary1 25

Rifampin

Decreased dapagliflozin peak plasma concentration and AUC 1 20 24

No adjustment of dapagliflozin dosage necessary1 24

Simvastatin

Increased simvastatin AUC1 26

No dosage adjustment necessary1

Sitagliptin

No clinically meaningful effect on pharmacokinetics of either drug (single-dose administration)1

No dosage adjustment necessary1 25

Urine glucose tests (e.g., 1,5-anhydroglucitol assay)

SGLT2 inhibitors increase urinary glucose excretion and will result in false-positive urine glucose tests1

Use alternative methods to monitor glycemic control1

Valsartan

Decreased peak plasma concentrations of valsartan and dapagliflozin and increased valsartan AUC1 20 26

No dosage adjustment necessary1

Voglibose (not commercially available in the US)

No clinically meaningful effect on dapagliflozin1

Warfarin

No clinically meaningful effect on warfarin pharmacokinetics or pharmacodynamics1 20 26

No warfarin dosage adjustment necessary1 20

Dapagliflozin Propanediol Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability: 78%.1 27 Peak plasma concentration usually attained within 2 hours after oral dosing in fasted state.1 18 19 20 23 30

Food

Administration with a high-fat meal decreased peak plasma concentration by up to 50% and prolonged time to peak plasma concentration by approximately 1 hour, but did not alter AUC.1 20 21 These changes are not considered clinically meaningful; administer dapagliflozin with or without food.1 20 21

Special Populations

Mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment: No clinically important differences in peak plasma concentration or AUC.1

Severe hepatic impairment (Child-Pugh class C): AUC and peak plasma concentration increased by 67 and 40%, respectively, compared with individuals with normal hepatic function following a single 10-mg dose of dapagliflozin.1 22

Mild renal impairment: Geometric mean systemic exposure of dapagliflozin at steady state increased by 45% compared with individuals with normal renal function.1

Moderate renal impairment: Geometric mean systemic exposure of dapagliflozin at steady state increased 2.04-fold compared with individuals with normal renal function.1

Severe renal impairment: Geometric mean systemic exposure of dapagliflozin at steady state increased 3.03-fold compared with individuals with normal renal function.1

Distribution

Extent

Extensively distributed.20

Plasma Protein Binding

Approximately 91%.1 19

Special Populations

Renal or hepatic impairment does not meaningfully alter plasma protein binding.1

Elimination

Metabolism

Metabolized principally by UGT1A9 to inactive metabolites.1

Elimination Route

75 and 21% of total radioactivity excreted in urine and feces, respectively, with <21 19 and approximately 15% in urine and feces, respectively, as parent drug.1 20

Half-life

Approximately 12.9 hours following a single oral dose of 10 mg.1

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).1

Actions

  • Inhibits SGLT2, a transporter expressed in proximal renal tubules and responsible for majority of reabsorption of filtered glucose from the tubular lumen.1 20

  • Reduces reabsorption of filtered glucose and lowers the renal threshold for glucose in a dose-dependent manner, leading to increased urinary glucose excretion.1 17 30 31

  • Increases glucose excretion independent of insulin secretion.36

  • Improves muscle insulin sensitivity;28 29 however, glucosuria induction appears to increase endogenous glucose production.28

  • Endogenous glucose production increases, accompanied by an increase in fasting plasma glucagon concentration.28

Advice to Patients

  • Importance of patient reading medication guide before initiating therapy and each time the drug is dispensed.1 38

  • Importance of informing patients of the potential risks and benefits of dapagliflozin and of alternative therapies.1 38 Importance of not using dapagliflozin in patients with type 1 diabetes mellitus or diabetic ketoacidosis.1 38

  • Importance of informing patients that ketoacidosis, which can be a life-threatening condition, has been reported with dapagliflozin therapy.1 Importance of informing patients and their caregivers of the signs and symptoms of ketoacidosis (e.g., tachypnea or hyperventilation, anorexia, abdominal pain, nausea, vomiting, lethargy, mental status change) and of instructing patients to discontinue dapagliflozin and seek medical attention immediately should they experience any such signs or symptoms.1 39 42 50 Advise patients to use a ketone dipstick to check for ketones in their urine (when possible) if symptoms of ketoacidosis occur, even if blood glucose is not elevated (e.g., <250 mg/dL).1 38 50

  • Importance of informing patients that symptomatic hypotension may occur with dapagliflozin and to report such symptoms to their clinicians.1 38 Inform patients that dapagliflozin-induced dehydration may increase the risk of hypotension and that patients should maintain adequate fluid intake.1 38

  • Importance of informing patients that acute kidney injury has been reported with dapagliflozin therapy.1 38 51 Advise patients to seek medical attention immediately if they experience decreased urine output or swelling of the legs or feet.51 Advise patients to seek medical advice immediately if they have reduced oral intake (such as due to acute illness or fasting) or increased fluid losses (such as due to vomiting, diarrhea, or excessive heat exposure), as it may be appropriate to temporarily discontinue dapagliflozin in those settings.1 51

  • Importance of informing patients that yeast infection may occur (e.g., vulvovaginitis, balanitis, balanoposthitis).1 38 Importance of informing female patients of the signs and symptoms of vaginal yeast infections (e.g., vaginal discharge, odor, itching) and male patients of the signs and symptoms of balanitis or balanoposthitis (e.g., rash or redness of the glans or foreskin of the penis).1 38 Advise patients of treatment options and when to seek medical advice.1 38

  • Importance of informing patients of the potential for urinary tract infections, which may be serious.1 38 Advise patients of the signs and symptoms of urinary tract infection and the need to contact a clinician promptly if such signs and symptoms occur.1 50

  • Importance of informing patients that due to the mechanism of action of dapagliflozin, patients taking the drug will test positive for glucose in their urine.1 Importance of not using urine glucose tests to monitor glycemic status while taking dapagliflozin.1

  • Risk of serious hypersensitivity reactions, such as urticaria and angioedema.1 38 If signs or symptoms of such a reaction occur, importance of discontinuing dapagliflozin and promptly informing clinician.1 38

    Importance of informing patients to promptly report any signs of macroscopic hematuria or other symptoms potentially indicative of bladder cancer.1 38

  • Importance of informing patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and glycosylated hemoglobin (hemoglobin A1c; HbA1c) testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications.1 38

  • Importance of promptly seeking medical advice during periods of stress such as fever, trauma, infection, or surgery as medication requirements may change.1 38

  • Importance of taking dapagliflozin exactly as directed by clinician.1 38 (See Administration under Dosage and Administration.)

  • Importance of women informing their clinicians immediately if they are or plan to become pregnant or plan to breast-feed.1 38

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 38

  • Importance of informing patients of other important precautionary information.1 38 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Dapagliflozin Propanediol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

5 mg (of dapagliflozin)

Farxiga

Bristol-Myers Squibb

10 mg (of dapagliflozin)

Farxiga

Bristol-Myers Squibb

AHFS DI Essentials. © Copyright 2017, Selected Revisions March 31, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Bristol-Myers Squibb Company. Farxiga (dapagliflozin) tablets prescribing information. Princeton, NJ; 2016 Jun.

2. Ferrannini E1, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010 Oct; 33:2217-24. [PubMed 20566676]

3. Bailey CJ, Iqbal N, T'joen C, List JF. Dapagliflozin monotherapy in drug-naïve patients with diabetes: a randomized-controlled trial of low-dose range. Diabetes Obes Metab. 2012 Oct; 14:951-9. [PubMed 22776824]

4. . Henry RR, Murray AV, Marmolejo MH, et al. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract. 2012 May; 66:446-56. [PubMed 22413962]

5. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Jun 26; 375:2223-33. [PubMed 20609968]

6. Nauck MA, Del Prato S, Meier JJ et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011 Sep; 34:2015-22. [PubMed 21816980]

7. Strojek K, Yoon KH, Hruba V. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2011 Oct; 13:928-38. [PubMed 21672123]

8. Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012 Jul; 35:1473-8. [PubMed 22446170]

9. Jabbour SA, Hardy E, Sugg J, Parikh S. Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Diabetes Care.. 2014 Mar; 37:740-50. [PubMed 24144654]

10. Wilding JP, Woo V, Rohwedder K, Sugg J, Parikh S. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. 2013 Aug; :. [PubMed 23911013]

11. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 202293 (dapagliflozin): Medical review(s). From FDA website.

12. Bailey CJ, Gross JL, Hennicken D, et al. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial. BMC Med. 2013 Feb 20; 11 [PubMed 23425012]

13. Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2013 Aug 1; :.

14. Bolinder J, Ljunggren Ö, Kullberg J, et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012 Mar; 97:1020-31. [PubMed 22238392]

15. Ji L, Ma J, Li H, et al. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther. 2014 Jan 1; 36:84-10. [PubMed 24378206]

16. Wilding JP, Norwood P, T'joen C, et al. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care. 2009 Sep; 32:1656-62. [PubMed 19528367]

17. DeFronzo RA, Hompesch M, Kasichayanula S et al. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013 Oct; 36:3169-76. [PubMed 23735727]

18. Yang L, Li H, Li H et al. Pharmacokinetic and pharmacodynamic properties of single- and multiple-dose of dapagliflozin, a selective inhibitor of SGLT2, in healthy Chinese subjects. Clin Ther. 2013 Aug; 35:1211-1222. [PubMed 23910664]

19. Obermeier M, Yao M, Khanna A et al. In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos. 2010 Mar;; :. [PubMed 19996149]

20. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan; 53:17-27. [PubMed 24105299]

21. Kasichayanula S, Liu X, Zhang W et al. Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects. Diabetes Obes Metab. 2011 Aug; 13:770-3. [PubMed 21435141]

22. Kasichayanula S, Liu X, Zhang W et al. Influence of hepatic impairment on the pharmacokinetics and safety profile of dapagliflozin: an open-label, parallel-group, single-dose study.. Clin Ther. 2011 Nov; 33:1798-808. [PubMed 22030444]

23. Kasichayanula S, Liu X, Pe Benito M et al. The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus. Br J Clin Pharmacol. 2013 Sep; 76:432-44. [PubMed 23210765]

24. Kasichayanula S, Liu X, Griffen SC, Lacreta FP, Boulton DW. Effects of rifampin and mefenamic acid on the pharmacokinetics and pharmacodynamics of dapagliflozin. Diabetes Obes Metab. 2013 Mar; 15:280-3. [PubMed 23061428]

25. Kasichayanula S, Liu X, Shyu WC et al. Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium-glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects. Diabetes Obes Metab. 2011 Jan; 13:47-54. [PubMed 21114603]

26. Kasichayanula S, Chang M, Liu X et al. Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Adv Ther. 2012 Feb; 29:163-77. [PubMed 22271159]

27. Boulton DW, Kasichayanula S, Keung CF et al. Simultaneous oral therapeutic and intravenous 14C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin. Br J Clin Pharmacol. 2013 Mar; 75:763-8. [PubMed 22823746]

28. Merovci A, , Solis-Herrera C, Daniele G et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014 Feb 3; 124:509-14. [PubMed 24463448]

29. Mudaliar S, Henry RR, Boden G et al. Changes in insulin sensitivity and insulin secretion with the sodium glucose cotransporter 2 inhibitor dapagliflozin. Diabetes Technol Ther. 2014 Mar; 16:137-44. [PubMed 24237386]

30. Komoroski B, Vachharajani N, Boulton D et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther. 2009 May; 85:520-6. [PubMed 19129748]

31. Komoroski B, Vachharajani N, Feng Y et al. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther. 2009 May; 85:513-9. [PubMed 19129749]

32. Ji L, Ma J, Li H et al. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther. 2014 Jan 1; 36:84-100. [PubMed 24378206]

33. Johnsson KM, Ptaszynska A, Schmitz B et al. Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013 Sep-Oct; 27:473-8. [PubMed 23849632]

34. Kaku K, Inoue S, Matsuoka O et al. Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2013 May; 15:432-40. [PubMed 23194084]

35. Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014 Apr; 85:962-71. [PubMed 24067431]

36. Riser Taylor S, Harris KB. The Clinical Efficacy and Safety of Sodium Glucose Cotransporter-2 Inhibitors in Adults with Type 2 Diabetes Mellitus. Pharmacotherapy. 2013; :. [PubMed 23744749]

37. Johnsson KM, Ptaszynska A, Schmitz B et al, , , . Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013 Sep-Oct; 27:479-84. [PubMed 23806570]

38. Bristol-Myers Squibb Company. Farxiga (dapagliflozin) tablets medication guide. Princeton, NJ; 2016 Jun.

39. US Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. 2015 May 15. From FDA website. Accessed 2015 July 6.

40. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015; 38:1638-42.

41. Erondu N, Desai M, Ways K et al. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015; 38:1680-6.

42. Peters AL, Buschur EO, Buse JB et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium–glucose cotransporter 2 inhibition. Diabetes Care. 2015; 38:1687–93.

43. US Food and Drug Administration. FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density. 2015 Sep 10. From FDA website. Accessed 2015 Sep 13.

50. US Food and Drug Administration. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. From FDA website.

51. US Food and Drug Administration. FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicine canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). From FDA website.

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