dapagliflozin

Inhibits proximal renal tubular sodium-glucose cotransporter 2 (SGLT2), which determines reabsorption of glucose from the tubular lumen. Inhibits reabsorption of glucose, lowers renal threshold for glucose, and increases excretion of glucose in urine.

Therapeutic effects:

Improved glycemic control.
Reduction in risk of HF hospitalizations in patients with type 2 diabetes mellitus.
Reduction in risk of cardiovascular death, HF hospitalizations, and urgent visits for HF in patients with HF.
Reduction in risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and HF hospitalizations in patients with chronic kidney disease at risk of progression.

Pharmacokinetics ⬆ ⬇

Absorption: 78% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized by UGT1A9 to inactive metabolites, which are primarily excreted in urine. 15% excreted in feces as unchanged drug.

Half-Life: 12.9 hr

Time/Action Profile ⬆ ⬇

(↓ in A1c)

ROUTE	ONSET	PEAK	DURATION
PO	within 4 wk	12 wk	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Moderate renal impairment (eGFR <45 mL/min/1.73 m²) (use not recommended to improve glycemic control in patients with type 2 diabetes mellitus);
Dialysis;
Type 1 diabetes;
Diabetic ketoacidosis;
Active bladder cancer;
OB: Not recommended for use during 2nd and 3rd trimesters of pregnancy (may cause adverse renal effects in infant);
Lactation: Lactation.

Use Cautiously in:

History of pancreatitis, pancreatic surgery, reduced caloric intake due to illness or surgery, or alcohol abuse (↑ risk of ketoacidosis);
Renal impairment (eGFR <60 mL/min/1.73 m²), age >65 yr, or concurrent use of loop diuretics (↑ risk of hypovolemia and hypotension);
History of bladder cancer;
Polycystic kidney disease or recent history of immunosuppressive therapy for kidney disease (use not recommended for treatment of chronic kidney disease);
OB: Use during 1st trimester of pregnancy only if potential maternal benefit justifies potential fetal risk (other agents recommended in pregnancy);
Pedi: Safety and effectiveness not established in children 10 yr (type 2 diabetes) or 18 yr (all other indications);
Geri: Appears on Beers list. Older adults may have risk of urogenital infections (especially women in the 1st mo of treatment) and euglycemic diabetic ketoacidosis. Use with caution in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Endo: hypoglycemia (↑ with other medications)

F and E: hyperphosphatemia, hypovolemia, KETOACIDOSIS

GU: ↑urination, acute kidney injury, genital mycotic infections, NECROTIZING FASCIITIS OF PERINEUM (FOURNIER'S GANGRENE), renal impairment, urinary tract infection(including pyelonephritis), UROSEPSIS

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS OR ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

↑risk of hypoglycemia with insulin or insulin secretagogues; dose adjustments may be required.
Concurrent use with loop diuretics may ↑ risk of hypovolemia and associated complications.
May ↓ lithium levels and effectiveness.

Route/Dosage ⬆ ⬇

Type 2 Diabetes Mellitus (for Glycemic Control)

PO (Adults and Children ≥10 yr): 5 mg once daily; may ↑ to 10 mg once daily, if needed.

Renal Impairment

PO (Adults and Children ≥10 yr): eGFR <45 mL/min/1.73 m²: Use not recommended.

Type 2 Diabetes (for Reduction in Risk of HF Hospitalizations), HF, or Chronic Kidney Disease

PO (Adults ): 10 mg once daily.

Renal Impairment

PO (Adults ): eGFR <25 mL/min/1.73 m²: Initiation of therapy not recommended; however, patients currently taking dapagliflozin may continue with 10 mg once daily.

Availability ⬆ ⬇

(Generic available)

Tablets: 5 mg; 10 mg
In combination with: metformin XR (Xigduo XR); saxagliptin (Qtern). See Appendix [not included in this PDA edition]

Assessment ⬆ ⬇

Observe for signs and symptoms of hypoglycemia (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety), especially in patients taking insulin or other hypoglycemic agents.
Assess cardiovascular status (BP, edema, dyspnea) before starting and periodically during therapy.
Assess volume status and correct before starting dapagliflozin. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m²), older adults, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Monitor BP after initiating and periodically during therapy; may cause hypotension.
Monitor for signs and symptoms of urinary tract infection (burning during urination, frequent urination, urgency, pain in pelvis, blood in urine, fever, back pain, nausea, vomiting) during therapy. Treat promptly.
Monitor for infection, new pain, tenderness, erythema, swelling, sores, or ulcers involving genital or perianal area, with fever or malaise; assess for necrotizing fasciitis (Fournier's gangrene). If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue dapagliflozin if these occur.

Lab Test Considerations:

Ensure negative pregnancy test prior to initiation.
Monitor serum glucose and A1c periodically during therapy to evaluate effectiveness of treatment.
Evaluate renal function prior to starting and periodically during therapy; may cause ↑ serum creatinine.
- May cause ↑ hematocrit and serum phosphorous.
Monitor for ketoacidosis, especially during prolonged fasting for illness or surgery. Consider temporarily discontinuing therapy for ≥3 days prior to surgery. Can resume therapy once patient stable and has resumed oral intake.
- Will cause urine to test positive for glucose; consider testing for urine ketones.

Toxicity and Overdose:

Overdose is manifested by symptoms of hypoglycemia. Mild hypoglycemia may be treated with administration of oral glucose. Treat severe hypoglycemia with IV push 50% dextrose in water followed by continuous IV infusion of 10% dextrose in water at a rate sufficient to keep serum glucose at approximately 100 mg/dL.

Implementation ⬆ ⬇

Do not confuse Farxiga with Fetzima.
Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
PO: Administer once daily in the morning without regard to food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of dapagliflozin. Instruct patient to take medication at same time each day. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
Explain to patient that this medication controls hyperglycemia but does not cure diabetes. Therapy is long term.
Inform patient dapagliflozin may cause dehydration and hypotension. Maintain adequate hydration and notify health care professional if dizziness, fainting, weakness, or orthostatic hypotension occur. Notify health care professional if fluid loss from nausea, vomiting, and diarrhea occurs.
Advise patient to notify health care professional if signs and symptoms of urinary tract infections or genital mycotic infections (females—vaginal odor, white or yellowish vaginal discharge, vaginal itching; males—rash or redness of glans or foreskin of penis, foul-smelling discharge from penis, pain in skin around penis) occur. Instruct patient on treatment options and when to notify health care professional.
Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to drink a glass of orange juice or ingest 2–3 teaspoons of sugar, honey, or corn syrup dissolved in water or an appropriate number of glucose tablets and notify health care professional.
Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes.
Instruct patient in proper testing of serum glucose and ketones, especially during periods of stress or illness. Inform patient that dapagliflozin will cause a positive test result when testing for urine glucose. Notify health care professional if significant changes occur.
Advise patient to notify health care professional immediately if new pain or tenderness, sores or ulcers, or infections involving the leg or foot occur and to immediately seek care if pain or tenderness, redness, or swelling of the genitals or area from the genitals back to the rectum, along with a fever above 100.4°F or malaise, occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Advise patient to inform health care professional of dapagliflozin use prior to treatment or surgery.
Advise patient to notify health care professional promptly if signs and symptoms of hypersensitivity reactions (rash; raised red patches on skin; difficulty breathing or swallowing; swelling of face, lips, tongue, or throat) or bladder cancer (blood or red color in urine, painful urination) occur.
Advise patient to carry a form of sugar (glucose tablets or gel, sugar packets, candy) and identification describing disease process and medication regimen at all times.
Rep: Insulin is the recommended method of controlling blood sugar during pregnancy. Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Effective contraception should be used especially during the 2nd and 3rd trimesters of pregnancy.
Emphasize the importance of routine follow-up exams.

Evaluation/Desired Outcomes ⬆ ⬇

Control of blood glucose levels without the appearance of hypoglycemic or hyperglycemic episodes.
Reduction in risk of HF hospitalizations.
Reduction in risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and HF hospitalizations in patients with chronic kidney disease at risk of progression.

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Code ⬆

NDC Code

0310- AstraZeneca Pharmaceuticals LP
- 0310-6205- FARXIGA
  - 0310-6205-30- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0310-6205-30)

0310- AstraZeneca Pharmaceuticals LP
- 0310-6205- FARXIGA
  - 0310-6205-95- 1 BLISTER PACK in 1 CARTON (0310-6205-95) > 7 TABLET, FILM COATED in 1 BLISTER PACK

0310- AstraZeneca Pharmaceuticals LP
- 0310-6210- FARXIGA
  - 0310-6210-30- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0310-6210-30)

0310- AstraZeneca Pharmaceuticals LP
- 0310-6210- FARXIGA
  - 0310-6210-95- 1 BLISTER PACK in 1 CARTON (0310-6210-95) > 7 TABLET, FILM COATED in 1 BLISTER PACK

50090- A-S Medication Solutions
- 50090-3481- FARXIGA
  - 50090-3481-0- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (50090-3481-0)

50090- A-S Medication Solutions
- 50090-3482- FARXIGA
  - 50090-3482-0- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (50090-3482-0)

55154- Cardinal Health
- 55154-6932- FARXIGA
  - 55154-6932-8- 1440 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (55154-6932-8)

55154- Cardinal Health
- 55154-6933- FARXIGA
  - 55154-6933-8- 840 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (55154-6933-8)

70748- Lupin Pharmaceuticals, Inc.
- 70748-105- Dapagliflozin
  - 70748-105-01- 100 TABLET in 1 BOTTLE (70748-105-01)

70748- Lupin Pharmaceuticals, Inc.
- 70748-105- Dapagliflozin
  - 70748-105-02- 500 TABLET in 1 BOTTLE (70748-105-02)

70748- Lupin Pharmaceuticals, Inc.
- 70748-105- Dapagliflozin
  - 70748-105-06- 30 TABLET in 1 BOTTLE (70748-105-06)

70748- Lupin Pharmaceuticals, Inc.
- 70748-105- Dapagliflozin
  - 70748-105-09- 90 TABLET in 1 BOTTLE (70748-105-09)

70748- Lupin Pharmaceuticals, Inc.
- 70748-106- Dapagliflozin
  - 70748-106-01- 100 TABLET in 1 BOTTLE (70748-106-01)

70748- Lupin Pharmaceuticals, Inc.
- 70748-106- Dapagliflozin
  - 70748-106-02- 500 TABLET in 1 BOTTLE (70748-106-02)

70748- Lupin Pharmaceuticals, Inc.
- 70748-106- Dapagliflozin
  - 70748-106-06- 30 TABLET in 1 BOTTLE (70748-106-06)

70748- Lupin Pharmaceuticals, Inc.
- 70748-106- Dapagliflozin
  - 70748-106-09- 90 TABLET in 1 BOTTLE (70748-106-09)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇