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 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.
Loop diuretics may ↑ risk of hypovolemia and associated complications.
May ↓ levels and effectiveness of lithium.

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). See Combination Drugs

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 volume status and correct before starting therapy. Monitor BP at initiation and periodically, as hypotension may occur. Patients with renal impairment (eGFR <60 mL/min/1.73 m²), older adults, or patients on loop diuretics may be at ↑ risk for volume depletion or 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. If urinary tract infection occurs, treat promptly.
Monitor for signs and symptoms of necrotizing fasciitis of the perineum (Fournier gangrene: tenderness, redness, or swelling of the genitals or perineum; fever, malaise, perineal skin discoloration or gangrenous appearance; drainage; sores; blisters; foul odor). If necrotizing fasciitis of the perineum suspected, permanently discontinue dapagliflozin; start treatment immediately with broad-spectrum antibiotics, and if necessary, perform surgical debridement.

Lab Test Considerations:

Verify negative pregnancy test prior to initiation.
Monitor serum glucose and A1c periodically during therapy to evaluate effectiveness of treatment.
Evaluate renal function prior to and periodically during therapy; May ↑ serum creatinine.
- May ↑ hematocrit and phosphorous.
Monitor for ketoacidosis, especially during prolonged fasting for illness or surgery. Hold therapy for ≥3 days prior to surgery, if possible. 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. Emphasize the importance of routine follow-up exams.
Inform patient that dapagliflozin may cause dehydration and hypotension. Maintain adequate hydration and notify health care provider if dizziness, fainting, weakness, or orthostatic hypotension occurs. Notify health care provider if fluid loss from nausea, vomiting, and diarrhea occurs.
Advise patient to notify health care provider if signs and symptoms of urinary tract infections or genital mycotic infections (women: vaginal odor, white or yellowish vaginal discharge, vaginal itching; men: 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 provider.
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 provider.
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 provider if significant changes occur.
Advise patient to notify health care provider 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 temperature >100.4°F or malaise, occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient to inform health care provider of dapagliflozin use prior to treatment or surgery.
Advise patients and family to call 911 and immediately seek treatment for signs and symptoms of hypersensitivity reactions, such as difficulty breathing; chest tightness; hives; rash; feeling light-headed; itching; or swelling of the face, lips, tongue, or throat.
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: May cause fetal harm. Insulin is the recommended method of controlling blood sugar during pregnancy. Advise patient to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Advise women that dapagliflozin use is not recommended during the 2nd and 3rd trimesters of pregnancy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇