Dapazin

Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
• As an adjunct to diet and exercise to improve glycemic control in adults.
• Heart Failure with Reduced Ejection Fraction (HFrEF):
• To reduce the risk of cardiovascular death and hospitalization for heart failure.
• Chronic Kidney Disease (CKD):
• To reduce the risk of sustained decline in renal function, end-stage renal disease, cardiovascular death, and hospitalization for heart failure in adults with CKD.

Clinically Accepted Off-label Uses:

• Prevention of progression of diabetic nephropathy.
• Potential use in Type 1 diabetes mellitus adjunctive therapy (off-label; investigational).

Adults:

• Type 2 Diabetes Mellitus:
• 10 mg orally once daily, with or without food.
• Heart Failure and CKD:
• 10 mg orally once daily.

Dose Adjustments:

• No dose adjustment needed for mild to moderate renal impairment (eGFR ≥ 45 mL/min/1.73 m²).
• Not recommended to initiate treatment if eGFR < 25–30 mL/min/1.73 m² depending on indication; discontinue if eGFR persistently below threshold.
• No dosage adjustment for hepatic impairment; use with caution in severe hepatic impairment.

Pediatrics:

• Safety and efficacy not established in patients under 18 years.

Elderly:

• No specific dose adjustment; monitor renal function and volume status.

Dapagliflozin is a selective inhibitor of sodium-glucose co-transporter 2 (SGLT2) located in the proximal renal tubules. By inhibiting SGLT2, dapagliflozin reduces glucose reabsorption in the kidneys, promoting urinary glucose excretion and thereby lowering plasma glucose levels. This glycosuric effect contributes to improved glycemic control. Additionally, dapagliflozin reduces sodium reabsorption, leading to osmotic diuresis and natriuresis, which contribute to decreased blood pressure, reduced preload and afterload on the heart, and renal protection.

Absorption:

• Rapidly absorbed; peak plasma concentration reached approximately 1 to 2 hours post-dose.
• Absolute bioavailability about 78%.

Distribution:

• Approximately 91% bound to plasma proteins.

Metabolism:

• Primarily metabolized by UDP-glucuronosyltransferase 1A9 (UGT1A9) to inactive metabolite dapagliflozin 3-O-glucuronide.

Elimination:

• Excreted mainly via urine (75%) and feces (21%) as metabolites.
• Elimination half-life approximately 12.9 hours, supporting once-daily dosing.

• Pregnancy:
• No assigned FDA category; limited human data. Animal studies showed adverse effects at high doses. Use only if potential benefits justify potential risks.
• Lactation:
• Unknown if excreted in human milk; caution advised. Breastfeeding is not recommended during treatment.

• Primary Class: Antidiabetic agent
• Subclass: Sodium-glucose co-transporter 2 (SGLT2) inhibitor

• Known hypersensitivity to dapagliflozin or any components.
• Severe renal impairment or end-stage renal disease.
• Type 1 diabetes mellitus (due to risk of diabetic ketoacidosis).
• History of serious hypersensitivity reactions to dapagliflozin.

• Ketoacidosis: Risk of diabetic ketoacidosis including euglycemic ketoacidosis; monitor for symptoms.
• Genital Mycotic Infections: Increased risk due to glycosuria; educate patients on hygiene and early signs.
• Volume Depletion: Due to osmotic diuresis; risk of hypotension and acute kidney injury especially in elderly or those on diuretics.
• Renal Function: Monitor eGFR before and during treatment.
• Bladder Cancer: Rare cases reported; evaluate if patients develop hematuria or urinary symptoms.
• Hypoglycemia: When combined with insulin or insulin secretagogues.

Common:

• Genital fungal infections (e.g., candidiasis)
• Urinary tract infections
• Increased urination
• Nasopharyngitis
• Back pain

Serious/Rare:

• Diabetic ketoacidosis
• Acute kidney injury
• Fournier’s gangrene (necrotizing fasciitis of the perineum)
• Hypersensitivity reactions

• Diuretics: Increased risk of volume depletion and hypotension.
• Insulin and Insulin Secretagogues: Increased risk of hypoglycemia; dose adjustment may be necessary.
• UGT1A9 Inducers (e.g., rifampin): May reduce dapagliflozin plasma concentrations and efficacy.
• UGT1A9 Inhibitors (e.g., probenecid): May increase dapagliflozin levels.

• Updated diabetes management guidelines incorporate SGLT2 inhibitors including dapagliflozin as first-line therapy for patients with T2DM and established cardiovascular disease or CKD.
• Expanded indication for heart failure with reduced ejection fraction and chronic kidney disease irrespective of diabetes status.
• FDA warnings on ketoacidosis and rare necrotizing fasciitis of the perineum added.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Do not freeze.
• Keep out of reach of children.