DAPAGLIFLOZIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DAPAGLIFLOZIN (DAPAGLIFLOZIN).

How it works

Selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubule, reducing renal glucose reabsorption and lowering blood glucose.

What the body does with it

Metabolism	Primarily metabolized via UGT1A9 to an inactive glucuronide conjugate; minor metabolism via CYP2C8 and CYP2C9.
Excretion	Primarily renal and fecal: ~75% of dose excreted in urine (as unchanged dapagliflozin and glucuronide conjugates), ~21% in feces. Biliary elimination is negligible.
Half-life	Terminal elimination half-life is approximately 12.9 hours (range 10-16 hours) for dapagliflozin, supporting once-daily dosing. At steady state, effective half-life is ~23 hours due to metabolite.
Protein binding	Approximately 91% bound to plasma proteins (primarily albumin), independent of concentration.
Volume of Distribution	Volume of distribution is approximately 118 L (about 1.7 L/kg based on 70 kg). Indicates extensive extravascular distribution.
Bioavailability	Oral bioavailability is approximately 78% (range 70-90%) after oral administration. Food has no clinically significant effect on AUC; peak concentration may be delayed.
Onset of Action	Oral: Onset of SGLT2 inhibition occurs within 1 hour; significant glucosuria observed within 3-4 hours after a single dose.
Duration of Action	Oral: Duration of action is >24 hours for glucosuria reduction, allowing once-daily dosing. Maximal effect on HbA1c reduction seen after 4-8 weeks of therapy.

Classification & Brands

Dosing & administration

10 mg orally once daily.

Dosage form	TABLET
Renal impairment	eGFR >=45 mL/min/1.73 m2: no adjustment. eGFR 30-44 mL/min/1.73 m2: not recommended for glycemic control; can be used for CKD with albuminuria at 10 mg daily. eGFR <30 mL/min/1.73 m2: contraindicated for glycemic control; for CKD with albuminuria, initiate only if eGFR >=25 mL/min/1.73 m2 and continue until dialysis or transplant.
Liver impairment	Child-Pugh Class A (mild): no adjustment. Child-Pugh Class B (moderate) or C (severe): not recommended due to limited data.
Pediatric use	Not approved for patients under 18 years; safety and efficacy not established.
Geriatric use	No dose adjustment required based on age alone. Assess renal function at baseline and periodically due to age-related decline in eGFR; monitor for volume depletion, hypotension, and electrolyte disturbances.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DAPAGLIFLOZIN (DAPAGLIFLOZIN).

Breastfeeding

Dapagliflozin is excreted in human milk in low amounts, with an estimated milk-to-plasma ratio (M/P) of approximately 0.14-0.2 based on animal data. Breastfeeding is not recommended due to potential adverse effects on neonatal renal development and risk of hypoglycemia. Alternative agents are preferred during lactation.

Teratogenic Risk

Dapagliflozin is contraindicated in the second and third trimesters due to an increased risk of fetal renal toxicity and impaired development based on animal studies. First-trimester exposure is not recommended due to potential effects on renal function and ossification. Human data are limited, but the drug's mechanism (SGLT2 inhibition) suggests risks of fetal oligohydramnios and renal anomalies.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to dapagliflozin","Severe renal impairment (eGFR < 30 mL/min/1.73 m²) or end-stage renal disease on dialysis","Use in type 1 diabetes (not indicated)"]

Clinical Precautions

Precautions

["Risk of volume depletion, hypotension, and renal impairment in patients with low intravascular volume or on diuretics","Ketoacidosis (euglycemic ketoacidosis reported), assess for ketones if indicated","Acute kidney injury; monitor renal function","Necrotizing fasciitis of the perineum (Fournier gangrene) reported","Genital mycotic infections (e.g., balanitis, vulvovaginitis)","Lower limb amputation (increased risk with history of amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers); monitor for signs of infection"]

Clinical Tips & Counseling

Drug interactions

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DAPAGLIFLOZIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DAPAGLIFLOZIN (DAPAGLIFLOZIN).

How it works

Selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubule, reducing renal glucose reabsorption and lowering blood glucose.

What the body does with it

Metabolism	Primarily metabolized via UGT1A9 to an inactive glucuronide conjugate; minor metabolism via CYP2C8 and CYP2C9.
Excretion	Primarily renal and fecal: ~75% of dose excreted in urine (as unchanged dapagliflozin and glucuronide conjugates), ~21% in feces. Biliary elimination is negligible.
Half-life	Terminal elimination half-life is approximately 12.9 hours (range 10-16 hours) for dapagliflozin, supporting once-daily dosing. At steady state, effective half-life is ~23 hours due to metabolite.
Protein binding	Approximately 91% bound to plasma proteins (primarily albumin), independent of concentration.
Volume of Distribution	Volume of distribution is approximately 118 L (about 1.7 L/kg based on 70 kg). Indicates extensive extravascular distribution.
Bioavailability	Oral bioavailability is approximately 78% (range 70-90%) after oral administration. Food has no clinically significant effect on AUC; peak concentration may be delayed.
Onset of Action	Oral: Onset of SGLT2 inhibition occurs within 1 hour; significant glucosuria observed within 3-4 hours after a single dose.
Duration of Action	Oral: Duration of action is >24 hours for glucosuria reduction, allowing once-daily dosing. Maximal effect on HbA1c reduction seen after 4-8 weeks of therapy.

Classification & Brands

Dosing & administration

10 mg orally once daily.

Dosage form	TABLET
Renal impairment	eGFR >=45 mL/min/1.73 m2: no adjustment. eGFR 30-44 mL/min/1.73 m2: not recommended for glycemic control; can be used for CKD with albuminuria at 10 mg daily. eGFR <30 mL/min/1.73 m2: contraindicated for glycemic control; for CKD with albuminuria, initiate only if eGFR >=25 mL/min/1.73 m2 and continue until dialysis or transplant.
Liver impairment	Child-Pugh Class A (mild): no adjustment. Child-Pugh Class B (moderate) or C (severe): not recommended due to limited data.
Pediatric use	Not approved for patients under 18 years; safety and efficacy not established.
Geriatric use	No dose adjustment required based on age alone. Assess renal function at baseline and periodically due to age-related decline in eGFR; monitor for volume depletion, hypotension, and electrolyte disturbances.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DAPAGLIFLOZIN (DAPAGLIFLOZIN).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to dapagliflozin","Severe renal impairment (eGFR < 30 mL/min/1.73 m²) or end-stage renal disease on dialysis","Use in type 1 diabetes (not indicated)"]