DAPAGLIFLOZIN AND SAXAGLIPTIN HYDROCHLORIDE

Clinical safety rating: safe

Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.

How it works

Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that blocks glucose reabsorption in the proximal renal tubule, reducing plasma glucose independent of insulin secretion. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that prolongs incretin hormone activity, increasing insulin release and decreasing glucagon secretion.

What the body does with it

Metabolism	Dapagliflozin is primarily metabolized via glucuronidation by UGT1A9; saxagliptin is metabolized via CYP3A4/5 to an active metabolite.
Excretion	Dapagliflozin: ~75% renal excretion (21% unchanged, 50% as major metabolite 3-O-glucuronide), ~21% fecal. Saxagliptin: ~75% renal excretion (12% unchanged, 22% as major metabolite 5-hydroxy saxagliptin, 41% as other metabolites), ~22% fecal.
Half-life	Dapagliflozin: Terminal half-life ~12.9 hours (supports once-daily dosing). Saxagliptin: Terminal half-life ~2.5 hours, but active metabolite 5-hydroxy saxagliptin has half-life ~3.1 hours (supports once-daily dosing due to prolonged DPP-4 inhibition).
Protein binding	Dapagliflozin: ~91% bound primarily to albumin. Saxagliptin: Negligible (<10% bound).
Volume of Distribution	Dapagliflozin: Vd ~118 L (1.5 L/kg based on 70 kg, indicating extensive extravascular distribution). Saxagliptin: Vd ~71 L (1.0 L/kg based on 70 kg, indicating distribution into tissues).
Bioavailability	Dapagliflozin: Oral bioavailability ~78% (high, influenced by food). Saxagliptin: Oral bioavailability ~75% (high, not significantly affected by food).
Onset of Action	Dapagliflozin: Onset within 1-2 hours post-dose (increased urinary glucose excretion). Saxagliptin: Onset within 1 hour (DPP-4 inhibition). Oral administration.
Duration of Action	Dapagliflozin: Duration ~24 hours (supports once-daily dosing). Saxagliptin: DPP-4 inhibition >80% at 24 hours post-dose (once-daily dosing).

Classification & Brands

Dosing & administration

Oral: 1 tablet (dapagliflozin 5 mg / saxagliptin 5 mg) once daily, taken with or without food, in combination with metformin or other glucose-lowering agents.

Dosage form	TABLET
Renal impairment	eGFR ≥45 mL/min/1.73 m²: No dose adjustment. eGFR 30–44 mL/min/1.73 m²: Not recommended due to limited data for saxagliptin. eGFR <30 mL/min/1.73 m²: Contraindicated due to dapagliflozin; do not initiate, discontinue if eGFR falls below 30.
Liver impairment	Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Not recommended for saxagliptin (limited data) and caution for dapagliflozin. Child-Pugh Class C: Contraindicated or not recommended.
Pediatric use	Not established. Safety and efficacy in pediatric patients (<18 years) have not been studied.
Geriatric use	No specific dose adjustment; monitor renal function (e.g., eGFR) and volume status due to age-related decrease in renal function and increased risk of hypotension, dehydration, and acute kidney injury.

Use during pregnancy

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

Clinical note

Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.

FDA category	Animal
Breastfeeding	No data on excretion in human milk. Dapagliflozin is present in rat milk; saxagliptin is excreted in rat milk. M/P ratio unknown. Caution advised due to potential for adverse effects in nursing infant.
Teratogenic Risk	Dapagliflozin is contraindicated in the second and third trimesters due to risk of fetal renal toxicity. Saxagliptin has limited human data; animal studies show no major malformations but potential for delayed ossification at high doses. First trimester: Use only if clearly needed; no well-controlled human studies. Second and third trimesters: Dapagliflozin not recommended; avoid.

Warnings & precautions

■ FDA Black Box Warning

There is no black box warning for this combination product.

Side Effect Profile

Common Effects	Nasopharyngitis
Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to dapagliflozin, saxagliptin, or any component","Severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease","Diabetic ketoacidosis","Type 1 diabetes mellitus"]

Clinical Precautions

Precautions

["Pancreatitis","Heart failure","Hypoglycemia when used with insulin or insulin secretagogues","Acute kidney injury","Genital mycotic infections","Urinary tract infections","Hypotension","Ketoacidosis","Necrotizing fasciitis of the perineum (Fournier’s gangrene)","Arthralgia","Bullous pemphigoid"]

Clinical Tips & Counseling

Drug interactions

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DAPAGLIFLOZIN AND SAXAGLIPTIN HYDROCHLORIDE

Clinical safety rating: safe

Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.

How it works

What the body does with it

Metabolism	Dapagliflozin is primarily metabolized via glucuronidation by UGT1A9; saxagliptin is metabolized via CYP3A4/5 to an active metabolite.
Excretion	Dapagliflozin: ~75% renal excretion (21% unchanged, 50% as major metabolite 3-O-glucuronide), ~21% fecal. Saxagliptin: ~75% renal excretion (12% unchanged, 22% as major metabolite 5-hydroxy saxagliptin, 41% as other metabolites), ~22% fecal.
Half-life	Dapagliflozin: Terminal half-life ~12.9 hours (supports once-daily dosing). Saxagliptin: Terminal half-life ~2.5 hours, but active metabolite 5-hydroxy saxagliptin has half-life ~3.1 hours (supports once-daily dosing due to prolonged DPP-4 inhibition).
Protein binding	Dapagliflozin: ~91% bound primarily to albumin. Saxagliptin: Negligible (<10% bound).
Volume of Distribution	Dapagliflozin: Vd ~118 L (1.5 L/kg based on 70 kg, indicating extensive extravascular distribution). Saxagliptin: Vd ~71 L (1.0 L/kg based on 70 kg, indicating distribution into tissues).
Bioavailability	Dapagliflozin: Oral bioavailability ~78% (high, influenced by food). Saxagliptin: Oral bioavailability ~75% (high, not significantly affected by food).
Onset of Action	Dapagliflozin: Onset within 1-2 hours post-dose (increased urinary glucose excretion). Saxagliptin: Onset within 1 hour (DPP-4 inhibition). Oral administration.
Duration of Action	Dapagliflozin: Duration ~24 hours (supports once-daily dosing). Saxagliptin: DPP-4 inhibition >80% at 24 hours post-dose (once-daily dosing).

Classification & Brands

Dosing & administration

Oral: 1 tablet (dapagliflozin 5 mg / saxagliptin 5 mg) once daily, taken with or without food, in combination with metformin or other glucose-lowering agents.

Dosage form	TABLET
Renal impairment	eGFR ≥45 mL/min/1.73 m²: No dose adjustment. eGFR 30–44 mL/min/1.73 m²: Not recommended due to limited data for saxagliptin. eGFR <30 mL/min/1.73 m²: Contraindicated due to dapagliflozin; do not initiate, discontinue if eGFR falls below 30.
Liver impairment	Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Not recommended for saxagliptin (limited data) and caution for dapagliflozin. Child-Pugh Class C: Contraindicated or not recommended.
Pediatric use	Not established. Safety and efficacy in pediatric patients (<18 years) have not been studied.
Geriatric use	No specific dose adjustment; monitor renal function (e.g., eGFR) and volume status due to age-related decrease in renal function and increased risk of hypotension, dehydration, and acute kidney injury.

Use during pregnancy

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

Clinical note

Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.

FDA category	Animal
Breastfeeding	No data on excretion in human milk. Dapagliflozin is present in rat milk; saxagliptin is excreted in rat milk. M/P ratio unknown. Caution advised due to potential for adverse effects in nursing infant.
Teratogenic Risk	Dapagliflozin is contraindicated in the second and third trimesters due to risk of fetal renal toxicity. Saxagliptin has limited human data; animal studies show no major malformations but potential for delayed ossification at high doses. First trimester: Use only if clearly needed; no well-controlled human studies. Second and third trimesters: Dapagliflozin not recommended; avoid.

Warnings & precautions

■ FDA Black Box Warning

There is no black box warning for this combination product.

Side Effect Profile

Common Effects	Nasopharyngitis
Serious Effects