DAPAGLIFLOZIN AND SAXAGLIPTIN HYDROCHLORIDE
Clinical safety rating
safeStrong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.
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.
| 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). |
| Molecular Weight | Dapagliflozin: 408.88 Da; Saxagliptin hydrochloride: 350.87 Da (free base 315.4 Da). Combined product: not applicable. Specified as individual weights. |
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. |
| 1st trimester | Category X: Due to potential for altered glucose metabolism and increased fetal malformations, use is contraindicated. Dapagliflozin is teratogenic in animal studies; saxagliptin shows no major risk but lack of human data. |
| 2nd trimester | Category X: Same risks persist. Alternative therapies should be considered. |
| 3rd trimester | Category X: Risk of neonatal hypoglycemia, volume depletion, and electrolyte imbalances. Avoid use. |
Clinical note
Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.
| FDA category | Animal |
| Placental transfer | Both agents cross the placenta. Dapagliflozin shows significant placental transfer in animal studies (up to 30% fetal exposure). Saxagliptin also crosses but to a lesser extent (~10% of maternal levels). Transfer is likely in humans based on molecular size and passive diffusion. |
| Breastfeeding | Both drugs are excreted in human milk in low amounts. Dapagliflozin may cause galactosemia in infants due to SGLT2 inhibition. Saxagliptin is unlikely to cause adverse effects. However, due to lack of long-term safety data, especially for dapagliflozin, breastfeeding is not recommended during therapy. |
| Lactation Rating | L4 (Possibly Hazardous) for dapagliflozin component; L3 (Moderately Safe) for saxagliptin. Overall rating: L4 due to dapagliflozin. |
| 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. |
| Fetal Monitoring | Monitor renal function (serum creatinine, eGFR) and blood glucose frequently. Fetal ultrasound to assess amniotic fluid volume and renal development. Monitor for hypoglycemia. Assess for signs of pancreatitis. |
| Fertility Effects | No human data on fertility effects. In animal studies, dapagliflozin had no effect on fertility at clinically relevant exposures. Saxagliptin showed no adverse effects on fertility in rats. Theoretical risk of hormonal imbalance due to improved glycemic control. |
■ FDA Black Box Warning
There is no black box warning for this combination product.
| Common Effects | Nasopharyngitis |
| Serious Effects |
Hypersensitivity to dapagliflozin, saxagliptin, or any componentHistory of serious hypersensitivity reaction (e.g., anaphylaxis, angioedema) to any DPP-4 inhibitorModerate to severe renal impairment (eGFR < 45 mL/min/1.73 m²) or dialysisType 1 diabetes mellitusDiabetic ketoacidosisPregnancy (Category X)
| 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 |
| Food/Dietary | No specific food restrictions; alcohol may increase hypoglycemia risk. |
| Clinical Pearls | Monitor renal function before initiation and periodically; contraindicated if eGFR <45 mL/min/1.73 m². Assess volume status due to diuretic effect. Watch for pancreatitis and hypersensitivity. Adjust insulin or sulfonylurea doses to reduce hypoglycemia risk. Discontinue if pancreatitis suspected. T1DM is not an indication. |
| Patient Advice | Take once daily with or without food; swallow tablets whole. · Stay hydrated to prevent dehydration from increased urination. · Genital mycotic infections may occur; report any symptoms. · Severe joint pain possible; advise seeking medical attention. · Do not share insulin pens or needles. · Store medication at room temperature away from moisture and heat. |
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