ONGLYZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ONGLYZA (ONGLYZA).
Selective inhibitor of dipeptidyl peptidase-4 (DPP-4), increasing incretin hormones (GLP-1, GIP) to enhance glucose-dependent insulin secretion and suppress glucagon release.
| Metabolism | Primarily hepatic via CYP3A4 and CYP3A5 isoenzymes; also undergoes hydrolysis by peptidases. |
| Excretion | Approximately 75% of the administered dose is excreted in urine, with about 21% recovered as parent drug, and the remainder as metabolites. Fecal excretion accounts for about 22% of the dose, primarily as parent drug and metabolites. |
| Half-life | Terminal elimination half-life is approximately 12.4 hours for saxagliptin. The half-life of its active metabolite is about 2.1 hours. The pharmacologically relevant half-life supports once-daily dosing. |
| Protein binding | Saxagliptin is approximately 33% bound to plasma proteins, independent of drug concentration. Its active metabolite is approximately 32% bound. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 1.5 L/kg, suggesting distribution into tissues beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 75% for saxagliptin, with a high fraction absorbed and moderate first-pass metabolism to its active metabolite. |
| Onset of Action | Oral administration: Inhibition of DPP-4 activity is observed within 30 minutes, with near-maximal inhibition achieved by 2 hours post-dose. |
| Duration of Action | Duration of DPP-4 inhibition extends beyond 24 hours, allowing for once-daily dosing. Clinically, the effect on glycemic control is maintained with continued daily administration. |
| Action Class | DPP-4 inhibitors |
| Brand Substitutes | Zaglivia 5mg Tablet, Zaxaglit 5mg Tablet, Riax 5mg Tablet, Saglipol 5 Tablet |
2.5 mg or 5 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | eGFR 45-89 mL/min: no adjustment; eGFR 30-44 mL/min: 2.5 mg once daily; eGFR <30 mL/min or dialysis: not recommended |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B or C: not recommended |
| Pediatric use | Not indicated in pediatric patients under 18 years |
| Geriatric use | No specific dose adjustment based on age; monitor renal function |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ONGLYZA (ONGLYZA).
| Breastfeeding | Saxagliptin is excreted in rat milk at concentrations similar to maternal plasma; no human data. M/P ratio is unknown. Breastfeeding is not recommended due to potential for adverse effects in the nursing infant. |
| Teratogenic Risk | Teratogenic risk profile for ONGLYZA (saxagliptin): Based on animal studies and limited human data, there is no evidence of teratogenicity in the first trimester. However, due to insufficient human data, it is classified as FDA Pregnancy Category B. Risks in second and third trimesters are not well-defined; potential for fetal hyperinsulinemia and hypoglycemia if maternal glucose control is poor. Avoid use unless clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Type 1 diabetes","Diabetic ketoacidosis","History of serious hypersensitivity reaction to saxagliptin"]
| Precautions | ["Pancreatitis (acute and hemorrhagic)","Hypoglycemia when used with sulfonylurea or insulin","Hypersensitivity reactions (angioedema, anaphylaxis)","Bullous pemphigoid","Heart failure risk (in patients with CV disease or risk factors)"] |
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| Fetal Monitoring | Monitor maternal blood glucose levels regularly. Assess for signs of hypoglycemia in the mother. In the fetus, no specific monitoring is required, but standard antenatal monitoring for women with diabetes is recommended. |
| Fertility Effects | No known adverse effects on fertility. Animal studies did not show impairment of fertility at doses up to 40-times human exposure. |