Trade Names:Onglyza- Tablets 2.5 mg- Tablets 5 mg
Competitive dipeptidyl peptidase-4 (DPP4) inhibitor that slows the inactivation of incretin hormones, thereby reducing fasting and postprandial glucose concentrations.
Following a 5 mg oral dose, mean AUC was 78 ng•h/mL for saxagliptin and 214 ng•h/mL for its active metabolite. C max and T max were 24 ng/mL and 2 h for saxagliptin and 47 ng/mL and 4 h for the active metabolite, respectively. Administration with a high-fat meal increased T max by 20 min and AUC by 27%.
Protein binding is negligible.
Metabolism by CYP3A4/5. The major metabolite is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.
Terminal half-life is 2.5 h for saxagliptin and 3.1 h for its active metabolite. Average renal Cl is approximately 230 mL/min. Approximately 22% is excreted in feces with 24% and 36% excreted in urine as saxagliptin and its active metabolite, respectively.
AUC was up to 2.1- and 4.5- fold higher in patients with moderate or severe renal impairment. Dosage adjustment required.Hepatic Function Impairment
C max and AUC were 8% and 77% higher, respectively, in patients with hepatic impairment (Child-Pugh class A, B, and C). The corresponding C max and AUC of the active metabolite were 59% and 33% lower, respectively. No dosage adjustment required.Elderly
Elderly patients had 23% and 59% higher C max and AUC values, respectively, compared with younger subjects. Dosage adjustment based on age alone not required.Gender
Women had approximately 25% higher exposure values for the active metabolite compared with men.Race
No significant differences in pharmacokinetics of saxagliptin were seen among different races.
Adjunct to diet and exercise in type 2 diabetes mellitus.
PO 2.5 or 5 mg once daily.Renal Function ImpairmentAdults
POModerate to severe renal impairment (CrCl 50 mL/min or less)
2.5 mg once daily.ESRD requiring hemodialysis
2.5 mg once daily after hemodialysis.Strong CYP3A4/5 Inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)Adults
PO 2.5 mg once daily.
Store at 59° to 86°F.
Saxagliptin plasma concentrations may be reduced slightly.CYP3A4/5 inducers (eg, rifampin)
Saxagliptin C max and AUC may be reduced; however, dosage adjustment is not recommended. Monitor the clinical response of the patient. If an interaction is suspected, adjust treatment as needed.Diltiazem, pioglitazone
Plasma concentrations of these agents may be elevated slightly by saxagliptin.Famotidine, simvastatin
Saxagliptin plasma concentrations may be elevated slightly.Glyburide
Glyburide and saxagliptin plasma concentrations may be elevated slightly.Ketoconazole
Ketoconazole plasma concentrations may be decreased slightly by saxagliptin.Moderate CYP3A4/5 inhibitors (eg, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil)
Saxagliptin exposure may be increased; however, dosage adjustment is not recommended. Monitor the clinical response of the patient. If a drug interaction is suspected, adjust the saxagliptin dose as needed.Strong CYP3A4/5 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)
Saxagliptin C max and AUC may be increased, increasing the pharmacologic effects and risk of adverse reactions. The dose of saxagliptin should be limited to 2.5 mg when administered with a strong CYP3A4/5 inhibitor. Monitor the clinical response of the patient.
None well documented.
Abdominal pain, gastroenteritis, vomiting (2%).
Decreased absolute lymphocyte count (2%); lymphopenia (1%).
Hypoglycemia (6%); peripheral edema (4%).
Upper respiratory tract infection (8%).
Hypersensitivity reactions (2%).
Assess renal function prior to initiation and periodically thereafter. Periodically measure blood glucose and A 1c . Measure lymphocyte count when clinically indicated (eg, unusual or prolonged infection).
Category B .
Safety and efficacy not established.
Take care in dose selection based on renal function.
Dosage adjustments are required in patients with moderate or severe renal impairment.
Do not use in these settings, as it would not be effective.
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