Saxagliptin

Trade Names:Onglyza- Tablets 2.5 mg- Tablets 5 mg

Pharmacology

Competitive dipeptidyl peptidase-4 (DPP4) inhibitor that slows the inactivation of incretin hormones, thereby reducing fasting and postprandial glucose concentrations.

Pharmacokinetics

Absorption

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%.

Distribution

Protein binding is negligible.

Metabolism

Metabolism by CYP3A4/5. The major metabolite is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.

Elimination

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.

Special Populations

AUC was up to 2.1- and 4.5- fold higher in patients with moderate or severe renal impairment. Dosage adjustment required.

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 patients had 23% and 59% higher C _max and AUC values, respectively, compared with younger subjects. Dosage adjustment based on age alone not required.

Women had approximately 25% higher exposure values for the active metabolite compared with men.

No significant differences in pharmacokinetics of saxagliptin were seen among different races.

Indications and Usage

Adjunct to diet and exercise in type 2 diabetes mellitus.

Contraindications

Standard considerations

Dosage and Administration

PO 2.5 or 5 mg once daily.

PO

2.5 mg once daily.

2.5 mg once daily after hemodialysis.

PO 2.5 mg once daily.

General Advice

• May be taken with or without food.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Saxagliptin plasma concentrations may be reduced slightly.

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.

Plasma concentrations of these agents may be elevated slightly by saxagliptin.

Saxagliptin plasma concentrations may be elevated slightly.

Glyburide and saxagliptin plasma concentrations may be elevated slightly.

Ketoconazole plasma concentrations may be decreased slightly by saxagliptin.

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.

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.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (7%).

EENT

Sinusitis (3%).

GI

Abdominal pain, gastroenteritis, vomiting (2%).

Genitourinary

UTI (7%).

Hematologic

Decreased absolute lymphocyte count (2%); lymphopenia (1%).

Metabolic-Nutritional

Hypoglycemia (6%); peripheral edema (4%).

Respiratory

Upper respiratory tract infection (8%).

Miscellaneous

Hypersensitivity reactions (2%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Take care in dose selection based on renal function.

Renal Function

Dosage adjustments are required in patients with moderate or severe renal impairment.

Type 1 diabetes mellitus/diabetic ketoacidosis

Do not use in these settings, as it would not be effective.

Overdosage

Symptoms

None reported.

Patient Information

• Advise patient to read the patient information leaflet before using product the first time and with each refill.
• Educate patient, family, or caregiver regarding type 2 diabetes and its management.
• Instruct patient that this drug is not a substitute for diet and exercise and to follow prescribed regimen.
• Emphasize the importance of regular daily blood glucose monitoring and periodic glycosylated hemoglobin tests.
• Review symptoms and management of hypoglycemia and hyperglycemia.
• Instruct patient to report hypoglycemic or hyperglycemic episodes to a health care provider.
• Advise patient that during periods of stress (eg, fever, trauma, infection, surgery), medication requirements may change and to seek medical advice promptly.
• Inform patients of the potential need to adjust their dose based on changes in renal function tests over time.

Copyright © 2009 Wolters Kluwer Health.