Saxagliptin

Indications

Saxagliptin is used for: Type 2 diabetes

Adult Dose

Oral Type 2 diabetes mellitus Adult: 2.5 or 5 mg once daily. Combination therapy: May need to reduce dosage of sulfonylurea or other insulin secretagogues when administered in combination Coadministration with strong CYP450 3A4/5 inhibitors: Not to exceed 2.5 mg PO qDay Elderly: No dosage adjustment. Hepatic Impairment No dosage adjustment.

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment CrCl >50 mL/min: No dose adjustment required CrCl <50 mL/min: Not to exceed 2.5 mg PO qDay ESRD requiring hemodialysis: Not to exceed 2.5 mg PO qDay administered postdialysis ESRD requiring peritoneal dialysis: Not studied

Administration

May be taken with or without food.

Contra Indications

Documented hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions)

Precautions

Renal impairment Decrease dose with strong CYP450 3A4/5 inhibitors Coadministration with thiazolidinediones (eg, rosiglitazone, pioglitazone) increases risk for peripheral edema Pancreatitis reported with saxagliptin; monitor for signs and symptoms and discontinue if pancreatitis suspected Serious hypersensitivity reactions with saxagliptin reported (typically within the first 3 months of therapy) History of angioedema Coadministration with a sulfonylurea or with insulin may increase hypoglycemia; monitor closely and adjust sulfonylurea and/or insulin dose accordingly Congestive heart failure (CHF) risks. Observe patients for signs and symptoms of heart failure during therapy; Lactation: Not known whether distributed in breast milk; caution advised

Pregnancy-Lactation

Pregnancy Limited available data in pregnant women are not sufficient to determine drug-associated risk for major birth defects and miscarriage; published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk No adverse developmental effects independent of maternal toxicity observed when saxagliptin and metformin were administered separately or in combination to pregnant rats and rabbits during period of organogenesis Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. also increases fetal risk for major malformations and macrosomia related morbidity Lactation There is no information regarding presence of metformin or alogliptin in human milk, effects on breastfed infant, or effects on milk production; limited published studies report that metformin is present in human milk; however, there is insufficient information to determine effects of metformin on breastfed infant and no available information on effects of metformin on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Interactions

Strong CYP3A4/5 inhibitors (eg ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir & telithromycin).

Adverse Effects

Side effects of Saxagliptin : 1-10% (selected) Urinary tract infection (7%), Headache (7%), Hypersensitivity-related events (<4%; eg, urticaria, facial edema), Peripheral edema (<4%; increased incidence when coadministered with thiazolidinediones), Upper respiratory tract infection (3%), Gastroenteritis (2%), Hypoglycemia (1.6%) Frequency Not Defined Increased creatinine phosphokinase, Increased creatinine, Idiopathic thrombocytopenic purpura rash

Mechanism of Action

Dipeptidyl peptidase IV (DPP-4) inhibition that results in increased incretin hormones and enhanced glycemic control.