Dosing and uses of Onglyza (saxagliptin)
Adult dosage forms and strengths
tablet
- 2.5mg
- 5mg
Diabetes Mellitus Type 2
2.5-5 mg PO qDay
Dosage modifications
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
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
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Onglyza (saxagliptin) adverse (side) effects
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
Postmarketing reports
Severe and disabling arthralgia
Warnings
Contraindications
Documented hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions)
Cautions
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
Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
Congestive heart failure (CHF) risks
- In the SAVOR-TIMI 53 trial (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) 16,492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo
- A higher incidence of hospitalization for CHF was observed in patients treated with saxagliptin compared with those treated with placebo (3.5% vs 2.8%; P=0.007); this increased risk was highest among patients with elevated levels of natriuretic peptides, previous heart failure, or chronic kidney disease
- Circulation. 2014 Oct 28;130(18):1579-88
- Observe patients for signs and symptoms of heart failure during therapy; inform patients of characteristic symptoms of heart failure and advise patients to immediately report them; if heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of therapy
Pregnancy and lactation
Pregnancy category: B
Lactation: Not known whether distributed in breast milk; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Onglyza (saxagliptin)
Mechanism of action
Dipeptidyl peptidase IV (DPP-4) inhibition that results in increased incretin hormones and enhanced glycemic controL
Absorption
Peak plasma time: 2hr (saxagliptin); 4 hr (5-hyroxy saxagliptin)
Distribution
Vd: Negligible
Metabolism
Hepatic by CYP450 3A4/5 to active metabolite (50% potency of parent compound)
Elimination
Half-life (elimination): 2.5 hr (saxagliptin); 3.1 hr (5-hydroxy saxagliptin)
Renal clearance: 7.2 L/hr
Excretion: Urine (75%); feces (22%)
Administration
Instructions
May administer with or without food
