ONGLYZA

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE ONGLYZA is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1.1) Limitations of use: • Not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. (1.2) 1.1 Monotherapy and Combination Therapy ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [ see Clinical Studies (14) ]. 1.2 Limitations of Use ONGLYZA is not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Dosage and administration 2 DOSAGE AND ADMINISTRATION • Recommended dosage is 2.5 mg or 5 mg orally once daily taken regardless of meals. (2.1) • Patients with an eGFR <45 mL/min/1.73 m2 (moderate or severe renal impairment, or end-stage renal disease): Recommended dosage is 2.5 mg once daily regardless of meals. (2.2) • Assess renal function before starting ONGLYZA and periodically thereafter. (2.2) • Limit the dosage of ONGLYZA to 2.5 mg daily for patients also taking strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (e.g., ketoconazole). (2.3) 2.1 Recommended Dosage The recommended dosage of ONGLYZA is 2.5 mg or 5 mg orally once daily taken regardless of meals. Do not cut, crush, or chew ONGLYZA tablets. If a dose is missed, advise patients not to take an extra dose. Resume treatment with the next dose. 2.2 Dosage in Patients with Renal Impairment Assess renal function prior to initiation of ONGLYZA and then as clinically indicated [see Use in Specific Populations (8.6) ]. The recommended dosage of ONGLYZA in patients with an eGFR greater than or equal to 45 mL/minute/1.73 m 2 is the same as the recommended dosage in patients with normal renal function [ see Dosage and Administration (2.1) ]. The dosage of ONGLYZA is 2.5 mg orally once daily for patients with eGFR <45 mL/min/1.73 m 2 [which includes a subset of moderate or severe renal impairment, or with end-stage renal disease (ESRD) requiring hemodialysis] [ see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ]. ONGLYZA should be administered following hemodialysis. ONGLYZA has not been studied in patients undergoing peritoneal dialysis. 2.3 Dosage Modification with Concomitant Use of Strong CYP3A4/5 Inhibitors The dosage of ONGLYZA is 2.5 mg orally once daily when used concomitantly with strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin) [ see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. Warnings and cautions 5 WARNINGS AND PRECAUTIONS • Pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue ONGLYZA. (5.1) • Heart Failure: Consider the risks and benefits of ONGLYZA in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. (5.2) • Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues: Consider a lower dosage of insulin or insulin secretagogue when used in combination wtih ONGLYZA. (5.3) • Hypersensitivity-Related Events There have been postmarketing reports of serious hypersensitivity reactions such as anaphylaxis, angioedema, and exfoliative skin conditions. If hypersensitivity reactions occur, discontinue ONGLYZA, treat promptly, and monitor until signs and symptoms resolve. (5.4) • Arthralgia: Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue drug if appropriate. (5.5) • Bullous Pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue ONGLYZA. (5.6) 5.1 Pancreatitis There have been postmarketing reports of acute pancreatitis in patients taking ONGLYZA. In a cardiovascular outcomes trial enrolling participants with established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (SAVOR trial), cases of definite acute pancreatitis were confirmed in 17 of 8240 (0.2%) patients receiving ONGLYZA compared to 9 of 8173 (0.1%) receiving placebo. Preexisting risk factors for pancreatitis were identified in 88% (15/17) of those patients receiving ONGLYZA and in 100% (9/9) of those patients receiving placebo. After initiation of ONGLYZA, observe patients for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue ONGLYZA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using ONGLYZA. 5.2 Heart Failure In a cardiovascular outcomes trial enrolling participants with establish