Transcript farxiga
Farxiga™ - Dapagliflozin Manufacturer: Bristol-Meyer Squibb FDA Approval Date: January 8, 2014 Farxiga™ - Dapagliflozin Clinical Application • Indications: • Adjunct to diet and exercise to improve glycemic control in Type 2 Diabetes • Place in therapy: • Alternative to existing add-on therapies by improving glycemic control without associated weight gain or hypoglycemic risk Farxiga™ - Dapagliflozin Clinical Application • Contraindications: • History of serous hypersensitivity reaction • Severe renal impairment, ESRD, dialysis • Warnings and Precautions • May cause symptomatic hypotension • Impairment in renal function may occur • Risk of hypoglycemia when used with insulin or insulin secretagogues • Increased risk of genital mycotic infections • May cause increased LDL-C elevation Farxiga™ - Dapagliflozin Clinical Application • Pregnancy: • Category C • Adverse events observed in animal studies • Lactation: • Excretion in breast milk unknown; use is not recommended Farxiga™ - Dapagliflozin Drug Facts • Pharmacology: • Selectively inhibits sodium-glucose cotransporter 2 (SGLT-2) in the proximal renal tubules, reduces absorption of filtered glucose from the tubular lumen, increases urinary excretion of glucose Farxiga™ - Dapagliflozin Drug Facts Pharmacokinetics A Tmax 2 hrs; absorption not affected by food D 91% protein bound M Extensive, primarily mediated by UGT1A9; CYPmediated (minor) E Primarily via urine (75%) and feces (21%) Farxiga™ - Dapagliflozin Drug Interactions • Drug Interactions – Object Drugs: • Duloxetine • Hypoglycemic agents Farxiga™ - Dapagliflozin Drug Interactions • Drug Interactions – Precipitant Drugs: • • • • • • Corticosteroids Loop diuretics MAO Inhibitors Salicylates SSRIs Thiazide diuretics Farxiga™ - Dapagliflozin Adverse Effects Female genital mycotic infections (6.9%) [1.5%] UTI (4.3%) [3.7%] Male genital mycotic infections (2.7%)[0.3%] Back pain (4.2%) [3.2%] Nasopharyngitis (6.3%) [6.2%] Dyslipidemia (2.5%) [1.5%] Increased urination (3.8%) [1.7%] Dysuria (2.1%) [0.7%] Pain in extremity (1.7%) [1.4%] Constipation (1.9%) [1.5%] Farxiga™ - Dapagliflozin Monitoring Parameters • Efficacy Monitoring: • Blood glucose, Hgb A1c • Toxicity Monitoring: • Renal function, LDL-C Farxiga™ - Dapagliflozin Prescription Information • Dosing: 5-10 mg once daily • Cost: $347 for 30-day supply • Source: Medi-Span (via Lexi-comp online) • Accessed 3/13/2014 Farxiga™ - Dapagliflozin Literature Review • A multicenter, double-blind, randomized, active-controlled, noninferiority, phase 3 study • [Dapagliflozin + metformin] vs. [Glipizide + metformin] • Primary endpoint • Absolute change in HbA1c from baseline to week 52 Nauck, et al. Diabetes Care 2011; 34:2015-22. Farxiga™ - Dapagliflozin Literature Review • Secondary Endpoints • Absolute change in total body weight (TBW) • Proportion of patients reporting at least one episode of hypoglycemia • Proportion of patients achieving a TBW decrease ≥5% Nauck, et al. Diabetes Care 2011; 34:2015-22. Farxiga™ - Dapagliflozin Literature Review • • • • N = 801 Age ≥ 18 yrs (mean age 59) 6.5% < HbA1c ≤ 10% (mean 7.7%) 57% receiving metformin monotherapy ≥ 1500 mg/day • Median metformin dose at randomization 2000 mg/day Nauck, et al. Diabetes Care 2011; 34:2015-22. Farxiga™ - Dapagliflozin Literature Review Nauck, et al. Diabetes Care 2011; 34:2015-22. Farxiga™ - Dapagliflozin Literature Review Nauck, et al. Diabetes Care 2011; 34:2015-22. Farxiga™ - Dapagliflozin Literature Review Nauck, et al. Diabetes Care 2011; 34:2015-22. Farxiga™ - Dapagliflozin Literature Review • Conclusions • Comparable long-term efficacy of dapagliflozin with glipizide with fewer hypoglycemic episodes along with sustained weight loss • Dapagliflozin is a potential valuable alternative to sulfonylureas as add-on therapy when metformin monotherapy fails to maintain adequate glycemic control Nauck, et al. Diabetes Care 2011; 34:2015-22. Farxiga™ - Dapagliflozin Summary • Farxiga, dapagliflozin, is the second in class agent that selectively inhibits SGLT2 receptor which modulates reabsorption of glucose in the kidney, resulting in excretion of glucose in the urine • Indicated as an adjunct to diet and exercise to improve glycemic control in adults with Type 2 Diabetes • Initially dosed 5 mg once daily in the morning • Most common side effects include genital infections, urinary tract infections, and nasopharyngitis • Alternative to existing add-on therapies by improving glycemic control without associated weight gain or hypoglycemic risk Farxiga™ - Dapagliflozin References 1. 2. 3. 4. 5. http://www.farxiga.com Farxiga package insert. Bristol-Meyers Squibb. January 2014. Farxiga. Lexicomp Drug Information. Accessed through UpToDate. Accessed on March 13, 2014. Nauck MA, et al. Dapagliflozin versus glipizide as add-on therapy in patients with Type 2 Diabetes who have inadequate glycemic control with metformin. Diabetes Care 2011; 34:2015-2022. Bailey CJ, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, double-blind, placebo-controlled trial. Lancet 2010; 375:2223-33.