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Daniel Hussar, Phd, New Drug Update

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Daniel Hussar, Phd, New Drug Update New Drug Update 2014* *Presentation by Daniel A. Hussar, Ph.D. Remington Professor of Pharmacy Philadelphia College of Pharmacy University of the Sciences in Philadelphia Objectives: After attending this program, the participant will be able to: 1. Identify the indications and routes of administration of the new therapeutic agents. 2. Identify the important pharmacokinetic properties and the unique characteristics of the new drugs. 3. Identify the most important adverse events and precautions of the new drugs. 4. Compare the new drugs to the older therapeutic agents to which they are most similar in activity. 5. Identify information regarding the new drugs that should be communicated to patients. New Drug Comparison Rating (NDCR) system 5 = important advance 4 = significant advantage(s) (e.g., with respect to use/effectiveness, safety, administration) 3 = no or minor advantage(s)/disadvantage(s) 2 = significant disadvantage(s) (e.g., with respect to use/effectiveness, safety, administration) 1 = important disadvantage(s) Additional information The Pharmacist Activist monthly newsletter: www.pharmacistactivist.com Dapagliflozin propanediol (Farxiga – Bristol-Myers Squibb; AstraZeneca) Antidiabetic Agent 2014 New Drug Comparison Rating (NDCR) = Indication: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Comparable drug: Canagliflozin (Invokana) Advantages: --May be less likely to cause hypersensitivity reactions and hyperkalemia --May be less likely to interact with other medications --May be used in patients with severe hepatic impairment, whereas canagliflozin has not been studied in patients with severe hepatic impairment and use is not recommended Disadvantages: --Bladder cancer has been infrequently reported in clinical studies and should not be used in patients with active bladder cancer --Recommendations for use in patients with impaired renal function are more restrictive (e.g., treatment should not be initiated in patients with an estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73 m2, whereas treatment with canagliflozin should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m2) Most important risks/adverse events: Renal function impairment (contraindicated in patients with severe renal impairment; renal function should be monitored during therapy); hypersensitivity reactions (contraindicated in patients with a history of a serious hypersensitivity reaction); hypotension (risk is increased in patients with impaired renal function or low systolic blood pressure, the elderly, and in patients treated with a diuretic); hypoglycemia (when used concomitantly with insulin or an insulin secretagogue [e.g., a sulfonylurea]); bladder cancer (reported infrequently in clinical studies but at a higher rate that in patients treated with comparator antidiabetic agents or placebo; should not be used in patients with active bladder cancer) Most common adverse events (and the incidence in patients treated with a dosage of 10 mg daily): Female genital mycotic infections (7%; e.g., vulvovaginal candidiasis), nasopharyngitis (6%), urinary tract infections (4%), increased urination (4%), back pain (4%), male genital mycotic infections (3%; e.g., balanitis), nausea (3%), dyslipidemia (3%; e.g., increased LDL-C) Usual dosage: Initially, 5 mg once a day in the morning; in patients who tolerate treatment and require additional glycemic control, dosage may be increased to 10 mg once a day in the morning; treatment should not be initiated in patients with an eGFR less than 60 mL/min/1.73 m2, and treatment should be discontinued if the eGFR is persistently below this value Products: Film-coated tablets – 5 mg, 10 mg Comments: Sodium-glucose cotransporter 2 (SGLT2) is expressed in the proximal renal tubules and is responsible for the reabsorption of the majority of glucose filtered by the kidney, Dapagliflozin is the second SGLT2 inhibitor, joining canagliflozin, and these agents reduce the reabsorption of filtered glucose, thereby increasing urinary glucose secretion and lowering blood glucose and glycosylated hemoglobin (hemoglobin A1c [HbA1c]) concentrations. Its effectiveness has been demonstrated in studies in which it has been used as monotherapy, or in combination regimens with metformin, glipizide, glimepiride, pioglitazone, sitagliptin (Januvia), or insulin. The use of dapagliflozin resulted in reductions in HbA1c and fasting plasma glucose (FPG) concentrations and, in many patients, weight reduction. In a placebo-controlled study, the percentage of patients achieving a HbA1c of less than 7% was 44% and 51% in patients receiving daily doses of 5 mg and 10 mg of dapagliflozin, respectively, compared with 32% of those receiving placebo. The use of dapagliflozin in combination with other antidiabetic agents resulted in greater reductions in HbA1c and FPG concentrations. Patients treated with regimens that included dapagliflozin typically lost an average of 1 to 3 kg of body weight over a 24-week period, whereas those who were treated with other antidiabetic agents usually either lost less weight or experienced weight gain. Empagliflozin (Jardiance – Boehringer-Ingelheim; Lilly) Antidiabetic Agent 2014 New Drug Comparison Rating (NDCR) = Indication: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Comparable drugs: Canagliflozin (Invokana), dapagliflozin (Farxiga) Advantages: --Recommendations for use in patients with impaired renal function are less restrictive (compared with dapagliflozin) --May be used in patients with severe hepatic impairment (compared with canagliflozin that has not been studied in patients with severe hepatic impairment and use is not recommended) --Has not been associated with reports of patients experiencing bladder cancer (compared with dapagliflozin) Disadvantages: --Additive benefit when used in combination regimens may be less pronounced (although agents have not been directly compared in clinical studies) --Not available in a combination formulation with metformin (compared with canagliflozin) Most important risks/adverse events: Renal function impairment (contraindicated in patients with severe renal impairment; renal function should be monitored during therapy); hypersensitivity reactions (contraindicated in patients with a history of a serious reaction); hypotension (risk is increased in patients with impaired renal function or low systolic blood pressure, the elderly, and in patients treated with a diuretic); hypoglycemia (when used concomitantly with insulin or an insulin secretagogue [e.g., a sulfonylurea]); positive urine glucose test results (alternative methods to monitor glycemic control should be used) Most common adverse events: Urinary tract infection (9%), female genital mycotic infection (5%; e.g., vulvovaginal candidiasis), dyslipidemia (4%; e.g., increased LDL-C), increased urination (3%), male genital mycotic infection (3%; e.g., balanitis), upper respiratory tract infection (3%) Usual dosage: 10 mg once a day in the morning; in patients who tolerate treatment and require additional glycemic control, dosage may be increased to 25 mg once a day; treatment should not be initiated in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m2, and treatment should be discontinued if the eGFR is persistently below this value Products: Film-coated tablets – 10 mg, 25 mg Comments: Sodium-glucose cotransporter 2 (SGLT2) is expressed in the proximal renal tubules and is responsible for the reabsorption of the majority of glucose filtered by the kidneys. Empagliflozin is the third SGLT2 inhibitor, joining canagliflozin and dapagliflozin, and these agents reduce the reabsorption of filtered glucose, thereby increasing urinary glucose excretion and lowering blood glucose and glycosylated hemoglobin (hemoglobin A1c [HbA1c]) concentrations. Its effectiveness has been demonstrated in studies in which it has been used as monotherapy, or in combination regimens with metformin, glimepiride, pioglitazone, or insulin. The use of empagliflozin resulted in reductions in HbA1c and fasting plasma glucose (FPG) concentrations and, in many patients, weight reduction. In a placebo-controlled study, the percentage of patients achieving an HbA1c of less than 7% at Week 24 was 35% and 44% in patients receiving daily doses of 10 mg and 25 mg of empagliflozin, respectively, compared with 12% of those receiving placebo. Patients treated with empagliflozin lost an average of approximately 3 kg of body weight, compared with an average loss of 0.4 kg in those receiving placebo. The reductions in HbA1c and FPG in patients treated with combination regimens that included empagliflozin, as well as the percentage of patients achieving an HbA1c of less than 7%, were generally similar to those attained with empagliflozin monotherapy. Albiglutide (Tanzeum – GlaxoSmithKline) Antidiabetic Agent 2014 New Drug Comparison Rating (NDCR) = Indication: Administered subcutaneously as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Comparable drugs: Exenatide (Byetta), exenatide extended-release (Bydureon), liraglutide (Victoza) Advantages: --Less frequent administration (once a week; compared with liraglutide [once a day] and exenatide [twice a day]; exenatide extended-release is also administered once a week) Disadvantages: --Less reduction in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) (compared with liraglutide;
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