藥物警訊

Diabetes Medications Containing Saxagliptin and Alogliptin: Drug Safety Communication - Risk of Heart Failure

Including:
‧ Onglyza (saxagliptin)
‧ Kombiglyze XR (saxagliptin and metformin extended release)
‧ Nesina (alogliptin)
‧ Kazano (alogliptin and metformin)
‧ Oseni (alogliptin and pioglitazone)

AUDIENCE: Pharmacy, Internal Medicine, Patient, Endocrinology

ISSUE: An FDA safety review has found that type 2 diabetes medicines containing saxagliptin and alogliptin may increase the risk of heart failure, particularly in patients who already have heart or kidney disease. As a result, FDA is adding new warnings to the drug labels about this safety issue.

This Communication is an update to the 02/11/2014 FDA Drug Safety Communication.

BACKGROUND: Saxagliptin and alogliptin are part of the class of dipeptidyl peptidase-4 (DPP-4) inhibitor drugs, which are used with diet and exercise to lower blood sugar in adults with type 2 diabetes.

FDA evaluated two large clinical trials conducted in patients with heart disease. These clinical trials were also discussed at the FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting in April 2015. Each trial showed that more patients who received saxagliptin- or alogliptin-containing medicines were hospitalized for heart failure compared to patients who received an inactive treatment called a placebo (see Data Summary in the FDA Drug Safety Communication for additional information). In the saxagliptin trial, 3.5% of patients who received the drug were hospitalized for heart failure versus 2.8% of patients who received a placebo. This is the same as 35 out of every 1,000 patients compared to 28 out of every 1,000 patients. Risk factors included a history of heart failure or kidney impairment. In the alogliptin trial, 3.9% of alogliptin-treated patients were hospitalized for heart failure versus 3.3% in the placebo group. This is the same as 39 out of every 1,000 patients compared to 33 out of every 1,000 patients.

RECOMMENDATION: Health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control. If a patient’s blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required.

Patients taking these medicines should contact their health care professionals right away if they develop signs and symptoms of heart failure such as:

‧ Unusual shortness of breath during daily activities
‧ Trouble breathing when lying down
‧ Tiredness, weakness, or fatigue
‧ Weight gain with swelling in the ankles, feet, legs, or stomach

Patients should not stop taking their medicine without first talking to their health care professionals.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494252.htm

Saxagliptin和alogliptin為dipeptidyl peptidase-4 (DPP-4) inhibitor，適應症為用於第二型糖尿病人搭配飲食及運動來達到血糖控制。

美國FDA評估兩項大型臨床試驗(SAVOR及EXAMINEtiral)，其試驗結果顯示曾有心臟疾病者服用含saxagliptin或alogliptin藥品，相較於對照組病人，因心衰竭住院之機率較高：Saxagliptin trial：3.5% vs. 2.8%；Alogliptin trial：3.9% vs. 3.3%。

因此，美國FDA發布藥物安全警訊，告知saxagliptin和alogliptin成分之第二型糖尿病藥品用於曾患有心臟或腎臟疾病之病人可能增加心衰竭風險。美國FDA已於藥品仿單中新增此訊息。

美國FDA提醒醫療人員，目前正在服用此兩種成分藥品之病人，若出現疑似心衰竭症狀，應考慮停藥並監測其血糖控制。若病人在現行治療下血糖值仍控制不佳，可考慮使用其他降血糖用藥。

正在服用此兩種成分藥品之病人，若出現以下症狀時，應立即就醫：

1. 日常生活作息時感到呼吸異常短促

2. 躺著的時候覺得呼吸困難

3. 覺得身體疲倦或虛弱

4. 體重增加伴隨踝關節、下肢腫脹

美國FDA也提醒病人，在未給醫療人員評估之前，請勿自行停藥。

相關訊息與連結請參考FDA網址：

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494252.htm

[Posted 04/05/2016]

資料來源：美國FDA之藥物安全警訊

資料提供：台大醫院藥劑部