近日，新型吸入性胰岛素Afrezza-吸入性胰岛素获FDA批准上市，用于改善成年1型和2型糖尿病患者的血糖控制.
FDA的药品评价和研究中心的代谢和内分泌产品部主任Jean-Marc Guettier，医学博士说：“Afrezza对有糖尿病需要进餐时胰岛素患者是一种新治疗选择，”“今天批准对需要控制血糖水平的糖尿病患者总体处理中扩展输送进餐时胰岛素选择。”
批准日期：2014年6月27日；公司：MannKind Corporation
AFREZZA(人胰岛素[insulin human])吸入粉
美国初次批准：2014
作用机制
胰岛素通过刺激周边骨骼肌和脂肪葡萄糖摄取降低血糖水平，和通过抑制肝葡萄糖生成。在脂肪细胞中胰岛素抑制脂肪分解，抑制蛋白水解，和增强蛋白合成。
适应证和用途
⑴AFREZZA® 是一种迅速作用吸入胰岛素适用在有糖尿病成年患者中改善血糖控制。
重要使用限制：
⑵在有1型糖尿病患者中，必须与一种长效胰岛素使用。
⑶建议不要为治疗糖尿病酮症酸中毒。
⑷建议不要治疗吸烟患者。
剂量和给药方法
⑴利用一个送药车架[carridge]每单次吸入给药
⑵在进餐开始前给药
⑶必须个体化给药
⑷在所有患者开始前，进行一个详细医疗病史，身体检查，和肺量测定(FEV1)鉴定潜在肺疾病
剂型和规格
可得到AFREZZA为单次使用送药车架：
⑴4单位
⑵8单位
禁忌证
⑴低血糖发作期间
⑵慢性肺疾病，例如哮喘，或慢性阻塞性肺病
⑶对常规人胰岛素或AFREZZA赋形剂任何组分超敏性。
警告和注意事项
⑴急性支气管痉挛：在有哮喘和COPD患者中曾观察到急性支气管痉挛。在所有患者中开始前，进行肺量测定(FEV1)。在有慢性肺疾病患者中不要使用。
⑵胰岛素方案中改变：进行严密医学监督和增加血糖监测频度。
⑶低血糖：可能是危及生命。随以下改变增加葡萄糖监测频度：胰岛素剂量，共同给予降低血糖药物，餐模式，体力活动；和有肾或肝受损和未意识到低血糖患者。
⑷肺功能减低：开始前，治疗后6个月，和每年，甚至没有肺症状评估肺功能(如，呼吸量测定)。
⑸肺癌：有活动性肺癌患者中不应使用AFREZZA。有肺癌病史或处于对肺癌风险患者，权衡AFREZZA使用获益应胜过潜在风险。
⑹糖尿病酮症酸中毒：在临床试验中用AFREZZA患者经受更多糖尿病酮症酸中毒。对糖尿病酮症酸中毒风险患者，监视和如指示改变胰岛素输送途径。
⑺超敏性反应：用胰岛素产品，包括AFREZZA可能发生严重，危及生命，全身过敏，包括过敏性反应。终止AFREZZA，监视和治疗如指示。
⑻低钾血症：可能危及生命。处于低钾血症风险患者中监视钾水平和如指示治疗。
⑼与噻唑烷二酮类(TZDs)同时使用体液潴留和心衰：观察心衰的征象和症状；如发生心衰考虑减低剂量或终止。
不良反应
伴随AFREZZA最常见不良反应(发生率2%或更多)是低血糖，咳嗽，和喉痛或刺激。
药物相互作用
⑴影响葡萄糖代谢药物：可能需要调整胰岛素剂量。
⑵抗-肾上腺能药物(如，β-阻滞剂，可乐定[clonidine]，胍乙啶[guanethidine]，和利血平[reserpine])：低血糖征象和症状可能减低或缺乏。
AFREZZA(insulin human)inhalation powder, for oral inhalation use
INDICATIONS AND USAGE FOR AFREZZA® (INSULIN HUMAN) INHALATION POWDER
Afrezza® is a rapid-acting inhaled insulin indicated to improve glycemic control in adult patients with diabetes mellitus.
LIMITATIONS OF USE
•Afrezza® is not a substitute for long-acting insulin. Afrezza® must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus.
•Afrezza® is not recommended for the treatment of diabetic ketoacidosis.
•The safety and efficacy of Afrezza® in patients who smoke has not been established. The use of Afrezza® is not recommended in patients who smoke or who have recently stopped smoking (less than 6 months).
RISK eva lUATION AND MITIGATION STRATEGY
Access the REMS website to learn more about the Afrezza® REMS program.
+Important Safety Information for Afrezza®,
including Boxed WARNING
WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE
•Acute bronchospasm has been observed in patients with asthma and COPD using Afrezza®
IMPORTANT SAFETY INFORMATION FOR AFREZZA® (INSULIN HUMAN) INHALATION POWDER
WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE
Acute bronchospasm has been observed in patients with asthma and COPD using Afrezza®.Afrezza® is contraindicated in patients with chronic lung disease such as asthma or COPD.Before initiating Afrezza®, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.CONTRAINDICATIONS Afrezza® is contraindicated in patients with the following:
•During episodes of hypoglycemia.•Chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD), because of the risk of acute bronchospasm.•Hypersensitivity to regular human insulin or any of the Afrezza® excipients.WARNINGS AND PRECAUTIONS Afrezza® is contraindicated in patients with chronic lung disease such as asthma or COPD. Prior to initiating therapy, patients should be eva luated with a medical history, physical examination and spirometry (FEV1) to identify potential underlying lung disease. Acute bronchospasm has been observed following Afrezza® dosing in patients with asthma and patients with COPD. The long-term safety and efficacy of Afrezza® in patients with chronic lung disease has not been established.
Monitor blood glucose in all patients treated with insulin. Modify insulin regimen and dose cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment.
Hypoglycemia is the most common adverse reaction of insulin therapy, including Afrezza®, and may be serious and life-threatening. Patients and caregivers must be educated on mitigating the risks associated with hypoglycemia.
Afrezza® has been shown to cause a decrease in lung function as measured by FEV1. In clinical trials lasting up to 2 years, Afrezza® treated patients experienced a small (40 ml) but greater FEV1 decline than comparator treated patients. Therefore, pulmonary function should be assessed with spirometry at baseline, after the initial 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. More frequent lung function assessment should be considered in patients with pulmonary symptoms, e.g., wheezing, bronchospasm, breathing difficulties, or cough.
In Afrezza® clinical trials, 2 cases of lung cancer were reported in patients exposed to Afrezza® while no cases were reported for the comparators. Two additional cases of lung cancer (squamous cell) were reported in non-smokers exposed to Afrezza® after the trial completion. In patients with active lung cancer, a prior history of lung cancer, or in patients at risk of lung cancer, consider whether the benefits of Afrezza® outweigh the risks.
Increase the frequency of glucose monitoring and consider an alternate route of administration of insulin in patients at risk for diabetic ketoacidosis (DKA). In clinical trials enrolling subjects with type 1 diabetes, DKA was more common in subjects receiving Afrezza® (0.43%; n=13) than in subjects receiving comparators (0.14%; n=3).
As with all insulins, Afrezza® use can lead to life-threatening hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated.
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Afrezza®, monitor and treat if indicated.
Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dose reduction or discontinuation of TZD must be considered.
DRUG INTERACTIONS Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia or decreasing the blood glucose lowering effect of Afrezza®. Dose adjustment and increased frequency of blood glucose monitoring may be required. The signs and symptoms of hypoglycemia may be reduced when taking Afrezza® concomitantly with beta-blockers, clonidine, guanethidine, and reserpine.
ADVERSE REACTIONS The most common adverse reactions associated with Afrezza® include hypoglycemia, cough (including productive cough), throat pain or irritation, and headache.
RISK eva lUATION AND MITIGATION STRATEGY
Access the REMS website to learn more about the Afrezza® REMS program.
IMPORTANT SAFETY INFORMATION FOR AFREZZA® (INSULIN HUMAN) INHALATION POWDER
WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE
Acute bronchospasm has been observed in patients with asthma and COPD using Afrezza®.
Afrezza® is contraindicated in patients with chronic lung disease such as asthma or COPD.
Before initiating Afrezza®, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.
CONTRAINDICATIONS
Afrezza® is contraindicated in patients with the following:
•During episodes of hypoglycemia.
•Chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD), because of the risk of acute bronchospasm.
•Hypersensitivity to regular human insulin or any of the Afrezza® excipients.
WARNINGS AND PRECAUTIONS
Afrezza® is contraindicated in patients with chronic lung disease such as asthma or COPD. Prior to initiating therapy, patients should be eva luated with a medical history, physical examination and spirometry (FEV1) to identify potential underlying lung disease. Acute bronchospasm has been observed following Afrezza® dosing in patients with asthma and patients with COPD. The long-term safety and efficacy of Afrezza® in patients with chronic lung disease has not been established.
Monitor blood glucose in all patients treated with insulin. Modify insulin regimen and dose cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment.
Hypoglycemia is the most common adverse reaction of insulin therapy, including Afrezza®, and may be serious and life-threatening. Patients and caregivers must be educated on mitigating the risks associated with hypoglycemia.
Afrezza® has been shown to cause a decrease in lung function as measured by FEV1. In clinical trials lasting up to 2 years, Afrezza® treated patients experienced a small (40 ml) but greater FEV1 decline than comparator treated patients. Therefore, pulmonary function should be assessed with spirometry at baseline, after the initial 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. More frequent lung function assessment should be considered in patients with pulmonary symptoms, e.g., wheezing, bronchospasm, breathing difficulties, or cough.
In Afrezza® clinical trials, 2 cases of lung cancer were reported in patients exposed to Afrezza® while no cases were reported for the comparators. Two additional cases of lung cancer (squamous cell) were reported in non-smokers exposed to Afrezza® after the trial completion. In patients with active lung cancer, a prior history of lung cancer, or in patients at risk of lung cancer, consider whether the benefits of Afrezza® outweigh the risks.
Increase the frequency of glucose monitoring and consider an alternate route of administration of insulin in patients at risk for diabetic ketoacidosis (DKA). In clinical trials enrolling subjects with type 1 diabetes, DKA was more common in subjects receiving Afrezza® (0.43%; n=13) than in subjects receiving comparators (0.14%; n=3).
As with all insulins, Afrezza® use can lead to life-threatening hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated.
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Afrezza®, monitor and treat if indicated.
Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dose reduction or discontinuation of TZD must be considered.
DRUG INTERACTIONS
Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia or decreasing the blood glucose lowering effect of Afrezza®. Dose adjustment and increased frequency of blood glucose monitoring may be required. The signs and symptoms of hypoglycemia may be reduced when taking Afrezza® concomitantly with beta-blockers, clonidine, guanethidine, and reserpine.
ADVERSE REACTIONS
The most common adverse reactions associated with Afrezza® include hypoglycemia, cough (including productive cough), throat pain or irritation, and headache.
RISK eva lUATION AND MITIGATION STRATEGY
Access the REMS website to learn more about the Afrezza® REMS program.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022472lbl.pdf
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=29f4637b-e204-425b-b89c-7238008d8c10