减肥药Osymia获得FDA批准

圣路易斯(MD Consult)——2012年7月17日，美国食品药品管理局(FDA)和Vivus制药公司宣布，Qsymia(苯丁胺与托吡酯的复方制剂)已获准用于需长期控制体重的成人肥胖患者，作为其减热量膳食与增加体力活动的辅助治疗药。该药适用于治疗初始体重指数(BMI)≥30 kg/m²(肥胖)或≥27 kg/m²(超重)且存在高血压、2型糖尿病或血脂异常等至少1种体重相关的合并症的患者。

Qsymia是获FDA批准的药物苯丁胺与托吡酯缓释剂的复方药。苯丁胺适用于当前采取运动和减热量膳食减重的超重或肥胖的成人患者，作为其短期减肥药。托吡酯适用于治疗癫痫患者的癫痫发作及预防偏头痛。

Qsymia的推荐日剂量包含7.5 mg的苯丁胺和46 mg的托吡酯缓释剂。Qsymia针对个别患者还设计了较高剂量的制剂(15 mg苯丁胺与92 mg托吡酯缓释剂)。

Qsymia的安全性和疗效在该公司开展的2项多中心、3期试验中得到了评估，总共纳入3,700名受试者。第1项研究的受试者为重度肥胖患者，而第2项试验纳入的是至少有2种肥胖相关合并症的超重或肥胖患者，比如高血压、血脂异常、2型糖尿病或中心型肥胖。所有患者均接受调整生活方式治疗，即减热量膳食结合常规体力活动。

在第1项研究中，接受Qsymia 15 mg/92 mg治疗的患者平均减重10.9%，而安慰剂组患者平均减重1.6%；在第2项研究中， Qsymia 15 mg/92 mg治疗组患者平均减重9.8%，而安慰剂组患者平均减重1.2%。

研究中接受Qsymia治疗的患者最常见的不良反应包括手脚发麻、头晕、味觉改变、失眠、便秘以及口干。

Qsymia不得用于青光眼或甲状腺功能亢进患者。使用Qsymia可增加心率；心肌梗死或卒中高危患者服用该药对心率的影响尚不清楚。因此，对近期(最近6个月内)曾发生心脏病或卒中或这2种疾病不稳定的患者不宜使用Qsymia。建议对接受Qsymia治疗的所有患者均进行常规心率监测，尤其是在开始治疗时及增加剂量时。

在临床试验中，Qsymia治疗12周时体重减幅<3%的患者继续采用该剂量的药物进行治疗，达到或维持减重的可能性较低。因此，到12周时，应该对Qsymia推荐日剂量治疗的疗效进行评估，以确定是该停用Qsymia还是增加剂量。使用较大剂量的Qsymia治疗12周后，若患者的体重减幅<5%，则宜停药。

FDA要求Vivus公司履行10项上市后要求，其中包括开展1项长期的心血管结局试验，用以评估Qsymia对心肌梗死和卒中等重大不良心脏事件风险的影响。

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ST LOUIS (MD Consult) - On July 17, 2012, the US Food and Drug Administration (FDA) and Vivus announced the approval of Qsymia (phentermine and topiramate) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients. Patients for whom the drug is indicated should have an initial body mass index (BMI) of 30 or greater (obese), or 27 or greater (overweight), in the presence of at least 1 weight-related comorbidity, such as hypertension, type 2 diabetes mellitus, or dyslipidemia.

Qsymia is a combination of the FDA-approved drugs phentermine and topiramate in an extended-release formulation. Phentermine is indicated for short-term weight loss in overweight or obese adults who are exercising and eating a reduced calorie diet. Topiramate is indicated for the treatment of seizures in patients with epilepsy and for the prevention of migraine headaches.

The recommended daily dose of Qsymia contains 7.5 mg of phentermine and 46 mg of topiramate extended-release. Qsymia is also available at a higher dose (15 mg phentermine and 92 mg of topiramate extended-release) for select patients.

The safety and efficacy of Qsymia were evaluated in 2 multicenter, phase 3 trials that included a total of 3700 participants. The first trial studied patients with severe obesity, and the second trial included overweight or obese patients with at least 2 weight-related comorbidities, such as hypertension, hypertriglyceridemia, type 2 diabetes, or central adiposity. All patients received lifestyle modification that consisted of a reduced-calorie diet and regular physical activity.

The average weight loss in the first study was 10.9% in patients who received Qsymia 15 mg/92 mg and 1.6% for patients who received placebo. The average weight loss in the second study was 9.8% in patients who received Qsymia 15 mg/92 mg, 7.8% in patients who received Qsymia 7.5 mg/46 mg, and 1.2% for patients who received placebo.

The most common adverse reactions for patients treated with Qsymia in studies included tingling sensations of the hands and feet, dizziness, altered taste, insomnia, constipation, and dry mouth.

Qsymia must not be used in patients with glaucoma or hyperthyroidism. Use of Qsymia can increase heart rate; the drug's effect on heart rate in patients at high risk for myocardial infarction or stroke is unknown. Therefore, the use of Qsymia in patients with recent (within the last 6 months) or unstable heart disease or stroke is not recommended. Regular monitoring of heart rate is recommended for all patients receiving Qsymia, especially when starting treatment or increasing the dose.

Patients in clincial trials who did not lose at least 3% of their body weight by week 12 of treatment with Qsymia were unlikely to achieve and sustain weight loss with continued treatment at this dose. Therefore, response to therapy with the recommended daily dose of Qsymia should be evaluated by 12 weeks to determine whether to discontinue Qsymia or increase to the higher dose. If, after 12 weeks on the higher dose of Qsymia, a patient does not lose at least 5% of body weight, then Qsymia should be discontinued.

Vivus will be required to conduct 10 postmarketing requirements, including a long-term cardiovascular outcomes trial to assess the effect of Qsymia on the risk for major adverse cardiac events such as myocardial infarction and stroke.