FDA批准阿伐那非治疗男性勃起功能障碍
2012年4月27日，美国食品与药物管理局（FDA）批准新药阿伐那非（Stendra）治疗勃起功能障碍（ED），ED患者可在进行性行为之前30分钟根据需要服用该药。FDA提示，医生应处方使患者获益的最小剂量阿伐那非。
阿伐那非属于5型磷酸二酯酶抑制剂（PDE5-I），它可增加阴茎的血流量。与其他PDE5-I相同，该药不能用于同时服用硝酸盐类治疗胸痛的男性患者，因为其联合使用会导致血压的急剧降低。
PDE5-I很少引起色视觉的改变，有报道在一些罕见的情况下，服用PDE5-I的男性突然出现单眼或双眼的视力丧失，还有可能突然发生听力丧失或下降。一旦出现上述情况，患者应停止服用PDE5-I，包括阿伐那非，并立即呼叫医生。
在临床试验中，超过2%的患者记录的最常见不良反应包括头痛，面部和身体其他部分的潮红，鼻充血，常见的感冒样症状（鼻咽炎）和后背痛。罕见有服用阿伐那非或其他PDE5-I的患者出现阴茎异常勃起可能持续4小时或更长时间。如果这一情况出现，患者应及时就医。
3项双盲、安慰剂对照临床试验确定了阿伐那非的安全性和有效性。试验纳入的1267例患者被随机分为阿伐那非组和安慰剂组，这些患者都在进行性行为之前的30分钟服用阿伐那非或安慰剂，阿伐那非组分别接受阿伐那非50mg、100 mg 或200 mg治疗12周。
研究的开始和此后的每4周对患者进行调查问卷，以评估其勃起功能等性交情况。结果显示，服用3个不同剂量的阿伐那非患者所有3项评估终点均有显著改善。
为进一步评估阿伐那非的安全性，两项亚组研究予患者起始应用阿伐那非100 mg治疗，但可能根据患者对治疗的反应情况，增量到200 mg或减量至50 mg。结果显示，随着时间变化，亚组患者记录的不良反应并没有恶化。
详情说明书
http://www.stendra.com/assets/pdf/STENDRA-avanafil-tablets-Patient-Information.pdf
IMPORTANT SAFETY INFORMATIONSTENDRA&(avanafil) is indicated for the treatment of erectile dysfunction (ED).
The use of STENDRA and organic nitrates in any form, at any time, is contraindicated.
Before treating ED, physicians should consider the impact of resuming sexual activity and the mild and transient vasodilatory effects of STENDRA on blood pressure.
Physicians should carefully consider whether patients with underlying cardiovascular disease or other more unusual conditions could be adversely affected by vasodilatory effects, especially in combination with sexual activity.
For patients taking concomitant strong CYP3A4 inhibitors (including anti-fungals ketoconazole, itraconazole; protease inhibitors for HIV ritonavir, atazanavir, indinavir, nelfinavir,saquinavir; antibiotics clarithromycin and telithromycin; and the antidepressant nefazodone,), use of STENDRA is not recommended.
As there have been infrequent reports of prolonged erections lasting more than 4 hours or priapism with all ED treatments in this drug class, patients should be advised to seek immediate medical attention should these occur. Erections lasting longer than 6 hours can result in penile tissue damage and long-term loss of potency.
Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported rarely post-marketing in temporal association with the use of PDE5 inhibitors. It is not possible to determine if these events are related to PDE5 inhibitors or to other factors. Physicians should advise patients to stop use of PDE5 inhibitors, including STENDRA, and seek medical attention in the event of sudden loss of vision.
Sudden decrease or loss of hearing has been reported in temporal association with the intake of PDE5 inhibitors. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors. Physicians should advise patients to stop taking PDE5 inhibitors, including STENDRA, and seek prompt medical attention in the event of sudden decrease or loss of hearing.
Physicians should advise patients of the potential for PDE5 inhibitors, including STENDRA, to augment the blood pressure lowering effect of alpha blockers and anti-hypertensive medications. In some patients concomitant administration of a PDE5 inhibitor and alpha blocker may lead to symptomatic hypotension. Patients should be stable on alpha-blocker therapy prior to taking STENDRA.
Patients should be made aware that both alcohol and PDE5 inhibitors including STENDRA act as vasodilators. When vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Physicians should inform patients that substantial consumption of alcohol (e.g., greater than 3 units) in combination with STENDRA may increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness and headache.
Physicians should inform patients not to take STENDRA with other PDE5 inhibitors as the safety and efficacy of these combinations have not been studied.
Use of STENDRA offers no protection against sexually transmitted diseases, including the human immunodeficiency virus (HIV); therefore, physicians should consider counseling their patients about protective measures.
The most common side effects of STENDRA were headache (5.6%), flushing(3.5%), nasopharyngitis (3.4%) and nasal congestion(2.1%).
http://www.stendra.com/assets/pdf/STENDRA-avanafil-tablets-full-PI.pdf
MOUNTAIN VIEW, Calif., Sept. 18, 2012 /PRNewswire/ -- VIVUS, Inc. (NASDAQ: VVUS) today announced the U.S. market availability of Qsymia™ (pronounced Kyoo sim ee' uh). Qsymia is FDA-approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 or greater (obese), or 27 or greater (overweight) in the presence of at least one weight-related comorbidity, such as hypertension, type 2 diabetes mellitus or high cholesterol (dyslipidemia). It is the first FDA-approved once daily combination therapy – and the first new medication available in 13 years – for the treatment of obesity.
VIVUS is formally introducing Qsymia to medical professionals this week at The Obesity Society's Annual Scientific Meeting in San Antonio, Texas.
"VIVUS is proud to be leading the way in the treatment of obesity, a disease with very serious health consequences," said Peter Tam, President of VIVUS. "Qsymia is the first ever combination treatment made available, and today's introduction marks a new beginning for many patients who struggle with obesity. We are excited about making this new treatment option available to patients because Qsymia is the first FDA-approved oral medication that has been shown to achieve an average weight loss of 10% in obese patients when used in conjunction with a lifestyle modification program."
To help ensure healthcare providers and patients are properly educated, VIVUS is emphasizing the Qsymia Risk Evaluation and Mitigation Strategy(REMS) program, which includes a Medication Guide, healthcare provider training, patient brochure and other education tools. As part of the REMS program, Qsymia is available only through certified mail order pharmacies that are part of the Qsymia Home Delivery Network including CVS Pharmacy and Walgreens.
"The battle against obesity can seem hopeless, yet given the health consequences, it is absolutely critical that people who are at risk improve their weight," said Donna Ryan, M.D., associate executive director for clinical research at Pennington Biomedical Research Center in Baton Rouge, La., and former president of The Obesity Society. "It is time that healthcare professionals have a new medical treatment option allowing them to engage their patients who are in need, and start to turn the tide on this growing crisis."
"With the availability of this new therapeutic option, Americans struggling with obesity finally have another important tool to help address their weight and related co-morbidities," added Joe Nadglowski, Obesity Action Coalition President and CEO.
Obesity and Losing Weight
Many factors contribute to excess weight gain. These include environmental factors, genetics, health conditions or certain medications, emotional factors and other behaviors.
All this contributes to more than 110 million Americans being obese or overweight with at least one weight-related comorbidity. Excess weight increases the risk of conditions including type 2 diabetes, high cholesterol, high blood pressure, heart disease, sleep apnea, stroke and osteoarthritis.
According to the National Institutes of Health (NIH), losing just 10% of body weight may help obese patients reduce the risk of developing other medical conditions, while making a meaningful difference in health and well-being.
About Qsymia
The safety and efficacy of Qsymia were evaluated in two multicenter, phase 3 trials that included more than 3,700 patients: severely obese patients (the EQUIP study) and overweight or obese patients with at least two weight-related comorbidities, such as hypertension, hypertriglyceridemia, type 2 diabetes or central adiposity (the CONQUER study). The average weight loss in EQUIP was 10.9% on Qsymia 15 mg/92 mg and 1.6% for placebo(ITT-LOCF, p<0.0001). The average weight loss in CONQUER was 9.8% on Qsymia 15 mg/92 mg, 7.8% on Qsymia 7.5 mg/46 mg and 1.2% for placebo (ITT-LOCF, p<0.0001).
The most common adverse reactions for patients treated with Qsymia included tingling sensation of hands and feet, dizziness, altered taste, insomnia, constipation and dry mouth.
The Qsymia REMS program is intended to inform prescribers and female patients of reproductive potential about the following: an increased risk of orofacial clefts in infants exposed to Qsymia during the first trimester of pregnancy; the importance of pregnancy prevention for females of reproductive potential receiving Qsymia; and the need to discontinue Qsymia immediately if pregnancy occurs.
For more information about Qsymia, go to www.Qsymia.com. For full prescribing information go to http://vivus.com/docs/QsymiaPI.pdf.
Important Safety Information
Qsymia(phentermine and topiramate extended-release) capsules CIV is contraindicated in pregnancy; in patients with glaucoma; in hyperthyroidism; in patients receiving treatment or within 14 days following treatment with monoamine oxidase inhibitors (MAOIs); or in patients with hypersensitivity to sympathomimetic amines,topiramate, or any of the inactive ingredients in Qsymia.
Qsymia can cause fetal harm. Females of reproductive potential should have a negative pregnancy test before treatment and monthly thereafter and use effective contraception consistently during Qsymia therapy. If a patient becomes pregnant while taking Qsymia, treatment should be discontinued immediately, and the patient should be informed of the potential hazard to the fetus.
The most commonly observed side effects in controlled clinical studies, 5% or greater and at least 1.5 times placebo, include paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.
To report negative side effects, contact VIVUS, Inc., at 1-888-998-4887 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
About STENDRA
STENDRA is a prescription medicine used to treat erectile dysfunction (ED). STENDRA (avanafil) is licensed from Mitsubishi Tanabe Pharma Corporation. VIVUS has development and commercial rights to STENDRA for the treatment of sexual dysfunction worldwide with the exception of certain Asian Pacific Rim countries. In South Korea, STENDRA is approved and is marketed by JW Pharma under the brand name Zepeed.
Important Safety Information
Do not take STENDRA if you take nitrates, often prescribed for chest pain, as this may cause a sudden, unsafe drop in blood pressure. Tell your healthcare provider about all the medicines you take and discuss your general health status to ensure that you are healthy enough to engage in sexual activity. If you experience chest pain, nausea, or any other discomforts during sex, seek immediate medical help.
In the rare event of an erection lasting more than 4 hours, seek immediate medical help to avoid long-term injury. STENDRA in combination with other treatments for erectile dysfunction is not recommended. STENDRA does not protect against sexually transmitted diseases, including HIV. The most common side effects of STENDRA are headache, flushing, runny nose and congestion.
About VIVUS
VIVUS is a biopharmaceutical company commercializing and developing innovative, next-generation therapies to address unmet needs in obesity, sleep apnea, diabetes and sexual health for U.S., Europe and other world markets. Qsymia is also in phase 2 clinical development for the treatment of type 2 diabetes and obstructive sleep apnea. For more information about the company, please visit www.vivus.com.
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995.
These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimate," "expect," "intend," "likely," "may," "plan," "potential," "predict," "opportunity" and "should," among others. There are a number of factors that could cause actual events to differ materially from those indicated by such
forward-looking statements.
These factors include, but are not limited to, our lack of commercial experience with Qsymia in the U.S.; the timing of initiation and completion of the clinical studies required as part of the approval of Qsymia by the United States Food and Drug Administration, or FDA; the response from the FDA to the data that VIVUS will submit relating to post-approval clinical studies; the impact of the indicated uses and contraindications contained in the Qsymia label and the REMS requirements; the impact of distribution of Qsymia through a certified pharmacy network; that we may be required to provide further analysis of previously submitted clinical trial data; our response to questions and requests for additional information including additional pre-clinical or clinical studies from the European Medicines Agency, or EMA, and the Committee for Medicinal Products for Human Use, or CHMP, for the Marketing Authorization Application, or MAA, for Qsymia; our ability to successfully commercialize or establish a marketing partnership for avanafil, which will be marketed in the U.S. under the name Stendra, or our partner's ability to obtain and maintain regulatory approval to manufacture and adequately supply avanafil for commercial use; our history of losses and variable quarterly results; substantial competition; risks related to the failure to protect our intellectual property and litigation in which we may become involved; uncertainties of government or third party payer reimbursement; our reliance on sole source suppliers; our limited sales and marketing and manufacturing experience; our reliance on third parties and our collaborative partners; our failure to continue to develop innovative investigational drug candidates and drugs; risks related to the failure to obtain FDA or foreign authority clearances or approvals and noncompliance with FDA or foreign authority regulations; our ability to demonstrate through clinical testing the safety and effectiveness of our investigational drug candidates; the timing of initiation and completion of clinical trials and submissions to foreign authorities; the volatility and liquidity of the financial markets; our liquidity and capital resources; and our expected future revenues, operations and expenditures.
As with any pharmaceutical in development, there are significant risks in the development, the regulatory approval, and commercialization of new products. There are no guarantees that our response to the CHMP's 180-day list of outstanding issues and subsequent meetings and communications will be sufficient to satisfy the CHMP's safety concerns regarding Qsymia, that the foreign authorities will not require us to conduct any additional prospectivestudiesorretrospectiveobservational studies, or that any product will receive foreign regulatory approval for any indication or prove to be commercially successful. VIVUS does not undertake an obligation to update or revise any forward-looking statements. Investors should read the risk factors set forth in VIVUS' Form 10-K for the year ending December 31, 2011, and periodic reports filed with the Securities and Exchange Commission.
SOURCE VIVUS, Inc.