| Revision as of 19:51, 1 July 2013 editAnypodetos (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers, Rollbackers39,350 editsm disambig; grammar← Previous edit | Revision as of 20:26, 28 October 2013 edit undo12.155.173.1 (talk)No edit summaryNext edit → | ||
| Line 1: | Line 1: | ||
| {{Unreliable sources|date=June 2012}} | |||
| {{Drugbox | {{Drugbox | ||
| | Watchedfields = changed | | Watchedfields = changed | ||
| Line 37: | Line 37: | ||
| }} | }} | ||
| The combination of the ] '''phentermine and topiramate''' (trade name '''Qsymia''', formerly '''Qnexa''') is a medication |
The combination of the ] '''phentermine and topiramate''' (trade name '''Qsymia''', formerly '''Qnexa''') is a medication indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: ≥30 kg/m<sup>2</sup> or ≥27 kg/m<sup>2</sup> (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia.<ref></ref> In clinical trials, Qsymia was associated with significant weight loss when compared with placebo.<ref></ref> This weight loss was associated with improvements in weight-related comorbidities such as improved glycemia, decreased blood pressure, and improved cholesterol.<ref></ref> | ||
| Qsymia was developed by ], Inc., a California pharmaceutical company.<ref></ref> ] is a sympathomimetic amine which acts as an ] and ]. <ref></ref> ] is an ] that has weight loss side effects. <ref></ref> The exact mechanism of action for both drugs is unknown. <ref></ref> | |||
| ⚫ | On February 22, 2012, U.S. ] (FDA) advisors voted 20 to 2 to recommend that the FDA adopt phentermine/topiramate ER for chronic weight management.<ref></ref> On July 17, 2012, the U.S. FDA approved Qsymia as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: ≥30 kg/m<sup>2</sup> or ≥27 kg/m<sup>2</sup> (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia.<ref></ref> Qsymia is available in certified retail pharmacies nationwide and also available through a certified mail-order pharmacy network.<ref></ref> | ||
| ==Available Doses== | |||
| The following doses of phentermine IR (immediate-release) and topiramate ER were used in Phase 3 testing<ref></ref>: | |||
| • Top dose: phentermine 15 mg and topiramate ER 92 mg | |||
| • Recommended dose: phentermine 7.5 mg and topiramate ER 46 mg | |||
| • Starting dose: phentermine 3.75 mg and topiramate ER 23 mg | |||
| ⚫ | On February 22, 2012, U.S. ] (FDA) advisors voted 20 to 2 to recommend that the FDA adopt phentermine/topiramate |
||
| ==Safety and effectiveness== | ==Safety and effectiveness== | ||
| Qsymia clinical trials have shown significant weight loss among subjects receiving Qsymia when compared with placebo.<ref></ref> The Phase 3 56-week EQUIP and CONQUER studies showed an average weight loss of 8% to 11% with the recommended dose or top dose (ITT-LOCF).<ref></ref> In addition, 62% to 70% of subjects receiving the recommended dose or top dose of Qsymia achieved ≥5% weight by week 56 (ITT-LOCF).<ref></ref> | |||
| Clinical studies have shown weight loss under treatment with Qnexa. The phase 3, 56-week EQUIP study showed that the average weight loss of 14.7% (37 lbs) was achieved by obese patients treated with Qnexa.<ref></ref> The following doses of phentermine IR and topiramate CR were used in Phase 3 testing: | |||
| *Full strength formula: 15 mg of phentermine IR (instant-release) and 92 mg of topiramate CR (controlled-release) | |||
| *Mid strength formula: 7.5 mg phentermine IR and 46 mg topiramate CR | |||
| The most common adverse events which occurred at a rate ≥5% and ≥1.5 times placebo included paraesthesia (tingling in fingers/toes), dizziness, dysguesia, insomnia, ], and ].<ref></ref> | |||
| *Low strength formula: 3.75 mg phentermine IR and 23 mg topiramate CR | |||
| Qsymia is contraindicated in pregnancy, glaucoma, hyperthyroidism, during or within 14 days of taking monoamine oxidase inhibitors, and in patients with hypersensitivity or idiosyncrasy to sympathomimetic amines. Qsymia can cause an increase in resting heart rate.<ref></ref> | |||
| Qsymia can cause fetal harm. Data from pregnancy registries and epidemiology studies indicate that a fetus exposed to topiramate, a component of Qsymia, in the first trimester of pregnancy has an increased risk of oral clefts (cleft lip with or without cleft palate).<ref></ref> If a patient becomes pregnant while taking Qsymia, treatment should be discontinued immediately, and the patient should be apprised of the potential hazard to a fetus. Females of reproductive potential should have a negative pregnancy test before starting Qsymia and monthly thereafter during Qsymia therapy. Females of reproductive potential should use effective contraception during Qsymia therapy.<ref></ref> | |||
| ==Qsymia Risk Evaluation and Mitigation Strategy (REMS)== | |||
| In 2009, Vivus reported that the main side effects during testing phases were ], a tingling in the fingers and toes and ].<ref></ref> However, in 2010 ]'s Dr. ] testified before the FDA Advisory Committee that studies showed that Qnexa carries a long list of relatively rare but potentially serious side effects, including possible birth defects<ref></ref> | |||
| Qsymia was approved with a REMS to assure that benefits of treatment outweigh the risks.<ref></ref> Because of the teratogenic risk associated with Qsymia therapy, Qsymia is available through a limited program under the REMS. Under the Qsymia REMS, only certified pharmacies may distribute Qsymia. Further information, is available at www.QsymiaREMS.com or by telephone at 1-888-998-4887. <ref></ref> | |||
| ==Studies and timeline== | |||
| ==Key Publications== | |||
| '''EQUIP''' | '''EQUIP''' | ||
| Investigated the safety and efficacy of the combination for 56 weeks in severely obese patients (BMI ≥35 kg/m2); published in Obesity. <ref></ref> | |||
| EQUIP investigated the combination for 56 weeks in severely obese patients.<ref>Controlled-Release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial (EQUIP), </ref> | |||
| '''CONQUER''' | '''CONQUER''' | ||
| A 56-week safety and efficacy trial, evaluating obese or overweight patients (BMI ≥27 and ≤45 kg/m2) with ≥2 weight-related comorbidities (such as type 2 diabetes, hypertension, dyslipidemia); published in ].<ref></ref> | |||
| A 56-week safety and efficacy trial, published in ].<ref>Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER)., </ref> | |||
| '''SEQUEL''' | '''SEQUEL''' | ||
| A 52-week extension of CONQUER, collecting long-term data over 108 weeks.<ref></ref> | |||
| A 108-week trial rolling-over patients from CONQUER, collecting long-term data.<ref>Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL), </ref> | |||
| ==Approval history== | |||
| In December 2009 VIVUS submitted a ] (NDA) to the FDA and on March 1, 2010, Vivus announced that the FDA accepted the NDA for review.<ref></ref> | |||
| On December 28, 2009 a ] (NDA) was submitted to the FDA for approval<ref></ref> and on March 1, 2010, Vivus announced that the agency accepted the NDA.<ref></ref> | |||
| In October 2010, the FDA announced its decision to not approve Qsymia in its current form and issued a Complete Response Letter (CRL) to VIVUS due to lack of long-term data and concerns about side effects including elevated heart rate, major adverse cardiovascular events, and birth defects.<ref></ref> | |||
| FDA approval was declined in October 2010 due to concerns about dangerous side effects, including suicidal thoughts, heart palpitations, memory lapses and birth defects.<ref>{{cite web |url=http://www.msnbc.msn.com/id/39905030/ns/health-diet_and_nutrition/ |title=FDA rejects second weight-loss drug in a week |date=10/29/2010 5:06:32 AM ET |publisher=msnbc.com news services |accessdate=29 October 2010}}</ref> | |||
| In January 2011, the FDA expressed concerns about the potential for Qnexa to cause birth defects and asked Vivus to examine this possibility before the drug can be approved.<ref>, ''Business Week'', January 21, 2011</ref> | |||
| The FDA expressed concerns about the potential for Qsymia to cause birth defects and requested that Vivus assess the feasibility of analyzing existing healthcare databases to determine the historical incidence of oral cleft in offspring of women treated with topiramate for migraine prophylaxis (100 mg).<ref></ref> | |||
| Qnexa's name was changed to ] and approved for sale on July 17, 2012 by the FDA.<ref>{{cite web|last=Hellmich|first=Nancy|title=New diet drug helps patients lose about 10% of weight|url=http://www.usatoday.com/news/health/story/2012-07-18/qsymia-diet-drug-approval/56271594/1|publisher=USA Today|accessdate=17 July 2012}}</ref><ref>{{cite web|title=Medications Target Long-Term Weight Control|url=http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm312380.htm|publisher=FDA.gov|accessdate=17 July 2012}}</ref> | |||
| In October 2011, VIVUS resubmitted the NDA to the FDA with responses to the issues addressed in the CRL. The FDA accepted the NDA in November 2011.<ref></ref> | |||
| On February 22, 2012, US FDA advisors on the Endocrine and Metabolism Advisory Committee voted 20 to 2 to recommend that the FDA adopt phentermine/topiramate ER for chronic weight management.<ref></ref> | |||
| The drug’s name was changed from Qnexa to Qsymia, and approved by the FDA on July 17, 2012.<ref></ref> | |||
| On September 18, 2012, Qsymia became available on the US market.<ref></ref> | |||
| ==Patents and other indications== | ==Patents and other indications== | ||
| ⚫ | Vivus currently has four U.S. patents covering Qsymia. <ref></ref> These patents are related to the product and methods of using the drug in various therapeutic applications. | ||
| ⚫ | Qsymia is also in phase 2 clinical development for the treatment of type 2 diabetes and ] (OSA). A phase 2 safety and efficacy study evaluating Qsymia in patients with OSA showed that patients who took Qsymia had improvements in sleep apnea events (apnea-hypopnea events) and lost more weight than those who took placebo.<ref></ref> | ||
| Further analyses from clinical studies demonstrated that Qsymia improves blood pressure.<ref></ref> Dr. Suzanne Oparil of the ] stated “The higher the dose, the more weight loss and the more blood pressure went down” presented at the American Society of Hypertension’s 25th annual meeting in New York.<ref></ref> | |||
| ⚫ | Vivus currently has four U.S. patents covering |
||
| Her co-authored study was subsequently accepted and published by the American Journal of Cardiology.19<ref></ref> | |||
| ⚫ | |||
| Further research data released indicates that Qnexa lowers blood pressure. Dr. Suzanne Oparil of the ] stated “The higher the dose, the more weight loss and the more blood pressure went down” presented at the American Society of Hypertension’s 25th annual meeting in New York.<ref></ref> Her co-authored study was subsequently accepted and published by the American Journal of Cardiology.<ref></ref> | |||
| ==References== | ==References== | ||
| {{reflist}} | {{reflist}} | ||
| == |
==External links== | ||
| * | |||
| {{Antiobesity preparations}} | {{Antiobesity preparations}} | ||
Revision as of 20:26, 28 October 2013
Pharmaceutical compound | |
 | |
| Combination of | |
|---|---|
| Phentermine | Appetite suppressant/stimulant of the amphetamine and phenethylamine class |
| Topiramate | Anticonvulsant |
| Clinical data | |
| Trade names | Qsymia |
| Routes of administration | Oral |
| ATC code |
|
| Legal status | |
| Legal status |
|
| Identifiers | |
| PubChem CID | |
| CompTox Dashboard (EPA) | |
| (verify) | |
The combination of the drugs phentermine and topiramate (trade name Qsymia, formerly Qnexa) is a medication indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: ≥30 kg/m or ≥27 kg/m (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia. In clinical trials, Qsymia was associated with significant weight loss when compared with placebo. This weight loss was associated with improvements in weight-related comorbidities such as improved glycemia, decreased blood pressure, and improved cholesterol.
Qsymia was developed by Vivus, Inc., a California pharmaceutical company. Phentermine is a sympathomimetic amine which acts as an appetite suppressant and stimulant. Topiramate is an anticonvulsant that has weight loss side effects. The exact mechanism of action for both drugs is unknown.
On February 22, 2012, U.S. Food and Drug Administration (FDA) advisors voted 20 to 2 to recommend that the FDA adopt phentermine/topiramate ER for chronic weight management. On July 17, 2012, the U.S. FDA approved Qsymia as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: ≥30 kg/m or ≥27 kg/m (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia. Qsymia is available in certified retail pharmacies nationwide and also available through a certified mail-order pharmacy network.
Available Doses
The following doses of phentermine IR (immediate-release) and topiramate ER were used in Phase 3 testing:
• Top dose: phentermine 15 mg and topiramate ER 92 mg
• Recommended dose: phentermine 7.5 mg and topiramate ER 46 mg
• Starting dose: phentermine 3.75 mg and topiramate ER 23 mg
Safety and effectiveness
Qsymia clinical trials have shown significant weight loss among subjects receiving Qsymia when compared with placebo. The Phase 3 56-week EQUIP and CONQUER studies showed an average weight loss of 8% to 11% with the recommended dose or top dose (ITT-LOCF). In addition, 62% to 70% of subjects receiving the recommended dose or top dose of Qsymia achieved ≥5% weight by week 56 (ITT-LOCF).
The most common adverse events which occurred at a rate ≥5% and ≥1.5 times placebo included paraesthesia (tingling in fingers/toes), dizziness, dysguesia, insomnia, constipation, and dry mouth.
Qsymia is contraindicated in pregnancy, glaucoma, hyperthyroidism, during or within 14 days of taking monoamine oxidase inhibitors, and in patients with hypersensitivity or idiosyncrasy to sympathomimetic amines. Qsymia can cause an increase in resting heart rate.
Qsymia can cause fetal harm. Data from pregnancy registries and epidemiology studies indicate that a fetus exposed to topiramate, a component of Qsymia, in the first trimester of pregnancy has an increased risk of oral clefts (cleft lip with or without cleft palate). If a patient becomes pregnant while taking Qsymia, treatment should be discontinued immediately, and the patient should be apprised of the potential hazard to a fetus. Females of reproductive potential should have a negative pregnancy test before starting Qsymia and monthly thereafter during Qsymia therapy. Females of reproductive potential should use effective contraception during Qsymia therapy.
Qsymia Risk Evaluation and Mitigation Strategy (REMS)
Qsymia was approved with a REMS to assure that benefits of treatment outweigh the risks. Because of the teratogenic risk associated with Qsymia therapy, Qsymia is available through a limited program under the REMS. Under the Qsymia REMS, only certified pharmacies may distribute Qsymia. Further information, is available at www.QsymiaREMS.com or by telephone at 1-888-998-4887.
Key Publications
EQUIP Investigated the safety and efficacy of the combination for 56 weeks in severely obese patients (BMI ≥35 kg/m2); published in Obesity.
CONQUER
A 56-week safety and efficacy trial, evaluating obese or overweight patients (BMI ≥27 and ≤45 kg/m2) with ≥2 weight-related comorbidities (such as type 2 diabetes, hypertension, dyslipidemia); published in The Lancet.
SEQUEL
A 52-week extension of CONQUER, collecting long-term data over 108 weeks.
Approval history
In December 2009 VIVUS submitted a new drug application (NDA) to the FDA and on March 1, 2010, Vivus announced that the FDA accepted the NDA for review.
In October 2010, the FDA announced its decision to not approve Qsymia in its current form and issued a Complete Response Letter (CRL) to VIVUS due to lack of long-term data and concerns about side effects including elevated heart rate, major adverse cardiovascular events, and birth defects.
The FDA expressed concerns about the potential for Qsymia to cause birth defects and requested that Vivus assess the feasibility of analyzing existing healthcare databases to determine the historical incidence of oral cleft in offspring of women treated with topiramate for migraine prophylaxis (100 mg).
In October 2011, VIVUS resubmitted the NDA to the FDA with responses to the issues addressed in the CRL. The FDA accepted the NDA in November 2011.
On February 22, 2012, US FDA advisors on the Endocrine and Metabolism Advisory Committee voted 20 to 2 to recommend that the FDA adopt phentermine/topiramate ER for chronic weight management.
The drug’s name was changed from Qnexa to Qsymia, and approved by the FDA on July 17, 2012.
On September 18, 2012, Qsymia became available on the US market.
Patents and other indications
Vivus currently has four U.S. patents covering Qsymia. These patents are related to the product and methods of using the drug in various therapeutic applications.
Qsymia is also in phase 2 clinical development for the treatment of type 2 diabetes and obstructive sleep apnea (OSA). A phase 2 safety and efficacy study evaluating Qsymia in patients with OSA showed that patients who took Qsymia had improvements in sleep apnea events (apnea-hypopnea events) and lost more weight than those who took placebo.
Further analyses from clinical studies demonstrated that Qsymia improves blood pressure. Dr. Suzanne Oparil of the University of Alabama at Birmingham stated “The higher the dose, the more weight loss and the more blood pressure went down” presented at the American Society of Hypertension’s 25th annual meeting in New York.
Her co-authored study was subsequently accepted and published by the American Journal of Cardiology.19
References
- Vivus Inc.
- http://ir.vivus.com/releasedetail.cfm?ReleaseID=692685
- http://ir.vivus.com/releasedetail.cfm?ReleaseID=447799
- http://ir.vivus.com/releasedetail.cfm?ReleaseID=620724
- http://usatoday30.usatoday.com/news/health/story/2012-07-18/qsymia-diet-drug-approval/56271594/1