| Revision as of 19:22, 20 September 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (no changed fields - updated 'ChemSpiderID_Ref', 'DrugBank_Ref', 'UNII_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'KEGG_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'ChEBI_Ref') per Chem/Drugbox validation (report [[Misplaced Pagesโ Previous edit |
Latest revision as of 19:28, 22 October 2024 edit undoAnders.Warga (talk | contribs)Extended confirmed users, Pending changes reviewers6,985 edits VIVUS version OK in Poland & Scandinavia. ๐ต๐ฑ๐ธ๐ช๐ซ๐ฎ๐ฎ๐ธ๐ณ๐ด๐ฉ๐ฐTags: Mobile edit Mobile app edit iOS app edit App section sourceย |
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{{Short description|Obesity medication}} |
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{{Use dmy dates|date=March 2024}} |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Drugbox |
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{{Drugbox |
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| Watchedfields = changed |
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| verifiedrevid = 414490995 |
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| verifiedrevid = 451550560 |
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⚫ |
| type = combo |
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| image = Phentermine and topiramate.svg |
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| width = 175 |
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| alt = |
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<!--Combo data--> |
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<!--Combo data--> |
| ⚫ |
| type = combo |
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| component1 = Phentermine |
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| component1 = Phentermine |
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| class1 = ]/] of the ] and ] class |
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| class1 = ]/] of the ] and ] class |
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| component2 = Topiramate |
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| component2 = Topiramate |
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| class2 = ] |
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| class2 = ] (extended release formulation is used) |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| pronounce = {{IPAc-en|k|juห|s|ษช|ห|m|iห|ษ}} {{respell|kew|sim|EE|ษ}} |
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| tradename = |
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| tradename = Qsymia, QSIVAยฎ |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| Drugs.com = {{drugs.com|ppa|phentermine-and-topiramate}} |
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⚫ |
| routes_of_administration = ] |
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| ATC_prefix = A08 |
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| ATC_suffix = AA51 |
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| ATC_supplemental = {{ATCvet|A08|AA51}} |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_US = Schedule IV |
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| legal_status = experimental, yet has been submitted to the FDA for approval |
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| legal_status = Rx-only |
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| routes_of_administration = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number = |
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| CAS_number = 960078-81-3 |
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| ATC_prefix = none |
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| PubChem = 56842108 |
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| ATC_suffix = |
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| DrugBank = |
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| PubChem = |
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| KEGG = D11710 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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<!--Chemical data--> |
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<!--Chemical data--> |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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The combination of the ] '''] and ]''' (trade name '''Qnexa''') is an investigational medication for the treatment of ] and related conditions such as ] and has been found to lower blood pressure and cholesterol.<ref>,</ref> Qnexa is being developed by ], a California pharmaceutical company.<ref></ref> ] is an ] and ] of the ] and ] class. ] is an ] that has weight loss side effects. |
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'''Phentermine/topiramate''', sold under the brand names '''Qsymia''' or '''QSIVA''', is a ] of ] and ] used to treat ].<ref name=MTM2019>{{cite web |title=Phentermine and topiramate Uses, Side Effects & Warnings |url=https://www.drugs.com/mtm/phentermine-and-topiramate.html |website=Drugs.com |access-date=13 April 2019 |language=en}}</ref><ref name=Vivus2024>{{cite web |title= VIVUS Announces Commercialization of QSIVA in Sweden, Denmark, Finland, Iceland, Norway, and Poland |url=https://www.vivus.com/pdf/press-releases/2024-10-7%5EQsymia%5EQSIVA_GLOBAL_Commercialization_in_Scandinavian_Countries_and_Poland.pdf} |access-date=22 October 2024 |website=vivus.com |date=October 7, 2024}}</ref> It is used together with dietary changes and exercise.<ref name=Daily2019/> If less than 3% weight loss is seen after 3 months it is recommended the medication be stopped.<ref name=Daily2019/> The weight loss is modest.<ref name=Daily2019 /> Effects on heart related health problems or death is unclear.<ref name=Daily2019/><!-- Quote = The effect of Qsymia on cardiovascular morbidity and mortality has not been established --> |
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<!-- Side effects and mechanism --> |
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Common side effects include tingling, dizziness, trouble sleeping, and constipation.<ref name=Daily2019/> Serious side effects may include ], ].<ref name=Daily2019>{{cite web |title=DailyMed - Qsymia - phentermine and topiramate capsule, extended release |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40dd5602-53da-45ac-bb4b-15789aba40f9 |website=dailymed.nlm.nih.gov |access-date=13 April 2019}}</ref> Use is not recommended during ].<ref name=MTM2019/> ] is a ] and ].<ref name="Daily2019"/> ] is an ] that has weight loss side effects.<ref name="Daily2019"/> The exact mechanism of action for both drugs is unknown.<ref name="Daily2019"/> |
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<!-- History and culture --> |
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Phentermine/topiramate was approved for medical use in the United States in 2012.<ref name=Daily2019/> In October 2012, approval was denied in Europe, due to concerns regarding safety.<ref name=emainitial>{{cite web |url=http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/002350/WC500139215.pdf |title=www.ema.europa.eu |website= |access-date= |archive-date=21 December 2014 |archive-url=https://web.archive.org/web/20141221004626/http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/002350/WC500139215.pdf |url-status=dead }}</ref><ref name=":0">{{cite journal | vauthors = Siebenhofer A, Winterholer S, Jeitler K, Horvath K, Berghold A, Krenn C, Semlitsch T | title = Long-term effects of weight-reducing drugs in people with hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD007654 | date = January 2021 | issue = 1 | pmid = 33454957 | doi = 10.1002/14651858.CD007654.pub5 | pmc = 8094237 }}</ref><ref name=ema>{{Cite web |date=13 June 2013 |title=Qsiva |url=https://www.ema.europa.eu/en/medicines/human/EPAR/qsiva |website=EMA}}</ref> It was approved in 2024 in ] and all of ].<ref name=Vivus2024/> |
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==Medical uses== |
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In clinical trials, people treated with the highest dose of phentermine/topiramate ER in combination with a program of diet and exercise lost 10% to 11% of their body weight compared to 1% to 2% for those who received placebo.<ref name="Daily2019"/> In addition, 62% to 70% of subjects receiving the recommended dose or top dose of phentermine/topiramate ER achieved โฅ5% weight reduction by week 56 (ITT-LOCF) compared to 17% to 21% of those receiving a ].<ref name="Daily2019"/> |
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A Cochrane review on the long-term effects of weight-reducing drugs on people with ] found that phentermine/topiramate reduced body weight (when compared to ], and ]) and also reduced blood pressure.<ref name=":0" /> |
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==Adverse effects== |
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In clinical trials, the most common adverse events which occurred at a rate โฅ5% and โฅ1.5 times placebo included paraesthesia (tingling in fingers/toes), dizziness, ], ], ], and ].<ref name="Daily2019"/> |
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In the US, the drug label contains warnings for increased heart rate, suicidal behavior and ideation, glaucoma, mood and sleep disorders, creatinine elevation, and metabolic acidosis. Some of these warnings are based on historical observations in epilepsy patients taking topiramate. The FDA is requiring the company to perform a post-approval cardiovascular outcomes trial, due in part to the observation of increased heart rate in some people taking the drug in clinical trials. |
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===Pregnancy=== |
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Phentermine and topiramate can cause fetal harm. Data from pregnancy registries and epidemiology studies indicate that a fetus exposed to topiramate in the first trimester of pregnancy has an increased risk of oral clefts (cleft lip with or without cleft palate).<ref name="Daily2019"/> If a patient becomes pregnant while taking phentermine/topiramate ER, 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 phentermine/topiramate ER and monthly thereafter during phentermine/topiramate ER therapy. Females of reproductive potential should use effective contraception during phentermine/topiramate ER therapy.<ref name="Daily2019"/> |
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===Risk evaluation and mitigation strategy=== |
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Phentermine and topiramate was approved with a ] (REMS) program to ensure that benefits of treatment outweigh the risks.<ref>{{cite web|url=http://ir.vivus.com/releasedetail.cfm?ReleaseID=692685 |title=Vivus, Inc. - Vivus Announces FDA Approval of Once Daily Qsymia (Phentermine and Topiramate Extended-release) Capsules CIV |publisher=Ir.vivus.com |date= |access-date=19 June 2014}}</ref> |
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==Contraindications== |
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Phentermine/topiramate ER is contraindicated in pregnancy, glaucoma, hyperthyroidism, during or within 14 days of taking monoamine oxidase inhibitors, and in patients with hypersensitivity or idiosyncrasy to ] amines. Phentermine/topiramate ER can cause an increase in resting heart rate.<ref name="Daily2019"/> |
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==History== |
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Qnexa is currently not approved for use in the United States. It was rejected by regulators in the United States Food and Drug Administration after a panel found that tests showed that it was associated with a number of 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> |
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Phentermine and topiramate was developed by ], a California pharmaceutical company. |
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In December 2009, Vivus, Inc. submitted a ] (NDA) to the FDA and on 1 March 2010, Vivus, Inc. announced that the FDA accepted the NDA for review. |
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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 where used in Phase 3 testing: |
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*Full strength formula: 15 mg of phentermine IR (instant-release) and 92 mg of topiramate CR (controlled-release) |
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*Mid strength formula: 7.5 mg phentermine IR and 46 mg topiramate CR |
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*Low strength formula: 3.75 mg phentermine IR and 23 mg topiramate CR |
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In October 2010, the FDA announced its decision to not approve phentermine/topiramate ER in its current form and issued a ] 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>{{cite web|url=http://ir.vivus.com/releasedetail.cfm?ReleaseID=524576 |title=Vivus, Inc. - FDA Issues Complete Response Letter to Vivus Regarding New Drug Application for QNEXA(R) |publisher=Ir.vivus.com |date= |access-date=19 June 2014}}</ref> |
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The main side effects reported during testing phases were dry mouth, a tingling in the fingers and toes, and constipation.<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> The target date for the FDA to complete its review of the Qnexa NDA is October 28, 2010.<ref></ref> The FDA's Endocrinologic and Metabolic Drugs Advisory Committee is tentatively scheduled to review Vivus' Qnexa on July 15, 2010. It is expected that this may provide an indication on whether it is approved or not.<ref></ref> |
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In January 2011, the FDA expressed concerns about the potential for phentermine/topiramate ER to cause ]s 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>{{cite web|url=http://www.businessweek.com/ap/financialnews/D9KSPDA00.htm |archive-url=https://web.archive.org/web/20110628195047/http://www.businessweek.com/ap/financialnews/D9KSPDA00.htm |url-status=dead |archive-date=28 June 2011 |title=Vivus says FDA asks about Qnexa birth defect link |publisher=BusinessWeek |date=21 January 2011 |access-date=19 June 2014}}</ref> |
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Qnexa is also in phase 2 clinical development for the treatment of type 2 diabetes and ] (OSA). A phase 2 safety and efficacy study evaluating Qnexa in patients with OSA showed that patients who took Qnexa had a 69 percent reduction in sleep apnea events and lost more weight than those who took placebo.<ref></ref> |
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In October 2011, Vivus resubmitted the NDA to the FDA with responses to the issues addressed in the CRL and the FDA accepted the NDA in November 2011.<ref>{{cite web|url=http://ir.vivus.com/releasedetail.cfm?ReleaseID=615313 |title=Vivus, Inc. - Vivus Resubmits Qnexa NDA to the FDA |publisher=Ir.vivus.com |date= |access-date=19 June 2014}}</ref><ref>{{cite web|url=http://ir.vivus.com/releasedetail.cfm?ReleaseID=620724 |title=Vivus, Inc. - FDA Accepts New Drug Application Filing for Qnexa |publisher=Ir.vivus.com |date= |access-date=19 June 2014}}</ref> |
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Vivus currently has four U.S. patents covering Qnexa. These patents are related to the product and methods of using the drug in various therapeutic applications.<ref></ref> |
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In September 2012, Qsymia became available on the US market.<ref>{{cite web|url=http://ir.vivus.com/releasedetail.cfm?ReleaseID=707450 |title=Vivus, Inc. - Vivus Announces Availability Of Once Daily Qsymia (Phentermine And Topiramate Extended-Release) Capsules CIV |publisher=Ir.vivus.com |date= |access-date=19 June 2014}}</ref> |
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Further research data released indicates that Qnexa lowers blood pressure. Dr. Suzanne Oparil of the University of Alabama at Birmingham stated โThe higher the dose, the more weight loss and the more blood pressure went downโ presented at the American Society of Hypertensionโs 25th annual meeting in New York.<ref></ref> |
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In October 2012, approval was denied in the European Union, due to concerns regarding safety.<ref name=emainitial/><ref name=":0"/><ref name=ema/> |
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In January 2011, the ] expressed concerns about the potential for Qnexa to cause birth defects and has asked Vivus to examine this possibility before the drug can be approved.<ref>, ''Business Week'', January 21, 2011</ref> |
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==References== |
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== References == |
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{{reflist}} |
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{{reflist}} |
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{{Antiobesity preparations}} |
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{{Portal bar | Medicine}} |
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{{Authority control}} |
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{{DEFAULTSORT:Phentermine Topiramate}} |
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