View source for Phentermine/topiramate

{{Short description|Obesity medication}}
{{Use dmy dates|date=March 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 451550560
| type = combo
| image = Phentermine and topiramate.svg
| width = 175
| alt = 

<!--Combo data-->
| component1 = Phentermine
| class1 = [[Appetite suppressant]]/[[stimulant]] of the [[amphetamine]] and [[phenethylamine]] class
| component2 = Topiramate
| class2 = [[Anticonvulsant]] (extended release formulation is used)

<!--Clinical data-->
| pronounce = {{IPAc-en|k|juː|s|ɪ|ˈ|m|iː|ə}} {{respell|kew|sim|EE|ə}}
| tradename = Qsymia, QSIVA® 
| Drugs.com = {{drugs.com|ppa|phentermine-and-topiramate}}
| routes_of_administration = [[Oral administration|By mouth]]
| ATC_prefix = A08
| ATC_suffix = AA51
| ATC_supplemental  = {{ATCvet|A08|AA51}}

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = Schedule IV
| legal_status = Rx-only

<!--Identifiers-->
| CAS_number = 960078-81-3
| PubChem = 56842108
| DrugBank =
| KEGG = D11710

<!--Chemical data-->
}}

<!-- Definition and medical uses -->
'''Phentermine/topiramate''', sold under the brand names '''Qsymia''' or '''QSIVA''', is a [[combination drug]] of [[phentermine]] and [[topiramate]] used to treat [[obesity]].<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 -->

<!-- Side effects and mechanism -->
Common side effects include tingling, dizziness, trouble sleeping, and constipation.<ref name=Daily2019/> Serious side effects may include [[suicide]], [[abuse]].<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 [[pregnancy]].<ref name=MTM2019/> [[Phentermine]] is a [[stimulant]] and [[appetite suppressant]].<ref name="Daily2019"/> [[Topiramate]] is an [[anticonvulsant]] that has weight loss side effects.<ref name="Daily2019"/> The exact mechanism of action for both drugs is unknown.<ref name="Daily2019"/>

<!-- History and culture -->
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 [[Poland]] and all of [[Scandinavia]].<ref name=Vivus2024/>

==Medical uses==
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 ≥5% weight reduction by week 56 (ITT-LOCF) compared to 17% to 21% of those receiving a [[placebo]].<ref name="Daily2019"/>

A Cochrane review on the long-term effects of weight-reducing drugs on people with [[hypertension]] found that phentermine/topiramate reduced body weight (when compared to [[orlistat]], and [[naltrexone/bupropion]]) and also reduced blood pressure.<ref name=":0" />

==Adverse effects==
In clinical trials, the most common adverse events which occurred at a rate ≥5% and ≥1.5 times placebo included paraesthesia (tingling in fingers/toes), dizziness, [[dysgeusia|altered taste]], [[insomnia]], [[constipation]], and [[dry mouth]].<ref name="Daily2019"/>

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.

===Pregnancy===
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"/>

===Risk evaluation and mitigation strategy===
Phentermine and topiramate was approved with a [[risk evaluation and mitigation strategy]] (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>

==Contraindications==
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 [[sympathomimetic]] amines. Phentermine/topiramate ER can cause an increase in resting heart rate.<ref name="Daily2019"/>

==History==
Phentermine and topiramate was developed by [[Vivus]], a California pharmaceutical company.

In December 2009, Vivus, Inc. submitted a [[new drug application]] (NDA) to the FDA and on 1 March 2010, Vivus, Inc. announced that the FDA accepted the NDA for review.

In October 2010, the FDA announced its decision to not approve phentermine/topiramate ER in its current form and issued a [[Complete Response Letter]] 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>

In January 2011, the FDA expressed concerns about the potential for phentermine/topiramate ER to cause [[birth defect]]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&nbsp;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>

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>

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>

In October 2012, approval was denied in the European Union, due to concerns regarding safety.<ref name=emainitial/><ref name=":0"/><ref name=ema/>

== References ==
{{reflist}}

{{Antiobesity preparations}}
{{Portal bar | Medicine}}
{{Authority control}}

{{DEFAULTSORT:Phentermine Topiramate}}
[[Category:Anorectics]]
[[Category:Anti-obesity drugs]]
[[Category:Combination anti-obesity drugs]]