PharmaceuticalAnti-obesity combinationStimulant anorecticAnticonvulsant

Phentermine/Topiramate (Qsymia)

Also known as Qsymia · phentermine-topiramate ER · VI-0521

Written by enwyReviewed 5 Aug 20261 sources0 comments

A fixed-dose combination of the stimulant anorectic phentermine with the anticonvulsant topiramate, FDA-approved as Qsymia in 2012 for chronic weight management. It is one of the more effective oral anti-obesity drugs, but carries stimulant effects, cognitive side effects and clear teratogenic (cleft palate) risk requiring pregnancy precautions.

01 Overview

Qsymia pairs low-dose phentermine, a noradrenaline-releasing appetite suppressant, with extended-release topiramate, which promotes satiety and weight loss through incompletely understood GABAergic and carbonic-anhydrase effects. The combination is titrated upward and delivers roughly 8-10% body-weight loss at top dose, more than most single-agent oral drugs.

It remains approved in the US but was not approved in Europe, partly over cardiovascular and teratogenicity concerns. Topiramate causes fetal oral clefts, so a risk-management program and pregnancy testing apply; phentermine contributes stimulant cardiovascular effects.

02 Mechanism

Phentermine releases noradrenaline (and some dopamine) to suppress appetite; topiramate adds satiety via GABA-A modulation, glutamate (AMPA/kainate) antagonism and carbonic anhydrase inhibition.

03 Dosing

Tier	Dose	Route	Notes
Starting dose	3.75–23 mg/day	Oral	3.75 mg phentermine / 23 mg topiramate ER once daily for 14 days.
Recommended dose	7.5–46 mg/day	Oral	7.5/46 mg once daily after titration.
Top dose	15–92 mg/day	Oral	15 mg phentermine / 92 mg topiramate ER for inadequate response.

04 Effects

Effect	Magnitude	Evidence
Substantial weight lossOne of the more effective oral regimens (EQUIP/CONQUER trials).	~8-10% body weight at top dose	Clinical
Appetite suppressionCombined noradrenergic and satiety effects reduce intake.	marked	Clinical

05 Side effects

Effect	Severity	Frequency	Evidence
Teratogenicity (oral clefts)Topiramate increases the risk of fetal cleft lip/palate.	Severe	Rare but serious in pregnancy	Clinical
Paresthesia and cognitive effectsTingling, dysgeusia, word-finding difficulty and concentration problems from topiramate.	Mild	Common	Clinical
Stimulant cardiovascular effectsIncreased heart rate and insomnia from phentermine.	Moderate	Common	Clinical

06 Legal status

United States

Schedule IV (phentermine component); REMS

Approved 2012; risk-management program for teratogenicity. · as of Jan 2026

Not approved

CHMP refused marketing authorisation. · as of Jan 2026

07 References

Effects of low-dose, controlled-release phentermine plus topiramate combination on weight and metabolic parameters (CONQUER)The Lancet, 2011 (Gadde et al.)

08 Discussion0 comments

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This page is reference information, not medical advice. Doses and protocols are documented as they appear in the clinical literature and in practice — describing them is not a recommendation to use them. Countermeasures listed here are not a substitute for a physician. Legal status varies by jurisdiction and changes.