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In June 2022, the Food and Drug Administration (FDA) approved a supplemental indication for Qsymia (phentermine and topiramate extended-release capsules) for chronic weight management in pediatric patients ages 12 years and older with body mass index (BMI) at or above the 95th percentile for sex and age (1). Qsymia was initially approved in July, 2012 for chronic weight management in adults with a BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with one weight-related comorbidity.
The supplemental pediatric indication was based on data from a 56-week, multicenter, randomized, double-blind, placebo-controlled trial in the United States (2). 223 adolescents with obesity ages 12 through 16 years received once daily placebo (n=56), mid-dose phentermine/topiramate 7.5 mg/46 mg (n=54), or high-dose phentermine/topiramate 15 mg/92 mg (n=113). Lifestyle modification was encouraged for all participants. Participants were required to have a Tanner stage above one and stable body weight without current use of antiobesity medications. Adolescents with history of bipolar disorder and major depressive disorder were excluded. At 56 weeks, the change in BMI was -10.4 percentage points (95% CI, −13.89 to −6.99; P<0.001) in participants taking high-dose phentermine/topiramate compared to participants receiving placebo and -8.1 percentage points (95% CI, −11.92 to −4.31; P<0.001) for mid-dose phentermine/topiramate compared to placebo.
Adverse events were generally similar among the three groups, although dizziness, pyrexia, and depression were more common in the treatment groups compared to placebo (2). Three serious adverse events occurred in two participants in the high-dose group including bile duct stone, depression, and suicide ideation. Dropout rates were 50% for placebo, 27.8% for mid-dose, and 38.9% for high-dose. The authors reported no clinically relevant differences across groups in mental health or cognition based on results of PHQ-9, C-SSRS, and CANTAB. They also reported no apparent effects on bone age, bone health, growth, and development. The study was funded by VIVUS LLC, which manufactures Qsymia.
Qsymia is taken orally, once daily in the morning. The starting dose is 3.75 mg/23 mg, which is given for 2 weeks. The dose is then increased to 7.5 mg/46 mg for 12 weeks. If BMI does not decrease by 3% during that time, the recommendation is to increase to 11.25 mg/69 mg for 2 weeks and then 15 mg/92 mg. If a 5% reduction from baseline BMI is not achieved after 12 weeks on 15 mg/92 mg, the recommendation is to discontinue Qsymia. Reduction to every other day dosing for at least one week is required before discontinuation to decrease the risk of seizure.
Qsymia is a Schedule IV controlled substance, as it contains phentermine. Qsymia increases the risk of orofacial clefts (cleft lip and palate) if used during the first trimester of pregnancy. Therefore, Qsymia has a Risk Evaluation and Mitigation Strategy (REMS) and is only available through certified pharmacies (https://qsymiarems.com/certified-pharmacy-network). Patients who could become pregnant should have counseling on risk of teratogenic effects and a negative pregnancy test prior to initiating therapy. The manufacturer’s label reports that Qsymia was associated with a reduction in height velocity of 1.3-1.4 cm/year compared to placebo-treated patients and recommends monitoring linear growth in pediatric patients (1). Additionally, the label notes decreased bone mineral acquisition in pediatric patients treated with Qsymia compared to placebo.
- Qsymia [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022580s021lbl.pdf Revised 6/2022. Accessed 7/15/2022.
- Kelly AS, Bensignor MO, Hsia DS, Shoemaker AH, Shih W, Peterson C, Varghese ST. Phentermine/Topiramate for the Treatment of Adolescent Obesity. NEJM Evidence. 2022;1(6):EVIDoa2200014. doi: doi:10.1056/EVIDoa2200014.
Prepared on behalf of the PES Drug & Therapeutics committee by: Laura C. Page, MD
Last updated: August 11, 2022