What are the indications and usage guidelines for Qsymia (phentermine and topiramate)?

Qsymia (Phentermine/Topiramate ER): Indications and Usage

Qsymia is indicated for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities (hypertension, type 2 diabetes, dyslipidemia, or obstructive sleep apnea), used as an adjunct to lifestyle interventions when diet and exercise alone have been inadequate. 1

Patient Selection Criteria

Eligible patients must meet these requirements:

• BMI ≥30 kg/m² without comorbidities, OR 1
• BMI ≥27 kg/m² with at least one weight-related comorbidity including hypertension, type 2 diabetes mellitus, dyslipidemia, or obstructive sleep apnea 1
• Inadequate response to lifestyle interventions (diet and exercise) alone 1

The 2022 American Gastroenterological Association guidelines provide moderate certainty evidence supporting Qsymia for long-term obesity management, making it one of the preferred pharmacological options alongside semaglutide 2.4 mg and liraglutide 3.0 mg. 1

Dosing and Titration Protocol

Start with gradual dose escalation to minimize adverse effects: 1, 2

• Initial dose: 3.75 mg phentermine/23 mg topiramate daily for 14 days 2
• Titration to recommended dose: 7.5 mg/46 mg daily after initial 14 days 1, 2
• Further escalation if needed: 11.25 mg/69 mg daily, then maximum dose of 15 mg/92 mg daily 1, 2

The available formulations include four dose strengths: 3.75/23 mg, 7.5/46 mg, 11.25/69 mg, and 15/92 mg. 2

Expected Weight Loss Outcomes

Clinical trial data demonstrates significant weight reduction:

• Mean weight loss of 6.6% at 1 year compared to placebo (intention-to-treat analysis) 1
• At the 7.5/46 mg dose: 7.8% weight loss 2
• At the 15/92 mg dose: 9.8% weight loss 2
• Long-term efficacy maintained at 108 weeks with 9.3% and 10.5% weight loss at the two doses respectively 2
• 62% of patients achieve ≥5% weight loss at the 7.5/46 mg dose, and 70% at the 15/92 mg dose 3

Efficacy Assessment and Discontinuation Criteria

Monitor treatment response systematically: 1, 2

• Assess efficacy and safety monthly for the first 3 months 1, 2
• Continue monitoring at least every 3 months thereafter 1, 2
• Discontinue if <5% weight loss after 12 weeks at maximum tolerated dose 1, 2

This discontinuation rule is critical—continuing ineffective therapy exposes patients to unnecessary risks without benefit. 1

Absolute Contraindications

Do not prescribe Qsymia in these situations: 1, 2, 4

• Pregnancy or inadequate contraception in women of childbearing potential (topiramate causes orofacial clefts in first trimester) 2, 4
• Cardiovascular disease (sympathomimetic effects of phentermine) 1
• Glaucoma 1, 4
• Hyperthyroidism 1
• During or within 14 days of MAOI use 1
• Concomitant use with other sympathomimetic amines 1
• History of drug abuse 1

The 2017 AGA guideline explicitly recommends against prescribing sympathomimetic agents like phentermine/topiramate ER in patients with cardiovascular disease, suggesting lorcaserin or orlistat as safer alternatives in this population. 1

Required Safety Monitoring

Implement these monitoring protocols: 2, 4

• Monthly pregnancy tests in all women of childbearing potential 2, 4
• Regular blood pressure and heart rate monitoring (phentermine can increase heart rate) 2, 4
• Periodic serum bicarbonate levels (topiramate causes metabolic acidosis) 4
• Kidney function monitoring in patients at risk for nephrolithiasis 4

Common Adverse Effects

Counsel patients about expected side effects: 1, 2

• Paresthesias (numbness/tingling) 1, 2
• Dysgeusia (altered taste) 1, 2
• Dry mouth 1, 2
• Constipation 1, 2
• Insomnia 1, 2
• Dizziness 1, 2

Depression-related and anxiety-related adverse events occur in 4-7% and 5-8% of patients respectively at therapeutic doses. 3

Critical Prescribing Considerations

Topiramate reduces the efficacy of hormonal contraceptives, requiring additional or alternative contraceptive methods in women of childbearing potential. 2 This is particularly important given the teratogenicity risk.

Qsymia is a Schedule IV controlled substance due to the phentermine component, requiring appropriate prescribing documentation and monitoring for potential abuse. 1

Never stop topiramate abruptly—taper by taking one capsule every other day for at least 1 week before complete cessation to prevent seizure risk. 4

Positioning in Treatment Algorithm

The 2022 AGA guidelines suggest Qsymia based on moderate certainty evidence, placing it alongside other first-line options like semaglutide 2.4 mg and liraglutide 3.0 mg. 1 However, the cardiovascular contraindication limits its use compared to GLP-1 agonists, which have demonstrated cardiovascular benefits. 1 For patients without cardiovascular disease who have failed lifestyle interventions, Qsymia represents an effective long-term pharmacological option with FDA approval for chronic weight management. 1