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

Qsymia (Phentermine/Topiramate ER): Indications and Dosing

Primary Indication

Qsymia is FDA-approved for chronic weight management in adults with BMI ≥27 kg/m² with at least one obesity-related comorbidity (type 2 diabetes, hypertension, or dyslipidemia) or BMI ≥30 kg/m², used as an adjunct to reduced-calorie diet and increased physical activity. 1

Available Dose Forms

Qsymia comes in four extended-release capsule strengths, each containing phentermine/topiramate: 2

• 3.75 mg/23 mg (starting dose)
• 7.5 mg/46 mg (recommended maintenance dose)
• 11.25 mg/69 mg (intermediate escalation dose)
• 15 mg/92 mg (maximum dose)

Dosing Algorithm

Initial Titration Schedule

Start with 3.75 mg/23 mg once daily in the morning for 14 days, then increase to 7.5 mg/46 mg once daily. 1, 2 The medication must be taken in the morning as a single daily dose, not divided throughout the day. 2

Dose Escalation Decision Points

At 12 weeks on the 7.5 mg/46 mg dose: 1, 2

• If weight loss is <3%: Discontinue the medication OR escalate to 11.25 mg/69 mg daily for 14 days, then to 15 mg/92 mg daily
• If weight loss is ≥3%: Continue at 7.5 mg/46 mg dose

At 12 weeks on the maximum 15 mg/92 mg dose: 1, 2

• If weight loss is <5%: Discontinue the medication by gradual taper
• If weight loss is ≥5%: Continue treatment

Discontinuation Protocol

Never stop Qsymia abruptly. Taper by taking one capsule every other day for at least 1 week before complete cessation to prevent seizure risk from topiramate withdrawal. 3

Expected Weight Loss Outcomes

Clinical trial data demonstrate: 1, 2

• 7.5 mg/46 mg dose: 7.8-9.8% weight loss at 1 year (compared to 1.2% with placebo)
• 15 mg/92 mg dose: 9.8-10.5% weight loss at 1 year (compared to 1.2-1.8% with placebo)
• Weight loss persists through 108 weeks with continued treatment (9.3-10.5% from baseline) 1

Absolute Contraindications

Qsymia is absolutely contraindicated in: 1, 3

• Pregnancy (topiramate causes orofacial clefts, particularly cleft lip/palate, with first-trimester exposure)
• Women actively trying to conceive
• Women of childbearing potential not using reliable contraception
• Concurrent use with monoamine oxidase inhibitors 1
• Untreated closed-angle glaucoma 1, 3

Critical Safety Monitoring Requirements

All women of childbearing potential must: 1, 2, 3

• Use effective contraception throughout treatment
• Have monthly pregnancy tests

Required laboratory and clinical monitoring: 2, 3

• Monthly visits for the first 3 months, then at least every 3 months thereafter
• Periodic serum bicarbonate levels (risk of metabolic acidosis from topiramate)
• Heart rate monitoring (phentermine can increase heart rate despite blood pressure reduction)
• Kidney function assessment in patients at risk for nephrolithiasis

Common Side Effects

The most frequent adverse effects include: 1, 2

• Paresthesias (tingling sensations)
• Dysgeusia (altered taste)
• Dry mouth (xerostomia)
• Constipation
• Insomnia
• Dizziness
• Nasopharyngitis

These side effects can be minimized through gradual dose escalation. 2

Additional Clinical Considerations

Qsymia is a Schedule IV controlled substance due to the phentermine component. 1 The combination targets different weight loss mechanisms simultaneously—phentermine suppresses appetite through noradrenergic effects while topiramate reduces caloric intake through unclear mechanisms, producing additive weight loss. 1, 2

Contraindicated in patients with: 1

• Uncontrolled hypertension
• History of seizure disorders (relative contraindication given topiramate's anticonvulsant properties)
• Significant cognitive impairment 3

The medication should not be used in: 1

• Women who are nursing
• Patients with chronic opioid therapy (if considering combination with naltrexone/bupropion)