What is the recommended approach for uptitration of Qsymia (phentermine and topiramate) in patients who do not achieve desired weight loss?

Qsymia Uptitration Protocol for Patients with Inadequate Weight Loss

For patients not achieving desired weight loss with Qsymia (phentermine/topiramate ER), the medication should be discontinued or escalated to the maximum dose if 3% weight loss is not achieved after 12 weeks at the 7.5/46 mg daily dose, and discontinued if 5% weight loss is not achieved after 12 additional weeks on the maximum dose of 15/92 mg daily. 1

Initial Dosing and Standard Titration

• Start with 3.75/23 mg daily for 14 days
• Increase to 7.5/46 mg daily (recommended dose)
• Evaluate effectiveness at 12 weeks on 7.5/46 mg daily

Uptitration Algorithm for Inadequate Response

At 12 Weeks on 7.5/46 mg Daily:

• If ≥5% weight loss achieved: Continue at current dose
• If 3-5% weight loss achieved: Consider increasing to 11.25/69 mg daily for 14 days, then to 15/92 mg daily
• If <3% weight loss achieved: Either discontinue medication OR increase to maximum dose 1

At 12 Additional Weeks on 15/92 mg Daily:

• If ≥5% weight loss achieved: Continue at current dose
• If <5% weight loss achieved: Discontinue medication 1

Monitoring During Uptitration

• Assess weight loss percentage from baseline at each visit
• Monitor for common side effects: paresthesias, dizziness, dysgeusia, insomnia, constipation, and dry mouth 1
• Monitor blood pressure and heart rate regularly, especially when increasing dose
• Assess for neuropsychiatric symptoms (depression, anxiety, suicidal ideation) 1

Clinical Considerations

• Gradual dose escalation helps minimize risks and adverse events 1
• The combination of phentermine and topiramate ER leads to additive weight loss by targeting different pathways simultaneously 1
• In clinical trials, weight loss of 7.8% and 9.8% was observed with 7.5/46 mg and 15/92 mg doses respectively, compared to 1.2% with placebo 1
• Long-term studies (SEQUEL) demonstrated persistent weight loss at 108 weeks with 9.3% and 10.5% weight loss in the 7.5/46 mg and 15/92 mg arms, respectively 1

Important Cautions

• Qsymia is contraindicated in pregnancy due to risk of orofacial clefts from topiramate 1
• Use caution in patients with cardiovascular disease due to the phentermine component 1
• Patients with a history of seizure disorders should be monitored closely as phentermine may lower seizure threshold 2
• The medication should be used as an adjunct to lifestyle modifications including diet and exercise 1

By following this structured approach to Qsymia uptitration, clinicians can maximize the likelihood of achieving meaningful weight loss while minimizing adverse effects in patients who initially show inadequate response to standard dosing.