What is the recommended treatment approach for Qysmia (phentermine and topiramate) for weight loss?

Phentermine/Topiramate Extended-Release (Qsymia) Treatment Approach for Weight Loss

Phentermine/topiramate extended-release (Qsymia) should be initiated at 3.75 mg/23 mg once daily for 14 days, then increased to a maintenance dose of 7.5 mg/46 mg daily, with potential escalation to a maximum dose of 15 mg/92 mg if needed, in combination with lifestyle modifications. 1

Patient Selection

• Indicated for adults with:
  • BMI ≥30 kg/m² (obesity) OR
  • BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes, dyslipidemia, or obstructive sleep apnea) 2
• Particularly beneficial for patients with comorbid migraine headaches due to topiramate component 1

Dosing Protocol

1. Initial dose: 3.75 mg/23 mg once daily for 14 days
2. Maintenance dose: 7.5 mg/46 mg once daily
3. Dose escalation:
   • If <3% weight loss after 12 weeks at 7.5/46 mg: increase to 11.25/69 mg daily for 14 days, then 15/92 mg daily
   • If <5% weight loss after 12 weeks at maximum dose: discontinue treatment 2, 1
4. Administration: Take once daily in the morning to minimize sleep disturbances 1

Expected Outcomes

• Average weight loss:
  • 6.7 kg with 7.5 mg/46 mg dose
  • 8.9 kg with 15 mg/92 mg dose 2, 1
• 45-70% of patients achieve ≥5% weight loss 2
• Clinical trials showed 7-10% greater weight loss compared to placebo 3
• Significant improvements in cardiovascular risk factors, including blood pressure, lipid profile, and glycemic control 4, 5

Required Monitoring

1. Before initiation:

   • Pregnancy test for women of childbearing potential (Category X medication)
   • Baseline serum bicarbonate levels
   • Blood pressure and heart rate
   • Kidney function 1

2. During treatment:

   • Monthly assessment for first 3 months, then every 3 months
   • Weight and BMI
   • Serum bicarbonate (risk of metabolic acidosis)
   • Kidney function and hydration status (risk of kidney stones)
   • Blood pressure and heart rate
   • Pregnancy testing for women of childbearing potential 2, 1

Contraindications

• Pregnancy or planning pregnancy
• Hyperthyroidism
• Uncontrolled hypertension
• Active/unstable coronary disease
• Concurrent use of monoamine oxidase inhibitors
• Glaucoma
• History of cardiovascular disease (phentermine component is a sympathomimetic agent) 2, 1

Common Side Effects and Management

• Paresthesia: Usually transient, may improve with time
• Dry mouth: Encourage adequate hydration
• Constipation: Increase fiber and fluid intake
• Dysgeusia: Usually transient
• Insomnia: Morning administration recommended
• Cognitive effects: Monitor for memory, attention, or language problems
• Depression/anxiety: Monitor mood changes 1, 3

Discontinuation Protocol

1. Indications for discontinuation:

   • <3% weight loss after 12 weeks at 7.5/46 mg dose
   • <5% weight loss after 12 weeks at maximum dose
   • Intolerable side effects
   • Pregnancy

2. Discontinuation method:

   • Gradual tapering (take medication every other day for at least one week)
   • Abrupt discontinuation may increase seizure risk 2, 1

Safety Considerations

• European Medicines Agency rejected phentermine/topiramate due to safety concerns 6
• Cardiovascular safety: Increases heart rate slightly but decreases blood pressure; appears safe for patients at low-to-intermediate cardiovascular risk 4
• Long-term safety data beyond 2 years is limited 6
• Women of childbearing potential must use effective contraception due to topiramate's teratogenic risk 1

Phentermine/topiramate ER, when combined with lifestyle modifications, offers significant weight loss benefits and improvements in metabolic parameters. However, careful patient selection, monitoring, and adherence to dosing protocols are essential to maximize benefits while minimizing risks.