What is the dosing regimen for phentermine (Phentermine) and topiramate (Topiramate) for weight loss?

From the Guidelines

Phentermine-topiramate for weight loss should be started at a low dose of 3.75 mg phentermine/23 mg topiramate once daily in the morning for 14 days, then increased to 7.5 mg/46 mg daily, with further escalation to 15 mg/92 mg daily as needed and tolerated, as recommended by the most recent guidelines 1. The dosing strategy for phentermine-topiramate is based on the principle of starting low and gradually increasing the dose to minimize side effects and maximize efficacy.

Key Considerations

• The medication should be taken in the morning to minimize sleep disturbances, and patients should avoid alcohol and stay well-hydrated while using it.
• Phentermine-topiramate works by suppressing appetite (phentermine) and reducing food cravings (topiramate), with common side effects including dry mouth, constipation, paresthesia, and cognitive effects.
• The medication is contraindicated in pregnancy, glaucoma, hyperthyroidism, and within 14 days of MAO inhibitor use, and regular monitoring of weight, blood pressure, and heart rate is necessary during treatment.

Dosing Schedule

• Start with 3.75 mg phentermine/23 mg topiramate once daily in the morning for 14 days
• Increase to 7.5 mg/46 mg daily
• After 12 weeks, if weight loss is less than 3% of baseline weight, either discontinue or increase to 11.25 mg/69 mg daily for 14 days, followed by 15 mg/92 mg daily
• If 5% weight loss isn't achieved after an additional 12 weeks at the highest dose, the medication should be gradually discontinued to avoid seizure risk from abrupt topiramate withdrawal, as recommended by the AGA clinical practice guideline on pharmacological interventions for adults with obesity 1.

Special Clinical Considerations

• Caution is advised in patients with a history of cardiovascular disease or uncontrolled hypertension, and the medication should be avoided in patients treated with, or within 14 days, of monoamine oxidase inhibitors.
• Female patients with child-bearing potential should be counseled on the risks of teratogenicity and consistent use of reliable contraception while using phentermine-topiramate, with monitoring with monthly pregnancy tests considered 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Dosage should be individualized to obtain an adequate response with the lowest effective dose. The recommended dose of phentermine is 15-30 mg once daily, taken before breakfast or 1-2 hours after breakfast.

• Phentermine Dosage: The recommended dose is 15-30 mg once daily.
• Topiramate Dosage: There is no direct information in the provided drug labels about the dosage of topiramate for weight loss when used in combination with phentermine.
• Combination Therapy: The labels do not provide guidance on dosing phentermine and topiramate together for weight loss, only that co-administration of phentermine with other drugs for weight loss is not recommended due to lack of established safety and efficacy of combination therapy 2. However, one label mentions a study where a combination capsule of 15 mg Phentermine and 92 mg topiramate was compared to each drug alone, but it does not provide dosing recommendations for the combination 2.

From the Research

Dosing Phentermine and Topiramate for Weight Loss

• The dosing of phentermine and topiramate for weight loss is based on clinical trials that have shown the combination to be effective in promoting weight reduction 3, 4, 5, 6, 7.
• The controlled-release formulation of phentermine and topiramate is available in different doses, with the full dose containing 15 mg of phentermine hydrochloride and 92 mg of topiramate 4.
• Clinical trial data suggest that the weight loss achieved with phentermine/topiramate is dose-dependent, with higher doses resulting in greater weight loss 7.
• The average weight loss achieved with phentermine/topiramate therapy was 7.73 kg (95% CI: 6.60-8.85) compared to placebo, with the weight loss related to the dose of phentermine/topiramate 7.
• Specifically, the average weight loss was 3.55 kg (95% CI: 2.22-4.88) for 3.75/23 mg, 7.27 kg (95% CI: 6.40-8.13) for 7.5/46 mg, and 8.25 kg (95% CI: 6.92-9.79) for 15/92 mg 7.

Adverse Events and Safety Considerations

• Phentermine/topiramate therapy has been associated with adverse events, including dysgeusia, paresthesia, dry mouth, disturbance in attention, irritability, hypoesthesia, constipation, and dizziness 7.
• The risk of nervous system-related adverse events was increased with phentermine/topiramate therapy 7.
• Patients who do not lose at least 5% of their body weight within 12 weeks of starting to take phentermine/topiramate should stop taking it, as stated in the prescribing information 3.