What is the recommended dosing schedule for phentermine and topiramate (Topamax) for weight loss in an adult with BMI ≥ 30 kg/m² (or ≥ 27 kg/m² with obesity‑related comorbidities) who has failed diet and exercise and has no contraindications?

Phentermine‑Topiramate Dosing for Weight Loss

For adults with BMI ≥30 kg/m² (or ≥27 kg/m² with obesity‑related comorbidities) who have failed diet and exercise, initiate the FDA‑approved phentermine‑topiramate extended‑release combination at 3.75 mg/23 mg once daily for 14 days, then escalate to 7.5 mg/46 mg daily, with further titration to a maximum of 15 mg/92 mg daily based on tolerability and weight‑loss response. 1, 2

Pre‑Treatment Evaluation

Before prescribing, you must:

• Confirm BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight‑related comorbidity (hypertension, dyslipidemia, type 2 diabetes, or obstructive sleep apnea). 1
• Obtain baseline blood pressure and heart rate to detect sympathomimetic effects during treatment. 1
• Perform pregnancy screening in all women of reproductive potential and confirm a negative result, as topiramate carries high teratogenic risk (neural‑tube defects, orofacial clefts). 1, 2
• Review medication list to exclude monoamine‑oxidase inhibitor (MAOI) use within the past 14 days or other sympathomimetic agents. 1, 2
• Screen for absolute contraindications: history of cardiovascular disease (coronary artery disease, stroke, arrhythmias, heart failure), uncontrolled hypertension, untreated hyperthyroidism, glaucoma, pregnancy, or inadequate contraception. 1, 2

Dosing Schedule

Initial Phase (Weeks 1–2)

• Start with 3.75 mg phentermine / 23 mg topiramate once daily for 14 days. 1, 2
• Administer early in the day (morning) to minimize insomnia from the phentermine component. 1, 2

Maintenance Phase (Week 3 Onward)

• Increase to 7.5 mg phentermine / 46 mg topiramate once daily after the initial 14‑day period. 1, 2
• Assess weight loss at 12 weeks: if the patient has achieved <5% weight loss on the 7.5/46 mg dose, escalate to the maximum dose. 1, 2

Maximum Dose

• Titrate to 15 mg phentermine / 92 mg topiramate once daily if weight loss is inadequate at the mid‑range dose and the patient tolerates the medication without significant adverse effects. 1, 2
• This maximum dose produces a mean weight loss of ≈10.9% of baseline body weight at 56 weeks, compared to 1.6% with placebo. 2, 3

Monitoring and Continuation Criteria

• Measure blood pressure and heart rate at every clinical visit throughout treatment to detect sympathomimetic cardiovascular effects. 1, 2
• Assess body weight monthly for the first 3 months, then every 3 months thereafter. 1
• Discontinue therapy if <5% weight loss after 12 weeks on the maximum tolerated dose, as early response predicts long‑term success. 1, 2
• Continue treatment beyond 12 weeks only if the patient achieves ≥5% weight loss, has no new cardiovascular contraindications, and tolerates the medication. 1

Reproductive Safety Counseling

• Women of childbearing potential must receive intensive counseling about the high teratogenic risk of topiramate, including neural‑tube defects and orofacial clefts. 1, 2
• Topiramate doses >200 mg/day reduce the efficacy of hormonal contraceptives; although the combination product contains ≤92 mg topiramate, recommend barrier methods or non‑hormonal alternatives as a precaution. 4, 2
• Perform monthly pregnancy testing throughout treatment. 1, 2

Common Adverse Effects

• Paresthesias occur in 33–50% of patients receiving 100 mg/day topiramate and are the leading cause of discontinuation. 4, 2
• Central nervous system effects include cognitive slowing, mental clouding, difficulty concentrating, dizziness, and fatigue. 1, 4, 2
• Gastrointestinal effects include dry mouth (13–21%), constipation (15–17%), and altered taste (dysgeusia). 3
• Psychiatric effects include insomnia (6–10%), depression‑related events (4–7%), and anxiety‑related events (5–8%). 3
• Metabolic acidosis may develop due to topiramate's carbonic anhydrase inhibition; consider periodic serum bicarbonate assessment. 4, 2
• Kidney‑stone formation is a risk; advise adequate hydration and monitor for nephrolithiasis. 4, 2

Discontinuation Protocol

• Taper gradually when stopping therapy by taking one capsule every other day for at least 1 week before complete cessation to reduce seizure risk. 2
• Do not abruptly discontinue, even when used solely for weight loss, as topiramate withdrawal can precipitate seizures. 2

Special Populations

Renal Impairment

• Initiate at half the usual adult dose and allow a longer interval to reach steady state at each titration step. 4, 2

Elderly Patients

• Use lower starting doses and titrate more slowly, especially when renal function is reduced. 4, 2

Controlled Hypertension

• Phentermine‑topiramate may be prescribed in patients whose hypertension is well‑controlled (systolic <140 mm Hg, diastolic <90 mm Hg) on antihypertensive therapy that does not include MAOIs. 1
• Blood pressure often decreases during treatment (≈−7 mm Hg systolic, −5 mm Hg diastolic at 52 weeks) due to weight loss, despite phentermine's sympathomimetic effects. 1, 3

Clinical Pitfalls to Avoid

• Do not use topiramate monotherapy as first‑line obesity treatment; the FDA‑approved phentermine‑topiramate combination provides superior efficacy (≈10.9% weight loss vs. ≈3–5% with topiramate alone) and established safety data. 2
• Do not omit reproductive counseling in women of childbearing potential, given the high teratogenic risk and potential hormonal contraceptive failure. 1, 2
• Do not accelerate titration; most dose‑limiting adverse events occur during the titration phase, and slower escalation improves tolerability. 4, 2
• Do not neglect tapering when discontinuing therapy, as abrupt cessation can precipitate seizures. 2
• Do not confuse phentermine monotherapy with the historic "fen‑phen" combination; valvular heart disease and pulmonary hypertension were caused by fenfluramine, not phentermine. 1
• Do not prescribe to patients with any history of cardiovascular disease, as this is an absolute contraindication. 1, 2

Alternative Agents for High‑Risk Patients

• For patients with cardiovascular contraindications, consider GLP‑1 receptor agonists (semaglutide 2.4 mg, liraglutide 3.0 mg, or tirzepatide 15 mg), which provide superior weight loss (≈21% with tirzepatide at 72 weeks) and favorable cardiovascular safety profiles. 1
• Orlistat is appropriate for patients with cardiovascular disease but has lower efficacy (≈3% weight loss at 1 year). 1