Short answer: Xenical (orlistat) is a 120 mg capsule taken with each fat-containing meal that blocks some fat from being absorbed. Qsymia (phentermine and topiramate) is a once-daily morning capsule that steps up over weeks, is a controlled substance, and is sold through certified pharmacies because it can cause birth defects.12 Neither label reports a trial against the other.
| Xenical (orlistat) | Qsymia (phentermine and topiramate ER) | |
|---|---|---|
| How it works | Blocks fat absorption in the gut1 | Two drugs in one capsule; phentermine is a Schedule IV controlled substance2 |
| Approved for | Weight loss and maintenance at BMI 30 or more, or 27 with other risk factors; studies support ages 12 to 161 | Weight loss in adults with obesity or overweight plus a weight-related condition, and children 12 and older with obesity2 |
| Label dosing | 120 mg three times a day with each main meal containing fat1 | 3.75/23 mg each morning for 14 days, then 7.5/46 mg; may step to 15/92 mg2 |
| Stop rule | None in the label1 | Under 5% weight loss after 12 weeks on 15/92 mg: stop, tapering over at least a week2 |
| Most common side effects | Oily spotting 26.6% vs 1.3%; gas with discharge 23.9% vs 1.4%; urgent bowel movements 22.1% vs 6.7%1 | Tingling 4% to 20% vs 2%; dry mouth 7% to 19% vs 3%; constipation 8% to 16% vs 6%2 |
| Pregnancy | Not used in pregnancy1 | Can cause birth defects; certified pharmacies only (REMS)2 |
| Vitamins | Daily multivitamin at least 2 hours apart, such as at bedtime1 | No vitamin rule; potassium checks with some diuretics2 |
| Boxed warning | None1 | None2 |
Xenical works in the gut: it blocks some of the fat in a meal from being absorbed, so it is taken with meals that contain fat and can be skipped when a meal is skipped or has no fat.1 Qsymia combines phentermine, a controlled stimulant, with extended-release topiramate, and is taken once each morning.2
Xenical's side effects are mostly bowel changes from unabsorbed fat. They usually started within 3 months, and 8.8% stopped because of side effects vs 5.0% on placebo. Low vitamin D on two or more visits was 12.0% vs 6.6% in adults not taking supplements.1
Qsymia's side effects rose with dose: tingling, dry mouth, constipation, taste change and insomnia. Its warnings include birth defects, mood and sleep problems, trouble with attention and memory (5.0% and 7.6% vs 1.5%), a faster heart rate, kidney stones and seizures if stopped suddenly.2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison.
Which suits you is a question for your prescriber. More detail: Xenical side effects, Qsymia side effects, the Xenical and Qsymia dosing schedules, and what to do if you miss a Xenical dose or miss a Qsymia dose.