Orlistat

What orlistat is and how it works

Orlistat is a weight-management medicine that works differently from most others: instead of acting on the brain or appetite, it works in the gut, blocking about one-third of the fat you eat from being absorbed by inhibiting pancreatic and gastric lipase enzymes. It is used alongside a reduced-calorie, reduced-fat diet, not as a replacement for one. It is sold at prescription strength (120 mg, as Xenical) in every market reviewed, and additionally as a half-strength (60 mg) over-the-counter product (Alli) in the United States. (1)

Orlistat carries a genuine, significant safety warning: rare postmarketing reports of severe liver injury, including hepatocellular necrosis or acute hepatic failure, with some cases resulting in liver transplant or death. Anyone taking orlistat should know to watch for symptoms such as loss of appetite, itching, yellowing of the skin or eyes, dark urine, pale stools, or pain in the upper right side of the abdomen, and to contact their prescriber immediately or seek emergency care if these occur. Orlistat also reduces absorption of fat-soluble vitamins (A, D, E, K) and beta-carotene, so a daily multivitamin taken well apart from dosing is recommended.

Mechanism of action: how orlistat works

Orlistat is a reversible inhibitor of gastrointestinal lipases. It acts locally in the lumen of the stomach and small intestine by forming a covalent bond with the active serine site of gastric and pancreatic lipases, inactivating these enzymes. The inactivated enzymes are unable to hydrolyse dietary fat (triglycerides) into absorbable free fatty acids and monoglycerides. Because undigested triglycerides are not absorbed, the resulting caloric deficit contributes to weight management. This mechanism is non-systemic (acting within the gut lumen), which is also why it can worsen malabsorption in patients with chronic malabsorption syndrome or cholestasis. (1)

What orlistat is used for

Before taking orlistat

Do not take / not appropriate for

• Do not take orlistat if you are pregnant. (United States, Canada, New Zealand) (1) (3) (5)
• Do not take orlistat if you have chronic malabsorption syndrome. (United States, Canada) (1) (3)
• Do not take orlistat if you have cholestasis. (United States, Canada) (1) (3)
• Do not take orlistat if you have a known hypersensitivity to orlistat or any component of the product. (United States, Canada) (1) (3)
• Do not use orlistat while breastfeeding, per the New Zealand data sheet reviewed, due to an absence of clinical data for this situation. (New Zealand) (5)

Tell your clinician about

• Whether you have any liver problems, or a history of gallstones (cholelithiasis) -- substantial weight loss itself can increase gallstone risk.
• Whether you have any kidney problems, or a history of kidney stones (oxalate nephrolithiasis) -- monitoring may be needed.
• Whether you have diabetes and take insulin or oral hypoglycaemic medicines -- your dose may need adjustment as you lose weight.
• Whether you take cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic medicines, or antiretroviral medicines.
• Whether an underlying cause of weight gain (such as hypothyroidism) has been excluded before starting treatment.
• Whether you are pregnant, plan to become pregnant, or are breastfeeding.

How to take orlistat

• Take one capsule with water immediately before, during, or up to 1 hour after each main meal that contains fat.
• If a meal is occasionally missed, or contains no fat, the dose for that meal can be omitted.
• Take a daily multivitamin containing fat-soluble vitamins (A, D, E, K) and beta-carotene, timed at least 2 hours before or after orlistat -- for example, at bedtime.
• Follow a nutritionally balanced, reduced-calorie diet with about 30% of daily calories from fat, spread across three main meals -- gastrointestinal side effects increase if a single meal is very high in fat.
• Doses above 120 mg three times a day have not been shown to provide additional benefit.
• Effects on fecal fat are seen within 24-48 hours of starting; after stopping, fecal fat content usually returns to pre-treatment levels within 48-72 hours.

Procedures and treatment changes

Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (5)

Missed dose

If a meal is missed, or contains no fat, that dose of orlistat can simply be omitted. do not take an extra dose to make up for it. Ask your prescriber or pharmacist if you are unsure.

Overdose

Seek medical advice if you think you or someone else has taken too much orlistat, or if you have concerns after a much larger than recommended dose. (1)

Side effects

Side effects and their urgency vary; report severe, persistent, or concerning symptoms.

Serious warnings

Interactions

• Cyclosporine: orlistat reduces cyclosporine plasma levels -- these should not be taken simultaneously; take cyclosporine 3 hours after orlistat and consider more frequent level monitoring. (1)
• Levothyroxine: take at least 4 hours apart from orlistat and monitor thyroid function, as changes have been reported with concomitant use. (1)
• Warfarin and other anticoagulants: patients on chronic stable warfarin doses who are prescribed orlistat should be monitored closely for changes in coagulation parameters. (1)
• Amiodarone: a reduction in amiodarone exposure was observed with concomitant orlistat use. (1)
• Antiepileptic drugs: convulsions have been reported in patients taking orlistat with antiepileptic drugs -- monitor for changes in frequency or severity of convulsions. (1)
• Antiretroviral drugs: loss of virologic control has been reported in HIV-infected patients -- monitor HIV RNA levels more frequently. (1)
• Fat-soluble vitamin supplements (A, D, E, K) and beta-carotene: orlistat reduces their absorption -- take a multivitamin at least 2 hours before or after orlistat. (1)
• Oral hypoglycaemic medication or insulin: dose reduction may be required as weight loss progresses, per your prescriber's assessment. (1)

Pregnancy, breastfeeding, kidney/liver function, age

Monitoring

Before starting

• Exclusion of organic causes of obesity (e.g. hypothyroidism)
• Baseline liver status discussion
• Assessment of diabetes medicines needing future adjustment
• Review of all other medicines for cyclosporine/levothyroxine/warfarin/amiodarone/antiepileptic/antiretroviral interactions

During treatment

• Watch for symptoms of liver injury (loss of appetite, itching, jaundice, dark urine, pale stools, right upper quadrant pain) and contact your prescriber immediately or seek emergency care if they occur.
• Monitor blood glucose in patients with diabetes, adjusting hypoglycaemic medicines as weight loss progresses.
• Monitor kidney function in patients at increased risk of oxalate nephropathy.
• Take a daily multivitamin containing fat-soluble vitamins, timed apart from dosing.

Storage

Store at room temperature, away from moisture and direct light, out of reach of children.

Frequently asked questions

References

1. XENICAL (orlistat) Capsules -- full prescribing information (Revised 11/2022)U.S. Food and Drug Administration (FDA) / accessdata.fda.gov · United States · dated 2022-11 · accessed 2026-07-30 · source 1
2. Xenical 120 mg hard capsules -- Summary of Product Characteristics (SmPC)electronic medicines compendium (emc), United Kingdom -- Xenical 120 mg Summary of Product Characteristics · United Kingdom · accessed 2026-07-30 · source 2
3. XENICAL (orlistat) -- Product MonographHealth Canada -- Product Monograph (Xenical, orlistat) · Canada · accessed 2026-07-30 · source 3
4. XENICAL (orlistat) 120 mg capsule -- ARTG registrationTherapeutic Goods Administration (TGA), Australia -- ARTG registration · Australia · accessed 2026-07-30 · source 4
5. New Zealand Data Sheet -- Xenical (120 mg capsules)Medsafe (New Zealand) -- Xenical Data Sheet · New Zealand · accessed 2026-07-30 · source 5

Brand names by country

Single-ingredient orlistat names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.

Priority countries