Gastrointestinal lipase inhibitor (anti-obesity)
Orlistat is a weight-loss medicine that works in the gut, preventing the absorption of part of the fat from food (about 30%). It is used in adults with obesity (BMI ≥30) or overweight with risk factors (BMI ≥27), always combined with a reduced-calorie diet. Because unabsorbed fat is eliminated in the stools, it can cause gastrointestinal effects (faecal urgency, flatulence, oily stools), especially with high-fat meals.
Also known as: Xenical, Alli, orlistate
Orlistat reduces levothyroxine absorption and may compromise hypothyroidism control.
Orlistat inhibits pancreatic lipase and reduces absorption of fats and fat-soluble vitamins. Its label lists "thyroid medicine" among drugs whose absorption may be altered and recommends that patients "take a multivitamin daily at bedtime" — which includes levothyroxine, although the mechanism is not solely fat-solubility (levothyroxine is an iodinated amino acid, but its absorption occurs in the proximal small intestine and can be affected by dietary fat and intestinal transit). Cases of raised TSH after starting orlistat in stable levothyroxine patients are reported, with normalisation after separating the doses. Administer levothyroxine at least 4 hours before or after orlistat (preferably on waking, fasting, as usual); monitor TSH 4–8 weeks after starting or adjusting orlistat and readjust the levothyroxine dose if needed.
Levothyroxine + orlistat: orlistat reduces levothyroxine absorption (fat-soluble vitamins). Separate administration by 4+ hours; monitor TSH.
Interference with fat-soluble absorption / levothyroxine absorption window.
Monitor TSH and hypothyroidism symptoms.
Decompensated hypothyroidism.
Separate administration times (4 hours) and monitor TSH.
DailyMed (FDA) — approved Orlistat label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f ; approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Orlistat may reduce vitamin K absorption and alter the INR in patients taking warfarin.
Orlistat inhibits gastrointestinal lipases and reduces absorption of dietary fats and fat-soluble vitamins, including vitamin K. Since warfarin is a vitamin K antagonist, the lower availability of the cofactor can increase the anticoagulant effect and the INR; cases of elevated INR and bleeding have been described, especially in the first weeks of treatment. The INR should be monitored at initiation and during orlistat treatment and the warfarin dose adjusted; maintain consistent vitamin K intake and watch for bleeding signs.
Orlistat reduces absorption of fats and fat-soluble vitamins, including vitamin K, potentially raising the INR. Monitor the INR when starting and during treatment.
Reduced fat-soluble vitamin K absorption interferes with synthesis of vitamin K-dependent clotting factors.
Monitor bleeding signs and INR.
Bleeding or thrombotic events from unstable INR.
Monitor the INR more frequently when starting, adjusting or stopping orlistat.
DailyMed (FDA) — approved Orlistat label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Orlistat reduces absorption of fat-soluble vitamins.
Take multivitamin supplements at least 2 hours after orlistat.
EMC-UK (MHRA) — approved Orlistat SmPC: https://www.medicines.org.uk/emc/product/6533/smpc
Very fatty meals increase orlistat gastrointestinal effects (steatorrhoea, flatulence).
Take orlistat with or up to 1 hour after meals; keep a moderate-fat diet.
EMC-UK (MHRA) — approved Orlistat SmPC: https://www.medicines.org.uk/emc/product/6533/smpc
Orlistat is contraindicated in cholestasis (SmPC).
Do not use in patients with cholestasis.
EMC-UK (MHRA) — approved Orlistat SmPC: https://www.medicines.org.uk/emc/product/6533/smpc
Orlistat worsens malabsorption of fats and fat-soluble vitamins.
Do not use in patients with chronic malabsorption syndrome.
EMC-UK (MHRA) — approved Orlistat SmPC: https://www.medicines.org.uk/emc/product/6533/smpc
Orlistat is not recommended in pregnancy (a weight-loss drug; there is no benefit and maternal weight loss is not desired).
Stop before becoming pregnant or as soon as pregnancy is confirmed.
Excretion into breast milk is unknown; not recommended during breastfeeding.
No specific additional contraception (keep usual contraception).
EMC-UK (MHRA) — approved Orlistat SmPC: https://www.medicines.org.uk/emc/product/6533/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Gastrointestinal lipase inhibitor used in obesity (BMI ≥30, or ≥27 with risk factors) together with a reduced-calorie diet; reduces dietary fat absorption by ~30%. GI adverse effects (steatorrhoea, oily spotting, faecal urgency) are the manifestation of the mechanism of action.
Covalently and irreversibly inhibits gastric and pancreatic lipases in the lumen of the stomach and small intestine, preventing hydrolysis of dietary triglycerides into absorbable free fatty acids and monoglycerides.
Minimal systemic absorption: plasma concentrations of intact orlistat <10 ng/mL (near the limit of detection); plasma radioactivity peak ~8 h after 360 mg of 14C-orlistat. ~97% of the dose excreted in faeces (83% as unchanged drug); renal excretion <2%.
The minimal absorbed fraction is metabolised to M1 (hydrolysis product of the β-lactone ring) and M3 (sequential metabolite), both with lipase-inhibitory activity 1000-2500x lower than orlistat — pharmacologically inconsequential. No accumulation.
Local action in the GI lumen (no relevant systemic half-life); plasma metabolites M1 t½ ~3 h and M3 ~13.5 h; complete faecal + urinary elimination within 3-5 days.
