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Orlistat

AEMPS

Peripherally acting antiobesity drug – intestinal lipase inhibitor

ATC code: A08AB01

Brand names: Orlistat Stada, Xenical, Alli

Updated · Methodology

Indications

B

Obesity

Second line

Obesity with BMI ≥30 or BMI ≥27 with risk factors (type 2 diabetes, dyslipidemia, hypertension) when 6 months of lifestyle modification have not produced ≥5% weight loss. Per EASO 2024 and SEEN 2023 – second-line after diet, physical activity, and behavioral therapy. Dose: 120 mg three times daily with or within one hour of a fat-containing meal. Skip the dose if the meal is fat-free. Effect at 4–6 weeks; discontinue if weight loss <5% by 12 weeks.

Sources

  1. AEMPS: Ficha técnica de Orlistat (2024)

ICD-10: E66 · ICD-11: 5B81

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Anti-aging and longevity

Not recommended

Orlistat is heavily marketed to non-obese people for quick weight loss, summer weight loss, and healthy weight loss at BMI 25-27. Per EASO 2024 and SEEN 2023, neither weight above ideal at BMI <27 nor cosmetic weight loss is an indication. Without concurrent dietary fat restriction the drug does not work; with more than 30 g of fat per meal it causes marked steatorrhea, fecal incontinence, and flatulence. Long-term use without monitoring risks deficiency of fat-soluble vitamins A, D, E, K and reduced bone mineral density. If prescribed at BMI <27 without mandatory dietary changes, consider getting a second opinion and reconsider whether you need this drug at all.

Sources

  1. AEMPS: Ficha técnica de Orlistat (2024)
  2. Cochrane: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases (2012)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Orlistat covalently binds the active site of gastric and pancreatic lipases in the small intestine – blocks dietary triglyceride hydrolysis to free fatty acids and monoglycerides. About 30% of dietary fat at the standard 120 mg three-times-daily dose is not absorbed and is excreted in feces. Systemic absorption of orlistat is minimal (<1%). Effect is on dietary fat only; no impact on carbohydrates or protein.

Safety

Contraindications

  • Hypersensitivity
  • Malabsorption syndrome
  • Cholestasis
  • Pregnancy and breastfeeding
  • Children under 12

Serious adverse effects

  • Acute hepatitis and liver failure (rare, FDA Safety Communication 2010)
  • Acute pancreatitis
  • Nephrolithiasis (oxalate stones)
  • Fat-soluble vitamin deficiency with long-term use without multivitamin

Common adverse effects

  • Steatorrhea and oily stools
  • Frequent defecation
  • Flatulence with discharge
  • Abdominal pain and cramping
  • Fecal urgency

Pregnancy: can you take Orlistat?

Contraindicated. Safety not studied; theoretical reduction of fat-soluble vitamins may affect fetal development.

Breastfeeding: can you take Orlistat?

Contraindicated. Theoretical reduction of fat-soluble vitamins is undesirable for the infant via milk.

Calculate RIDFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Monitoring

Weight and waist circumference every 4–6 weeks in the first 6 months, then every 3 months. 25(OH)D and vitamin E every 6–12 months on long-term use. In type 2 diabetes – glucose and (hypoglycemia possible with glucose-lowering drugs).

Drug interactions

Reduces absorption of cyclosporine (separate by 3 hours), levothyroxine (4 hours), warfarin (monitor INR), and antiepileptics (monitor levels). Take fat-soluble vitamins 2 hours before or after orlistat – typically a multivitamin at bedtime.
Label mentions35 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • MajorCiclosporin
    «Ciclosporina: En un estudio de interacciones farmacológicas se ha observado un descenso de las concentraciones plasmáticas de la ciclosporina, lo cual también ha sido notificado en varios casos tras…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateAmiodarone
    «Amiodarona: Tras la administración de amiodarona en dosis únicas, se ha observado un ligero descenso de sus niveles plasmáticos en un número limitado de voluntarios sanos que recibieron orlistat…»

    AEMPS, section 4.5 · Open on CIMA

  • Moderateanticoagulantesclass named in the label
    «Anticoagulantes orales: Cuando se administre warfarina u otros anticoagulantes orales en combinación con orlistat, se deben monitorizar los valores del índice internacional normalizado (INR) (ver…»

    AEMPS, section 4.5 · Open on CIMA

  • Moderateanticoagulantsclass named in the label
    «Anticoagulants including Warfarin: Vitamin K absorption may be decreased with XENICAL. Reports of decreased prothrombin, increased INR and unbalanced anticoagulant treatment resulting in change of…»

    FDA, section 7 · Open on DailyMed

  • Moderateantidiabéticosclass named in the label
    «En ensayos clínicos, la disminución de peso producida por el tratamiento con orlistat fue menor en pacientes con diabetes tipo II que en pacientes no diabéticos. El tratamiento antidiabético debe…»

    AEMPS, section 4.4 · Open on CIMA

  • Moderateantiepilépticosclass named in the label
    «En pacientes tratados concomitantemente con orlistat y antiepilépticos, p. ej. valproato, lamotrigina, se han notificado convulsiones que no se puede descartar que sean debidas a una interacción. Por…»

    AEMPS, section 4.5 · Open on CIMA

  • Moderateantiepilepticsclass named in the label
    «DRUG INTERACTIONS: Antiepileptic Drugs: Convulsions have been reported in patients taking XENICAL with antiepileptic drugs. Patients should be monitored for possible changes in frequency or severity…»

    FDA, section 7 · Open on DailyMed

  • ModerateAtazanavir
    «Antiretroviral Drugs: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs such as atazanavir, ritonavir, tenofovir…»

    FDA, section 7 · Open on DailyMed

  • ModerateEfavirenz
    «Antiretroviral Drugs: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs such as atazanavir, ritonavir, tenofovir…»

    FDA, section 7 · Open on DailyMed

  • ModerateLamotrigine
    «En pacientes tratados concomitantemente con orlistat y antiepilépticos, p. ej. valproato, lamotrigina, se han notificado convulsiones que no se puede descartar que sean debidas a una interacción. Por…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateRitonavir
    «Antiretroviral Drugs: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs such as atazanavir, ritonavir, tenofovir…»

    FDA, section 7 · Open on DailyMed

  • ModerateWarfarin
    «Anticoagulantes orales: Cuando se administre warfarina u otros anticoagulantes orales en combinación con orlistat, se deben monitorizar los valores del índice internacional normalizado (INR) (ver…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateWarfarin
    «DRUG INTERACTIONS: Warfarin: Patients on chronic stable doses of warfarin who are prescribed XENICAL should be monitored closely for changes in coagulation parameters. ( 7.4 )»

    FDA, section 7 · Open on DailyMed

  • Amiodarone
    «DRUG INTERACTIONS: Amiodarone: A reduction in exposure to amiodarone was observed when XENICAL was co-administered. ( 7.5 )»

    FDA, section 7 · Open on DailyMed

  • Amitriptyline
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • anticonceptivos hormonalesclass named in the label
    «Ausencia de interacciones: En estudios específicos de interacción fármaco-fármaco se ha demostrado la ausencia de interacciones entre los anticonceptivos orales y orlistat. sin embargo, el orlistat…»

    AEMPS, section 4.5 · Open on CIMA

  • antipsicóticosclass named in the label
    «Medicamentos antirretrovirales, antidepresivos, antipsicóticos (incluido el litio) y benzodiazepinas»

    AEMPS, section 4.5 · Open on CIMA

  • Atorvastatin
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • benzodiazepinasclass named in the label
    «Medicamentos antirretrovirales, antidepresivos, antipsicóticos (incluido el litio) y benzodiazepinas»

    AEMPS, section 4.5 · Open on CIMA

  • Beta-carotene
    «DRUG INTERACTIONS: Fat-soluble Vitamin Supplements and Analogues: All patients should take a daily multivitamin that contains vitamins A, D, E, K, and beta-carotene. ( 7.2 )»

    FDA, section 7 · Open on DailyMed

  • Digoxin
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • fibratosclass named in the label
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • Fluoxetine
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • Lithium
    «Medicamentos antirretrovirales, antidepresivos, antipsicóticos (incluido el litio) y benzodiazepinas»

    AEMPS, section 4.5 · Open on CIMA

  • Losartan
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • Nifedipine
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • Phenytoin
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

  • Pravastatin
    «Ausencia de interacciones: No se han observado interacciones con amitriptilina, atorvastatina, biguanidas, digoxina, fibratos, fluoxetina, losartán, fenitoina, fentermina, pravastatina, nifedipino…»

    AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

  • ModerateLevothyroxine sodium
    «El hipotiroidismo y/o el control reducido del hipotiroidismo pueden ocurrir cuando se administran conjuntamente orlistat y levotiroxina (ver sección 4.5). Se debe aconsejar a los pacientes que toman…»

    AEMPS, section 4.4 · Open on CIMA

  • ModerateLevothyroxine sodium
    «Drugs Known to Affect Thyroid Hormone Pharmacokinetics: Orlistat Monitor patients treated concomitantly with orlistat and levothyroxine sodium for changes in thyroid function.»

    FDA, section 7 · Open on DailyMed

  • ModerateRetinol
    «- Colestiramina, colestipol , orlistat ,a ceite mineral : posible reducción de la absorción de las vitaminas liposolubles como la A, con reducción de su eficacia; en su caso, se debe separar lo más…»

    AEMPS, section 4.5 · Open on CIMA

  • Alpha-tocopherol
    «- Orlistat : podría reducir la absorción de la vitamina E; se recomienda separar su administración al menos 2 horas.»

    AEMPS, section 4.5 · Open on CIMA

  • Cholecalciferol
    «El tratamiento simultáneo con una resina de intercambio iónico como colestiramina, hidrocloruro de colestipol, orlistat o laxantes como el aceite de parafina puede reducir la absorción…»

    AEMPS, section 4.5 · Open on CIMA

  • Ciclosporin
    «Fármacos que disminuyen los niveles de ciclosporina: Barbitúricos, carbamazepina, oxcarbazepina, fenitoina; nafcilina, sulfadimidina intravenosa; probucol; orlistat, Hypericum perforatum (hierba de…»

    AEMPS, section 4.5 · Open on CIMA

  • Propafenone
    «DRUG INTERACTIONS: • Orlistat may reduce propafenone concentrations. Abrupt cessation of orlistat in patients stable on propafenone hydrochloride extended-release capsules has resulted in…»

    FDA, section 7 · Open on DailyMed

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Frequently asked

What is Orlistat used for?

Orlistat is evaluated for the following indications with varying evidence strength: Obesity (evidence tier B), Anti-aging and longevity (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Orlistat?

Common side effects of Orlistat (≥ 1 in 100): Steatorrhea and oily stools, Frequent defecation, Flatulence with discharge, Abdominal pain and cramping, Fecal urgency. See the Safety section for uncommon and serious reactions.

Is Orlistat safe during pregnancy?

Contraindicated. Safety not studied; theoretical reduction of fat-soluble vitamins may affect fetal development.

Is Orlistat compatible with breastfeeding?

Contraindicated. Theoretical reduction of fat-soluble vitamins is undesirable for the infant via milk.

Who should not take Orlistat?

Orlistat is contraindicated in: Hypersensitivity; Malabsorption syndrome; Cholestasis; Pregnancy and breastfeeding; Children under 12. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

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