Orlistat side effects: A complete, evidence-based guide.

DoktorABC editorial team

Accurate, up-to-date health information written by our editorial team and reviewed by UK-registered prescribers.

How orlistat causes side effects

Orlistat works by blocking the enzymes that break down dietary fat in the gut, preventing approximately one third of the fat consumed from being absorbed. That unabsorbed fat has to go somewhere: it passes through the digestive tract and is excreted.

The gastrointestinal side effects of orlistat are therefore a direct consequence of the medicine working as intended. The more fat consumed in a meal, the more unabsorbed fat passes through the bowel, and the more pronounced the side effects. This is why the recommended low-fat diet (with no more than 30% of calories from fat, spread evenly across three meals) is not optional, it is central to both tolerability and effectiveness.

Very common side effects (affecting more than 1 in 10 people)

The following side effects are classified as very common in the orlistat 120 mg Summary of Product Characteristics (SmPC) and are all related to the excretion of unabsorbed fat.

• Oily or fatty stools: The most frequently reported side effect. Stools may appear oily, greasy, or have an oily film.
• Oily spotting on underwear: Leakage of oily discharge from the rectum, particularly between bowel movements.
• Flatus with discharge: Wind accompanied by oily or liquid discharge, which can be unpredictable.
• Urgent bowel movements: A sudden and difficult-to-defer urge to open the bowels.
• Increased frequency of bowel movements: Needing to go to the toilet more often than usual.
• Oily evacuation: Passage of oily liquid during or instead of a normal bowel movement.

These effects are most common in the first weeks of treatment and after high-fat meals. They typically reduce significantly as dietary habits adjust.

Common side effects (affecting 1 to 10 in 100 people)

The following are classified as common side effects and are experienced by a meaningful proportion of people taking orlistat. As with the very common side effects, most are related to the passage of unabsorbed fat through the digestive tract, though some have less clearly established causes. 

• Soft or liquid stools: Changes in stool consistency beyond the oily texture described above
• Abdominal pain or discomfort: Cramping or general discomfort in the stomach area
• Rectal pain or discomfort: Irritation or discomfort at the rectum, often related to the passage of oily stools
• Tooth and gum disorders: Reported in clinical trials, though the mechanism is not fully established

Rare but serious side effects

The following side effects are uncommon or rare but require prompt medical attention if they occur.

Liver injury

Serious liver injury, including cases of liver failure, has been reported very rarely in patients taking orlistat. The MHRA has issued safety updates on this risk. Warning signs include yellowing of the skin or whites of the eyes (jaundice), dark urine, persistent nausea or vomiting, and upper right abdominal pain. Stop taking orlistat and seek urgent medical advice if any of these symptoms develop.

Pancreatitis

Acute pancreatitis has been reported in patients taking orlistat. The risk is not fully established but is thought to be related to changes in fat metabolism. Symptoms include severe, persistent abdominal pain that may radiate to the back, accompanied by nausea and vomiting. This requires immediate medical attention.

Kidney stones (oxalate nephropathy)

Orlistat can increase the absorption of oxalate from the gut, which may contribute to kidney stone formation in susceptible individuals. This risk is higher in people with pre-existing kidney conditions. Symptoms include severe pain in the back or side, blood in the urine, and pain on urination. Maintaining adequate hydration reduces this risk.

Orlistat dangers: Putting the risks in context

Orlistat has a well-established safety record at approved doses when used as directed. It has been available in the UK since 1998 and has been extensively studied in long-term clinical trials. The serious risks described above are rare, and the medicine is considered safe for most people who meet the eligibility criteria and use it under appropriate medical supervision.

The risks increase with misuse. Taking orlistat without following the recommended low-fat diet increases GI side effects significantly. Using it without medical supervision means interactions with other medicines may go undetected. Taking it during pregnancy or with certain contraindications in place poses genuine clinical risk.

Long-term side effects: Fat-soluble vitamin depletion

One of the most clinically important long-term considerations with orlistat is its effect on fat-soluble vitamins. Because orlistat prevents fat absorption, it also reduces the absorption of fat-soluble vitamins A, D, E, and K, as well as beta-carotene.

The orlistat SmPC recommends that patients take a daily multivitamin supplement containing these vitamins to compensate for this reduction. The supplement should be taken at a different time of day from orlistat, such as at bedtime, to avoid the absorption of the supplement itself being impaired.

Vitamin D deficiency in particular is already common in the UK population, and long-term orlistat use without supplementation can exacerbate this. Vitamin K depletion is clinically relevant for patients taking warfarin, as discussed below.

Drug interactions

Orlistat interacts with several commonly prescribed medicines. Always disclose your full medication list to your prescriber before starting orlistat.

• Warfarin: Orlistat can reduce vitamin K absorption, which affects blood clotting and may alter the effect of warfarin. More frequent INR monitoring is recommended in patients taking both medicines.
• Ciclosporin: Orlistat reduces the absorption of ciclosporin, an immunosuppressant used after organ transplants and for certain autoimmune conditions. These medicines should not be taken together; if orlistat is required, specialist advice is essential.
• Levothyroxine: Orlistat may reduce the absorption of levothyroxine, used for hypothyroidism. The two medicines should be taken at least four hours apart, and thyroid function should be monitored.
• Antiretroviral HIV medicines: Orlistat may reduce the absorption of certain antiretroviral medicines. HIV-positive patients should discuss this with their specialist before starting orlistat.
• Oral contraceptives: In cases of severe diarrhoea, orlistat may reduce the effectiveness of oral contraceptives. Additional contraceptive methods are recommended if significant GI side effects occur.

Is orlistat safe?

For most people who meet the eligibility criteria and use it as prescribed, the answer is yes. Orlistat is contraindicated in people who:

• Have cholestasis (a liver condition affecting bile flow)
• Have chronic malabsorption syndrome
• Are pregnant or breastfeeding

It should be used with caution in people with kidney disease, a history of kidney stones, or those taking medicines that interact with orlistat as described above.

A medical assessment before starting is essential. Your prescriber will review your health history, current medications, and any contraindications before recommending orlistat.

When to seek medical advice

Contact your GP or NHS 111 if you experience:

• Yellowing of the skin or eyes, dark urine, or persistent nausea (possible liver problems)
• Severe abdominal pain, particularly radiating to the back (possible pancreatitis)
• Severe pain in the back or side, blood in the urine (possible kidney stones)
• Significant changes in bowel habits that do not improve with dietary fat reduction
• Any side effect that significantly affects your daily life

Final thoughts

Orlistat's side effects are directly linked to how it works, which makes them largely predictable and manageable with the right dietary approach. The medicine has a well-established safety record at approved doses, and the serious risks, while real, are rare. The key to tolerating orlistat well is straightforward: follow the recommended low-fat diet, take a daily multivitamin, and ensure your prescriber is aware of all your current medications.

If you have questions about whether orlistat is appropriate for your circumstances, DoktorABC connects UK patients with licensed prescribers and GPhC-registered pharmacies for private access to treatment, with a full medical assessment completed online.

FAQ

The DoktorABC medical advisory board

Dr. Roland Ruiken

Medical advisor, Norway

Dr. Viktor Simunovic

Medical advisor, Croatia

To the medical advisory board