7 Orlistat (Xenical, Alli) Interactions: Levothyroxine, Vitamins, and More

Orlistat (Alli, Xenical) is an oral prescription and over-the-counter (OTC) medication used for weight loss. It works by preventing you from absorbing fat in your diet. But it can also interfere with how your body absorbs other medications, too.

Some orlistat interactions can be managed by spacing out your orlistat dose from when you take other medications. Others may require close monitoring. Below, we cover what you should know about seven orlistat interactions. Keep in mind that this list isn’t comprehensive. Your healthcare team can review your current medication and supplement list to check for potential interactions.

1. Levothyroxine

Levothyroxine (Synthroid, Levoxyl, Tirosint) treats hypothyroidism, a condition caused by low levels of thyroid hormone. Levothyroxine has many drug interactions. That’s because other medications can affect how it’s absorbed. This also seems to be the case with orlistat.

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The best way to take levothyroxine is first thing in the morning on an empty stomach — at least 30 minutes to 1 hour before your first meal. And wait at least 4 hours before taking orlistat.

Your prescriber may check your thyroid levels more often after you start orlistat. If needed, they may adjust your levothyroxine dosage. Tell them if you experience symptoms of hypothyroidism, such as fatigue, weight gain, or dry skin.

2. Fat-soluble vitamin supplements

Vitamins A, D, E, and K are fat-soluble vitamins. They’re absorbed by your body with fat from your diet. But since orlistat prevents you from absorbing fat from meals, it may also prevent you from absorbing fat-soluble vitamins.

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To help ensure you get the nutrition you need, the manufacturer of orlistat recommends taking a multivitamin that contains fat-soluble vitamins. You should take the multivitamin at least 2 hours before or after orlistat.

Keep in mind: Prescription vitamin D supplements (ergocalciferol) may be recommended to help maintain bone strength and to help treat conditions like osteoporosis. Orlistat can also interact with prescription vitamins. So it’s important to let your prescriber know if you’re taking orlistat.

3. Blood thinners such as warfarin

Blood thinners help prevent unwanted blood clots. Some examples include warfarin (Jantoven), apixaban (Eliquis), and others. Orlistat can affect how well blood thinners work.

Vitamin K plays an important role in blood clotting. Warfarin works to prevent blood clots by blocking vitamin K’s effects. But orlistat can affect vitamin K absorption. That can enhance warfarin’s effects and increase your risk of bleeding. In this case, your warfarin dose may need to be adjusted. Your prescriber may also check your blood work more often after starting orlistat.

Orlistat’s effects on other blood thinners are less clear. But the manufacturer recommends caution and close monitoring if you take orlistat with these medications. Get medical attention right away if you notice signs of bleeding or blood clots. Go to the ER if you experience symptoms such as chest pain or difficulty breathing.

4. Amiodarone

Amiodarone (Pacerone) is an antiarrhythmic medication. It helps manage irregular heart rhythms. Orlistat can keep you from absorbing as much amiodarone. That could make amiodarone less effective.

But this interaction hasn’t been heavily studied. So it’s not clear how much this interaction can impact your treatment. If you take amiodarone, talk to your prescriber before starting orlistat. They can help you better understand the potential risks in your situation.

5. Cyclosporine

Cyclosporine (Gengraf, Neoral, Sandimmune) is an immunosuppressant medication. It’s used to help prevent the body from attacking a transplanted organ. Orlistat can lower the amount of cyclosporine absorbed into the body, making it less effective. 

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Cyclosporine is a narrow therapeutic index medication. This means small changes in your dosage can have big effects on how it works. For this reason, talk to your transplant team before starting orlistat. If they say it’s OK, take cyclosporine at least 3 hours after your orlistat dose.

Your transplant team will continue monitoring your cyclosporine levels to make sure you’re getting the right dose. If orlistat seems to be affecting your levels too much, they may adjust your dose. Or they may recommend stopping orlistat altogether.

6. Antiepileptic medications such as lamotrigine

Antiepileptic medications are used to prevent and treat seizures. And orlistat can impact the effectiveness of these medications, specifically those that are lipophilic (attach to fat molecules). Orlistat seems to lower the absorption of these medications. This can potentially make them less effective, increasing the risk of seizures.

Orlistat may affect these antiepileptic medications:

• Lamotrigine (Lamictal)

• Valproic acid

• Carbamazepine (Tegretol, Epitol, others)

• Vigabatrin (Sabril, others)

• Gabapentin (Neurontin, Horizant, Gralise)

If you take antiepileptic medications, you should talk to your prescriber before taking orlistat. They can help determine whether it’s OK to take orlistat. In some situations, they may recommend avoiding it completely.

7. HIV medications like ritonavir

Orlistat may also block the absorption of certain antiretroviral HIV medications. So it may make those HIV medications less effective. It’s best to check with your prescriber before starting orlistat if you’re prescribed an HIV regimen.

HIV antiretroviral medications that may be affected by orlistat include:

• Atazanavir (Reyataz)

• Ritonavir (Norvir)

• Tenofovir disoproxil fumarate (Viread)

• Emtricitabine (Emtriva)

• Combination HIV medications that contain these components, such as Kaletra (lopinavir / ritonavir) and efavirenz / emtricitabine / tenofovir disoproxil fumarate

If you take orlistat with your HIV regimen, your prescriber will likely closely monitor your viral load (how much of the virus is in your bloodstream). If your HIV viral load is increasing, you should stop taking orlistat.

Good to know: Other medications beyond those used to treat HIV contain antiretrovirals. For example, Paxlovid (nirmatrelvir / ritonavir) is a well-known treatment for COVID-19. It contains ritonavir, an antiretroviral, and may also be affected by orlistat. Be sure to let your healthcare team know if you’re taking orlistat so they can help check for interactions.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Alex Evans, PharmD, MBA

Alex Evans, PharmD, MBA, has been a pharmacist for 12 years. His first job was floating in a community chain pharmacy.

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