Apremilast Drug Interactions: What to Avoid and What to Tell Your Doctor

Knowing What Interacts With Apremilast Can Help You Stay Safe

Before starting any new medication, it's important to understand what else it might interact with. Drug interactions can make a medication less effective, increase side effects, or cause unexpected problems.

The good news about Apremilast (brand name Otezla): compared to many other medications used for psoriasis and psoriatic arthritis, it has a relatively short list of drug interactions. But the ones that do exist are significant, and you need to know about them.

Here's what the FDA labeling and clinical data say about Apremilast interactions — and what you should tell your doctor before starting treatment.

How Drug Interactions Work With Apremilast

To understand why certain drugs interact with Apremilast, it helps to know a little about how your body processes it.

Apremilast is broken down in your liver by a group of enzymes called CYP450 enzymes (specifically CYP3A4, with minor contribution from CYP1A2 and CYP2A6). These enzymes are like processing plants — they metabolize the drug so your body can use it and eventually clear it.

The main interaction risk with Apremilast is: if another drug speeds up those processing plants, Apremilast gets broken down too fast, and there isn't enough of it left in your body to work properly.

Major Drug Interactions: Medications That Significantly Reduce Apremilast's Effectiveness

These are the most important interactions to know about. The FDA specifically recommends not using Apremilast together with these medications:

Rifampin (Rifadin)

Rifampin is an antibiotic used to treat tuberculosis and some other infections. It's one of the most powerful CYP450 inducers known — meaning it dramatically speeds up the enzymes that break down Apremilast.

The impact: Rifampin can reduce Apremilast levels in your blood by up to 72%. At that point, Apremilast essentially stops working. Concomitant use is not recommended.

Phenobarbital

Phenobarbital is an anticonvulsant (seizure medication) and a strong CYP450 inducer. It will significantly reduce Apremilast blood levels, making the medication ineffective.

Carbamazepine (Tegretol)

Carbamazepine is used for epilepsy, bipolar disorder, and nerve pain. Like Rifampin and Phenobarbital, it's a strong CYP450 inducer that will substantially decrease Apremilast exposure.

Phenytoin (Dilantin)

Phenytoin is another anticonvulsant and strong CYP450 inducer. If you take Phenytoin, Apremilast is likely not going to work for you at standard doses.

Bottom line: If you take any of these four medications, your doctor will likely need to consider an alternative treatment instead of Apremilast.

Moderate Drug Interactions: Worth Discussing With Your Doctor

Other Moderate CYP450 Inducers

While the strong inducers listed above are the biggest concern, other moderate CYP450 inducers may also reduce Apremilast's effectiveness to some degree. These include:

• Bosentan (Tracleer) — used for pulmonary arterial hypertension
• Modafinil (Provigil) — used for sleep disorders
• Efavirenz (Sustiva) — an HIV medication

If you take any of these, let your doctor know. They may want to monitor your response to Apremilast more closely.

Supplements and OTC Medications to Watch

St. John's Wort

This is the biggest one. St. John's Wort is a popular herbal supplement used for mild depression and anxiety. Unfortunately, it's also a CYP450 inducer — meaning it can speed up the breakdown of Apremilast and reduce its effectiveness.

This is especially important because Apremilast is sometimes prescribed for people who've avoided other immunosuppressants, and some of those patients may be using natural supplements like St. John's Wort. Tell your doctor if you take it, and they may recommend stopping it or choosing a different psoriasis treatment.

Other Supplements and OTC Drugs

There are no other major documented supplement interactions with Apremilast. However, it's always good practice to tell your doctor about everything you take, including:

• Herbal supplements
• Vitamins (especially high-dose formulations)
• Over-the-counter pain relievers (Ibuprofen, Acetaminophen, Naproxen)
• Antacids and acid reducers
• Sleep aids

While these are unlikely to cause problems with Apremilast, your doctor can check for any potential issues with your complete medication list.

Food and Drink Interactions

Apremilast has no significant food interactions. You can take it with or without food, at any time of day (as long as you maintain your dosing schedule).

Some patients find that taking Apremilast with a meal reduces nausea and stomach discomfort — this is a comfort preference, not a drug interaction. For more tips on managing side effects, see our side effects guide.

What About Alcohol?

There's no specific interaction between Apremilast and alcohol in the FDA labeling. However, both alcohol and Apremilast can affect your GI system (stomach and intestines), and alcohol can affect mood. Since Apremilast carries a warning about depression, it's reasonable to be mindful about alcohol consumption. Discuss your drinking habits with your doctor.

What About Caffeine?

No interaction. You can drink coffee, tea, and other caffeinated beverages while taking Apremilast.

What to Tell Your Doctor Before Starting Apremilast

Before your doctor prescribes Apremilast, give them a complete picture:

• All prescription medications you currently take — especially seizure medications, antibiotics, HIV medications, and anything for pulmonary hypertension
• All supplements and herbal products — especially St. John's Wort
• Over-the-counter medications you use regularly
• Your mental health history — Apremilast carries a warning about depression, and some interacting medications (like anticonvulsants) also affect mood
• Kidney function — if you have kidney problems, your dose may need adjustment
• Plans for pregnancy or breastfeeding

It's also a good idea to mention if you've recently stopped any medication. Some strong CYP450 inducers (like Rifampin) continue to affect your system for days to weeks after you stop taking them.

What If You Need a Medication That Interacts With Apremilast?

If you need to take a strong CYP450 inducer (for example, if you need Rifampin for tuberculosis treatment), your doctor will likely need to switch you to a different psoriasis or arthritis medication. Options include:

• Methotrexate — doesn't depend on CYP450 metabolism the same way
• Biologics like Adalimumab (Humira) or Secukinumab (Cosentyx) — injectable but effective
• Deucravacitinib (Sotyktu) — another oral option with a different metabolic pathway

Never stop or change medications on your own. Always work with your doctor to find the safest combination for your situation.

Final Thoughts

Apremilast has fewer drug interactions than many other psoriasis treatments, but the ones that exist are clinically significant. The key takeaway: strong CYP450 inducers (Rifampin, Phenobarbital, Carbamazepine, Phenytoin) and St. John's Wort can dramatically reduce Apremilast's effectiveness and should be avoided.

Always keep your doctor informed about everything you take — prescription, OTC, and supplements. It's the simplest way to avoid interaction problems and get the best results from your treatment.

Need help finding or affording Apremilast? Medfinder can help you locate a pharmacy with it in stock and connect you with savings programs.