Otezla Side Effects: What to Expect and When to Call Your Doctor

Before starting any new medication, understanding what side effects to expect helps you distinguish normal adjustment reactions from symptoms that need medical attention. Otezla (apremilast) has a well-characterized safety profile from clinical trials involving thousands of patients. Most side effects are manageable and tend to occur in the first few weeks of treatment — but there are some important warnings to be aware of. Here's what you need to know.

Does Otezla Have a Boxed Warning?

No. Otezla does not have a boxed warning (also called a black box warning) — the FDA's most serious safety alert. This is one clinical advantage of Otezla compared to some other specialty medications used for inflammatory conditions. However, Otezla does have several important warnings and precautions that you and your doctor should discuss before starting treatment.

Most Common Side Effects of Otezla

According to clinical trial data, the most common side effects occurring in 5% or more of patients with plaque psoriasis include:

Diarrhea — affects approximately 25% of patients; typically mild to moderate in severity

Nausea — common in first few weeks, often improves with continued dosing

Upper respiratory tract infection (URTI) — cold-like symptoms; common and generally mild

Headache (including tension headache) — reported in a significant proportion of patients

Vomiting — less common than nausea/diarrhea; usually occurs with nausea

Upper abdominal pain — discomfort or pain in the upper belly, often associated with GI side effects

Nasopharyngitis — inflammation of the nose and throat (common cold)

Back pain — reported in some patients across clinical trials

Managing GI Side Effects in the First Weeks

Gastrointestinal side effects — especially diarrhea and nausea — are the primary reason patients discontinue Otezla prematurely. These effects are most pronounced in the first 2 weeks and typically improve with continued use. The 5-day titration schedule (starting at 10 mg and gradually increasing to 30 mg twice daily) is specifically designed to minimize GI side effects during the adjustment period.

Practical tips to manage GI side effects:

Take Otezla with food to help reduce nausea (food does not affect absorption)

Stay well hydrated, especially during episodes of diarrhea or vomiting

Eat bland, simple foods and avoid greasy, fried, or spicy foods during the first few weeks

Contact your doctor if symptoms are severe — dose reduction or temporary pause of treatment may be appropriate

Serious Side Effect: Depression and Mood Changes

One of the most important warnings with Otezla is its potential association with depression, mood changes, and suicidal thoughts. In clinical studies, a small number of patients reported depression or suicidal behavior while taking Otezla. This led the FDA to include a precaution in the prescribing information about monitoring for new or worsening depression and mood changes.

If you or a loved one experience new or worsening feelings of depression, hopelessness, anxiety, agitation, or any thoughts of self-harm while taking Otezla, contact your doctor right away. If you are having thoughts of hurting yourself, call or text 988 (Suicide & Crisis Lifeline) or go to the nearest emergency room. Your doctor will weigh the risks and benefits and may recommend stopping Otezla.

It's worth noting that psoriasis and psoriatic arthritis are themselves associated with higher rates of depression due to their impact on quality of life and appearance. Your doctor will consider your complete history when evaluating any mood changes during treatment.

Weight Loss During Otezla Treatment

Otezla has been associated with weight loss in clinical trials. Approximately 10% of patients experienced a 5 to 10% decrease in body weight (compared to 3.3% of placebo-treated patients). For some patients, particularly those who are overweight, modest weight loss may be a welcome effect. However, clinically significant or unexplained weight loss warrants evaluation.

Monitor your weight regularly throughout treatment. If you lose more than 5% of your body weight without intentional dietary changes, inform your doctor. In some cases, dose reduction or discontinuation of Otezla may be recommended.

Rare but Serious: Hypersensitivity Reactions

Rare cases of serious allergic reactions — including angioedema (swelling of the face, lips, tongue, or throat) and anaphylaxis — have been reported during post-marketing surveillance. If you develop trouble breathing or swallowing, hives, a severe rash, or swelling of the face or throat after taking Otezla, stop the medication and seek emergency medical care immediately. Do not take another dose.

When to Call Your Doctor Immediately

Severe or persistent diarrhea, nausea, or vomiting that doesn't improve in 2 weeks or leads to signs of dehydration

New or worsening feelings of depression, hopelessness, or any thoughts of self-harm

Unexplained or significant weight loss (more than 5% of body weight)

Symptoms of a serious allergic reaction: difficulty breathing, hives, swelling of face or throat

For information about what drugs to avoid while taking Otezla, see our guide on Otezla Drug Interactions. If you're having trouble accessing your Otezla prescription, medfinder can help you find pharmacies that can fill it.