Otezla (apremilast) Side Effects, Warnings, and Drug Interactions

Otezla (apremilast) is a phosphodiesterase 4 (PDE4) inhibitor used to treat adults with active psoriatic arthritis (a form of arthritis that affects some people with psoriasis). 

It is also used to treat moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy.

Otezla works by reducing production of an enzyme known as phosphodiesterase 4 (PDE4). This may lead to a reduction in chemicals that cause inflammation in the body. 

Common side effects of Otezla include:

• diarrhea,
• nausea,
• headache,
• and upper respiratory tract infections. 

Serious side effects of Otezla include:

• depression,
• upper abdominal pain,
• and weight loss.

Drug interactions of Otezla include:

• rifampin,
• St. John's wort,
• and carbamazepine, which may reduce blood levels of Otezla by increasing its breakdown when taken together. 

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Pregnant women should be advised of the potential risk of fetal loss. Pregnancy planning and prevention should be considered for females of reproductive potential taking Otezla. It is unknown if Otezla is secreted into breast milk. Consult your doctor before breastfeeding.

The most common side effects associated with apremilast are:

• diarrhea,
• nausea,
• and headache.

It also can cause upper respiratory tract infections.

The following were also reported in clinical studies:

• depression,
• upper abdominal pain,
• and weight loss.

The following adverse reactions are described elsewhere in the labeling:

• Diarrhea
• Nausea
• Vomiting
• Depression
• Weight Decrease
• Drug Interactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Psoriatic Arthritis Clinical Trials

Otezla was evaluated in 3 multicenter, randomized, double-blind, placebo-controlled trials [Studies PsA-1, PsA-2, and PsA-3] of similar design in adult patients with active psoriatic arthritis.

• Across the 3 studies, there were 1493 patients randomized equally to placebo, Otezla 20 mg twice daily or Otezla 30 mg twice daily. Titration was used over the first 5 days.
• Placebo patients whose tender and swollen joint counts had not improved by at least 20% were re-randomized 1:1 in a blinded fashion to either Otezla 20 mg twice daily or 30 mg twice daily at week 16 while Otezla patients remained on their initial treatment.
• Patients ranged in age from 18 to 83 years, with an overall median age of 51 years.

The majority of the most common adverse reactions presented in Table 2 occurred within the first 2 weeks of treatment and tended to resolve over time with continued dosing.

The most commonly reported adverse reactions were:

• diarrhea,
• headache,
• and nausea.

The most common adverse reactions leading to discontinuation for patients taking Otezla were:

• nausea (1.8%),
• diarrhea (1.8%),
• and headache (1.2%).

The proportion of patients with psoriatic arthritis who discontinued treatment due to any adverse reaction was 4.6% for patients taking Otezla 30 mg twice daily and 1.2% for placebo-treated patients.

Table 2: Adverse Reactions Reported in ≥2% of Patients on Otezla 30 mg Twice Daily and ≥1% Than That Observed in Patients on Placebo for up to Day 112 (Week 16)

Other adverse reactions reported in patients on Otezla in clinical studies including extension studies:

Immune system disorders: Hypersensitivity

Investigations: Weight decrease

Gastrointestinal Disorders: Frequent bowel movement, gastroesophageal reflux disease, dyspepsia

Metabolism and Nutrition Disorders: Decreased appetite*

Nervous System Disorders: Migraine

Respiratory, Thoracic, and Mediastinal Disorders: Cough

Skin and Subcutaneous Tissue Disorders: Rash

*1 patient treated with Otezla 30 mg twice daily experienced a serious adverse reaction.

Psoriasis Clinical Trials

• The safety of Otezla was assessed in 1426 subjects in 3 randomized, double-blind, placebo-controlled trials in adult subjects with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy.
• Subjects were randomized to receive Otezla 30 mg twice daily or placebo twice daily. Titration was used over the first 5 days.
• Subjects ranged in age from 18 to 83 years, with an overall median age of 46 years.

The most commonly reported adverse reactions were:

• diarrhea,
• nausea,
• and upper respiratory tract infection.

The most common adverse reactions leading to discontinuation for subjects taking Otezla were:

• nausea (1.6%),
• diarrhea (1.0%),
• and headache (0.8%).

The proportion of subjects with psoriasis who discontinued treatment due to any adverse reaction was 6.1% for subjects treated with Otezla 30 mg twice daily and 4.1% for placebo-treated subjects.

Table 3: Adverse Reactions Reported in ≥1% of Subjects on Otezla and With Greater Frequency Than in Subjects on Placebo; up to Day 112 (Week 16)

Severe worsening of psoriasis (rebound) occurred in 0.3% (4/1184) subjects following discontinuation of treatment with Otezla.

Behcet's Disease Clinical Trials

• Otezla was evaluated in a Phase 3, multicenter, randomized, placebo-controlled study (BCT-002) in adult patients with Behcet's Disease (BD) with active oral ulcers.
• A total of 207 patients were randomized to receive Otezla 30 mg twice daily or placebo twice daily.
• Titration was used over the first 5 days. After Week 12, all patients received treatment with Otezla 30 mg twice daily.
• Patients ranged in age from 19 to 72, with a mean age of 40 years.

The most commonly reported adverse reactions were:

• diarrhea,
• nausea,
• headache,
• and upper respiratory tract infection.

The proportion of patients with BD who discontinued treatment due to any adverse reaction during the placebo-controlled period of the study, was 2.9% for patients treated with Otezla 30 mg twice daily and 4.9% for placebo-treated patients.

Table 4: Adverse Reactions Reported in ≥5% of Patients on Otezla and with at least 1% Greater Frequency than Patients on Placebo; up to Week 12

Strong CYP450 Inducers

Apremilast exposure is decreased when Otezla is co-administered with strong CYP450 inducers (such as rifampin) and may result in loss of efficacy.