Apremilast (Otezla): Uses, Dose, MOA, Side effects

Apremilast (Otezla)

Apremilast is a prescription medication available as an oral pill for treating certain inflammatory conditions, including psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s syndrome.

It is a type of drug called a phosphodiesterase 4 (PDE4) inhibitor, which works by blocking the activity of an enzyme called PDE4.

This enzyme is involved in the inflammation process, and blocking it helps to reduce inflammation and its associated symptoms.

Apremilast was first approved by the US Food and Drug Administration (FDA) in 2014 for the treatment of psoriatic arthritis, and in 2015 for the treatment of moderate-to-severe plaque psoriasis. Since then, it has also been approved for the treatment of oral ulcers associated with Behçet’s syndrome.

Apremilast is marketed by Celgene Corporation, which is now a subsidiary of Bristol Myers Squibb following a merger in 2019.

Celgene initially developed Apremilast and obtained FDA approval for its use. After the merger, Bristol Myers Squibb took over the marketing of the drug. Apremilast is sold under the brand name Otezla.

Apremilast Class: Phosphodiesterase Inhibitor

Apremilast Category: immunomodulatory drug

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Apremilast (Otezla) FDA-approved indications:

The FDA has approved Apremilast (Otezla) for the following indications:

  1. Moderate to severe plaque psoriasis in adult patients who are candidates for phototherapy or systemic therapy.
  2. Active psoriatic arthritis in adult patients, alone or in combination with DMARDs (disease-modifying antirheumatic drugs), such as methotrexate.
  3. Oral ulcers associated with Behçet’s syndrome in adults.
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Apremilast (Otezla) Dose:

The usual daily maintenance dose of Apremilast (Otezla) for the treatment of plaque psoriasis, psoriatic arthritis, and oral ulcers due to Behcet’s syndrome is 60 mg in two equally divided doses.

Treatment is usually initiated in a low dose and titrated upwards as mentioned in the table below [Ref]:

Apremilast (Otezla) DoseTotal Daily DoseAmPm
Day 110 mg10 mg
Day 220 mg10 mg10 mg
Day 330 mg10 mg20 mg
Day 440 mg20 mg20 mg
Day 550 mg20 mg30 mg
Day 6 and onwards60 mg30 mg30 mg

The maximum recommended dose in patients with severe renal impairment is 30 mg orally once a day.

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Apremilast (Otezla) Contraindications:

There are a few contraindications to the use of Apremilast (Otezla). These include:

  • Hypersensitivity:

Apremilast is contraindicated in patients with a known hypersensitivity to the drug or any of its components.

  • PDE4 inhibitors:

Apremilast is a PDE4 inhibitor, and its use is contraindicated in patients who are taking other PDE4 inhibitors, such as roflumilast.

  • Pregnancy:

Apremilast may cause fetal harm if taken during pregnancy. It is contraindicated in pregnant women and women who are planning to become pregnant.

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Apremilast (Otezla) Side effects:

Some of the important side effects of Apremilast are mentioned in the table below:


Side Effect

GastrointestinalDiarrhea, nausea, vomiting, abdominal pain
PsychiatricDepression, suicidal behavior, or ideation
DermatologicSkin rash
MusculoskeletalBack pain, muscle spasms
RespiratoryNasopharyngitis, upper respiratory tract infection
MetabolicWeight loss

Apremilast and Depression:

Depression is a possible side effect of Apremilast, although it is not a common side effect. In clinical trials, depression was reported in a small percentage of patients taking Apremilast, and it was generally mild to moderate in severity.

Patients taking Apremilast should be aware of the potential for depression and should promptly report any symptoms of depression to their healthcare provider, such as feelings of sadness, hopelessness, loss of interest in activities, changes in sleep patterns, or thoughts of self-harm.

In some cases, Apremilast may not be the best treatment option for patients with a history of depression or other mood disorders.

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Apremilast (Otezla) Drug Interactions:

Drug Class

Examples of Drugs

Degree of Interaction

Strong CYP450 3A4 Inhibitors
  • Ketoconazole,
  • itraconazole,
  • ritonavir,
  • clarithromycin
Increase Apremilast levels

Moderate to Strong

Strong CYP450 3A4 Inducers
  • Rifampin,
  • phenobarbital,
  • phenytoin,
  • carbamazepine
Decrease Apremilast levels


P-glycoprotein (P-gp) Inhibitors
  • Cyclosporine,
  • verapamil,
  • quinidine,
  • ketoconazole
Increase the drug levels

Moderate to Strong

P-glycoprotein (P-gp) Inducers
  • Rifampin,
  • St. John’s wort
The effect is not well known but may decrease the drug levels


CYP450 2C8 Substrates
  • Repaglinide,
  • pioglitazone
Otezla increases the levels of these drugs in the blood increasing their side effects


CYP450 2C9 Substrates
  • Warfarin,
  • phenytoin,
  • tolbutamide
Otezla increases the levels of these drugs in the blood increasing their side effects


CYP450 2C19 Substrates
  • Diazepam,
  • omeprazole
Otezla increases the levels of these drugs and increases their side effects


CYP450 3A4 Substrates
  • Simvastatin,
  • atorvastatin,
  • fentanyl,
  • cyclosporine
Otezla increases the levels of these drugs in the blood and increases their side effects

Weak to Moderate

MethotrexateMay increase the risk of liver toxicityOtezla and Methotrexate, when combined, increase liver toxicity



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Apremilast (Otezla) Mechanism of action (MOA):

Apremilast is a medication that works by inhibiting the activity of an enzyme called phosphodiesterase 4 (PDE4).

PDE4 is involved in the regulation of inflammation and immune response. By inhibiting PDE4, it reduces the production of certain pro-inflammatory cytokines and increases the production of anti-inflammatory cytokines.

This helps to reduce inflammation and modify the immune response, which can lead to improvement in certain inflammatory conditions.



BioavailabilityApproximately 73%
Protein bindingGreater than 99%
MetabolismPrimarily hepatic metabolism via CYP3A4, with minor contributions from CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6
Half-lifeApproximately 6-9 hours
ExcretionApproximately 58% of the dose is excreted in the feces, and approximately 39% is excreted in the urine
Time to peak concentrationApproximately 2-3 hours
Peak concentrationAchieved within 1-2 days of starting treatment
Steady-state concentrationAchieved within 7-14 days of starting treatment
Food effectIt can be taken with or without food, although taking it with food may reduce the risk of gastrointestinal side effects


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Apremilast cost:

According to GoodRx, as of February 2023, the average retail price for:

  • 10mg (30 tablets): $2,800,
  • 30 mg (30 tablets): $3,600.

Apremilast Vs Roflumilast: Are they the same:

Roflumilast is also a phosphodiesterase inhibitor, however, it is indicated only for the treatment of COPD.

Here is a table comparing Apremilast vs Roflumiast:




Mechanism of actionPDE4 inhibitorPDE4 inhibitor
FDA-approved indicationsPsoriasis, Psoriatic arthritisCOPD
Chemical structureSmall moleculeSmall molecule
Target organsSkin, JointsLungs
Side effectsNausea, diarrhea, abdominal painNausea, diarrhea, abdominal pain, increased risk of respiratory infections, cough


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Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

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