Otezla (Apremilast)

What Is Otezla and What Is It Used For?

Otezla (apremilast) is an oral PDE4 inhibitor that reduces inflammation by modulating the immune response from within. It is approved for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, and oral ulcers caused by Behçet's disease.

Otezla contains the active substance apremilast, which belongs to a class of medications called phosphodiesterase 4 (PDE4) inhibitors. PDE4 is an enzyme that plays a central role in the inflammatory process. By blocking this enzyme, Otezla increases levels of cyclic adenosine monophosphate (cAMP) within immune cells, which in turn reduces the production of pro-inflammatory cytokines (such as TNF-α, IL-17, and IL-23) while increasing anti-inflammatory mediators (such as IL-10). This dual action helps control the excessive inflammation seen in psoriasis, psoriatic arthritis, and Behçet's disease.

In patients with psoriatic arthritis, Otezla is used when disease-modifying antirheumatic drugs (DMARDs) such as methotrexate cannot be used or have proven ineffective. It can reduce joint swelling and tenderness, improve physical function, and slow the progression of joint damage. The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) recognise PDE4 inhibitors as a treatment option for psoriatic arthritis, particularly when biologic therapies are not suitable or are unavailable.

For moderate to severe chronic plaque psoriasis, Otezla is prescribed for adults and children aged 6 years and older (weighing at least 20 kg) when phototherapy or systemic treatments such as cyclosporine or methotrexate have been unsuccessful, are contraindicated, or cannot be tolerated. Clinical trials, including the landmark ESTEEM 1 and ESTEEM 2 studies, demonstrated that apremilast significantly reduces the severity and extent of psoriatic skin plaques, with approximately 33% of patients achieving a PASI 75 response (75% improvement in psoriasis severity) at 16 weeks compared with 5% in the placebo group.

In Behçet's disease, Otezla is used to treat oral ulcers, which are the most common and often the most debilitating manifestation of this rare systemic inflammatory condition. The RELIEF study showed that apremilast significantly reduced the number and pain of oral ulcers and, in some patients, led to complete ulcer resolution. It is the first oral therapy specifically approved for this indication in many countries.

It is important to understand that psoriatic arthritis, psoriasis, and Behçet's disease are chronic, lifelong conditions for which there is currently no cure. Otezla does not cure these diseases but helps to control inflammation, reduce symptoms, and improve quality of life. Treatment is typically long-term, and your doctor will regularly assess whether Otezla continues to be the most appropriate therapy for your condition.

What Should You Know Before Taking Otezla?

Do not take Otezla if you are pregnant or may be pregnant, or if you are allergic to apremilast. Inform your doctor about any history of depression, kidney problems, or if you are underweight, as special precautions or dose adjustments may be needed.

Contraindications

You should not take Otezla if any of the following apply to you:

• Allergy to apremilast or any other ingredient in the tablets (including lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, or the film-coating components)
• Pregnancy – Otezla must not be taken if you are pregnant or think you may be pregnant. Animal studies have shown harmful effects on the developing foetus, and there is insufficient data on use in pregnant women

Warnings and Precautions

Talk to your doctor or pharmacist before taking Otezla if you have or have had any of the following:

• Severe kidney problems – if you have severe renal impairment (creatinine clearance less than 30 mL/min), your dose will need to be reduced. See the dosage section for details
• Underweight – talk to your doctor during treatment if you experience unintentional weight loss, as weight loss has been reported in clinical trials
• Severe gastrointestinal problems – if you develop severe diarrhoea, nausea, or vomiting during treatment, contact your doctor. Persistent gastrointestinal symptoms may require treatment interruption

Use in Children and Adolescents

Otezla is approved for children and adolescents aged 6 years and older who weigh at least 20 kg for the treatment of moderate to severe plaque psoriasis when systemic therapy is considered appropriate by their doctor. It has not been studied in children under 6 years of age or in children weighing less than 20 kg, and therefore should not be used in these groups. For all other indications (psoriatic arthritis and Behçet's disease), Otezla is not recommended for patients under 18 years, as safety and efficacy have not been established.

Pregnancy and Breastfeeding

Do not take Otezla if you are pregnant or think you may be pregnant. There is limited information about the effects of apremilast during pregnancy, but animal studies have demonstrated adverse developmental effects. Women of childbearing potential must use an effective method of contraception throughout the duration of treatment and for at least 28 days after the last dose.

It is not known whether apremilast passes into breast milk. You should not use Otezla while breastfeeding. If you are breastfeeding, your doctor will discuss whether you should stop breastfeeding or stop taking Otezla, taking into account the benefit of breastfeeding for the child and the benefit of therapy for you.

Driving and Operating Machinery

Otezla has no known effect on the ability to drive or operate machinery. However, if you experience dizziness as a side effect, exercise caution until you know how the medication affects you.

Lactose Content

Otezla tablets contain lactose (a type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

How Does Otezla Interact with Other Drugs?

Otezla has relatively few drug interactions compared to many other immunomodulators. However, strong CYP3A4 inducers such as rifampicin, phenytoin, phenobarbital, carbamazepine, and St. John's Wort can significantly reduce the effectiveness of Otezla and should be avoided.

Apremilast is primarily metabolised by the liver enzyme CYP3A4, with minor contributions from other enzyme systems. Drugs that strongly induce CYP3A4 can accelerate the breakdown of apremilast, leading to lower blood levels and reduced efficacy. Unlike many biologic therapies, apremilast itself does not significantly inhibit or induce major drug-metabolising enzymes, which contributes to its relatively favourable drug interaction profile.

Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or might take. This includes prescription medicines, over-the-counter drugs, herbal medicines, and dietary supplements.

Major Interactions – Avoid Co-administration

Other Considerations

In clinical pharmacology studies, apremilast showed no clinically meaningful interactions with the following commonly used medicines:

• Methotrexate – no dose adjustment needed for either drug when used together. This is particularly relevant as many psoriatic arthritis patients may be taking methotrexate
• Oral contraceptives (ethinylestradiol and norgestimate) – apremilast does not reduce the effectiveness of hormonal contraception
• Ketoconazole (a strong CYP3A4 inhibitor) – no clinically significant increase in apremilast levels was observed, so no dose adjustment is needed with CYP3A4 inhibitors
• Warfarin and other anticoagulants – no significant interaction has been observed, but standard monitoring of INR is still recommended

One of the advantages of Otezla over many biologic therapies is that it generally does not require dose adjustment when combined with other systemic treatments for psoriasis or psoriatic arthritis. However, always inform your healthcare provider about all the medications you are taking to ensure safe use.

What Is the Correct Dosage of Otezla?

The recommended maintenance dose for adults is 30 mg twice daily (morning and evening, approximately 12 hours apart). Treatment begins with a gradual dose increase over the first 5 days using a starter pack. Otezla can be taken with or without food.

Always take Otezla exactly as your doctor has told you. The dose escalation during the first week is designed to minimise gastrointestinal side effects such as diarrhoea and nausea. You only need to go through this dose escalation once, even if you restart treatment after a break.

Adults – Dose Titration Schedule

The starter pack is designed as a fold-out wallet clearly labelled to ensure you take the correct tablet at the correct time. After completing the titration, you will receive standard 30 mg tablet packs for ongoing treatment.

Children and Adolescents (6 years and older, ≥20 kg)

The dose for children is based on body weight:

Patients with Severe Kidney Problems

Missed Dose

If you forget to take a dose, take it as soon as you remember. If it is almost time for your next scheduled dose, skip the missed dose. Do not take a double dose to make up for a forgotten dose. Take your next dose at the usual time.

Overdose

Stopping Treatment

You should continue taking Otezla for as long as your doctor instructs. Do not stop taking Otezla without talking to your doctor first, even if you are feeling better. Stopping treatment may cause your symptoms to return. If your condition has not improved after 24 weeks (6 months) of treatment, discuss with your doctor whether it is appropriate to continue.

What Are the Side Effects of Otezla?

The most common side effects of Otezla are diarrhoea, nausea, headache, and upper respiratory tract infections. These are generally mild and tend to improve during the first two weeks of treatment. The gradual dose increase in the starter pack helps reduce the severity of gastrointestinal side effects.

Like all medicines, Otezla can cause side effects, although not everybody gets them. Most side effects are transient and occur predominantly during the initial weeks of treatment. The dose titration schedule was specifically designed to reduce the incidence and severity of gastrointestinal side effects. If any side effects become severe or persistent, contact your doctor.

If you are 65 years or older, you may have a higher risk of complications such as severe diarrhoea, nausea, and vomiting. Contact your doctor promptly if gastrointestinal symptoms become severe.

If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. Reporting suspected side effects to your national medicines regulatory authority helps ensure ongoing monitoring of the medicine's benefit-risk balance.

How Should You Store Otezla?

Store Otezla below 30°C in its original packaging. Keep out of reach and sight of children. Do not use the tablets after the expiry date printed on the blister or carton.

Store Otezla tablets at a temperature not exceeding 30°C. No other special storage conditions are required. Keep the tablets in their original blister packaging or wallet card to protect them from moisture. The expiry date (EXP) is printed on the blister pack and carton and refers to the last day of the stated month.

Do not use Otezla if you notice any damage to the packaging or signs of tampering. Do not flush unused tablets down the toilet or place them in household waste. Return any unused or expired medication to your pharmacy for safe and environmentally responsible disposal.

What Does Otezla Contain?

Each Otezla tablet contains apremilast as the active ingredient. The tablets are film-coated, diamond-shaped, and come in three strengths: 10 mg (pink), 20 mg (brown), and 30 mg (beige). All tablets are engraved with "APR" on one side and the strength on the other.

Active Ingredient

The active substance is apremilast. Otezla 10 mg tablets contain 10 mg of apremilast. Otezla 20 mg tablets contain 20 mg of apremilast. Otezla 30 mg tablets contain 30 mg of apremilast.

Inactive Ingredients (Excipients)

The other ingredients in the tablet core are: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, and magnesium stearate. The film coating contains poly(vinyl alcohol), titanium dioxide (E171), macrogol (3350), talc, and red iron oxide (E172). The 20 mg and 30 mg tablets also contain yellow iron oxide (E172), and the 30 mg tablets additionally contain black iron oxide (E172).

Tablet Appearance

• 10 mg tablets: Pink, diamond-shaped, film-coated, engraved with "APR" on one side and "10" on the other
• 20 mg tablets: Brown, diamond-shaped, film-coated, engraved with "APR" on one side and "20" on the other
• 30 mg tablets: Beige, diamond-shaped, film-coated, engraved with "APR" on one side and "30" on the other

Pack Sizes

Starter packs (fold-out wallet format):

• 27 tablets: 4 × 10 mg + 23 × 20 mg (for patients reaching 20 mg twice daily maintenance dose)
• 27 tablets: 4 × 10 mg + 4 × 20 mg + 19 × 30 mg (for patients reaching 30 mg twice daily maintenance dose)

Standard monthly packs:

• 56 × 20 mg tablets (for 20 mg twice daily maintenance dose)
• 56 × 30 mg tablets (for 30 mg twice daily maintenance dose)
• 168 × 30 mg tablets (3-month supply for 30 mg twice daily maintenance dose)

How Does Otezla Work in the Body?

Otezla works by selectively inhibiting the enzyme phosphodiesterase 4 (PDE4), which increases intracellular cAMP levels in immune cells. This modulates the inflammatory response by reducing pro-inflammatory cytokines and increasing anti-inflammatory mediators, without broadly suppressing the immune system.

Phosphodiesterase 4 (PDE4) is the predominant phosphodiesterase enzyme found in inflammatory cells such as T cells, monocytes, macrophages, neutrophils, and dendritic cells. PDE4 breaks down cyclic adenosine monophosphate (cAMP), a critical intracellular signalling molecule that acts as a natural brake on inflammation. When PDE4 is overactive, cAMP levels are low, and inflammatory cells produce excessive amounts of pro-inflammatory cytokines.

By blocking PDE4, apremilast allows cAMP levels to rise within these immune cells. Elevated cAMP activates protein kinase A (PKA), which phosphorylates transcription factors such as CREB (cAMP response element-binding protein). This cascade leads to a reduction in pro-inflammatory mediators including tumour necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), interleukin-23 (IL-23), and interferon-gamma (IFN-γ). Simultaneously, it increases the production of anti-inflammatory cytokines such as interleukin-10 (IL-10).

This dual modulation – reducing inflammation while promoting anti-inflammatory pathways – distinguishes Otezla from many other treatments. Unlike biologic therapies that target a single specific cytokine (such as TNF-α inhibitors or IL-17 inhibitors), Otezla modulates a broad range of inflammatory mediators intracellularly. This approach provides anti-inflammatory effects while preserving much of the body's normal immune surveillance, which is why Otezla is generally not associated with the increased risk of serious or opportunistic infections seen with some immunosuppressants.

Pharmacokinetic Profile

After oral administration, apremilast is well absorbed with an absolute bioavailability of approximately 73%. Peak plasma concentrations are reached within approximately 2.5 hours of dosing. Food does not significantly affect absorption, so Otezla can be taken with or without meals.

Apremilast is approximately 68% bound to plasma proteins. It is extensively metabolised, primarily by the CYP3A4 enzyme, with minor contributions from CYP1A2 and CYP2A6. The major circulating metabolite (M12, a glucuronide conjugate) is pharmacologically inactive. The terminal elimination half-life is approximately 6–9 hours, which is why twice-daily dosing is required to maintain therapeutic blood levels. Approximately 58% of the administered dose is recovered in urine and 39% in faeces, primarily as metabolites.

Frequently Asked Questions About Otezla