Apremilast is a prescription tablet used to treat long-lasting inflammatory conditions of the skin and joints. It contains a single active ingredient that belongs to a group of medicines called phosphodiesterase 4 (PDE4) inhibitors. Doctors prescribe it for psoriatic arthritis (joint pain and swelling linked to psoriasis), plaque psoriasis (red, scaly skin patches), and painful mouth ulcers caused by Behcet's disease. Apremilast works inside immune cells to calm the signals that drive inflammation. It helps control these conditions over time rather than making them go away for good, so it is usually taken every day for as long as your doctor advises.

Apremilast is a medicine taken by mouth. It blocks an enzyme called phosphodiesterase 4 (PDE4), which is found inside immune cells. When this enzyme is blocked, levels of a messenger molecule called cyclic AMP (cAMP) rise inside the cell. Higher cAMP levels turn down the release of several inflammatory chemicals, including TNF-alpha, IL-12 and IL-23. In people treated with Apremilast, blood levels of IL-17, IL-22 and TNF-alpha have been seen to fall. Because it acts on the inflammation process itself, Apremilast is used in conditions where the immune system is overactive.

In adults, Apremilast is approved for active psoriatic arthritis, plaque psoriasis in people who are candidates for light therapy (phototherapy) or whole-body treatment, and mouth ulcers linked to Behcet's disease. The current US label also allows its use in children aged 6 years and older who weigh at least 20 kg, for psoriatic arthritis and moderate to severe plaque psoriasis.

One practical difference from many other treatments for these conditions is that Apremilast is a tablet, not an injection. It also does not need routine blood test monitoring, which some patients find easier for long-term care.

Treatment is started at a low dose and slowly raised over the first 5 days. This step-up helps reduce stomach upset, which is the most common problem people notice early on. Diarrhoea, nausea and vomiting can sometimes be severe, and in some cases people have needed hospital care. Most of these events happen within the first few weeks.

Apremilast has also been linked to depression and weight loss. Your doctor will ask about your mental health history before you start, and will check your weight during treatment. For these reasons, Apremilast should only be used under the care of a doctor who can review how you are doing at regular visits.

Each tablet contains Apremilast as its only active ingredient. The regular tablets are made in strengths of 10 mg, 20 mg and 30 mg, and a starter pack with the lower strengths is used during the first days of treatment. In the US, an extended-release (long-acting) tablet of 75 mg is also approved for once-daily use. Chemically, Apremilast belongs to the isoindole class of compounds.

Apremilast is used to treat the following conditions:

• Psoriatic arthritis - a condition that causes joint pain and swelling along with scaly skin, in adults with active disease. It is also approved for children aged 6 years and older who weigh at least 20 kg.
• Plaque psoriasis - a skin disease in which red, scaly patches form, in adults who are candidates for phototherapy or systemic (whole-body) treatment. It is also approved for children aged 6 years and older who weigh at least 20 kg with moderate to severe disease.
• Mouth ulcers in Behcet's disease - painful sores in the mouth in adults with Behcet's syndrome.

1. Tablet form - Apremilast is taken by mouth, which many people find simpler than the injections used for some other treatments of psoriasis and psoriatic arthritis.
2. No routine blood test monitoring - it does not need regular lab monitoring, which can make long-term treatment easier to manage.
3. Works on inflammation at its source - by blocking the PDE4 enzyme inside immune cells, it lowers several inflammatory signals that drive skin and joint symptoms.
4. Treats more than one condition - the same medicine is approved for psoriatic arthritis, plaque psoriasis and mouth ulcers in Behcet's disease.

Common Side Effects (Usually Mild and may lessen with continued use)

• Diarrhoea
• Nausea (feeling sick)
• Headache, including tension headache
• Upper respiratory tract infection (cold-like nose and throat infection), with sore throat, cough, sneezing, runny or blocked nose
• Vomiting
• Stomach pain
• Tiredness
• Reduced appetite
• Back pain

Serious Side Effects (Seek Urgent Medical Attention)

• Severe diarrhoea, nausea or vomiting - some people have needed hospital care. This mostly happens in the first few weeks. People aged 65 or older, and people taking medicines that lower blood pressure or cause fluid loss, are at higher risk of problems such as dehydration.
• Depression and suicidal thoughts - Apremilast has been linked to new or worsening depression. Rarely, suicidal thoughts or behaviour have been reported. Tell your doctor or a family member right away about low mood, changes in behaviour, or thoughts of self-harm.
• Weight loss - some people lose a noticeable amount of weight. In one set of studies, 10% of people with psoriatic arthritis on Apremilast lost 5% to 10% of their body weight, compared with 3.3% on a dummy pill.
• Serious allergic reactions - cases of angioedema (sudden swelling of the face, lips, tongue or throat) and anaphylaxis (a severe, whole-body allergic reaction that can cause trouble breathing, faintness and a drop in blood pressure) have been reported. These are emergencies.

• Take Apremilast exactly as your doctor has prescribed. The regular tablets are usually taken twice a day, and the extended-release tablet once a day.
• You can take it with or without food. Food does not have a meaningful effect on how the regular tablet is absorbed.
• Swallow the tablet whole with a glass of plain water. Do not crush, split or chew it.
• Take your doses at around the same time or times every day. This helps keep a steady level of medicine in your body.
• Your doctor will start you on a low dose and slowly raise it over the first 5 days. Follow the starter schedule you are given, and do not skip ahead.
• If you take the extended-release tablet, you may see an empty tablet shell in your stool. This is expected and does not mean the medicine did not work.
• Keep taking Apremilast even when you feel well. Do not stop it without talking to your doctor, as it controls the condition rather than making it go away permanently.

Inside many immune cells there is an enzyme called phosphodiesterase 4, or PDE4. An enzyme is a protein that speeds up a chemical reaction. The job of PDE4 is to break down a messenger molecule called cyclic AMP (cAMP).

cAMP acts like a brake on inflammation inside the cell. When cAMP levels are high, the cell makes fewer inflammatory chemicals. When PDE4 breaks cAMP down, that brake is released and inflammation can build up.

Apremilast is a selective PDE4 inhibitor, which means it blocks this one enzyme. With PDE4 blocked, cAMP is not broken down as quickly, so its level inside the cell rises. This lowers the production of inflammatory messengers such as TNF-alpha, IL-2, IL-8, IL-12 and IL-23. These messengers, called cytokines, are signals the immune system uses to call in more inflammation. In people treated with Apremilast, blood levels of IL-17, IL-22 and TNF-alpha have been seen to fall.

The exact way these changes lead to improvement in psoriasis, psoriatic arthritis and Behcet's mouth ulcers is still being studied. What is clear is that Apremilast works by calming the overactive immune signals that drive these conditions, rather than by relieving pain directly.

Once swallowed, about 73% of the dose is absorbed, and blood levels peak in about 2.5 hours. The liver breaks it down, mainly through an enzyme called CYP3A4, and its half-life (the time for the body to clear half of it) is about 6 to 9 hours.

• Follow the 5-day starter schedule exactly, as the slow step-up helps reduce stomach upset.
• Swallow tablets whole with plain water; do not crush, split or chew them.
• If you get diarrhoea or vomiting, drink enough fluids and tell your doctor if it is severe, especially if you are over 65.
• Watch your mood. Report low mood, loss of interest, or thoughts of self-harm to your doctor right away.
• Weigh yourself from time to time and tell your doctor about any unexplained weight loss.
• Tell your doctor about every medicine and herbal product you take, including St. John's wort.
• Tell your doctor or vaccinator that you are taking Apremilast before any vaccination, so they can advise you.

• Store the regular tablets below 30°C (86°F).
• Store the extended-release tablets between 20°C and 25°C (68°F and 77°F); short periods between 15°C and 30°C (59°F and 86°F) are allowed.
• Keep the tablets in the container they came in, tightly closed.
• Protect from light, excess heat and moisture.
• Keep out of reach and sight of children and pets.

• Food - Apremilast can be taken with or without food. Food has no meaningful effect on how the regular tablets are absorbed. With the extended-release tablet, a high-fat meal raised blood levels by about 28%.
• St. John's wort - using this herbal product with Apremilast is not recommended, as it can make the medicine work less well.
• Alcohol - no specific interaction is listed on the label. Ask your doctor for advice, especially if you have stomach upset.

• Strong enzyme-inducing medicines and herbal products (rifampicin, phenobarbitone, carbamazepine, phenytoin, St. John's wort) - these speed up the breakdown of Apremilast by liver enzymes. Using them together is not recommended because Apremilast may stop working well. In one study, rifampicin lowered the amount of Apremilast in the blood by 72%.
• Medicines that cause fluid loss or low blood pressure - people taking these may be at higher risk of complications if severe diarrhoea or vomiting occurs, so the doctor will monitor more closely.

• Depression or past suicidal thoughts - Apremilast has been linked to depression. If you have a history of depression, suicidal thoughts or behaviour, your doctor will weigh the risks and benefits carefully and check on your mood regularly.
• Low body weight - Apremilast can cause weight loss. Your doctor will monitor your weight and may review treatment if you lose a meaningful amount.
• Severe kidney disease - in severe kidney disease (creatinine clearance, a measure of how well the kidneys filter blood, below 30 mL/min), the label lowers the regular tablet to once a day - 30 mg once daily in adults and children weighing 50 kg or more, or 20 mg once daily in children weighing 20 kg to less than 50 kg. The extended-release tablet is not recommended in severe kidney disease.
• Conditions that make dehydration risky - older age, or medicines that lower blood pressure or cause fluid loss, raise the risk of complications from severe diarrhoea or vomiting.
• Allergy to Apremilast - people with a known allergy to Apremilast or any ingredient in the tablet should not take it.
• Pregnancy - should not be used during pregnancy, based on the European product information.

Always take the dose your doctor prescribes. Do not change or stop your dose on your own.

• According to the US prescribing label, treatment starts with a low dose that is raised step by step over the first 5 days.
• From day 6, the label's usual adult maintenance dose is 30 mg twice a day for the regular tablet, or 75 mg once a day for the extended-release tablet.
• For children weighing 20 kg to less than 50 kg, the label's maintenance dose is 20 mg twice a day. Children weighing 50 kg or more follow the adult dose.
• In severe kidney disease (creatinine clearance, a measure of how well the kidneys filter blood, below 30 mL/min), the label lowers the regular tablet to once a day - 30 mg once daily in adults and children weighing 50 kg or more, or 20 mg once daily in children weighing 20 kg to less than 50 kg. The extended-release tablet is not recommended in severe kidney disease.
• Your doctor may lower or pause the dose if you get severe diarrhoea, nausea or vomiting.

If you think you or someone else has taken too much Apremilast, contact your doctor or a poison control centre right away. The European product information notes that in a short study, healthy volunteers were given up to 100 mg a day (50 mg twice a day) for 4.5 days without side effects severe enough to stop the study dose. In case of an overdose, doctors watch closely for any signs of side effects and treat symptoms as they appear with supportive care. If the person has collapsed or has trouble breathing, call emergency services immediately. Take the medicine pack with you to the hospital so the doctors know what was taken.

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and carry on with your usual schedule. Do not take a double dose to make up for a missed one.

Contact your doctor or get emergency help right away if you notice:

• Swelling of the face, lips, tongue or throat, trouble breathing, or a sudden rash, which may be signs of a serious allergic reaction
• Severe or ongoing diarrhoea, nausea or vomiting, especially if you feel dizzy, weak or very thirsty
• New or worsening depression, sudden mood or behaviour changes, or thoughts of harming yourself
• Unexplained or large weight loss
• Pregnancy while taking Apremilast
• In children, slow growth or failure to gain weight as expected