Apremilast

Apremilast (Otezla) is a prescription medication used to treat plaque psoriasis, psoriatic arthritis, and mouth ulcers in Behcet's disease. Apremilast improves the symptoms of plaque psoriasis, including scaling, itching, and skin redness, and reduces symptoms in the nails and scalp. When used to treat psoriatic arthritis, apremilast helps reduce inflammation, joint swelling, and pain.

Apremilast tablets are taken once or twice daily, depending on the formulation (immediate or extended-release).

Apremilast works by blocking an enzyme called PDE4, which drives inflammation and the disease processes of these conditions. Apremilast's mechanism of action is an oral phosphodiesterase-4 (PDE-4) inhibitor; it is a selective immunosuppressant agent and is considered a class of immunomodulatory or immunosuppressive medication. It is not a biologic or steroid.

Apremilast’s brand name is Otezla; it is not available as a generic medicine.

Apremilast received FDA approval on March 21, 2014, for psoriatic arthritis and is now also FDA-approved in specific patients to treat types of plaque psoriasis and mouth ulcers in Behcet’s disease.

• Plaque Psoriasis: Adult patients with plaque psoriasis who require systemic therapy or light treatment (phototherapy). Pediatric patients 6 years of age and older and weighing at least 20 kg with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
• Psoriatic Arthritis: Treatment for adult patients with active psoriatic arthritis.
• Oral Ulcers Associated with Behçet's Disease: Treatment for adult patients with oral ulcers associated with Behçet's Disease (a disease-causing inflammation in blood vessels).

Take apremilast exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Apremilast tablets can be taken with or without food.

Swallow the tablet whole, and do not crush, chew, or break it.

Keep track of your body weight while you are taking this medicine, and tell your doctor about any major weight loss.

Depression: Some people have thoughts about suicide while taking this medicine. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor. Carefully weigh the risks and benefits of treatment in patients with a history of depression and/or suicidal thoughts or behavior.

Nausea, vomiting, and diarrhea can be severe complications of apremilast, and patients should contact their doctor if this occurs.

Hypersensitivity: Cases of swelling (angioedema) and anaphylaxis have been reported. Do not use this medicine in patients with known hypersensitivity to apremilast or any of the inactive ingredients:

Weight loss: This medicine may cause weight loss. Monitor weight regularly. If clinically significant or unexpected weight loss occurs, evaluate the reason for weight loss and consider stopping this medicine.

Drug interactions: Medications that are strong cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) are not recommended because loss of efficacy may occur. See the Interactions section below.

You should not use apremilast if you are allergic to it.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• kidney disease; or
• depression or suicidal thoughts, or actions.

Some people have thoughts about suicide while taking apremilast. Your doctor will need to check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Pregnancy

Apremilast may harm an unborn baby. It is important to use effective birth control to prevent pregnancy, and tell your doctor if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of apremilast on the baby.

Breastfeeding

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risks.

Common apremilast side effects

Common apremilast side effects are nausea, diarrhea, headache, vomiting, upper respiratory tract infection, upper abdominal pain, and cold symptoms such as a stuffy nose, sneezing, and sore throat.

These were the side effects that occurred for apremilast 30mg twice daily from day 6 to day 112 in the psoriatic arthritis clinical trials PsA-1 (NCT01172938), PsA-2 (NCT01212757), and PsA-3 (NCT01212770). Side effects that caused patients to stop taking tablets during the trials included nausea (1.8%), diarrhea (1.8%), and headache (1.2%).

Gastrointestinal side effects can occur when first starting therapy. To help reduce these side effects, the dose is started low and increased over the first 5 days. Apremilast starter packs are available with the first 5 days of tablets, which makes initial dosing easy and convenient.

Serious apremilast side effects

Get emergency medical help if you have signs of an allergic reaction to this medicine: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Apremilast may cause other serious side effects. Call your doctor at once if you have:

• severe diarrhea, nausea, and vomiting;
• unexplained weight loss, or if you lose a lot of weight;
• mood changes, new or worsening depression; or
• thoughts of suicide or hurting yourself.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual adult dose for psoriatic arthritis, plaque psoriasis, and Behcet’s disease

Adult starting dose:

• Day 1: 10 mg once a day in the morning
• Day 2: 10 mg twice a day (morning and evening)
• Day 3: 10 mg in the morning and 20 mg in the evening
• Day 4: 20 mg twice a day (morning and evening)
• Day 5: 20 mg in the morning and 30 mg in the evening, followed by a maintenance dose.

Adult maintenance dose:

• Apremilast 30 mg orally twice a day (morning and evening)

or

• Apremilast XR 75 mg once daily

Usual dose for pediatric patients

For Moderate to Severe Plaque Psoriasis who are 6 Years of Age and Older and Weighing at Least 20kg.

Starting dose for pediatric patients (20kg to less than 50 kg):

• Day 1: 10 mg once a day in the morning
• Day 2: 10 mg twice a day (morning and evening)
• Day 3: 10 mg in the morning and 20 mg in the evening
• Day 4: 20 mg twice a day (morning and evening), then maintenance dose.

Maintenance dose for pediatric patients (20kg to less than 50 kg):

• 20 mg twice a day (morning and evening)

Starting dose for pediatric patients (50 kg or more):

• Day 1: 10 mg once a day in the morning
• Day 2: 10 mg twice a day (morning and evening)
• Day 3: 10 mg in the morning and 20 mg in the evening
• Day 4: 20 mg twice a day (morning and evening)
• Day 5: 20 mg in the morning and 30 mg in the evening, followed by a maintenance dose.

Maintenance dose for pediatric patients (50 kg or more):

• Apremilast 30 mg orally twice a day (morning and evening)

or

• Aprelimast XR 75 mg once a day

Apremilast starter pack

Apremilast starter packs (Otezla brand) contain the tablets required for the 5-day titration period, making initial dosing easier, but it is still important to follow your doctor's instructions carefully.

General dosing comments

Keep track of your body weight while you are taking this medicine, and tell your doctor about any major weight loss.

Dosage adjustments are required in renal impairment.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Sometimes, it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

When you are taking apremilast, tell your doctor about all your current medications and any medicine you start or stop using. It is especially important that you tell your healthcare professional about any of the medications in the list below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using apremilast with any of the following medicines may not be recommended, but may be necessary in some cases. If both medicines are to be used together, your doctor may change the dose or how often you use one or both of the medicines.

• Carbamazepine
• Enzalutamide
• Fosphenytoin
• Mitotane
• Phenytoin
• Primidone
• Rifabutin
• Rifampin
• Rifapentine
• St John's Wort
• Tofacitinib

This list is not complete, and many other drugs can interact with apremilast. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Active ingredient: apremilast

Otezla Inactive ingredients:

Otezla 10mg tablet: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, polyvinyl alcohol (unspecified), titanium dioxide, polyethylene glycol (unspecified), talc, ferric oxide red.

Otezla 20mg tablet: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, polyvinyl alcohol (unspecified), titanium dioxide, polyethylene glycol (unspecified), talc, ferric oxide red, ferric oxide yellow.

Otezla 30mg tablet: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, polyvinyl alcohol (unspecified), titanium dioxide, polyethylene glycol (unspecified), talc, ferric oxide red, ferric oxide yellow, ferrosoferric oxide.

Otezla 75mg XR tablet: cellulose acetate, colloidal silicon dioxide, ferrosoferric oxide, hydroxypropyl methylcellulose acetate succinate, hypromellose, iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, polyethylene oxide, sodium chloride, titanium dioxide.

Otezla Amgen Inc. Thousand Oaks, CA 91320-1799 U.S.A