Patient leaflet - Treatment Initiation Pack -, Apremilast 10 mg + 20 mg + 30 mg film-coated tablets

1. What Apremilast is and what it is used for What Apremilast is

Apremilast contains the active substance 'apremilast'. This belongs to a group of medicines called phosphodiesterase 4 inhibitors, which help to reduce inflammation.

What Apremilast is used for

Apremilast is used to treat adults with the following conditions: · Active psoriatic arthritis - if you cannot use another type of medicine called

'Disease-Modifying Antirheumatic Drugs' (DMARDs) or when you have tried one of these medicines and it did not work.

Moderate to severe chronic plaque psoriasis - if you cannot use one of the
following treatments or when you have tried one of these treatments and it did not work:
- phototherapy - a treatment where certain areas of skin are exposed to
  ultraviolet light
- systemic therapy - a treatment that affects the entire body rather than just one
  local area, such as 'ciclosporin', 'methotrexate' or 'psoralen'. · Behçet's disease (BD) - to treat the mouth ulcers which is a common problem for

people with this illness.

Apremilast is used to treat children and adolescents 6 years of age and older and weighing at least 20 kg with the following condition:

Moderate to severe plaque psoriasis – if your doctor determines that it is
appropriate for you to take a systemic therapy like Apremilast.

What psoriatic arthritis is

Psoriatic arthritis is an inflammatory disease of the joints, usually accompanied by psoriasis, an inflammatory disease of the skin.

What plaque psoriasis is

Psoriasis is an inflammatory disease of the skin, which can cause red, scaly, thick, itchy, painful patches on your skin and can also affect your scalp and nails.

What Behçet's disease is

Behçet's disease is a rare type of inflammatory disease which affects many parts of the body. The most common problem is mouth ulcers.

How Apremilast works

Psoriatic arthritis, psoriasis and Behçet's disease are usually lifelong conditions and there is currently no cure. Apremilast works by reducing the activity of an enzyme in the body called 'phosphodiesterase 4', which is involved in the process of inflammation. By reducing the activity of this enzyme, Apremilast can help to control the inflammation associated with psoriatic arthritis, psoriasis and Behçet's disease, and thereby reduce the signs and symptoms of these conditions.

In adults with psoriatic arthritis, treatment with Apremilast results in an improvement in swollen and painful joints, and can improve your general physical function.

In adults and in children and adolescents from the age of 6 years and weighing at least 20 kg with psoriasis, treatment with Apremilast results in a reduction in psoriatic skin plaques and other signs and symptoms of the disease.

In adults with Behçet's disease, treatment with Apremilast reduces the number of mouth ulcers and can stop them completely. It can also reduce the associated pain.

Apremilast has also been shown to improve the quality of life in adult and paediatric patients with psoriasis, adult patients with psoriatic arthritis and adult patients with Behçet's disease. This means that the impact of your condition on daily activities, relationships and other factors should be less than it was before.

2. What you need to know before you take Apremilast

Do not take Apremilast:

if you are allergic to apremilast or any of the other ingredients of this medicine
(listed in section 6).
if you are pregnant or think you may be pregnant.

Warnings and precautions

Talk to your doctor or pharmacist before taking Apremilast.

Depression and suicidal thoughts

Tell your doctor before starting Apremilast if you have depression which is getting worse with thoughts of suicide.

You or your caregiver should also tell your doctor straight away of any changes in behaviour or mood, feelings of depression and of any suicidal thoughts you may have after taking Apremilast.

Severe kidney problems

If you have severe kidney problems, your dose will be different – see section 3.

If you are underweight

Talk to your doctor while taking Apremilast if you lose weight without meaning to.

Gut problems

If you experience severe diarrhoea, nausea, or vomiting, you should talk to your doctor.

Children and adolescents

Apremilast is not recommended for use in children who have moderate to severe plaque psoriasis and are below 6 years of age or weigh less than 20 kg, because it has not been studied in these age and weight groups.

Apremilast is not recommend for use in children and adolescents below 18 years of age in other indications, because safety and efficacy have not been established in this age group.

Other medicines and Apremilast

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription and herbal medicines. This is because Apremilast can affect the way some other medicines work. Also some other medicines can affect the way Apremilast works.

In particular, tell your doctor or pharmacist before taking Apremilast if you are taking any of the following medicines:

rifampicin – an antibiotic used for tuberculosis
phenytoin, phenobarbital and carbamazepine - medicines used in the treatment of seizures or epilepsy
St John's Wort – a herbal medicine for mild anxiety and depression.

Pregnancy and breast-feeding

Do not take Apremilast if you are pregnant or think you may be pregnant.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

There is little information about the effects of Apremilast in pregnancy. You should not become pregnant while taking this medicine and should use an effective method of contraception during treatment with Apremilast.

It is not known if this medicine passes into human milk. You should not use Apremilast while breast-feeding.

Driving and using machines

Apremilast has no effect on the ability to drive and use machines.

Apremilast contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Apremilast contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially 'sodium-free'.

3. How to take Apremilast

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

How much to take

When you first start taking Apremilast, you will receive a 'treatment initiation pack' which contains enough tablets for a total of two weeks of treatment. · The 'treatment initiation pack' is clearly labelled to make sure you take the correct tablet at the correct time.
Your treatment will start at a lower dose and will gradually be increased during the first week of treatment (titration phase).
The 'treatment initiation pack' will also contain enough tablets for another week at the recommended dose.
Once the recommended dose has been reached, you will only get a single tablet strength in your prescribed packs. You will only ever need to go through the stage of gradually increasing your dose once even if you re-start treatment. Adults
The recommended dose of Apremilast for adult patients is 30 mg twice a day after the titration phase is completed, as shown in the table below - one 30 mg dose in the morning and one 30 mg dose in the evening, approximately 12 hours apart, with or without food. This is a total daily dose of 60 mg.

Children and adolescents 6 years of age and older

The Apremilast dose will be based on body weight.

For patients who weigh from 20 kg to less than 50 kg: The recommended dose of Apremilast is 20 mg twice a day, after the titration phase is completed, as shown in the table below - one 20 mg dose in the morning and one 20 mg dose in the evening,

Day	Morning Dose	Evening Dose	Total Daily Dose
Day 1	10 mg (yellow)	Do not take a dose	10 mg
Day 2	10 mg (yellow)	10 mg (yellow)	20 mg
Day 3	10 mg (yellow)	20 mg (blue)	30 mg
Day 4	20 mg (blue)	20 mg (blue)	40 mg
Day 5	20 mg (blue)	30 mg (white to off white)	50 mg
Day 6 onwards	30 mg (white to off white)	30 mg (white to off white)	60 mg

approximately 12 hours apart, with or without food. This is a total daily dose of 40 mg.

For patients who weigh at least 50 kg: The recommended dose of Apremilast is 30 mg twice a day after the titration phase is completed (the same as the adult dose), as shown in the table below - one 30 mg dose in the morning and one 30 mg dose in the evening, approximately 12 hours apart, with or without food. This is a total daily dose of 60 mg.

People with severe kidney problems

If you are an adult with severe kidney problems, then the recommended dose of Apremilast is 30 mg once a day (morning dose).

In children and adolescents 6 years of age and older with severe renal impairment, the recommended dose of Apremilast is 30 mg once a day (morning dose) for patients who weigh at least 50 kg, and 20 mg once a day (morning dose) for children who weigh 20 kg to less than 50 kg.

Your doctor will talk to you about how to increase your dose when you first start taking Apremilast. Your doctor may advise that you only take the morning dose shown in the table above that applies to you (for adults or for children/adolescents) and that you skip the evening dose.

How and when to take Apremilast

Apremilast is for oral use.
Swallow the tablets whole, preferably with water.
You can take the tablets either with or without food.
Take Apremilast at about the same time each day, one tablet in the morning and
one tablet in the evening.

If your condition has not improved after six months of treatment, you should talk to your doctor.

If you take more Apremilast than you should

If you take more Apremilast than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack and this leaflet with you.

If you forget to take Apremilast

If you miss a dose of Apremilast, take it as soon as you remember. If it is close to
the time for your next dose, just skip the missed dose. Take the next dose at your regular time.
Do not take a double dose to make up for a forgotten dose.

If you stop taking Apremilast

You should continue taking Apremilast until your doctor tells you to stop. · Do not stop taking Apremilast without talking to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects – depression and suicidal thoughts

Tell your doctor straight away about any changes in behaviour or mood, feelings of depression, thoughts of suicide or suicidal behaviour (this is uncommon).

Very common side effects (may affect more than 1 in 10 people) · diarrhoea

nausea
headache
upper respiratory tract infections such as cold, runny nose, sinus infection

Common side effects (may affect up to 1 in 10 people)

cough
back pain
vomiting
feeling tired
stomach pain
- loss of appetite
- frequent bowel movements
- difficulty sleeping (insomnia)
- indigestion or heartburn
- inflammation and swelling of the tubes in your lungs (bronchitis) · common cold (nasopharyngitis)
- depression
- migraine
- tension headache

Uncommon side effects (may affect up to 1 in 100 people)

rash
hives (urticaria)
weight loss
allergic reaction
bleeding in the bowel or in the stomach
suicidal ideation or behaviour
anxiety
mood changes

Not known side effects (frequency cannot be estimated from the available data): · severe allergic reaction (may include swelling of the face, lips, mouth, tongue, or throat that may lead to difficulty breathing or swallowing)

If you are 65 years of age or older, you might have a higher risk of complications of severe diarrhoea, nausea and vomiting. If your gut problems become severe, you should talk to your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Apremilast

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister or on the wallet or on the carton after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Apremilast contains

The active substance is apremilast.

Each film-coated tablet contains 10 mg of apremilast.

Each film-coated tablet contains 20 mg of apremilast.

Each film-coated tablet contains 30 mg of apremilast.

The other ingredients are:

Tablet core: Cellulose microcrystalline, croscarmellose sodium, lactose monohydrate & magnesium stearate.

Film-coating: Hypromellose 3 mPas (E464), titanium dioxide (E171), macrogol 4000 (E1521) & talc (E553b).

For 10 mg: Iron oxide yellow (E172).

For 20 mg: Indigo carmine aluminum lake (E132).

What Apremilast looks like and contents of the pack

Apremilast 10 mg film-coated tablets

Yellow oval shaped, approximately 7.8 mm x 4.2 mm, biconvex, film coated tablets debossed with 'H' on one side and “10” on the other side.

Apremilast 20 mg film-coated tablets

Blue oval shaped, approximately 9.8 mm x 5.3 mm, biconvex, film coated tablet debossed with 'H' on one side and “20” on the other side.

Apremilast 30 mg film-coated tablets

White to off white oval shaped, approximately 11.6 mm x 5.7 mm, biconvex, film coated tablet debossed with 'H' on one side and “30” on the other side.

Pack sizes

Apremilast 10 mg, 20 mg, 30 mg film-coated tablets

The treatment initiation pack is a folding wallet containing 27 film-coated tablets: 4 x 10 mg tablets, 4 x 20 mg tablets and 19 x 30 mg tablets.