Apremilast krka

Package leaflet: Information for the patient

Apremilast Krka, 10 mg, film-coated tablets
Apremilast Krka, 20 mg, film-coated tablets
Apremilast Krka, 30 mg, film-coated tablets
Apremilastum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific person only. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Apremilast Krka is and what it is used for
2. Important information before taking Apremilast Krka
3. How to take Apremilast Krka
4. Possible side effects
5. How to store Apremilast Krka
6. Contents of the pack and other information

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

What Apremilast Krka is
Apremilast Krka contains the active substance "apremilast". It belongs to a group of medicines known as phosphodiesterase 4 inhibitors, and its action may help reduce inflammation.

What Apremilast Krka is used for
Apremilast Krka is used to treat adults with the following conditions:

• Active psoriatic arthritis – if the patient cannot take another type of medicine known as "disease-modifying antirheumatic drugs (DMARDs)", or if they have tried such medicines without success.
• Moderate to severe chronic plaque psoriasis – if the patient cannot take one of the following treatments, or if they have tried one of these therapies without success:
  • Phototherapy – a treatment in which areas of skin are exposed to ultraviolet light.
  • Systemic therapy – treatment that affects the whole body rather than a specific part; examples include medicines such as "cyclosporine", "methotrexate", or "psoralen".
• Behçet’s disease (BD) – to treat oral ulcers, which are a common symptom in people with this condition.

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

• Moderate to severe plaque psoriasis – if the doctor determines that systemic treatment, such as Apremilast Krka, is appropriate for the patient.

What is psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease, which is usually associated with psoriasis, an inflammatory skin condition.

What is plaque psoriasis
Psoriasis is an inflammatory skin disease that may cause red, scaly, thick, itchy, and painful skin lesions; it may also affect the scalp and nails.

What is Behçet’s disease
Behçet’s disease is a rare type of inflammatory disorder affecting multiple parts of the body. The most common symptom is oral ulcers.

How Apremilast Krka works
Psoriatic arthritis, psoriasis, and Behçet’s disease are generally lifelong conditions, as there is currently no cure. Apremilast Krka works by reducing the activity of an enzyme called "phosphodiesterase 4", which plays a key role in the inflammatory process. By reducing the activity of this enzyme, Apremilast Krka may help control the inflammation associated with psoriatic arthritis, psoriasis, and Behçet’s disease, thereby reducing the signs and symptoms of these diseases.

In adults with psoriatic arthritis, treatment with Apremilast Krka leads to improvement in swollen and painful joints and may improve the patient’s overall physical function.

In adults, and in children and adolescents aged 6 years and weighing at least 20 kg with psoriasis, treatment with Apremilast Krka reduces psoriatic skin lesions and other signs and symptoms of the disease.

In Behçet’s disease, treatment with Apremilast Krka in adults reduces the number of oral ulcers and may lead to their complete resolution. It may also reduce associated pain.

Apremilast Krka has also been shown to improve quality of life in adult patients and in children and adolescents with psoriasis, in adults with psoriatic arthritis, and in adults with Behçet’s disease. This means a reduced impact of the disease on the patient’s daily activities, relationships with others, and other factors compared to before.

2. Important information before using Apremilast Krka

When not to use Apremilast Krka

• if the patient is allergic to apremilast or any of the other ingredients of this medicine (listed in section 6).
• if the patient is pregnant or suspects she may be pregnant.

Warnings and precautions
Before starting Apremilast Krka, discuss this with your doctor or
pharmacist.
Depression and suicidal thoughts
If the patient suffers from worsening depression with suicidal thoughts, this should be discussed with the doctor before starting treatment with Apremilast Krka.
The patient or their caregiver should also inform the doctor immediately about any changes in behaviour or mood, feelings of depression, or any suicidal thoughts that occur after starting Apremilast Krka.
Severe kidney disease
If the patient has severe kidney disease, the dose taken will be different – see section 3.
Weight loss
If the patient experiences unexplained weight loss while taking Apremilast Krka, inform the doctor.
Gastrointestinal problems
Inform the doctor if severe diarrhoea, nausea or vomiting occurs.
Children and adolescents
The use of Apremilast Krka is not recommended in children with moderate to severe plaque psoriasis under 6 years of age and weighing less than 20 kg, as the medicine has not been studied in these age and weight groups.
The use of Apremilast Krka is not recommended in children and adolescents under 18 years of age for other indications, as safety and efficacy have not been established in this age group.
Apremilast Krka and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. This includes medicines available without a prescription and herbal medicines. This is important because Apremilast Krka may affect the action of other medicines. Conversely, other medicines may affect the action of Apremilast Krka.
In particular, inform your doctor or pharmacist before starting Apremilast Krka if the patient is taking any of the following medicines:

• rifampicin – an antibiotic used to treat tuberculosis;
• phenytoin, phenobarbital and carbamazepine – medicines used to treat seizures or epilepsy;
• St. John’s wort – a herbal medicine used for mild anxiety and depression.

Pregnancy and breastfeeding
Do not use Apremilast Krka if the woman is pregnant or suspects she may be pregnant.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
There is limited information on the use of Apremilast Krka in pregnant women. The woman should not become pregnant while taking this medicine and should use an effective method of contraception during treatment with Apremilast Krka.
It is not known whether the medicine passes into human milk. Apremilast Krka should not be used during breastfeeding.
Driving and operating machinery
Apremilast Krka has no influence on the ability to drive or operate machinery.
Apremilast Krka contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning the medicine is considered "sodium-free".

3. How to use Apremilast Krka

This medicine should always be taken exactly as prescribed by the doctor. In case of doubts, consult
your doctor or pharmacist.
Recommended dose of the medicine

• If the patient is starting treatment with Apremilast Krka for the first time, they will receive a "starter pack" containing enough tablets for two weeks of treatment.
• The "starter pack" is clearly labeled to ensure that the patient takes the correct tablet at the correct time.
• Treatment will begin with a lower dose, which will be gradually increased during the first week of treatment (dose-escalation period).
• The "starter pack" also contains tablets at the recommended dose for the following week.
• After reaching the recommended dose, the patient will receive only one tablet strength in the prescribed packaging.
• The patient needs to go through this dose-escalation phase only once, even if treatment needs to be restarted later.

Adults

• The recommended dose of Apremilast Krka for adult patients after completion of the dose-escalation period is 30 mg twice daily, 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. The total daily dose is 60 mg.

Total
Day Morning dose Evening dose daily
dose
Day 1 10 mg (pink) No evening dose 10 mg
Day 2 10 mg (pink) 10 mg (pink) 20 mg
Day 3 10 mg (pink) 20 mg (orange-brown) 30 mg
Day 4 20 mg (orange-brown) 20 mg (orange-brown) 40 mg
Day 5 20 mg (orange-brown) 30 mg (light brown-violet) 50 mg
Day 6 and onwards 30 mg (light brown-violet) 30 mg (light brown-violet) 60 mg
Children and adolescents aged at least 6 years

• The dose of Apremilast Krka depends on body weight.

Patients with body weight from 20 kg to less than 50 kg*: The recommended dose of Apremilast Krka after
completion of the dose-escalation period is 20 mg twice daily, as shown in the table below – one 20 mg dose in the morning and one 20 mg dose in the evening, approximately 12 hours apart, with or without food. The total daily dose is 40 mg.
Body weight from 20 kg to less than 50 kg
Total
Day Morning dose Evening dose daily
dose
Day 1 10 mg (pink) No evening dose 10 mg
Day 2 10 mg (pink) 10 mg (pink) 20 mg
Day 3 10 mg (pink) 20 mg (orange-brown) 30 mg
Day 4 20 mg (orange-brown) 20 mg (orange-brown) 40 mg
Day 5 20 mg (orange-brown) 20 mg (orange-brown) 40 mg
Day 6 and onwards 20 mg (orange-brown) 20 mg (orange-brown) 40 mg
* Apremilast Krka is not available in pack sizes allowing dose adjustment and continuation of treatment in children and adolescents with body weight from 20 kg to less than 50 kg. Treatment of children and adolescents with body weight from 20 kg to less than 50 kg with Apremilast Krka is not possible; other apremilast-containing medicines available in appropriate pack sizes should be used in these patients.
Patients with body weight at least 50 kg: The recommended dose of Apremilast Krka after completion of the dose-escalation period is 30 mg twice daily (as in adults), 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. The total daily dose is 60 mg.
Body weight at least 50 kg
Total
Day Morning dose Evening dose daily
dose
Day 1 10 mg (pink) No evening dose 10 mg
Day 2 10 mg (pink) 10 mg (pink) 20 mg
Day 3 10 mg (pink) 20 mg (orange-brown) 30 mg
Day 4 20 mg (orange-brown) 20 mg (orange-brown) 40 mg
Day 5 20 mg (orange-brown) 30 mg (light brown-violet) 50 mg
Day 6 and onwards 30 mg (light brown-violet) 30 mg (light brown-violet) 60 mg
Patients with severe kidney disease
If the adult patient has severe kidney disease, the recommended dose of Apremilast Krka is 30 mg once
daily (morning dose).
In children and adolescents aged at least 6 years with severe renal impairment, the recommended
dose of Apremilast Krka is 30 mg once daily (morning dose) for patients with body weight at least 50 kg and 20 mg once daily (morning dose) for children with body weight from 20 kg to less than 50 kg.
Your doctor will inform you how to increase the dose when starting treatment with Apremilast Krka for the first time. Your doctor may advise you to take only the appropriate morning dose indicated in the table above (for adults or children/adolescents) and omit the evening dose.
How and when to take Apremilast Krka

• Apremilast Krka is intended for oral administration.
• Tablets should be swallowed whole, preferably with water.
• Tablets may be taken with or without food.
• Apremilast Krka should be taken at the same time each day, one tablet in the morning and one tablet in the evening.

If the patient's condition does not improve after six months, they should contact their doctor.
Taking more than the recommended dose of Apremilast Krka
If the patient takes more than the recommended dose of Apremilast Krka, they should contact their doctor immediately or go to hospital. The package and this leaflet should be taken along.
Missed dose of Apremilast Krka

• If the patient forgets to take a dose of Apremilast Krka, they should take it as soon as possible. If it is almost time for the next dose, the missed dose should be skipped and the next dose taken at the usual time.
• Do not take a double dose to make up for a missed dose.

Stopping treatment with Apremilast Krka

• The patient should continue taking Apremilast Krka until their doctor advises stopping treatment.
• Do not stop taking Apremilast Krka without first consulting the doctor.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Serious adverse reactions – depression and suicidal thoughts
You should immediately inform your doctor about any changes in behaviour or mood, feelings of depression, suicidal thoughts or suicidal behaviour (these occur not commonly).

Very common adverse reactions (may occur in more than 1 in 10 patients)

• Diarrhoea
• Nausea
• Headache
• Upper respiratory tract infections, such as the common cold, nasal congestion, sinus infection (infection)

Common adverse reactions (may occur in up to 1 in 10 patients)

• Cough
• Back pain
• Vomiting
• Feeling tired
• Abdominal pain
• Loss of appetite
• Frequent bowel movements
• Sleep problems (insomnia)
• Indigestion or heartburn
• Inflammation and swelling of the bronchial tubes (bronchitis)
• Common cold (nasopharyngitis)
• Depression
• Migraine
• Tension headache

Uncommon adverse reactions (may occur in up to 1 in 100 patients)

• Rash
• Urticaria
• Weight loss
• Allergic reaction
• Bleeding in the intestines or stomach
• Suicidal thoughts or behaviour
• Anxiety
• Mood changes

Adverse reactions with unknown frequency (frequency cannot be estimated from available data)

• Severe allergic reaction (may include swelling of the face, lips, mouth, tongue or throat, which may lead to difficulty breathing and swallowing)

In patients aged 65 years and older, there may be an increased risk of complications such as severe diarrhoea, nausea and vomiting. If gastrointestinal problems worsen, you should inform your doctor.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Apremilast Krka

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and outer packaging following the word EXP. The expiry date refers to the last day of the stated month.
No special storage conditions apply for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Apremilast Krka contains

• The active substance is apremilast. Each coated tablet contains 10 mg, 20 mg or 30 mg of apremilast, respectively.

• The other ingredients (excipients) are:
  Tablet core: mannitol (E421), microcrystalline cellulose, sodium croscarmellose (see section 2 "Apremilast Krka contains sodium") and magnesium stearate (E 470b).

  Tablet coating: polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171), talc, iron oxide red (E 172), iron oxide yellow (E 172) – for 20 mg and 30 mg only, and iron oxide black (E 172) – for 30 mg only.

What Apremilast Krka looks like and contents of the pack

Apremilast Krka 10 mg, coated tablets
Pink, round, biconvex coated tablets marked with "10" on one side of the tablet. Tablet dimensions: approximately 6 mm in diameter.

Apremilast Krka 20 mg, coated tablets
Orange-brown, round, biconvex coated tablets marked with "20" on one side of the tablet. Tablet dimensions: approximately 8 mm in diameter.

Apremilast Krka 30 mg, coated tablets
Light brown-violet, round, biconvex coated tablets marked with "30" on one side of the tablet. Tablet dimensions: approximately 10 mm in diameter.

Apremilast Krka 30 mg, coated tablets

• 56 coated tablets in blisters, in a cardboard box.
• Starter pack: Each package contains 27 coated tablets:
  • 4 coated tablets of Apremilast Krka 10 mg
  • 4 coated tablets of Apremilast Krka 20 mg
  • 19 coated tablets of Apremilast Krka 30 mg

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

For further information regarding this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
tel. 22 57 37 500