LUPKYNIS 7.9 mg Soft capsule

Зміст інструкції

1. Lupkynis 7.9 mg soft capsules
   1. What is Lupkynis and what is it used for
   2. What you need to know before taking Lupkynis
   3. How to take Lupkynis
   4. Possible side effects
   5. How to store Lupkynis
   6. Package contents and other information

Lupkynis 7.9 mg soft capsules

voclosporin (voclosporinum)

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What Lupkynis is and what it is used for
• 2. What you need to know before you take Lupkynis
• 3. How to take Lupkynis
• 4. Possible side effects
• 5. How to store Lupkynis
• 6. Contents of the pack and other information

1. What is Lupkynis and what is it used for

Lupkynis contains the active substance voclosporin. It is used for the treatment of adults starting
from 18 years of age affected by lupus nephritis (kidney inflammation caused by lupus).
The active substance of Lupkynis belongs to a group of medicines known as calcineurin inhibitors which can be used to control the body's immune response
(immunosuppressants). In lupus, the immune system (the body's natural defenses
) mistakenly attacks parts of the body itself, including the kidneys (lupus nephritis).
By reducing the response of the immune system, the medicine reduces kidney inflammation and alleviates
symptoms, such as swelling of the legs, ankles or feet, high blood pressure and
fatigue, as well as improving kidney function.

2. What you need to know before taking Lupkynis

Do not take Lupkynis

• If you are allergic to voclosporin or any of the other ingredients of this medicine (listed in section 6).
• If you are taking other medicines such as, for example, ketoconazole tablets (used to treat Cushing's syndrome, when the body produces an excess of cortisol), itraconazole or clarithromycin (used to treat some fungal and bacterial infections).

Warnings and precautions
Talk to your doctor or pharmacist before taking Lupkynis if any of the following conditions apply to
you:

• if your kidney disease gets worse, it may be necessary to change the dose of this medicine. Your doctor will regularly check your kidney function.
• if you have risk factors for pure red cell aplasia (PRCA), a rare condition in which the bone marrow does not produce enough red blood cells. Risk factors are a previous infection with parvovirus B19 or other treatments in the past that can cause PRCA.
• if you have or develop high blood pressure. Your doctor will check your blood pressure every two weeks for the first month, then at regular intervals. They may give you medicine to lower your blood pressure, or tell you to stop taking this medicine.
• This medicine can increase the risk of nervous system disorders, such as headache, tremors, vision changes, seizures, confusion or weakness of one or more limbs. If you experience any of these new symptoms, or a worsening of existing symptoms, your doctor may consider stopping or reducing the dose of this medicine (see section 4).
• if you are planning to receive a vaccination or if you have had a vaccination in the last 30 days. This medicine can affect the response to vaccination, and the vaccination may be less effective during treatment with this medicine.
• do not take this medicine if you have already had severe and life-threatening allergic reactions (anaphylactic reactions) to soy or peanuts.

This medicine can increase potassium levels in the blood, which can be a serious condition
and require treatment. During treatment, your doctor will periodically check potassium levels.
This medicine has not been studied in patients with severe liver problems and is therefore
not recommended in these patients.
This medicine can affect the electrical activity of the heart (QT prolongation). This can lead
to a serious heart rhythm disorder, the initial symptoms of which are dizziness and fainting.

Sunlight and UV rays
This medicine can increase the risk of developing certain types of cancer, particularly of the
skin. Avoid or limit exposure to sunlight and UV rays by wearing appropriate protective
clothing and frequently applying a sunscreen with a high protection factor.

Infections
This medicine can increase the risk of developing infections, some of which may be
serious or even fatal. Contact your doctor if you have signs of infection, such as fever, chills or
sore throat. Your doctor will decide whether you should stop taking this medicine (see section 4).

Children and adolescents
Do not take this medicine if you are under 18 years of age because it has not been studied in this age
group.

Elderly
This medicine is not recommended if you are over 75 years of age because it has not been studied in this
age group.

Other medicines and Lupkynis
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
In particular, tell your doctor if you are taking:

• Medicines used to treat a fungal infection, such as itraconazole and fluconazole.
• Medicines used to treat Cushing's syndrome (when the body produces an excess of cortisol), such as ketoconazole tablets.
• Medicines used to treat high blood pressure or heart problems, such as digoxin, diltiazem and verapamil.
• Medicines that prevent blood clots, such as dabigatran etexilate.
• Medicines used to treat epilepsy, such as carbamazepine and phenobarbital.
• Herbal remedies containing St John's wort, used to treat mild depression.
• Medicines used to relieve the symptoms associated with seasonal allergic rhinitis, such as fexofenadine.
• Antibiotic medicines used to treat bacterial infections, such as rifampicin, clarithromycin and erythromycin.
• Medicines that lower cholesterol such as simvastatin, atorvastatin, rosuvastatin and pravastatin.
• Medicines used to treat HIV infections, such as the antiretroviral efavirenz.

Lupkynis with food and drink
The medicine can be taken with or without food. During treatment with this medicine, avoid
eating grapefruit and drinking grapefruit juice as this can affect the action of the
medicine.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor for advice before taking this medicine.
This medicine is not recommended during pregnancy and in women of childbearing potential who are not using
contraceptive measures.
Tell your doctor if you are breastfeeding. The medicine can pass into breast milk and it is
not known whether it can have effects on the baby. Your doctor will discuss with you whether to stop
treatment with this medicine during breastfeeding, or to stop breastfeeding.
There are no data on the effect of this medicine on human fertility.

Driving and using machines
Lupkynis is not expected to affect your ability to drive and operate machinery.

Lupkynis contains alcohol
This medicine contains 21.6 mg of alcohol (ethanol) in each capsule. Therefore, a dose of 3 capsules
of Lupkynis contains 64.8 mg of ethanol, equivalent to less than 2 mL of beer or 1 mL of wine. The
small amount of alcohol in this medicine will not produce significant effects.

Lupkynis contains sorbitol
This medicine contains 28.7 mg of sorbitol per capsule.

Lupkynis may contain soy lecithin
This medicine may contain traces of soy lecithin. If you experience anaphylactic reactions to soy
or peanuts, you should not use this medicine.

3. How to take Lupkynis

Take this medicine following exactly the instructions of your doctor. If you have any doubts, ask your
doctor or pharmacist.
The recommended dose of Lupkynis is three capsules twice a day, to be taken by mouth.
The capsules must be swallowed whole and can be taken with or without food.
Take the daily doses at approximately the same time each day, at least 8 hours apart
and ideally as close as possible to 12 hours (for example, at 8:00 am and 8:00
pm).
This medicine must be used in combination with another immunosuppressant medicine,
mycophenolate mofetil.

If you take more Lupkynis than you should
In case of accidental intake of an excessive number of capsules, contact your
doctor or the emergency room of the nearest hospital immediately. Symptoms of overdose may include
rapid heartbeat and tremors (shivering or uncontrolled tremors in one or more parts of the body).

If you forget to take Lupkynis
If you miss a dose, take it as soon as possible and within 4 hours of forgetting the dose. If
more than 4 hours have passed since the time you normally take the medicine, skip that dose and take
the next dose at the usual time. Do not take a double dose to make up for a missed dose.

If you stop taking Lupkynis
Do not stop treatment unless your doctor tells you to do so.
If you have any doubts about 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.
With this medicine the following side effects may occur:

Serious side effects
If any of these happen, tell your doctor immediately, who may
advise you to stop taking this medicine or reduce the dose.

Very common(may affect more than 1 in 10 people)

• Symptoms of infection (e.g. fever, generalised body pain, feeling tired, cough or sneezing, nausea, vomiting or diarrhoea). Common(may affect up to 1 in 10 people)
• Development of new symptoms relating to nerve or brain problems, for example fits/seizures.

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

• Upper chest infection
• Reduction in red blood cells, which can make the skin pale and cause weakness or shortness of breath (anaemia)
• Headache
• Increased blood pressure
• Cough
• Diarrhoea
• Abdominal (stomach) pain
• Changes in kidney function which may reduce the amount of urine produced and cause swelling in the legs or feet to appear or worsen

Common(may affect up to 1 in 10 people)

• Fever, cough, difficulty or painful breathing, wheezing, chest pain when breathing (possible symptoms of pneumonia)
• Infections, which can be bacterial, such as urinary tract infections, or viral, such as shingles.
• Inflammation of the stomach and intestines
• Flu
• Increased levels of potassium observed in blood tests
• Loss of appetite
• Tremor
• Feeling unwell
• Swelling, bleeding and/or inflammation of the gums
• Mouth ulcers
• Indigestion
• Hair loss
• Excessive and/or abnormal hair growth on any part of the body

Not known(frequency cannot be estimated from the available data)

• Hypersensitivity

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Lupkynis

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 package and on the blister after the
wording "Scad." or “EXP”. The expiry date refers to the last day of that month.
Store in the original blister to protect the medicine from moisture.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Lupkynis contains

• The active ingredient is voclosporin. Each soft capsule of Lupkynis contains 7.9 mg of voclosporin.
• The other ingredients are: Capsule contents: ethanol, vitamin E (E307) polyethylene glycol succinate (tocopheryl succinate), polysorbate 40 and medium chain triglycerides. Capsule shell: gelatin, sorbitol, glycerin, purified water, titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172). Processing aid: soybean lecithin

Description of the appearance of Lupkynis and package contents
Lupkynis 7.9 mg, pink/orange colored soft capsules approximately 13 mm × 6 mm in size, packaged in
blisters. Each blister contains 18 soft capsules. One carton contains 180 or 576 soft capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Otsuka Pharmaceutical Netherlands B.V.
Herikerbergweg 292
1101 CT Amsterdam
Netherlands

Manufacturer
Millmount Healthcare Limited
Block-7, City North Business Campus, Stamullen, Co. Meath, K32 YD60,
Ireland
For further information on this medicine, contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
Otsuka Pharmaceutical Netherlands B.V.
Tél/Tel: +31 (0) 20 85 46 555

Lietuva
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

България
Otsuka Pharmaceutical Netherlands B.V.
Teл: +31 (0) 20 85 46 555

Luxembourg/Luxemburg
Otsuka Pharmaceutical Netherlands B.V.
Tél/Tel: +31 (0) 20 85 46 555

Česká republika
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Magyarország
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Danmark
Otsuka Pharma Scandinavia AB
Tlf: +46 (0) 8 545 286 60

Malta
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Deutschland
Otsuka Pharma GmbH
Tel: +49 (0) 69 1700 860

Nederland
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Eesti
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Norge
Otsuka Pharma Scandinavia AB
Tlf: +46 (0) 8 545 286 60

Ελλάδα
Otsuka Pharmaceutical Netherlands B.V.
Thλ: +31 (0) 20 85 46 555

Österreich
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

España
Otsuka Pharmaceutical S.A
Tel: +34 (0) 93 208 1020

Polska
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

France
Otsuka Pharmaceutical France SAS
Tél: +33 (0) 1 47 08 00 00

Portugal
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Hrvatska
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

România
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Ireland
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Slovenija
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Ísland
Otsuka Pharma Scandinavia AB
Sími: +46 (0) 8 545 286 60

Slovenskárepublika
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Italia
Otsuka Pharmaceutical Italy S.r.l.
Tel: +39 (0) 2 0063 2710

Suomi/Finland
Otsuka Pharma Scandinavia AB
Puh/Tel: +46 (0) 8 545 286 60

Κύπρος
Otsuka Pharmaceutical Netherlands B.V.
Thλ: +31 (0) 20 85 46 555

Sverige
Otsuka Pharma Scandinavia AB
Tel: +46 (0) 8 545 286 60

Latvija
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

United Kingdom (Northern Ireland)
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and related
therapeutic treatments are also provided.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION(S)
Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Reports (PSUR) for voclosporin, the PRAC’s scientific
conclusions are as follows:
In light of the available data on hypersensitivity emerging from clinical studies and post-
marketing reports, including 10 cases with a strong temporal association, 6 cases of positive
dechallenge and 2 cases of positive rechallenge, the PRAC considers that there is at least a
reasonable possibility of a causal relationship between voclosporin and hypersensitivity.
In light of the available data on pulmonary infection emerging from clinical studies and post-
marketing reports, including 24 cases with a strong temporal association, and in the face of a
plausible mechanism of action, the PRAC considers that there is at least a reasonable possibility of a
causal relationship between voclosporin and pulmonary infection.
In light of the available data on oral ulceration emerging from clinical studies and post-
marketing reports, including 11 cases with a strong temporal association, the PRAC considers that
there is at least a reasonable possibility of a causal relationship between voclosporin and oral
ulceration.
The PRAC concluded that the product information for products containing voclosporin should be
modified accordingly.
Having examined the PRAC’s recommendation, the Committee for Human Medicinal Products
(CHMP) agrees with the general conclusions and with the justification for the recommendation.

Justification for variation of the terms of the marketing authorisation(s)
Based on the scientific conclusions on voclosporin, the CHMP considers that the benefit/risk
balance of the medicines containing voclosporin remains unchanged, subject to the proposed
changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation(s).