omaveloxolone: package leaflet

What is Skyclarys?
Skyclarys contains the active substance omaveloxolone, which activates a specific protein, Nrf2, in your body.

What is Skyclarys used for?
Skyclarys is used to treat adults and adolescents who are at least 16 years of age who have Friedreich’s ataxia, a neurodegenerative movement disorder. Friedreich’s ataxia is a rare inherited disease that causes progressive damage to your nervous system and movement problems.

How does Skyclarys work?
The protein called Nrf2 in your body has a key role in managing oxidative stress (a condition that can damage cells in your body) and has a protective role against neurodegenerative diseases. In patients with Friedreich’s ataxia, Nrf2 activity is reduced. Skyclarys activates Nrf2 so it can manage oxidative stress.

In a clinical trial patients treated with Skyclarys scored better on tests of neurological function than patients who were treated with an inactive substance.

Do not take Skyclarys if you are allergic to omaveloxolone or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor before taking Skyclarys:
- If you have problems with your liver, your doctor may decide to change the dose or not start treatment with Skyclarys.
- Tell your doctor about all the medicines you are taking before you start Skyclarys.

Your doctor will check to see how well your liver is working and will check your cholesterol level before you start taking Skyclarys. Your doctor will also check your level of BNP (B-type natriuretic peptide, a blood test for heart problems) before you start taking Skyclarys.

Talk to your doctor while taking Skyclarys
Contact your doctor immediately if you have sudden weight gain, swelling of legs, ankles, or feet, or shortness of breath, which may be signs or symptoms of heart problems while taking Skyclarys. Your doctor will decide on treatment and whether Skyclarys should be continued.

Talk to your doctor if you get any hypersensitivity reactions (an allergic or allergic-like reaction that may include itchy rash and skin rash).

Your doctor will be checking blood tests while you are taking Skyclarys. This will include liver blood tests to see how your liver is working while taking Skyclarys. Your doctor will decide on whether to discontinue Skyclarys if liver problems develop. Other blood tests that your doctor will do will check cholesterol and BNP after you start Skyclarys.

Tell your doctor if you have weight loss with Skyclarys.

Children and adolescents
Do not give Skyclarys to children and adolescents below the age of 16 years because it has not yet been studied in this group of patients.

Other medicines and Skyclarys
Tell your doctor if you are taking, have recently taken, or might take any other medicines. This is because some medicines may affect the way Skyclarys works. Also, Skyclarys may affect the way some medicines work.

Certain medicines may increase the risk of side effects of Skyclarys by increasing the levels of Skyclarys in the blood. Some of these medicines include:
- itraconazole, fluconazole, or ketoconazole (antifungal medicines used to treat a number of fungal infections)
- cyclosporine (a medicine used after organ transplant)
- ciprofloxacin or clarithromycin (antibiotics used for bacterial infections)
- fluvoxamine (an antidepressant known as a selective serotinin reuptake inibitor [SSRI]) If your doctor prescribes one of these medicines, your dose of Skyclarys may be reduced to prevent side effects when taking both drugs at the same time.

Certain medicines may reduce how well Skyclarys works by decreasing the amount of Skyclarys in the blood. Some of these medicines include:
- St. John’s wort (a herbal remedy used for mild depression)
- rifampicin (used to treat tuberculosis)
- carbamazepine, phenobarbital, phenytoin, primidone (used to treat epilepsy)
- efavirenz (medicine used for HIV)

Skyclarys may reduce how well some other medicines work by decreasing the amount of these medicines in the blood. Some of these medicines include:
- midazolam (used as a sedative and to treat severe agitation)
- repaglinide (a medicine to control type II diabetes)
- rosuvastatin (a statin medicine used to reduce harmful lipids)

• hormonal contraceptives (a type of birth control that uses homones to prevent pregnancy, such as the pill, patch, or ring)
• omeprazole (a medicine to treat heartburn and indigestion)

Talk to your doctor if you are taking any medicines, particularly those mentioned above, as they may affect the way Skyclarys or other medicines work.

Skyclarys with food and drink
Avoid eating grapefruit or grapefruit juice while taking Skyclarys.

Pregnancy
You should not take Skyclarys if you are pregnant, think you may be pregnant, or are planning to have a baby. Tell your doctor immediately if you become pregnant while you are being treated with Skyclarys.

Birth Control
Using Skyclarys can reduce the effectiveness of hormonal birth control. You should use a different method of birth control, such as a non-hormonal IUD (intrauterine device) or barrier contraceptives such as condoms. A reliable method of birth control should be used during Skyclarys treatment and for 28 days after stopping treatment with Skyclarys. Talk to your doctor about the most suitable birth control for you.

Breast-feeding
Skyclarys passes into breast milk. You and your doctor should discuss the risks and benefits of taking Skyclarys during breast-feeding.

Driving and using machines
Some patients may feel tired after taking this medicine. If you feel tired after taking Skyclarys, avoid driving and using machines.

Skyclarys contains a negligible amount of sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium free’.

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

The recommended dose is 150 mg (3 capsules) once per day.

Taking Skyclarys
- Take the capsules on an empty stomach at least one hour before or two hours after eating.
- Take the capsules at about the same time during the day.
- Swallow the capsules whole with a glass of water.
- If you are unable to swallow the capsules whole, open them and sprinkle the entire contents onto 2 tablespoonfuls of apple puree. You must eat all the apple puree/medicine mixture immediately after making it. Do not store the apple puree/medicine mixture for future use.
If you have problems with your liver, your doctor may decide to change the dose or not start treatment with Skyclarys.

Some medicines may cause side effects when taken at the same time as Skyclarys. If your doctor prescribes one of these medicines while you are taking Skyclarys, your doctor may reduce the dose of Skyclarys to prevent side effects when taking both drugs at the same time.

If you are sick after taking your usual dose, do not take replacement capsules. Take the capsules as usual the following day.

If you take more Skyclarys than you should
If you take more Skyclarys than your doctor prescribed, talk to a doctor immediately. Take this leaflet with you.

If you forget to take Skyclarys
If you miss a dose of Skyclarys, take the next dose as usual the following day. Do not take a double dose to make up for a forgotten dose.

If you stop taking Skyclarys
Do not stop taking this medicine unless your doctor tells you.
If you have any further questions on the use of this medicine, ask your doctor.

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

Some side effects with Skyclarys could be or could become serious

Talk to your doctor immediately if you have any of these side effects:
Very common (may affect more than 1 in 10 people)
- digestive problems. You may have symptoms such as
− nausea (feeling sick)
− diarrhoea
− vomiting
− stomach pain
− decrease in weight
If you have any of these side effects, talk to your doctor.

Based on your blood tests, your doctor may tell you that you have:
- high liver enzymes in your blood (very common, may affect more than 1 in 10 people)
- increased BNP (a marker for heart problems); (common, may affect up to 1 in 10 people)
- changes in your blood cholesterol and triglycerides (common, may affect up to 1 in 10 people) Your doctor will decide on treatment and whether Skyclarys should be continued.

Other possible side effects of Skyclarys
Very common (may affect more than 1 in 10 people)
- headache
- tiredness
- sore throat
- back pain
- muscle spasm
- flu
- decreased appetite
- hypersensitivity (an allergic or allergic-like reaction that may include itchy rash and skin rash)

Common (may affect up to 1 in 10 people)
- urinary tract infection (infection of the structures that carry urine, UTI)
- period pains in women (menstrual cramps)

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

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 carton after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

If the capsule is opened and mixed with apple puree you must eat all the apple puree/medicine mixture immediately after making it. See section 3, Taking Skyclarys.

Do not use this medicine if you notice that the pack is damaged or shows signs of tampering.

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.

What Skyclarys contains
- The active substance is omaveloxolone.
- Each capsule contains 50 mg omaveloxolone.
- The other ingredients are:
Capsule fill: pregelatinized maize starch, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, silica, colloidal anhydrous Capsule shell: hypromellose, titanium dioxide (E171), Brilliant Blue FCF (E133), ferric oxide yellow (E172) Printing ink: shellac (E904), titanium dioxide (E171)

What Skyclarys looks like and contents of the pack
Skyclarys 50 mg hard capsules are made of an opaque light green body imprinted with “RTA 408” in white ink and a blue cap imprinted with “50” in white ink.

Skyclarys 50 mg is available in a pack containing 90 hard capsules and in a pack of 3 bottles, each containing 90 hard capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands

Manufacturer(s)
BIOGEN DISTRIBUTION SERVICES LIMITED
United Drug House
Magna Drive
Magna Business Park
Citywest Road

Dublin 24
D24 XKE5
Ireland

Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Biogen Belgium N.V./S.A.
Tél/Tel: +32 2 219 12 18

Lietuva
Biogen Lithuania UAB
Tel: +370 5 259 6176
България
ЕВОФАРМА ЕООД
Teл.: +359 2 962 12 00

Luxembourg/Luxemburg
Biogen Belgium N.V./S.A.
Tél/Tel: +32 2 219 12 18

Česká republika
Biogen (Czech Republic) s.r.o.
Tel: +420 255 706 200

Magyarország
Biogen Hungary Kft.
Tel.: +36 1 899 9880
Danmark
Biogen (Denmark) A/S
Tlf.: +45 77 41 57 57

Malta
Pharma MT limited
Tel: +356 213 37008/9

Deutschland
Biogen GmbH
Tel: +49 (0) 89 99 6170

Nederland
Biogen Netherlands B.V.
Tel: +31 20 542 2000
Eesti
Biogen Estonia OÜ
Tel: + 372 618 9551

Norge
Biogen Norway AS
Tlf: +47 23 40 01 00
Ελλάδα
Genesis Pharma SA
Τηλ: +30 210 8771500

Österreich
Biogen Austria GmbH
Tel: +43 1 484 46 13

España
Biogen Spain SL
Tel: +34 91 310 7110

Polska
Biogen Poland Sp. z o.o.
Tel.: +48 22 351 51 00

France
Biogen France SAS
Tél: +33 (0)1 41 37 95 95
Portugal
Biogen Portugal
Tel.: +351 21 318 8450

Hrvatska
Biogen Pharma d.o.o.
Tel: +385 (0) 1 775 73 22

România
Ewopharma România SRL
Tel: + 40 21 260 13 44

Ireland
Biogen Idec (Ireland) Ltd.
Tel: +353 (0)1 463 7799

Slovenija
Biogen Pharma d.o.o.
Tel.: +386 1 511 02 90

Ísland
Icepharma hf
Sími: +354 540 8000

Slovenská republika
Biogen Slovakia s.r.o.
Tel.: +421 2 323 340 08
Italia
Biogen Italia s.r.l.
Tel: +39 02 584 9901

Suomi/Finland
Biogen Finland Oy
Puh/Tel: +358 207 401 200

Κύπρος
Genesis Pharma Cyprus Ltd
Τηλ: +357 22765715

Sverige
Biogen Sweden AB
Tel: +46 8 594 113 60

Latvija
Biogen Latvia SIA
Tel: + 371 68 688 158

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.