ORLADEYO

Package leaflet: Information for the patient

Orladeyo 150 mg hard capsules

berotralstat
Please read this leaflet carefully before taking this medicine because 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 may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Orladeyo is and what it is used for

Orladeyo is a medicine that contains the active substance berotralstat. It is used to prevent attacks of angioedema in adults and adolescents aged 12 years and older who have hereditary angioedema.

What is hereditary angioedema
Hereditary angioedema is a disease that is often inherited genetically. It can limit daily activities by causing episodes of swelling and pain in various parts of the body, including:

• hands and feet
• face, eyelids, lips or tongue
• larynx, making breathing difficult
• genitals, stomach and intestines

How Orladeyo works
In hereditary angioedema, the blood either does not have enough of a protein called C1-inhibitor or the protein does not work properly. This leads to an excess of the enzyme plasma kallikrein, which in turn increases levels of bradykinin in the bloodstream. Excess bradykinin causes the symptoms of hereditary angioedema. Berotralstat, the active substance in Orladeyo, blocks the activity of plasma kallikrein and thereby reduces bradykinin levels. This helps prevent the swelling and pain caused by hereditary angioedema.

2. What you need to know before taking Orladeyo

Do not take Orladeyo

• if you are allergic to berotralstat or to any of the other ingredients of this medicine (listed in section 6)

Warnings and precautions
Talk to your doctor or pharmacist before taking Orladeyo if:

• you have moderate or severe liver function impairment, which may increase berotralstat levels in the blood;
• you have severe renal impairment;
• you are at risk of a specific heart rhythm disorder known as QT interval prolongation.

Treat an attack of hereditary angioedema with your regular on-demand therapy without taking additional
doses of Orladeyo. It is not known whether Orladeyo is effective for the immediate treatment of
hereditary angioedema attacks.
Children and adolescents
Orladeyo is not recommended for children under 12 years of age, as it has not been studied in this age group.
Orladeyo has not been studied in adolescents weighing less than 40 kg.
Other medicines and Orladeyo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor before taking Orladeyo if you are using:

• thioridazine or pimozide, medicines used to treat mental disorders
• amlodipine, a medicine used to treat high blood pressure or a type of chest pain called angina
• ciclosporin, an immunosuppressant medicine used to treat severe skin diseases and severe eye or joint inflammation
• dabigatran etexilate, a medicine used to prevent blood clotting
• rifampicin: a medicine used to treat tuberculosis or certain other infections
• desipramine, St. John’s wort, and other medicines used to treat depression known as tricyclic antidepressants
• dextromethorphan, a cough suppressant
• digoxin, a medicine used to treat heart problems and irregular heartbeat
• fentanyl, a strong painkiller
• midazolam, a medicine used to treat sleep disorders and for anesthesia
• tolbutamide, a medicine used to lower blood glucose
• oral contraceptives, medicines used for birth control

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding,
please consult your doctor or pharmacist before taking this medicine.
Information on the use of Orladeyo during pregnancy and breastfeeding is limited. As a precautionary
measure, it is preferable to avoid using Orladeyo during pregnancy and breastfeeding. Your doctor
will discuss with you the benefits and risks of taking this medicine.
Women of childbearing potential must use effective contraception during treatment and for at least
one month after the last dose. Orladeyo is not recommended for women of childbearing potential who do not use
contraceptive measures.
Driving and using machines
Orladeyo does not affect or affects negligibly the ability to drive and use machines.

3. How to take Orladeyo

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
The recommended dose for adults and adolescents aged 12 years and older with body weight ≥40 kg is one
capsule once daily.
Orladeyo is not recommended in patients with moderate to severe hepatic impairment.
If renal function is severely reduced, treatment with Orladeyo should be avoided.
However, if your doctor considers Orladeyo treatment necessary, additional monitoring may be required, including monitoring of heart rhythm with tests such as an
electrocardiogram (ECG, a test measuring the heart's electrical activity). If you are on dialysis due to kidney disease, treatment with Orladeyo should be avoided.
Method of administration
Take the capsule with food and a glass of water at the same time each day. This may be at any
time of day.
If you take more Orladeyo than you should
Contact your doctor immediately if this occurs.
If you forget to take Orladeyo
Do not take a double dose to make up for the missed capsule. Take the missed dose as soon as you remember; however, do not take more than one dose per day.
If you stop taking Orladeyo
It is important to take this medicine regularly and for as long as your doctor prescribes it. Do not stop treatment without consulting your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Side effects may occur with the following frequencies:
Very common: may affect more than 1 in 10 people

• headache
• stomach pain, including abdominal discomfort, abdominal tenderness
• diarrhoea and frequent bowel movements

Common: may affect up to 1 in 10 people

• vomiting
• heartburn
• flatulence
• blood tests showing increased levels of liver enzymes known as ALT and AST
• skin rash

Not known: frequency cannot be estimated from the available data
nausea

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via 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 Orladeyo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via 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 Orladeyo contains

• The active substance is berotralstat. Each hard capsule contains 150 mg of berotralstat (as dihydrochloride).
• The other components are:
  • pregelatinized starch, crospovidone (type A), anhydrous colloidal silicon dioxide, magnesium stearate, gelatin, titanium dioxide (E 171)
  • colourants: indigo carmine (E 132), black iron oxide (E 172), red iron oxide (E 172)
  • edible printing ink: black iron oxide (E 172), potassium hydroxide, shellac, propylene glycol (E 1520)

Description of the appearance of Orladeyo and package contents
Orladeyo hard capsules (capsule) have an opaque white body printed with "150" and an opaque blue cap printed with "BCX" (19.4 mm × 6.9 mm). They are packaged in plastic/aluminum blisters in a box containing 7 capsules per blister.
Pack sizes: 28 or 98 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
BioCryst Ireland Limited
Block 4, Harcourt Centre, Harcourt Road, DUBLIN 2, D02HW77
Ireland

Manufacturer
Millmount Healthcare Limited
Block-7, City North Business Campus,
Stamullen,
Co. Meath, K32 YD60
Ireland

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu