Prospect: information for the patient

Orladeyo 150 mg hard capsules

berotralstat

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

Orladeyo is a medication that contains the active ingredient berotralstat. It is usedto prevent angioedema attacksin adults and adolescents 12 years of age and older with hereditary angioedema.

What is hereditary angioedema

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

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

How Orladeyo works

In hereditary angioedema, the blood does not have enough of a protein called C1 inhibitor or this protein does not function correctly. This leads to an excessive amount of the enzyme kalikrein in the plasma, which in turn increases the levels of bradykinin in the bloodstream. An excessive amount of bradykinin causes symptoms of hereditary angioedema. Berotralstat, the active ingredient in Orladeyo, blocks the activity of plasma kalikrein and therefore reduces bradykinin. This prevents the swelling and pain that can cause hereditary angioedema.

Do not take Orladeyo

• if you are allergic to berotralstat or any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Orladeyo:

• if you have moderate or severe liver insufficiency that may increase berotralstat blood concentrations
• if you have severe kidney insufficiency
• if you are at risk of a certain heart rhythm abnormality known as QT interval prolongation

Treat angioedema hereditario attacks with your usual rescue medication without taking additional doses of Orladeyo. The efficacy of Orladeyo for the immediate treatment of angioedema hereditario attacks is unknown.

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 medications and Orladeyo

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Particularly, inform your doctor before taking Orladeyo if you are using:

• thioridazine or pimozide, medications for treating mental disorders
• amlodipine, a medication for treating high blood pressure or a type of chest pain called angina
• ciclosporin, a medication for suppressing the immune system, treating severe skin diseases, or severe eye or joint inflammations
• dabigatran, a medication for preventing blood clot formation
• rifampicin, a medication for treating tuberculosis or other infections
• desipramine, hyoscyamus, and other medications for treating depression known as tricyclic antidepressants
• dextromethorphan, a medication for relieving cough
• digoxin, a medication for treating heart problems and irregular heart rhythm
• fentanyl, a potent analgesic
• midazolam, a medication for treating sleep disorders and used as an anesthetic
• tolbutamide, a medication for reducing blood sugar levels
• oral contraceptives, medications used for controlling fertility

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

There is limited information available on the use of Orladeyo during pregnancy and breastfeeding. As a precaution, it is preferable to avoid the use of Orladeyo during pregnancy and breastfeeding. Your doctor will explain the risks and benefits of taking this medication.

Women of childbearing age should use effective contraceptive methods during treatment and for at least one month after the last dose. Orladeyo is not recommended for women of childbearing age who are not using contraceptive methods.

Driving and operating machinery

The influence of Orladeyo on the ability to drive and operate machinery is negligible or insignificant.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose for adults and adolescents 12 years of age or older who weigh ≥40 kg is one capsule once a day.

Orladeyo is not recommended for use in patients with moderate or severe liver insufficiency.

Treatment with Orladeyo should be avoided in patients with severe kidney failure. However, if your doctor considers that treatment with Orladeyo is necessary, additional monitoring may be required, including heart rhythm monitoring using tests such as an electrocardiogram (ECG, a test that measures the heart's electrical activity). Treatment with Orladeyo should be avoided if you are on dialysis due to kidney disease.

Administration Form

Take the capsule with food and a glass of water at the same time every day. You can take it at any time of the day.

If you take more Orladeyo than you should

Contact your doctor immediately.

If you forgot to take Orladeyo

Do not take a double dose to make up for a missed capsule. Take the missed dose as soon as you remember; however, do not take more than one dose a day.

If you interrupt treatment with Orladeyo

It is essential to take this medication regularlywhile your doctor prescribes it. Do not stop taking it without your doctor's approval.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

Adverse effects may appear with the following frequencies:

Very frequent, may affect more than 1 in 10 people

• Headache
• Abdominal pain, including abdominal discomfort (bloating), and pain upon palpation
• Diarrhea and frequent bowel movements

Frequent, may affect up to 1 in 10 people

• Vomiting
• Heartburn
• Gas
• Blood tests showing an increase in liver enzymes called ALT and AST
• Skin rash

Unknown frequency,which cannot be estimated from available data

• Nausea

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

Do not use this medication after the expiration date that appears on the box and the blister pack after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Orladeyo

• The active ingredient is berotralstat. Each capsule contains 150 mg of berotralstat (as dihydrochloride).
• The other components are:

• pregelatinized starch, crospovidone (type A), anhydrous colloidal silica, magnesium stearate, gelatin, titanium dioxide (E 171)
• colorants: indigo carmine (E 132), iron oxide black (E 172), iron oxide red (E 172)
• edible printing ink: iron oxide black (E 172), potassium hydroxide, shellac, propylene glycol (E 1520)

Appearance of the product and contents of the packaging

Orladeyo capsules have an opaque white body with the imprint "150" and an opaque light blue cap with the imprint "BCX" (19.4 mm x 6.9 mm). They are presented in plastic/aluminum blisters in a box with 7 capsules per blister.

Package size: 28 or 98 hard capsules

Marketing authorization holder and responsible manufacturer

• Marketing authorization holder

BioCryst Ireland Limited

Block 4, Harcourt Centre, Harcourt Road, DUBLIN 2, D02HW77

Ireland

• Responsible manufacturer

Millmount Healthcare Limited

Block-7, City North Business Campus,

Stamullen,

Co. Meath, K32 YD60

Ireland

Last review date of this leaflet: 07/2024

Other sources of information

Detailed information about this medicine is available on the European Medicines Agency website:https://www.ema.europa.eu.