Jaypirca

Patient Information Leaflet

Jaypirca 50 mg film-coated tablets, 100 mg film-coated tablets

pirtobrutinib
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Jaypirca is and what it is used for

Jaypirca is an anticancer medicine that contains the active substance pirtobrutinib. It belongs to a
class of medicines called Bruton tyrosine kinase (BTK) inhibitors.
It is used alone (monotherapy) to treat the following blood cancers in adult patients previously treated with another BTK inhibitor:

• Mantle cell lymphoma (MCL). MCL is an aggressive (fast-growing) cancer of a type of white blood cells called B-cells. B-cells are part of the immune system (the body's natural defenses). This medicine is used when the cancer has returned (relapsed) or treatment has not worked (refractory).
• Chronic lymphocytic leukemia (CLL): a type of cancer affecting white blood cells called lymphocytes. This medicine is used when the cancer has returned (relapsed) or treatment has not worked (refractory).

How Jaypirca works
Jaypirca works by blocking BTK, a protein in the body that enables MCL and CLL cells to grow and survive. By blocking BTK, Jaypirca helps kill these cells and may reduce their numbers, slowing down the progression of the cancer.

2. What you should know before taking Jaypirca

Do not take Jaypirca

• If you are allergic to pirtobrutinib or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Jaypirca:

• if you have an infection or are at higher risk of developing an opportunistic infection (infections seen in patients with weakened immune systems). Your doctor may prescribe medicines to treat or prevent infections.
• if you have or have previously had unusual bruising or bleeding, or if you are taking medicines or supplements that could increase the risk of bleeding. See the section “Other medicines and Jaypirca” below.
• if you have recently had low levels of red blood cells (anaemia), neutrophils (a type of white blood cell that fights infections), or platelets (components that help blood clotting).
• if you have recently undergone or are about to undergo surgery. Your doctor may ask you to stop taking Jaypirca for a short period (3 to 5 days) before and after the procedure.
• if you have or have previously had an irregular heartbeat or other heart and/or blood vessel problems, such as high blood pressure, history of heart attack, or heart valve damage.

During treatment with Jaypirca, you may develop infections. Contact your doctor if you have fever,
chills, weakness, confusion, muscle aches, cough, cold symptoms, flu-like symptoms, feel tired, experience shortness of breath, or have pain or a burning sensation when urinating. These
could be signs of an infection.
Talk to your doctor if you develop a new skin lesion or any changes in the appearance of an area of skin, as treatment with Jaypirca may increase the risk of developing skin cancer. Use sun protection and have regular skin examinations.
Rarely, during treatment with Jaypirca, unusual levels of chemicals in the blood caused by the rapid breakdown of tumour cells, known as tumour lysis syndrome (TLS), have been reported. This may lead to impaired kidney function, abnormal heartbeat, or seizures. Your doctor or another healthcare professional may perform blood tests to check for TLS.
Your doctor will monitor you for signs and symptoms of bleeding (see section 4) and may check your blood cell counts as needed during treatment.
Your doctor may monitor your heart rhythm for any irregularities during treatment.

Children and adolescents
Do not give Jaypirca to children or adolescents under 18 years of age, as it has not been studied in this age group.

Other medicines and Jaypirca
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Jaypirca may make bleeding more likely. This means you must inform your doctor if you are taking other medicines that increase the risk of bleeding. This includes medicines such as:

• acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen,
• anticoagulants such as warfarin, heparin, and other medicines used to treat or prevent blood clots,
• supplements that may increase the risk of bleeding, such as fish oil, vitamin E, or flaxseed. If any of the above conditions apply to you (or if you are unsure), talk to your doctor, pharmacist, or nurse before taking Jaypirca.

Inform your doctor or pharmacist if you are taking any of the following medicines, as Jaypirca may affect their effectiveness:

• repaglinide, rosiglitazone, or pioglitazone (used to treat diabetes)
• dasabuvir (used for hepatitis C infection)
• selexipag (used to treat a type of high lung pressure called pulmonary arterial hypertension)
• rosuvastatin (a statin, a type of medicine used to treat high cholesterol)
• montelukast (used to treat asthma)
• digoxin (used to treat heart conditions)
• dabigatran etexilate (an anticoagulant, a type of medicine used to prevent blood clots)
• phenobarbital (a barbiturate, a type of medicine used to treat seizures)
• mephenytoin, phenytoin, and carbamazepine (types of medicines used to treat seizures)
• midazolam (a sedative)
• alfentanil (a medicine used in anaesthesia)
• tacrolimus (used to prevent organ rejection and skin disorders)
• rifampicin (an antibiotic)
• methotrexate (a medicine used to treat other cancers or immune system disorders)
• mitoxantrone (a medicine used to treat other cancers)

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not use Jaypirca during pregnancy. If you are a woman of childbearing potential, you must use an effective method of contraception during treatment and for 5 weeks after the last dose of Jaypirca. Inform your doctor immediately if you become pregnant.
If you are a man, you must use an effective method of contraception during treatment and for 3 months after the last dose of Jaypirca.
Do not breastfeed during treatment with Jaypirca and for one week after the last dose of Jaypirca. It is not known whether Jaypirca passes into breast milk.
It is not known whether Jaypirca will affect fertility. Talk to your doctor or pharmacist for advice if you are planning to have a child.

Driving and using machines
Jaypirca has a minor influence on the ability to drive and use machines. After taking Jaypirca, you may experience fatigue, dizziness, or weakness, which could affect your ability to drive or operate machinery.

Jaypirca contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

Jaypirca contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 200 mg daily dose, i.e. essentially ‘sodium-free’.

3. How to take Jaypirca

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

The recommended dose of Jaypirca is 200 mg once daily.

If you experience certain side effects while taking Jaypirca, your doctor may temporarily interrupt treatment or reduce the dose.

Jaypirca should be taken at approximately the same time each day. You may take the tablets with or without food. Swallow the tablet whole with a glass of water. Do not chew, crush, or divide the tablets before swallowing, to ensure you receive the correct dose.

If you take more Jaypirca than you should

If you have taken more Jaypirca than prescribed, contact a doctor or go to hospital immediately for assistance. Take the tablets and this patient information leaflet with you. Medical treatment may be necessary.

If you forget to take Jaypirca

• If less than 12 hours have passed since the usual time for taking a dose: take the missed dose immediately. Then take the next dose at the usual scheduled time the following day.
• If more than 12 hours have passed since the usual time for taking a dose: skip the missed dose. Take the next dose at the usual scheduled time the following day.
• Do not take a double dose of Jaypirca to make up for a forgotten dose. Take the next dose at the usual scheduled time.
• Do not take a double dose of Jaypirca if you vomit. Take the next dose at the usual scheduled time.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Jaypirca and contact a doctor immediately if you notice any of the following
side effects:

• itchy, raised rash, difficulty breathing, swelling of the face, lips, tongue or throat – you may be having an allergic reaction to the medicine.

Contact your doctor immediately if you experience any of the following side effects:

• fever, chills, feeling weak or confused, cough, cold or flu-like symptoms, shortness of breath, pain or burning sensation when urinating; these could be signs of an infection. These may include very common side effects (may affect more than 1 in 10 people) such as lung infection (pneumonia), nose, sinusitis or throat infection (upper respiratory tract infection), or urinary tract infection (may affect up to 1 in 10 people).
• bleeding, which may affect more than 1 in 10 people. Signs may include common side effects (may affect up to 1 in 10 people) such as nosebleeds, blood accumulation under tissues (bruising), or bleeding into the tissue lining the eye. Other signs of bleeding may include pink or brown urine, black stools or blood in stools, bleeding gums, vomiting or coughing up blood.
• irregular heartbeat, weak or irregular pulse, feeling lightheaded, shortness of breath, chest discomfort, as these may be symptoms of heart rhythm problems (may affect up to 1 in 10 people).

Tell your doctor, pharmacist, or nurse if you notice any of the following other side effects:
Very common (may affect more than 1 in 10 people)

• tiredness
• low levels of neutrophils (a type of white blood cells that fight infections; neutropenia)
• frequent or loose stools (diarrhoea)
• bruising
• contusions
• feeling unwell (nausea)
• low number of red blood cells (anaemia), which may cause tiredness and pale skin
• joint pain (arthralgia)
• low number of platelets in the blood (cells that help blood to clot; thrombocytopenia)
• rash
• stomach (abdominal) pain
• swollen hands, ankles or feet
• headache

Common (may affect up to 1 in 10 people)

• lymphocytosis (higher than normal amount of lymphocytes, a type of white blood cells, in the blood)
• small spots of blood under the skin (petechiae)

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

• increased levels of liver enzymes

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. 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 Jaypirca

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after “Exp.” and on the
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 no longer required. This will help protect the environment.

6. Package contents and other information

What Jaypirca contains
The active substance is pirtobrutinib. Each film-coated tablet contains 50 or 100 mg of
pirtobrutinib.
The other components are:

• tablet core: hypromellose acetate succinate; microcrystalline cellulose; lactose monohydrate (see section 2 “Jaypirca contains lactose”); sodium croscarmellose (see section 2 “Jaypirca contains sodium”); magnesium stearate; silica, colloidal anhydrous
• tablet coating: hypromellose; titanium dioxide; triacetin; indigo carmine (E132).

Description of the appearance of Jaypirca and pack contents
Jaypirca 50 mg is supplied as a blue, film-coated, triangular tablet with rounded edges, imprinted with “Lilly 50” on one side and “6902” on the other. It is available in blister packs containing 28, 30 or 84 film-coated tablets.
Jaypirca 100 mg is supplied as a blue, round, film-coated tablet, imprinted with “Lilly 100” on one side and “7026” on the other. It is available in blister packs containing 28, 30, 56, 60, 84 or 168 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Eli Lilly Nederland B.V.,
Papendorpseweg 83,
3528 BJ Utrecht,
The Netherlands

Manufacturer
Lilly S.A.,
Avda. de la Industria 30,
28108 Alcobendas,
Madrid, Spain

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600

България Luxembourg/Luxemburg
TP "Eli Lilly Nederland" B.V. - Bulgaria Eli Lilly Benelux S.A./N.V.
тел. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf.: +45 45 26 60 00 Tel: + 356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: +372 6 817 280 Tlf: + 47 22 88 18 00

Ελλάδα Österreich
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε. Eli Lilly Ges.m.b.H.
Τηλ: +30 210 629 4600 Tel: + 43-(0) 1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France Lilly Portugal Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0)1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Τηλ: +357 22 715000 Tel: + 46-(0) 8 7378800

Latvija
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā
Tel: + 371 67364000

This medicinal product has been granted a conditional marketing authorisation.
This means that further data on this medicinal product are required.
The European Medicines Agency will review new information on this medicinal product at least annually, and this package leaflet will be updated as necessary.

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.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATIONS

Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Report (PSUR) for pirtobrutinib, the scientific conclusions of the PRAC are as follows:
In light of the available data on pirtobrutinib from clinical studies and spontaneous reports, including cases with a close temporal relationship, including positive de-challenge and re-challenge (one case having multiple positive re-challenges), the PRAC considers that a causal relationship between pirtobrutinib and increased liver enzyme levels is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing pirtobrutinib should therefore be amended accordingly.

Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the overall conclusions and the rationale of the recommendation.

Reasons for the variation of the terms of the marketing authorisations
Based on the scientific conclusions on pirtobrutinib, the CHMP considers that the benefit-risk balance of medicinal products containing pirtobrutinib remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisations.