AUGTYRO 40 mg Hard Capsules

Зміст інструкції

1. AUGTYRO 40 mg hard capsules, 160 mg hard capsules
   1. What is AUGTYRO and what is it used for
   2. What you need to know before taking AUGTYRO
   3. How to take AUGTYRO
   4. Possible side effects
   5. How to store AUGTYRO
   6. Contents of the pack and other information

AUGTYRO 40 mg hard capsules, 160 mg hard capsules

repotrectinib

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, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, 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, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is AUGTYRO and what is it used for

What is AUGTYRO
AUGTYRO is an anti-cancer medicine that contains the active substance repotrectinib.

What is AUGTYRO used for
AUGTYRO is used to treat:

• adults with a type of lung cancer called “non-small cell lung cancer” (NSCLC) caused by a change in the ROS1gene, or
• adults and children aged 12 years and over with solid tumours (cancer) in various parts of the body caused by a change in the NTRKgene.

ROS1-positive non-small cell lung cancer
AUGTYRO is used when:

• a test has shown that the cancer cells have a change in a gene called “ROS1” (see “How AUGTYRO works” below) and
• the cancer is in an advanced stage, for example, it has spread to other parts of the body (metastatic).

NTRKgene fusion-positive solid tumour
AUGTYRO is used when:

• a test has shown that the cancer cells have a change in a gene called “NTRK” and have spread within the affected organ or to other organs of the body, or

in the case where surgery to remove the cancer would likely
cause serious complications (see “How AUGTYRO works” below) and

• you have previously been treated with medicines called NTRKinhibitors, or
• you have not been treated with medicines called NTRKinhibitors and other treatments are not suitable for you.

How AUGTYRO works
AUGTYRO works by blocking the action of proteins that are not working correctly due to the
presence of changes in the NTRKor ROS1genes that produce them. These abnormal proteins can
cause uncontrolled growth of cancer cells. By blocking the abnormal proteins, AUGTYRO can
slow down or stop the growth of cancer cells and help reduce the cancer.

2. What you need to know before taking AUGTYRO

Do not take AUGTYRO

• if you are allergic to repotrectinib or any of the other ingredients of this medicine (listed in section 6). If you are unsure, ask your doctor, pharmacist or nurse before taking AUGTYRO.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking AUGTYRO if

• you have recently experienced dizziness, memory loss, confusion, hallucinations, changes in mental status, loss of muscle coordination or unsteady or uncoordinated walking
• you have had other lung problems. Tell your doctor immediately if you develop new or worsening symptoms including shortness of breath, cough or fever
• you have a history of bone fractures or a condition that may increase your risk of bone fractures
• you have liver problems.

Other medicines and AUGTYRO
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
In particular, tell your doctor or pharmacist if you are taking any of the following medicines
for:

• acquired immunodeficiency syndrome (AIDS)/human immunodeficiency virus (HIV) infection, such as ritonavir, saquinavir, efavirenz
• fungal infections (antifungals), such as ketoconazole, itraconazole, voriconazole, posaconazole
• stopping seizures or epileptic fits (antiepileptics), such as carbamazepine or phenytoin
• tuberculosis, such as rifampicin
• depression, such as bupropion, fluvoxamine or a herbal remedy: St John's wort ( Hypericum perforatum)
• cancers, such as apalutamide, everolimus
• suppressing your body’s immune system or preventing your body from rejecting an organ transplant, such as sirolimus, tacrolimus, cyclosporine, sulfasalazine
• inflamed joints or autoimmune joint disease (rheumatoid arthritis), methotrexate
• severe pain, such as alfentanil, fentanyl
• high blood pressure, such as verapamil, nifedipine, felodipine, valsartan
• reducing cholesterol in the blood, such as lovastatin, simvastatin, rosuvastatin
• reducing blood sugar levels, such as repaglinide, tolbutamide, metformin
• acid reflux (heartburn), such as cisapride, omeprazole
• preventing blood clots, such as warfarin, dabigatran etexilate
• heart problems, such as digoxin, edoxaban
• allergies, such as fexofenadine
• birth control: if you are using hormonal oral contraceptives, you must also use a reliable barrier method of contraception (see “Pregnancy and breastfeeding”).

AUGTYRO with food and drinks
Do not drink grapefruit juice or eat grapefruits or Seville oranges while being treated with
AUGTYRO, as they can increase the amount of the medicine in your blood to a harmful level.

Pregnancy and breastfeeding
Women and contraception
You must avoid becoming pregnant while being treated with this medicine as it can
harm the baby. If you are of childbearing potential, you must use highly effective methods of contraception during
treatment and for at least 2 months after stopping treatment.
It is not known whether AUGTYRO may reduce the effect of contraceptive medicines (pills or
implanted hormonal contraceptives). If you are using a hormonal method of contraception, you must use a
reliable non-hormonal additional method of contraception, such as a barrier method (e.g. a
condom), so that you do not become pregnant while taking AUGTYRO and for 2 months after
stopping treatment.
Talk to your doctor about suitable methods of contraception for you and your partner.
Men and contraception
Your partner must avoid becoming pregnant while being treated with this medicine as it can
harm the baby. If your partner is of childbearing potential, she must use a condom during
treatment and for at least 4 months after stopping treatment.
Talk to your doctor about suitable methods of contraception for you and your partner.
Pregnancy

• Do not take AUGTYRO if you are pregnant, as it can harm the baby.
• If you are a woman of childbearing potential, your doctor will make you have a pregnancy test before starting treatment with AUGTYRO.
• If you become pregnant while taking the medicine or within 2 months of taking the last dose, tell your doctor immediately.

Breastfeeding
Do not breastfeed while being treated with this medicine, as it is not known whether AUGTYRO
can pass into breast milk and potentially harm the baby.

Driving and using machines
AUGTYRO can have effects on your ability to drive or operate machines. AUGTYRO can
cause:

• dizziness
• impaired balance or coordination
• fainting (loss of consciousness)
• fatigue
• changes in mental status, feeling confused or seeing things that are not there (hallucinations)
• blurred vision. If you experience any of these conditions, do not drive, ride a bicycle or operate machinery until the symptoms have gone. Ask your doctor or pharmacist if it is safe for you to drive, ride a bicycle or operate machinery.

AUGTYRO contains sodium
AUGTYRO contains less than 1 mmol (23 mg) of sodium per capsule, that is to say essentially “sodium-free”.

3. How to take AUGTYRO

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.

What dosage to take
The recommended dose is 160 mg once a day for the first 14 days, followed by 160 mg twice
a day as long as your doctor considers it necessary.
Depending on the response to treatment, your doctor may suggest a lower dose or even a brief
suspension of treatment. For lower doses, you may need to take a 120 mg dose
(three 40 mg capsules) or an 80 mg dose (two 40 mg capsules).
Take this medicine following exactly as stated in this leaflet or the instructions of your doctor, pharmacist or nurse. If you have any doubts, consult your doctor, pharmacist or
nurse.

How to take AUGTYRO
Take AUGTYRO by mouth, with or without food. Swallow each capsule whole. The capsules should not
be opened, crushed or chewed, and their contents should not be dissolved.

If you take more AUGTYRO than you should
If you take more AUGTYRO than you should, contact your doctor or go to the hospital immediately.

If you forget to take AUGTYRO
If you have missed a dose or vomited after taking one, take the next dose as
prescribed. Do not take a double dose to make up for the missed dose.

If you stop taking AUGTYRO
Do not stop taking this medicine without first talking to your doctor. It is
important to take AUGTYRO every day for the entire period of time that your doctor has
prescribed. If you have any doubts about the use of this medicine, contact your doctor, pharmacist or
nurse.

4. Possible side effects

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

Serious side effects
Tell your doctor immediately if you notice any of the following effects after taking
AUGTYRO:

• feels dizzy, confused, has mood changes, hallucinations (sees things that do not exist) or problems with memory (cognitive impairment) or loss of muscle coordination, walks in a clumsy or unsteady way (ataxia)
• develops shortness of breath (dyspnea), cough, fever (pyrexia) or conditions that cause scarring in the lungs
• notes any joint pain, bone pain, deformity or changes in the ability to move, as these may be signs of fractures.

Your doctor may reduce the dose, suspend treatment for a short period or stop it altogether.

Other side effects
Adults
Side effects very common(may affect more than 1 in 10 people):

• lung infection
• decrease in the number of healthy red blood cells that carry oxygen throughout the body (anemia)
• dizziness
• loss of muscle coordination, instability when walking (ataxia)
• significant changes in thought patterns (cognitive impairment)
• sensations such as numbness and tingling (paresthesia)
• inflammation (swelling and redness) or degeneration of peripheral nerves (nerves outside the brain and spinal cord) resulting in numbness, tingling, burning (peripheral sensory neuropathy)
• sleep disturbances
• headache
• altered taste (dysgeusia)
• seeing flashes of light, blurred vision, sensitivity to light, moving bodies or double vision (vision disorders)
• shortness of breath
• cough
• feeling the need to vomit (nausea)
• vomiting
• constipation
• diarrhea
• muscle weakness
• pain in legs and/or arms
• joint pain (arthralgia)
• muscle pain (myalgia)
• back pain
• fever
• feeling tired (fatigue)
• decreased appetite
• swelling of ankles, feet and hands
• increased level in the blood of the enzyme (creatine phosphokinase) of the muscle
• weight gain
• increased amounts of the liver enzymes aspartate aminotransferase or alanine aminotransferase

Side effects common(may affect up to 1 in 10 people)

• increased level in the blood of the enzyme (uric acid) (hyperuricemia)
• inflammation and scarring conditions in the lungs
• fluid around the lungs (pleural effusion)
• abdominal pain
• bone fractures
• increased amount of the liver enzymes gamma-glutamyltransferase or alkaline phosphatase in the blood
• decrease in the number of a type of white blood cells called lymphocytes
• decrease in the level of white blood cells
• decrease in the number of a type of white blood cells called neutrophils
• falls

Patients aged 18 years or younger
Side effects very common(may affect more than 1 in 10 people):

• decrease in the number of healthy red blood cells that carry oxygen throughout the body (anemia)
• increased appetite
• high levels of potassium in the blood
• increased level in the blood of the enzyme (uric acid) (hyperuricemia)
• dizziness
• loss of muscle coordination, instability when walking (ataxia)
• significant changes in thought patterns (cognitive impairment)
• sensations such as numbness and tingling (paresthesia)
• sleep disturbances
• headache
• altered taste (dysgeusia)
• seeing flashes of light, blurred vision, sensitivity to light, moving bodies or double vision (vision disorders)
• shortness of breath
• cough
• feeling the need to vomit (nausea)
• vomiting
• constipation
• diarrhea
• abdominal pain
• bone fractures
• joint pain (arthralgia)
• fever
• feeling tired (fatigue)
• increased level in the blood of the enzyme (creatine phosphokinase) of the muscle
• weight gain
• decrease in the number of white blood cells called lymphocytes
• decrease in the number of a type of white blood cells
• decrease in the number of a type of white blood cells called neutrophils
• increased amount of the liver enzymes aspartate aminotransferase or alkaline phosphatase in the blood

Side effects common(may affect up to 1 in 10 people)

• lung infection
• inflammation (swelling and redness) or degeneration of peripheral nerves (nerves outside the brain and spinal cord) resulting in numbness, tingling, burning (peripheral sensory neuropathy)
• fluid around the lungs (pleural effusion)
• sensations such as numbness and tingling of the lips, tongue or entire mouth (oral paresthesia), muscle pain (myalgia)
• muscle weakness
• falls

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any 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 AUGTYRO

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, bottle or
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 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. Contents of the pack and other information

What AUGTYRO contains
The active substance is repotrectinib.
AUGTYRO 40 mg: each capsule contains 40 mg of repotrectinib
AUGTYRO 160 mg: each capsule contains 160 mg of repotrectinib
The other ingredients are:

• Capsule contents: microcrystalline cellulose, sodium lauryl sulfate, sodium croscarmellose, anhydrous colloidal silica and magnesium stearate (only 160 mg hard capsules) (see section 2).
• Capsule shell: gelatin, titanium dioxide (E171), brilliant blue (E133, only for 160 mg hard capsules).
• Printing ink (40 mg hard capsules): shellac (E904) and aluminium lake containing indigo carmine (E132).
• Printing ink (160 mg hard capsules): shellac and titanium dioxide.

Description of the appearance of AUGTYRO and contents of the pack
The hard capsules (capsules) of AUGTYRO 40 mg are opaque white in colour with the inscription
“REP 40” printed in blue.
The hard capsules (capsules) of AUGTYRO 160 mg are opaque blue in colour with the inscription “REP 160”
printed in white.
AUGTYRO 40 mg is supplied in a carton containing a bottle with 60 or 120 hard capsules.
AUGTYRO 160 mg is packaged in blister packs containing 10 hard capsules. Each pack
contains 20 or 60 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland

Manufacturer
Swords Laboratories Unlimited Company
T/A Bristol-Myers Squibb Pharmaceutical Operations
External Manufacturing
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

Belgique/België/Belgien
N.V. Bristol-Myers Squibb Belgium S.A.
Tél/Tel: + 32 2 352 76 11
[email protected]

Lietuva
Swixx Biopharma UAB
Tel: + 370 52 369140
[email protected]

България
Swixx Biopharma EOOD
Teл.: + 359 2 4942 480
[email protected]

Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A.
Tél/Tel: + 32 2 352 76 11
[email protected]

Česká republika
Bristol-Myers Squibb spol. s r.o.
Tel: + 420 221 016 111
[email protected]

Magyarország
Bristol-Myers Squibb Kft.
Tel.: + 36 1 301 9797
[email protected]

Danmark
Bristol-Myers Squibb Denmark
Tlf: + 45 45 93 05 06
[email protected]

Malta
A.M. Mangion Ltd
Tel: + 356 23976333
[email protected]

Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA
Tel: 0800 0752002 (+ 49 89 121 42 350)
[email protected]

Nederland
Bristol-Myers Squibb B.V.
Tel: + 31 (0)30 300 2222
[email protected]

Eesti
Swixx Biopharma OÜ
Tel: + 372 640 1030
[email protected]

Norge
Bristol-Myers Squibb Norway AS
Tlf: + 47 67 55 53 50
[email protected]

Ελλάδα
Bristol-Myers Squibb A.E.
Τηλ: + 30 210 6074300
[email protected]

Österreich
Bristol-Myers Squibb GesmbH
Tel: + 43 1 60 14 30
[email protected]

España
Bristol-Myers Squibb, S.A.
Tel: + 34 91 456 53 00
[email protected]

Polska
Bristol-Myers Squibb Polska Sp. z o.o.
Tel.: + 48 22 2606400
[email protected]

France
Bristol-Myers Squibb SAS
Tél: + 33 (0)1 58 83 84 96
[email protected]

Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa, S.A.
Tel: + 351 21 440 70 00
[email protected]

Hrvatska
Swixx Biopharma d.o.o.
Tel: + 385 1 2078 500
[email protected]

România
Bristol-Myers Squibb Marketing Services S.R.L.
Tel: + 40 (0)21 272 16 19
[email protected]

Ireland
Bristol-Myers Squibb Pharmaceuticals uc
Tel: 1 800 749 749 (+ 353 (0)1 483 3625)
[email protected]

Slovenija
Swixx Biopharma d.o.o.
Tel: + 386 1 2355 100
[email protected]

Ísland
Vistor hf.
Sími: + 354 535 7000
[email protected]
[email protected]

Slovenská republika
Swixx Biopharma s.r.o.
Tel: + 421 2 20833 600
[email protected]

Italia
Bristol-Myers Squibb S.r.l.
Tel: + 39 06 50 39 61
[email protected]

Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab
Puh/Tel: + 358 9 251 21 230
[email protected]

Κύπρος
Bristol-Myers Squibb A.E.
Τηλ: 800 92666 (+ 30 210 6074300)
[email protected]

Sverige
Bristol-Myers Squibb Aktiebolag
Tel: + 46 8 704 71 00
[email protected]

Latvija
Swixx Biopharma SIA
Tel: + 371 66164750
[email protected]
An authorisation “subject to conditions” has been granted for this medicinal product. This means that
further data must be provided on this medicinal product.
The European Medicines Agency will review the new information at least annually on this

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

ANNEX IV
CONCLUSIONS RELATING TO THE GRANT OF THE MARKETING AUTHORISATION
SUBJECT TO CONDITIONS PRESENTED BY THE EUROPEAN
MEDICINES AGENCY
Conclusions presented by the European Medicines Agency on:

• Grant of a marketing authorisation subject to conditions

Following the evaluation of the application for a marketing authorisation, the
Committee for Medicinal Products for Human Use (CHMP) considers that the benefit/risk ratio is
favourable in order to recommend the grant of a marketing authorisation
subject to conditions, as further described in the European Public Assessment Report (EPAR).