TAGRISSO 80 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Tagrisso40mg film-coated tablets

Tagrisso80mg film-coated tablets

osimertinib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is TAGRISSO and what is it used for

TAGRISSO contains the active substance osimertinib, which belongs to a group of medicines called protein kinase inhibitors, used to treat cancer. TAGRISSO is used to treat adults with a type of lung cancer called "non-small cell lung cancer". It is likely that your cancer will respond to treatment with TAGRISSO if a test has shown that your cancer has certain changes (mutations) in a gene called "EGFR" (epidermal growth factor receptor).

TAGRISSO as monotherapy may be prescribed to you:

• after the complete removal of your cancer as post-surgical treatment (adjuvant)

or

• for cancer that cannot be removed (resected) by surgery and has responded or stabilized after treatment with chemotherapy and radiation

or

• as the first medicine you receive for your cancer that has spread to other parts of the body

or

• under certain circumstances, if you have previously received treatment for your cancer with other protein kinase inhibitor medicines.

TAGRISSO may be prescribed to you in combination with other cancer medicines, such as:

• pemetrexed and platinum-based chemotherapy as the first medicine you receive for your cancer that has spread to other parts of the body

When TAGRISSO is given in combination with other cancer medicines, it is important that you also read the package leaflet for these other medicines. If you have any questions about these medicines, ask your doctor.

How TAGRISSO works

TAGRISSO works by blocking EGFR and may help your lung cancer stop growing or slow down its growth. It may also help reduce the size of the tumor and prevent the tumor from coming back after surgical removal.

• If you are receiving TAGRISSO after the complete removal of your cancer, this means that your cancer contained defects in the EGFR gene, "exon 19 deletion" or "exon 21 substitution mutation".

• If you are receiving TAGRISSO for cancer that cannot be removed (resected) by surgery and has responded or stabilized after treatment with chemotherapy and radiation, this means that your cancer contains defects in the EGFR gene, "exon 19 deletion" or "exon 21 substitution mutation".

• If TAGRISSO is the first protein kinase inhibitor medicine you are taking, this means that your cancer contains defects in the EGFR gene called "exon 19 deletion" or "exon 21 substitution mutation".

• If your cancer has progressed while being treated with another protein kinase inhibitor medicine, this means that your cancer contains a defective gene called "T790M". Due to this defect, it is possible that other protein kinase inhibitor medicines may no longer work.

If you have any questions about how this medicine works or why it has been prescribed for you, ask your doctor.

2. What you need to know before you take TAGRISSO

Do not take TAGRISSO if:

• you are allergic (hypersensitive) to osimertinib or any of the other ingredients of this medicine (listed in section 6).
• you are taking St. John's Wort (Hypericum perforatum).

In case of doubt, consult your doctor, pharmacist, or nurse before taking TAGRISSO.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take TAGRISSO if:

• you have had inflammation of your lungs (a condition called "interstitial lung disease")
• you have had heart problems - your doctor may want to keep a close eye on you.
• you have had a history of eye problems.

If any of the above applies to you (or you are not sure), consult your doctor, pharmacist, or nurse before taking this medicine.

Tell your doctor immediately while taking this medicine if:

• you have sudden difficulty breathing together with cough or fever.
• you have severe skin peeling.
• you have fast or irregular heartbeats, dizziness, fainting, chest discomfort, difficulty breathing, and fainting.
• you have watery eyes, sensitivity to light, eye pain, redness of the eyes, or changes in vision. For more information, see "Serious side effects" in section 4.
• you develop persistent fever, bruising or bleeding more easily, increased fatigue, pale skin, and infection. For more information, see "Serious side effects" in section 4.

Children and adolescents

TAGRISSO has not been studied in children or adolescents. Do not give this medicine to children or adolescents under 18 years of age.

Taking TAGRISSO with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription and herbal medicines. This is because TAGRISSO may affect the way other medicines work, and other medicines may have an effect on TAGRISSO.

Tell your doctor before taking TAGRISSO if you are taking any of the following medicines:

The following medicines may reduce the effectiveness of TAGRISSO:

• Phenytoin, carbamazepine, or phenobarbital - used to treat epilepsy or convulsions.
• Rifabutin or rifampicin - used to treat tuberculosis (TB).
• St. John's Wort (Hypericum perforatum) - a herbal medicine used for depression.

TAGRISSO may affect the effectiveness of the following medicines and/or increase their side effects:

• Rosuvastatin - used to lower cholesterol.
• Hormonal oral contraceptive - used to prevent pregnancy.
• Bosentan - used for high blood pressure in the lungs.
• Efavirenz and etravirine - used for the treatment of HIV/AIDS.
• Modafinil - used for sleep disorders.
• Dabigatran - used to prevent blood clots.
• Digoxin - used for irregular heartbeats or other heart problems.
• Aliskiren - used for high blood pressure.

If you are taking any of the above medicines, tell your doctor before taking TAGRISSO.Your doctor will discuss with you the appropriate treatment options.

Pregnancy– information for women

• If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. If you become pregnant during treatment, tell your doctor immediately. Your doctor will decide with you whether you should continue to take TAGRISSO.
• Do not become pregnant while taking this medicine. If you can become pregnant, you must use effective contraception. See section "Contraception - information for women and men" below.
• Ask your doctor for advice if you plan to become pregnant after taking the last dose of this medicine. This is because some medicine may remain in your body (see advice on contraception below).

Pregnancy– information for men

• If your partner becomes pregnant while you are taking this medicine, tell your doctor immediately.

Contraception– information for women and men

You must use effective contraception during treatment.

• TAGRISSO may interfere with the effectiveness of hormonal oral contraceptives. Discuss with your doctor the most suitable contraceptive methods.
• TAGRISSO may pass into human semen. Therefore, it is important that men also use effective contraception.

You must also do the following after stopping treatment with TAGRISSO:

• Women-continue to use effective contraception for 2 months after stopping treatment.
• Men-continue to use effective contraception for 4 months after stopping treatment.

Breast-feeding

Do not breast-feed while taking this medicine, as it is not known whether there is a risk to your baby.

Driving and using machines

TAGRISSO does not affect or does not significantly affect your ability to drive or use machines.

TAGRISSO contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take TAGRISSO

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

What dose should you take

• The recommended dose is one 80 mg tablet per day when TAGRISSO is given as monotherapy.
• The recommended dose of TAGRISSO is one 80 mg tablet per day when given with pemetrexed and platinum-based chemotherapy.
• If necessary, your doctor may reduce your dose to one 40 mg tablet per day.

How to take

• TAGRISSO is taken by mouth. Swallow the tablet whole with water. Do not crush, divide, or chew the tablet.
• Take TAGRISSO every day at the same time.
• You can take this medicine with or without food.

If you have problems swallowing the tablet, you can mix it with water:

• Put the tablet in a glass.
• Add 50 ml (about two-thirds of a glass) of non-carbonated water - do not use any other liquid.
• Stir the water until the tablet breaks into very small pieces - the tablet will not dissolve completely.
• Drink the liquid immediately.
• To make sure you take all the medicine, rinse the glass completely with another 50 ml of water and drink it.

If you take more TAGRISSO than you should

If you take more than the dose prescribed for you, talk to your doctor or go to the nearest hospital immediately.

If you forget to take TAGRISSO

If you forget to take a dose, take it as soon as you remember. However, if it is less than 12 hours until your next dose, do not take the missed dose. Take the next dose at the usual time.

If you stop taking TAGRISSO

Do not stop taking this medicine - consult your doctor first. It is important that you take this medicine every day for as long as your doctor has prescribed it.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects

Inform your doctor immediately if you experience the following severe adverse effect (see also section 2):

• Sudden difficulty breathing along with cough or fever - this may be a sign of lung inflammation (a condition called "interstitial lung disease"). Most cases can be treated, but some have been fatal. Your doctor may want to discontinue TAGRISSO treatment if you experience this adverse effect. This is a frequent adverse effect: it may affect up to 1 in 10 people.
• Stevens-Johnson syndrome and toxic epidermal necrolysis, which can appear as reddish spots or circular patches, often with central blisters on the trunk, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. Stevens-Johnson syndrome is rare: it may affect up to 1 in 1,000 people. The frequency of toxic epidermal necrolysis cannot be determined as only cases have been reported since the marketing of TAGRISSO.
• Changes in the heart's electrical activity (QTc prolongation), such as rapid or irregular heartbeats, dizziness, fainting, chest discomfort, shortness of breath, and fainting. This side effect is frequent: it may affect up to 1 in 10 people.
• If you notice tearful eyes, sensitivity to light, eye pain, redness of the eyes, or changes in vision. This effect is infrequent: it may affect up to 1 in 100 people.
• A blood disorder called aplastic anemia, in which the bone marrow stops producing new blood cells – signs suggesting this blood disorder may include persistent fever, bruising or bleeding more easily, increased fatigue, and a decreased ability to fight infections. This adverse effect is rare: it may affect up to 1 in 1,000 people.
• A condition in which the heart, when beating, does not pump enough blood out of the heart as well as it should, which could cause difficulty breathing, fatigue, and swelling of the ankles (suggestive of heart failure or reduced left ventricular ejection fraction).

Inform your doctor immediately if you notice the above severe adverse effect.

Other Adverse Effects

VeryFrequent(may affect more than 1 in 10 people)

• Diarrhea - may appear intermittently during treatment. Inform your doctor if diarrhea does not disappear or worsens.
• Itching of the skin (pruritus) - regular application of moisturizing creams to your skin may help improve this.
• Skin and nail problems - including signs such as pain, itching, dry skin, rash, and redness around the fingernails. This is more likely in sun-exposed areas. Regular application of moisturizing creams to your skin and nails may help improve this. Inform your doctor if your skin or nail problems worsen.
• Stomatitis: inflammation of the lining of the mouth or the formation of ulcers in the mouth.
• Loss of appetite.

Frequent(may affect up to 1 in 10 people):

• Inflammation of the lungs caused by radiation therapy to the chest (radiation pneumonitis).
• Nosebleeds (epistaxis).
• Hair loss (alopecia).
• Hives (urticaria) - raised patches that itch in any part of the skin, which can be pink or red and round in shape. Inform your doctor if you notice this adverse effect.
• Hand-foot syndrome – may include redness, swelling, tingling, or burning sensation with cracking of the skin on the palms of the hands and/or the soles of the feet.
• Increased levels of a substance in the blood called creatinine (produced by the body and eliminated by the kidneys).

• Increased levels of a substance in the blood called creatine phosphokinase (an enzyme released into the blood when muscle is damaged).
• Decreased number of white blood cells in the blood (leukocytes, lymphocytes, or neutrophils).

• Decreased number of platelets in the blood.

Infrequent(may affect up to 1 in 100 people)

• Target lesions, which are ring-shaped skin reactions (suggesting erythema multiforme).
• Inflammation of the blood vessels in the skin. This can give the appearance of bruising or skin redness that does not lose color when pressed (does not disappear).
• Inflammation of the muscle that can cause muscle pain or weakness.
• Grayish or darkened skin (hyperpigmentation).

The following adverse effects have been reported in a clinical trial with patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy:

Very Frequent(may affect more than 1 in 10 people)

• Diarrhea - may appear and disappear during treatment. Inform your doctor if diarrhea does not disappear or worsens.
• Skin and nail problems – including signs such as pain, itching, dry skin, rash, and redness around the fingernails. This is more likely in sun-exposed areas. Regular application of moisturizing creams to your skin and nails may help improve this. Inform your doctor if your skin or nail problems worsen.
• Stomatitis - inflammation of the lining of the mouth or the formation of ulcers in the mouth.
• Loss of appetite.
• Decreased number of white blood cells in the blood (leukocytes, lymphocytes, or neutrophils).
• Decreased number of platelets in the blood.
• Increased levels of a substance in the blood called creatinine (produced by the body and eliminated by the kidneys).

Frequent(may affect up to 1 in 10 people)

• Nosebleeds (epistaxis).
• Itching of the skin (pruritus) - regular application of moisturizing creams to your skin may help improve this.
• Hair loss (alopecia).
• Target lesions, which are ring-shaped skin reactions (suggesting erythema multiforme).
• Hives (urticaria) - raised patches that itch in any part of the skin, which can be pink or red and round in shape. Inform your doctor if you notice this adverse effect.
• Hand-foot syndrome - may include redness, swelling, tingling, or burning sensation with cracking of the skin on the palms of the hands and/or the soles of the feet.
• Increased levels of a substance in the blood called creatine phosphokinase (an enzyme released into the blood when muscle is damaged).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of TAGRISSO

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

Do not use this medicine after the expiration date stated on the blister pack and on the carton after EXP. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Do not use this medicine if the packaging is damaged or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of TAGRISSO

• The active ingredient is osimertinib (as mesylate). Each 40 mg film-coated tablet contains 40 mg of osimertinib. Each 80 mg film-coated tablet contains 80 mg of osimertinib.
• The other ingredients (excipients) are mannitol, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sodium stearyl fumarate, polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, yellow iron oxide, red iron oxide, black iron oxide (see section 2 "TAGRISSO contains sodium").

Appearance of TAGRISSO and Package Contents

TAGRISSO 40 mg is supplied as beige, film-coated, round, and biconvex tablets, marked with "AZ" and "40" on one face and smooth on the other.

TAGRISSO 80 mg is supplied as beige, film-coated, oval, and biconvex tablets, marked with "AZ" and "80" on one face and smooth on the other.

TAGRISSO is supplied in blisters containing 30 x 1 film-coated tablets, packaged in cartons containing 3 blisters of 10 tablets each.

TAGRISSO is supplied in blisters containing 28 x 1 film-coated tablets, packaged in cartons containing 4 blisters of 7 tablets each.

Marketing Authorization Holder

AstraZeneca AB

SE-151 85 Södertälje

Sweden

Manufacturer

AstraZeneca AB

Gärtunavägen

SE-152 57 Södertälje

Sweden

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

Other Sources of Information

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