TEGSEDI 284 mg Injectable Solution in Pre-filled Syringe

Introduction

Package Leaflet: Information for the User

Tegsedi 284 mg solution for injection in pre-filled syringe

Inotersen

This medicine is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of section 4 will tell you how to report side effects.

Read all of this leaflet carefully before you start using 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 Tegsedi and what is it used for
2. What you need to know before you use Tegsedi
3. How to use Tegsedi
4. Possible side effects
5. Storage of Tegsedi
6. Contents of the pack and other information

1. What is Tegsedi and what is it used for

Tegsedi contains the active substance inotersen. Inotersen is used to treat adults with hereditary transthyretin-mediated amyloidosis. Hereditary transthyretin-mediated amyloidosis is a genetic disease that causes the accumulation of small fibers of a protein called transthyretin in the organs of your body, preventing them from working properly. Tegsedi is used when the disease causes symptoms of polyneuropathy (nerve damage).

The active substance in Tegsedi, inotersen, is a type of medicine called an antisense oligonucleotide inhibitor. It works by reducing the production of transthyretin by the liver, and thus reduces the risk of transthyretin fibers being deposited in the organs and causing symptoms.

2. What you need to know before you use Tegsedi

Do not use Tegsedi:

• if you are allergic to inotersen or any of the other ingredients of this medicine (listed in section 6).
• if the tests indicate that you have a very low platelet count (the cells in the blood that help the blood to clot).
• if the kidney function tests or protein in urine tests show signs of severe kidney problems.
• if you have severe liver function impairment (liver failure).

Warnings and precautions

Before starting treatment with Tegsedi, your doctor will check your blood cells, liver function, kidney function, vitamin A, and protein levels in the urine. They may also do a pregnancy test to make sure you are not pregnant. Unless your doctor recommends it, you will only be treated with Tegsedi if all these test results are acceptable, and your pregnancy test result is negative. Your doctor will repeat these tests regularly during treatment. It is important that you have these blood and urine tests regularly while you are taking Tegsedi.

Thrombocytopenia

Tegsedi may reduce the blood cells responsible for clotting (platelets), which can lead to a condition called thrombocytopenia at any time during treatment with Tegsedi (see section 4). When you do not have enough platelets, as in thrombocytopenia, your blood may not clot quickly enough to stop bleeding. This can cause bruising, as well as more serious problems such as excessive bleeding or internal bleeding. Your doctor will do blood tests to check your platelet levels before treatment and regularly during treatment with Tegsedi. It is important that you have these blood tests regularly while you are taking Tegsedi due to the risk of serious bleeding caused by low platelet counts. If you stop using Tegsedi, your blood values should be checked 8 weeks after stopping the medicine.

If you notice unexplained bruising or a rash of small red spots that appear on the skin (called petechiae), bleeding from cuts in the skin that do not stop, nosebleeds or bleeding gums, blood in the urine or stools, or bleeding in the white part of the eyes, you should contact your doctor immediately. You should seek immediate help if you have a stiff neck or an unusual and severe headache, as these symptoms can be caused by a brain bleed.

Glomerulonephritis/kidney problems

Glomerulonephritis is a condition of the kidneys, in which they do not work properly due to inflammation and kidney damage. Some patients treated with inotersen have developed this condition. The symptoms of glomerulonephritis are foam in the urine, urine that is pink or brown, blood in the urine, and urinating less than usual.

Some patients treated with inotersen have also developed a decline in kidney function without having glomerulonephritis.

Your doctor will check your kidney function before treatment and regularly during treatment with Tegsedi. It is essential that you have these blood tests regularly while you are taking Tegsedi due to the risk of serious bleeding caused by low platelet counts. If you stop using Tegsedi, your kidney function should be checked 8 weeks after stopping the medicine. If you develop glomerulonephritis, your doctor will treat you for this condition.

Vitamin A deficiency

Tegsedi may decrease the levels of vitamin A (also called retinol) in your body. Your doctor will measure these levels, and if they are already low, this should be corrected and all symptoms should be resolved before starting treatment with Tegsedi. The symptoms of low vitamin A include:

• Dry eyes, poor vision, decreased night vision, blurred or cloudy vision

If you have any problems with your vision or any other problems with your eyes while taking Tegsedi, you should inform your doctor. Your doctor may refer you to an eye specialist for a check-up if necessary.

Your doctor will ask you to take a daily vitamin A supplement during treatment with Tegsedi.

Both high and low levels of vitamin A can harm the development of the unborn child. Therefore, women of childbearing age must rule out pregnancy before starting treatment with Tegsedi and must use effective contraceptive methods (see section "Pregnancy and breastfeeding" below).

If you plan to become pregnant, you will stop taking inotersen, including vitamin A supplements, and check that your vitamin A levels have returned to normal before trying to conceive.

If you have an unplanned pregnancy, you will stop taking inotersen. However, due to the prolonged activity of Tegsedi, your reduced vitamin A levels may persist. It is not known whether continuing vitamin A supplementation at a dose of 3000 IU per day will be harmful to your unborn child during the first trimester of your pregnancy, but this dose should not be exceeded. You will resume vitamin A supplementation during the second and third trimesters of your pregnancy if your vitamin A levels have not returned to normal, due to the higher risk of vitamin A deficiency in the third trimester.

Liver damage and liver monitoring

Tegsedi may cause severe liver problems. Before starting to take inotersen, you will need to have a blood test to check that your liver is working properly. You will also need to have these blood tests regularly while taking this medicine. It is essential that you have these blood tests regularly while taking Tegsedi.

Liver transplant rejection

Consult your doctor before using Tegsedi if you have had a liver transplant. There have been reports of liver transplant rejection in patients treated with Tegsedi. Your doctor will monitor this aspect regularly during treatment with Tegsedi.

Children and adolescents

Tegsedi should not be used in children and adolescents under 18 years of age.

Other medicines and Tegsedi

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is essential that you inform your doctor if you are already being treated with any of the following:

• Medicines to prevent blood clots or that decrease the number of platelets in the blood, such as acetylsalicylic acid, heparin, warfarin, clopidogrel, rivaroxaban, and dabigatran.
• Any medicine that may alter kidney function or that may damage the kidneys, such as sulfonamides (used as antibiotics), anilides (used to treat fever and pain), aldosterone antagonists (used as a diuretic), and natural and other opioid alkaloids (used to treat pain).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Women of childbearing age

Tegsedi reduces the level of vitamin A in your body, which is essential for normal fetal development during pregnancy. It is not known whether vitamin A supplementation can compensate for the risk of vitamin A deficiency that may affect your unborn child (see "Warnings and precautions" above). If you are a woman of childbearing age, you must use effective contraceptive methods, and pregnancy should be ruled out before starting treatment with Tegsedi.

Pregnancy

You should not use Tegsedi if you are pregnant, unless your doctor advises you to do so.

Breastfeeding

Inotersen may pass into breast milk. The risk to the breastfed child cannot be ruled out. You should consult your doctor if you need to interrupt breastfeeding or discontinue Tegsedi treatment.

Driving and using machines

The use of Tegsedi has not been shown to affect the ability to drive or use machines.

Tegsedi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 1.5 ml, which is essentially "sodium-free".

3. How to use Tegsedi

Follow your doctor's instructions for administering this medication exactly. If in doubt, consult your doctor or pharmacist again.

The recommended dose of Tegsedi is a dose of 284 mg of inotersen.

Doses should be administered once a week. All subsequent doses should be injected once a week, on the same day of each week.

Route and method of administration

Tegsedi is for subcutaneous injection only.

Instructions for use

Before using the pre-filled syringe, your doctor will show you or your caregiver how to use it correctly. If you or your caregiver have any doubts, ask your doctor.

Read the instructions for use before starting to use the pre-filled syringe and each time you have the prescription repeated, as there may be new information.

Guide to parts

Each pre-filled syringe contains a dose and is for single use only.

If you use more Tegsedi than you should

Contact your doctor or pharmacist, or go immediately to the emergency department of a hospital, even if you do not have any symptoms.

If you forget to use Tegsedi

If you miss a dose of Tegsedi, the next dose will be given as soon as possible, unless the next scheduled dose is within 2 days, in which case you should skip the missed dose and give the next dose as scheduled.

Do nottake a double dose to make up for missed doses.

If you interrupt treatment with Tegsedi

Do not interrupt treatment with Tegsedi unless your doctor tells you to do so.

If you have any further questions about the use of this medication, ask 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

If you experience any of the following side effects, stop using Tegsedi and contact your doctor immediately:

• Symptoms that may indicate glomerulonephritis (where your kidneys do not work properly), such as foam in the urine, pink or brown urine, blood in the urine, or urinating less than usual. Glomerulonephritis is a frequent side effect of inotersen (it may affect up to 1 in 10 people).
• Symptoms that may indicate thrombocytopenia (the blood does not clot due to low platelet levels in the blood), such as unexplained bruising or a rash of small red patches on the skin (called petechiae), bleeding from cuts in the skin that does not stop or oozes, nosebleeds or bleeding from the gums, blood in the urine or stool, or bleeding in the white part of the eyes. Low platelet levels in the blood are a very frequent side effect of inotersen (it may affect up to 1 in 10 people).
• Symptoms that may indicate liver damage, such as yellowing of the eyes or skin, or dark urine, possibly accompanied by itching of the skin, pain in the upper right part of the stomach (abdomen), loss of appetite, bleeding or bruising more easily than normal, or feeling tired.

Seek immediate attention if you experience stiffness in the neck or an unusual and severe headache, as these symptoms can be caused by a brain hemorrhage.

Other side effects

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

• Decrease in red blood cells that can cause paleness of the skin and lead to weakness or difficulty breathing (anemia)
• Headache
• Vomiting or nausea (feeling sick) - Increased body temperature
• Feeling cold or chills
• Pain at the injection site, redness, itching, or bruising
• Swelling in the ankles, feet, or fingers (peripheral edema)

Common(may affect up to 1 in 10 people)

• Increased levels of white blood cells called eosinophils (eosinophilia)
• Decreased appetite
• Feeling dizzy or faint, especially when standing up (low blood pressure, hypotension)
• Bruising
• Accumulation of blood in the tissues, which can be seen as significant bruising (hematomas)
• Itching
• Rash
• Kidney damage that can cause impaired kidney function or kidney failure
• Changes in blood and urine test results (this may indicate liver or kidney damage)
• Flu-like symptoms, such as high temperature, pain, and chills
• Swelling or discoloration of the skin at the injection site

Uncommon(may affect up to 1 in 100 people)

• Allergic reaction

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Tegsedi

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

Do not use this medicine after the expiration date stated on the carton, tray, and pre-filled syringe after EXP. The expiration date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Tegsedi can be stored without refrigeration for up to 6 weeks at a temperature below 30°C. If not refrigerated and not used within 6 weeks, the medicine should be discarded.

Store in the original packaging to protect it from light.

Do not use this medicine if you notice that the contents are cloudy or contain particles.

Medicines should not be disposed of 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 additional information

Composition of Tegsedi

• The active substance is inotersen.

Each ml contains 189 mg of inotersen (as inotersen sodium). Each pre-filled syringe contains 284 mg of inotersen (as inotersen sodium) in 1.5 ml of solution.

• The other ingredients are water for injections, sodium hydroxide, and hydrochloric acid (see "Tegsedi contains sodium" in section 2).

Appearance and package contents

Tegsedi is a clear, colorless to pale yellow injectable solution in a pre-filled syringe.

Tegsedi is available in pack sizes of 1 or 4 pre-filled syringes.

Not all pack sizes may be marketed.

Marketing authorization holder

Akcea Therapeutics Ireland Ltd

St. James House,

72 Adelaide Road, Dublin 2

D02 Y017, Ireland

Manufacturer

ABF Pharmaceutical Services GmbH

Brunnerstraße 63/18-191230 Vienna

Austria

Date of last revision of this leaflet: 11/2023

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