Prospect: information for the user

Tegsedi 284 mg injectable solution in pre-filled syringe

Inotersen

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 use this medicine, because 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, pharmacist or nurse.
• This medicine has been prescribed only for 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, pharmacist or nurse, even if they are not listed in this prospect. See section 4.

Tegsedi contains the active ingredient inotersen. Inotersen is used to treat adults with hereditary transthyretin amyloidosis. Hereditary transthyretin 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 functioning correctly. Tegsedi is used when the disease causes symptoms of polyneuropathy (nerve damage).

The active ingredient in Tegsedi, inotersen, is a type of medication called an antisense oligonucleotide inhibitor. It acts by reducing the production of transthyretin by the liver, thereby decreasing the risk of transthyretin fibers depositing in organs and causing symptoms.

Do not use Tegsedi:

• If you are allergic to inotersen or any of the other components of this medication (listed in section 6).
• If blood tests indicate that you have an excessively low platelet count (the blood cells that help with clotting).
• If kidney function or urine protein tests show signs of severe kidney problems.
• If you have severe liver dysfunction (liver insufficiency).

Warnings and precautions

Before starting treatment with Tegsedi, your doctor will evaluate your blood cells, liver function, kidney function, vitamin A levels, and urine protein levels. They may also perform pregnancy tests to ensure you have a negative result. Unless your doctor explicitly recommends it, you will only be treated with Tegsedi if all these results are within acceptable levels, and your pregnancy test is negative. Your doctor will repeat these controls regularly during treatment. It is essential to have these blood and urine tests regularly while 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 occurs in thrombocytopenia, your blood may not clot quickly enough to stop bleeding. This can cause the formation of bruises, as well as more severe problems such as excessive bleeding or internal bleeding. Your doctor will perform blood tests to monitor platelet levels before treatment and regularly during treatment with Tegsedi. It is essential to have these blood tests regularly while taking Tegsedi due to the risk of severe bleeding caused by low platelet counts. If you stop using Tegsedi, your blood values should be checked 8 weeks after stopping the medication.

Consult your doctor immediately if you experience unexplained bruises or a rash of small red patches on the skin (called petechiae), bleeding from cuts on the skin that does not stop or oozes, nasal bleeding or bleeding gums, blood in the urine or stool, or bleeding in the white part of the eyes. Seek immediate assistance if you experience stiffness in the neck or an unusual and intense headache, as these symptoms may be caused by a cerebral hemorrhage.

Glomerulonephritis/Renal problems

Glomerulonephritis is a kidney condition where the kidneys do not work properly due to inflammation and renal 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 monitor your kidney function before treatment and regularly during treatment with Tegsedi. It is essential to have these blood tests regularly while taking Tegsedi due to the risk of severe bleeding caused by low platelet counts. If you stop using Tegsedi, your kidney function should be checked 8 weeks after stopping the medication. If you develop glomerulonephritis, your doctor will treat this condition.

Vitamin A deficiency

Tegsedi may decrease your body's vitamin A levels (also known as retinol). Your doctor will measure these levels, and if they are already low, this will be corrected, and all symptoms will resolve before starting treatment with Tegsedi. The symptoms of low vitamin A include:

If you have vision problems or any other eye issues while taking Tegsedi, inform your doctor. You may be referred 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.

Vitamin A levels both above and below normal can harm the developing fetus. Therefore, women of childbearing age should exclude pregnancy before starting treatment with Tegsedi, and use effective contraceptive methods (see section “Pregnancy and breastfeeding” below).

If you intend to become pregnant, you will stop taking inotersen, including vitamin A supplements, and verify that your vitamin A levels have returned to normal before attempting conception.

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. The safety of continuing 3000 IU of vitamin A per day during the first trimester of pregnancy is unknown, but this dose should not be exceeded. You will resume vitamin A supplementation during the second and third trimesters of pregnancy if your vitamin A levels have not returned to normal, due to the increased risk of vitamin A deficiency in the third trimester.

Liver damage and liver control

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 functioning correctly. You will also need to have these blood tests regularly while taking this medication. It is essential to have these blood tests regularly while taking Tegsedi.

Rejection of liver transplant

Consult your doctor before using Tegsedi if you have received a liver transplant. Cases of liver transplant rejection have been reported 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 or adolescents under 18 years old.

Other medications and Tegsedi

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. It is essential to inform your doctor if you are already being treated with any of the following:

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication.

Women of childbearing age

Tegsedi reduces your body's vitamin A levels, which is essential for normal fetal development during pregnancy. The safety of vitamin A supplementation to compensate for the risk of vitamin A deficiency that could affect your unborn child is unknown. If you are a woman of childbearing age, you should use effective contraceptive methods, and pregnancy should be excluded before starting treatment with Tegsedi.

Pregnancy

You should not use Tegsedi if you are pregnant, unless your doctor explicitly advises it.

Breastfeeding

Inotersen may pass into breast milk. The risk to the infant cannot be ruled out. Consult your doctor if you should interrupt breastfeeding or stop treatment with Tegsedi.

Driving and operating machinery

The use of Tegsedi has not been shown to affect your ability to drive or operate machinery.

Tegsedi contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 1.5 ml, making it essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of 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.

Administration route and form

Tegsedi is only for subcutaneous injection.

Usage instructions

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 usage instructions before starting to use the pre-filled syringe and each time the prescription is repeated, as there may be new information.

Guide to parts

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

If you use more Tegsedi than you should

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

If you forget to use Tegsedi

If you forget a dose of Tegsedi, administer the next dose as soon as possible, unless the next scheduled dose is within two days, in which case you should skip the missed dose and administer the next dose as scheduled.

Do nottake a double dose to compensate for missed doses.

Do notinterrupt treatment with Tegsedi unless your doctor tells you to.

If you have any other questions about using this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe 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 correctly), such as foam in the urine, urine of a pink or brown color, blood in the urine, or urinating less than usual. Glomerulonephritis is a frequent side effect of inotersen (it can 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 bruises or a rash of small red patches on the skin (called petechiae), bleeding from cuts in the skin that does not stop or suppurates, nasal bleeding or in the gums, blood in the urine or stool, or hemorrhage in the white part of the eyes. Low platelet levels in the blood are a very frequent side effect of inotersen (it can 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 on the skin, pain in the upper right area of the stomach (abdomen), loss of appetite, bleeding or bruising more easily than usual, or feeling tired.

Seek immediate assistance if you experience stiffness in the neck or an unusual and intense headache, as these symptoms may be caused by a cerebral hemorrhage.

Other side effects

Very frequent(can affect more than 1 in 10 people)

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

Frequent(can affect up to 1 in 10 people)

• Increased number of white blood cells called eosinophils (eosinophilia)
• Loss of appetite
• Sensation of dizziness or fainting, especially when standing (low blood pressure, hypotension)
• Cardinal
• Accumulation of blood in the tissues, which can be seen as significant cardinal (hematomas)
• Itching
• Rash
• Renal damage that can cause poor kidney function or renal insufficiency
• Changes in blood and urine test results (this may indicate liver or kidney damage)
• Symptoms similar to the flu, such as high temperature, pain, and chills
• Swelling or discoloration of the skin at the injection site

Rare(can affect up to 1 in 100 people)

-Allergic reaction

Reporting side effects

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

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, tray, and pre-filled syringe after CAD/EXP. The expiration date is the last day of the month indicated.

Store in 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 medication must be discarded.

Store in the original packaging to protect it from light.

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

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Tegsedi

• The active ingredient is inotersen.

Each milliliter 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 components are injectable water, sodium hydroxide, and hydrochloric acid (see “Tegsedi contains sodium” in section 2).

Appearance of the product and contents of the container

Tegsedi is a transparent, colorless to pale yellow injectable solution (pH 7.5 – 8.8) in a pre-filled syringe.

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

Only some container sizes may be marketed.

Marketing authorization holder

Akcea Therapeutics Ireland Ltd

St. James House,

72 Adelaide Road, Dublin 2

D02 Y017, Ireland

Responsible manufacturer

ABF Pharmaceutical Services GmbH

Brunnerstraße 63/18-19
1230 Vienna

Austria

Last review date of this leaflet: 11/2023

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