284 mg solution for injection in a pre-filled syringe
inotersen
What Tegsedi is and what it is used for
Tegsedi contains the active substance inotersen. It is used to treat adults with hereditary transthyretin amyloidosis (Skelleftea disease). Hereditary transthyretin amyloidosis is a genetic disease that causes the accumulation of small fibers of the protein transthyretin in the body’s organs. When this happens, the organs cannot function 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 in the liver and thus reduces the risk of transthyretin fibers being deposited in the body’s organs and causing symptoms.
What you need to know before using 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 tests show that you have a very low number of platelets (the blood cells that help the blood to clot).
- if tests of kidney function or protein in the urine show signs of severe kidney problems.
- if you have severely impaired liver function.
Warnings and precautions
Before you can start treatment with Tegsedi, the doctor will check blood cells, liver function, kidney function, and protein levels in the urine. You will only receive treatment with Tegsedi if all test results are at acceptable levels. The doctor will repeat these tests regularly during treatment.
Thrombocytopenia
Tegsedi can reduce the number of blood cells responsible for clotting the blood ( platelets ), which can lead to a condition called thrombocytopenia (see section 4). If you don’t have enough platelets, as in thrombocytopenia, the blood may not clot quickly enough to stop a bleed. This can lead to bruising as well as other more serious problems such as extensive bleeding and internal bleeding. The doctor will check the number of platelets in the blood before treatment and regularly during treatment with Tegsedi. If you stop taking Tegsedi, blood levels should be checked for 8 weeks after stopping treatment.
If you are taking other medicines that can reduce the number of blood platelets or prevent the blood from clotting, e.g. acetylsalicylic acid, clopidogrel, warfarin, heparin, rivaroxaban, and dabigatran, you must tell the doctor before using Tegsedi.
You should see a doctor immediately if you get unexplained bruising or a rash with small red spots on the skin (called petechiae ), bleeding from a cut on the skin that does not stop or oozes, bleeding from the gums or nose, blood in the urine or stool, bleeding in the whites of the eyes. Seek immediate help if you have a stiff neck or unusual and severe headaches, as these symptoms may be caused by bleeding in the brain.
Glomerulonephritis/kidney problems
Glomerulonephritis is a condition of the kidneys that means they don’t work properly due to inflammation and kidney damage. Some patients treated with inotersen have developed this condition. Symptoms of glomerulonephritis are foamy urine, pink or brown colored urine, blood in the urine and you urinating less than usual.
Some patients treated with inotersen have also developed deterioration of kidney function without having had glomerulonephritis.
The doctor will check kidney function before treatment and regularly during treatment with Tegsedi. If you stop taking Tegsedi, your kidney function should be checked for 8 weeks after stopping treatment. If you develop glomerulonephritis, you will receive treatment for this.
Tell the doctor if you are using medicines that damage the kidneys or affect kidney function, e.g. sulfonamides, aldosterone antagonists, and certain types of pain relievers.
Vitamin A deficiency
Tegsedi can reduce the body’s levels of vitamin A (also called retinol). The doctor will check these levels and if they are already low they should be corrected and any symptoms addressed before you start treatment with Tegsedi. Symptoms of vitamin A deficiency include:
- dry eyes, reduced vision, reduced night vision, or blurred vision.
If you have vision problems or other eye problems while using Tegsedi, talk to your doctor. If necessary, the doctor can refer you to an eye specialist for a check-up.
The doctor may ask you to take vitamin A supplements daily during treatment with Tegsedi.
Both too high and too low levels of vitamin A can damage fetal development. Fertile women must therefore rule out pregnancy before starting treatment with Tegsedi and use an effective contraceptive method (see the section ” Pregnancy and breast-feeding” below).
If you are planning to become pregnant, stop taking inotersen including vitamin A supplements. Make sure your vitamin A levels have returned to normal before trying to conceive.
In the event of an unplanned pregnancy, you should stop taking inotersen. However, due to Tegsedi’s prolonged activity, your reduced levels of vitamin A may persist. It is not known whether continued supplementation of 3,000 IU of vitamin A per day is harmful to the fetus during the first trimester of pregnancy, but this dose should not be exceeded. You should continue vitamin A supplementation during the second and third trimesters of pregnancy if vitamin A levels have not yet returned to normal, as there is an increased risk of vitamin A deficiency during the third trimester.
Liver transplant rejection
Talk to your doctor before using TEGSEDI if you have had a liver transplant. Cases of liver transplant rejection have been reported in patients treated with Tegsedi. Your doctor will check you regularly for this during treatment with Tegsedi.
Children and young people
Tegsedi should not be used in children or adolescents under 18 years of age.
Other medicines and Tegsedi
Tell your doctor or pharmacist if you are taking, have recently taken, or might be taking any other medicines. You must tell the doctor if you are already being treated with any of the following:
- Medicines to prevent blood clots or reduce the number of platelets in the blood, e.g. aspirin, heparin, warfarin, clopidogrel, rivaroxaban, and dabigatran.
- Medicines that can change kidney function or damage the kidneys, e.g. sulfonamides (used as antibacterial agents), anilides (used to treat fever, aches, and pain), aldosterone antagonists (used as diuretics ), and natural opium alkaloids and other opioids (used to treat pain).
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult a doctor before using this medicine.
Fertile women
Tegsedi reduces the level of vitamin A in the body. Vitamin A is important for normal fetal development during pregnancy. It is not known whether vitamin A supplementation can compensate for the risk of vitamin A deficiency affecting the unborn child (see “Warnings and precautions” above). If you are a fertile woman, you must use an effective contraceptive method and possible pregnancy must be ruled out before starting treatment with Tegsedi.
Pregnancy
You should not use Tegsedi if you are pregnant unless your doctor has specifically advised you to do so. If you are a fertile woman, you must use an effective method of contraception.
Breast-feeding
Tegsedi can pass into breast milk. You should contact your doctor to determine whether you should either stop breastfeeding or stop treatment with Tegsedi.
Driving ability and use of machinery
The use of Tegsedi has not been shown to affect the ability to drive or use machines.
How to use Tegsedi
Always use this medicine as directed by your doctor. Ask your doctor or pharmacist if you are unsure.
The recommended dose is a dose corresponding to 284 mg of inotersen.
Dose er should be administered once per week. All subsequent doses should be injected once a week, on the same day of the week each week.
Route of administration and method of administration
Tegsedi is only intended for injection under the skin ( subcutaneous use).
Instructions for use
Before using the pre-filled syringe, your doctor or caregiver should show you how to use it correctly. If you or your caregiver have questions, contact the doctor.
Read the instructions for use before you start using the pre-filled syringe and each time you get a new prescription. There may be new information.
If you have used too much Tegsedi
Contact a doctor or pharmacist immediately or go to the nearest emergency department, even if you have no symptoms.
If you have forgotten to use Tegsedi
If you miss a dose of Tegsedi, take the next dose as soon as possible, unless the next scheduled dose is within two days. If the next scheduled dose is within two days, do not administer the missed dose and take the next dose as scheduled.
Do not take a double dose to make up for a missed dose.
If you stop using Tegsedi
Do not stop using Tegsedi unless your doctor tells you to.
If you have further questions about this medicine, contact your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects are
If you notice any of the following serious side effects, stop using Tegsedi and contact your doctor immediately:
- Symptoms that may indicate glomerulonephritis (which means the kidneys are not working properly), such as foamy urine, pink or brown-colored urine, blood in the urine, and urinating less than usual.
- Symptoms that may indicate thrombocytopenia (which means that the blood does not clot), such as unexplained bruising or a rash with small red spots on the skin (called petechiae ), bleeding from cuts on the skin that do not stop or ooze, bleeding from the gums or nose, blood in the urine or stool or bleeding in the whites of the eyes.
Seek immediate help if you have a stiff neck or unusual and severe headaches, as these symptoms may be caused by bleeding in the brain.
Other side effects are
Very common (may affect more than 1 in 10 users)
- Decreased number of red blood cells which can make your skin pale and make you feel weak or short of breath (anemia)
- Headache
- Vomiting or nausea
- Increased body temperature
- Feeling cold or chills
- Pain at the injection site, redness, itching, or bruising
- Swelling of ankles, feet, or fingers (peripheral edema)
Common (may affect up to 1 in 10 users)
- An increase in the number of white blood cells called eosinophils ( eosinophilia )
- Reduced appetite
- Feeling faint or dizzy, especially if you stand up (low blood pressure, hypotension )
- Bruises
- Accumulation of blood in tissue that may resemble severe bruising (hematoma)
- Itching
- Rash
- Kidney damage that leads to poor kidney function or kidney failure
- Changes in blood and urine test results (which may indicate infection or liver or kidney damage)
- Flu-like symptoms, such as high fever, aches, and chills (flu-like illness)
- Swelling or discoloration of the skin at the injection site
Uncommon (may affect up to 1 in 100 users)
- Allergic reaction
How Tegsedi should be stored
Keep this medicine out of sight and reach of children.
Use before the expiry date which is stated on the carton, tray, and pre-filled syringe after EXP/EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2 °C–8 °C).
Do not freeze.
Tegsedi can be stored outside the refrigerator for up to 6 weeks at a maximum of 30 °C. If the medicine is stored outside the refrigerator and not used within 6 weeks, it must be discarded.
Store in the original packaging. Light sensitive.
Do not use this medicine if you notice that the contents are cloudy or contain particles.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
- The active substance is inotersen.
- Each pre-filled syringe contains 284 mg of inotersen.
- Other ingredients are water for injections, sodium hydroxide, and hydrochloric acid.
Appearance and package sizes of the medicine
Tegsedi is a clear, colorless pale yellow solution for injection ( pH 7.5-8.8) ( solution for injection ) in a pre-filled syringe.
Tegsedi is available in pack sizes of either 1 or 4 pre-filled syringes.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Akcea Therapeutics Ireland Ltd
Regus House,
Harcourt Centre, Harcourt Road
Dublin 2, Ireland
Manufacturer
ABF Pharmaceutical Services GmbH
Brunnerstraße 63/18-19
1230 Vienna
Austria