InfoCons Consumer Protection informs you – Onpattro – Package Leaflet

Before anything else

Read all of this leaflet carefully before you are given 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 or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

ℹ️ 1. What Onpattro is and what it is used for

The active substance in Onpattro is patisiran.

Onpattro is a medicine that treats an illness which runs in families called heredi tary transthyretin -mediated amyloidosis (hATTR amyloidosis ). hATTR amyloidosis is caused by problems with a protein in the body called ‘transthyretin’ (TTR).

• This protein is made mostly in the liver and carries vitamin A and other substances around the body.
• In people with this illness, abnormally shaped TTR proteins clump together to make deposits called ‘amyloid’.
• Amyloid can build up around the nerves, heart, and other places in the body, preventing them from working normally. This causes the symptoms of the illness.

Onpattro works by lowering the amount of TTR protein that the liver makes.

• This means there is less TTR protein in the blood that can form amyloid.
• This can help to reduce the effects of this illness.

Onpattro is used in adults o nly.

⚠️ 2. What you need to know before you are given Onpattro

You must not be given Onpattro

• if you have ever had a severe allergic reaction to patisiran, or any of the other ingredients of this medicine (listed in section 6). If you are not sure, talk t o your doctor or nurse before you are given Onpattro.

27 Warnings and precautions Infusion -related reactions Onpattro is given as a drip into a vein (called an ‘intravenous infusion’). Reactions to this infusion may happen during treatment with Onpattro. Before each infusion you will be given medicines that help to lower the chance of infusion -related reactions (see “Medicines given during treatment with Onpattro” in section 3).

Tell your doctor or nurse straight away if you get any signs of an infusion -related reaction. These signs are listed at the beginning of section 4.

If you have an infusion -related reaction, your doctor or nurse may slow down or stop your infusion, and you may need to take other medicines to control the symptoms. When the se reactions stop, or get better, your doctor or nurse may decide to start the infusion again.

Vitamin A deficiency Treatment with Onpattro lowers the amount of vitamin A in your blood. Your doctor will measure your vitamin A levels . If your vitamin A le vels are low, your doctor will wait until your vitamin A levels have returned to normal and any symptoms due to vitamin A deficiency have resolved before you start treatment with Onpattro. . Symptoms of vitamin A deficiency may include:

• Decrease in night vi sion, dry eyes, poor vision, hazy or cloudy vision If you have problems with your vision or any other eye problems whilst using Onpattro, you should talk to your doctor. Your doctor may refer you to an eye specialist for a check -up if it is necessary.

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

Both too high and too low levels of vitamin A can harm the development of your unborn child.

Therefore, women of child -bearing age should not be pregnant when star ting treatment with Onpattro and should practi se effective contraception (see section “Pregnancy, breast -feeding and contraception” below).

Tell your doctor if you are planning to become pregnant. Your doctor may tell you to stop taking Onpattro. Your doc tor will ensure that your vitamin A levels have returned to normal before you try to become pregnant.

Tell your doctor if you have an unplanned pregnancy. Your doctor may tell you to stop taking Onpattro. During the first 3 months of your pregnancy, your doctor may tell you to stop your vitamin A supplement. During the last 6 months of your pregnancy you should resume vitamin A supplementation if the vitamin A levels in your blood have not yet returned to normal, because of an increased ris k of vitamin A deficiency during the last 3 months of your pregnancy.

Children and adolescents

Onpattro is not recommended in children and adolescents under 18 years of age.

Other medicines and Onpattro

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. It is important to tell your doctor or nurse if you are taking any of the following medicines as your doctor may need to change the dose:

• Bupropion, a medicine used to treat depression or to help you to st op smoking
• Efavirenz, a medicine used to treat HIV infection and AIDS 28 Pregnancy, breast -feeding and contraception If you are pregnant or breast -feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before starting this medicine.

Women of child -bearing age Onpattro will reduce the level of vitamin A in your blood, which is important for normal development of your unborn child. If you are a woman of child -bearing age, you should practi se effective contraception during treatment with Onpattro. Talk to your doctor or nurse about suitable methods of contraception. Pregnancy should be excluded before starting treatment with Onpattro.

Pregnancy

You should not use Onpattro if you are pregnant, unless advised by your doctor. If you are of child – bearing age and intend to use Onpattro, you should practise effective contraception.

Breast -feeding Ingredients of Onpattro may pass into breast milk. Talk to your doctor about stopping breast -feeding or treatment with Onpattro.

Driving and using machines

Onpattro is believed to have no or negligible influence on the ability to drive or use machines. Your doctor will tell you whether your condition allows you to drive vehicles and use machines safely.

Onpattro contains sodium

This medicine contains 3.99 milligrams (mg) of sodium (main component of cooking/table salt) per millilitre (mL). This is 0.2% of the recommended maximum daily dietary intake of sodium for an adult.

💊 3. How Onpattro is g iven

How much Onpattro is given

• Your doctor will work out how much Onpattro to give you – this will depend on your body weight.
• The usual dose of Onpattro is 300 micrograms per kilogram (kg) of body weight given once every 3 weeks .

How Onpattro is given

• Onpattro will be given to you by a doctor or nurse.
• It is given as a drip into a vein (‘intravenous infusion’) usually over about 80 minutes.

If you do not have problems with your infusions in the clinic, your doctor may talk with you about a healt hcare professional giving you your infusions at home.

Medicines given during treatment with Onpattro About 60 minutes b efore each infusion of Onpattro, you will be given medicines that help to lower the risk of infusion -related reactions (see section 4). These include anti -histamines, a corticosteroid (a medicine that suppresses inflammation), and a pain reliever.

29 How long to use Onpattro Your doctor will tell you how long you need to receive Onpattro. Do not stop treatment with Onpattro unless your doctor tells you to.

If you are given more Onpattro than you should receive

This medicine will be given to you by your doctor or nurse. In the unlikely event that you are given too much (an overdose) your doctor or nurse will check you for side effects.

If you miss your dose of Onpattro If you miss an appointment to have Onpattro, ask your doctor or nurse when to book your next treatment.

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

❗ 4. Possible side effects

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

Infusion -related reactions Infusion -related reactions are very common (may affect more than 1 in 10 people).

Tell your doctor or nurse straight away if you get any of the following signs of an infusion -related reaction during treatment. The infusion may need to be slowed down or stopped, and you may need to take other medicines to manage the reaction.

• Stomach pain
• Feeling sick (nausea)
• Body aches or pain, including pain in the back, neck, or joints
• Headache
• Feeling tired (fatigue)
• Chills
• Dizziness
• Cough, feeling short of breath, or other breathing problems
• Reddening of the face or body (flushing), warm skin, rash or itching
• Chest discomfort or chest pain
• Rapid heart rate
• Low or high blood pressure; some patients have fainted during the infusion due to low blood pressure
• Pain, redness, burning sensation, or s welling at or near the infusion site
• Swelling of the face
• Changes in the sound or tone of your voice (hoarseness)

Other side effects

Tell your doctor or nurse if you notice any of the following side effects:

Very common: may affect more than 1 in 10 peo ple

• Swelling of the arms or legs (peripheral oedema)

Common: may affect up to 1 in 10 people

• Pain in the joints (arthralgia)
• Muscle spasms 30 • Indigestion (dyspepsia)
• Shortness of breath (dyspnoea)
• Redness of the skin (erythema)
• Feeling dizzy or faint (vertigo)
• Stuffy or runny nose (rhinitis)
• Irritation or infection of the airways (sinusitis, bronchitis)

Uncommon: may occur in up to 1 in 100 infusions

• Leakage of the medicine into the surrounding tissue at the site of infusion, which may cause swelling or redness Tell your doctor or nurse if you notice any of the side effects listed above.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. Yo u can also report side effects directly via the national reporting system listed in Appendix V . By reporting side effects you can help provide mor e information on the safety of this medicine.

🌡️ 5. How to store Onpattro

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 carton after ‘EXP’. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C). Do not freeze.

If refrigeration is not available, Onpattro can be stored at room temperature (up to 25°C) for up to 14 days.

Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will throw away any medicines that are no longer being used. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What Onpattro contains

• The active substance is pa tisiran.
• Each mL contains patisiran sodium equivalent to 2 mg patisiran.
• Each vial contains patisiran sodium equivalent to 10 mg patisiran.
• The other ingredients are DLin -MC3 -DMA ((6Z,9Z,28Z,31Z) -heptatriaconta -6,9,28,31 -tetraen -19-yl-4- (dimethylamino) butanoate), PEG 2000-C-DMG (α – (3’-{[1,2 -di(myristyloxy)propanoxy]carbonylamino}propyl) -ω-methoxy, polyoxyethylene), DSPC (1,2-distearoyl -sn-glycero -3-phosphocholine), cholesterol, disodium hydrogen phosphate, heptahydrate, potassium dihydrogen phosphate, anh ydrous, sodium

chloride, and water for injections (see “Onpattro contains sodium” in section 2).

What Onpattro looks like and contents of the pack

• Onpattro is a white to off -white, opalescent, homogeneous concentrate for solution for infusion (sterile concentrate) .

31 • Onpattro is supplied in cartons containing one vial each.

Marketing Authorisation Holder and Manufacturer

Alnylam Netherlands B.V.

Antonio Vivaldistraat 150 1083 HP Amsterdam Netherlands For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Alnylam Netherlands B.V.

Tél/Tel: 0800 81 443 (+32 234 208 71) [email protected] Luxembourg/Luxemburg Alnylam Netherlands B.V.

Tél/Tel: 80085235 (+352 203 014 48) [email protected] България Genesis Pharma Bulgaria EOOD Teл.: +359 2 969 3227 [email protected] Lietuva Medison Pharma Lithuania UAB Tel: +370 37 213824 medinfo.lithuania@m edisonpharma .com Česká republika Medison Pharma s.r.o.

Tel: +420 221 343 336 medinfo .czechia @medisonpharma .com Magyarország Medison Pharma Hungary Kft Tel.: +36 1 293 0955 medinfo.hungary@m edisonpharma .com Danmark Alnylam Sweden AB Tlf.: 433 105 15 (+45 787 453 01) [email protected] Malta Genesis Pharma (Cyprus) Ltd Tel: +357 22765715 [email protected] Deutschland Alnylam Germany GmbH Tel: 0800 2569526 (+49 89 20190112) [email protected] Nederland Alnylam Netherlands B.V.

Tel: 0800 282 0025 (+31 20 369 7861) [email protected] Eesti Medison Pharma Estonia OÜ Tel: +372 679 5085 medinfo.estonia@m edisonpharma .com Norge Alnylam Sweden AB Tlf: 800 544 00 (+472 1405 657) [email protected] Ελλάδα ΓΕΝΕΣΙΣ ΦΑΡΜΑ Α.Ε Τηλ: +30 210 87 71 500 [email protected] Österreich Alnylam Austria GmbH Tel: 0800 070 339 (+43 720 778 072) [email protected] España Alnylam Pharmaceuticals Spain SL Tel: 900810212 (+34 910603753) [email protected] Polska Medison Pharma Sp. z o.o.

Tel.: +48 22 152 49 42 medinfo.poland@ medisonpharma .com France Alnylam France SAS Tél: 0805 542 656 (+33 187650921 ) [email protected] Portugal Alnylam Portugal Tel: 707201512 (+351 21 269 8539) [email protected] Hrvatska Genesis Pharma Adriatic d.o.o Tel: +385 1 5530 011 [email protected] România Genesis Biopharma Romania SRL Tel: +40 21 403 4074 [email protected] Ireland Alnylam Netherlands B.V.

Tel: 1800 924260 (+353 818 882213) [email protected] Slovenija Genesis Biopharma SL d.o.o.

Tel: +386 1 292 70 90 [email protected] Ísland Alnylam Netherlands B.V.

Sími: +31 20 369 7861 [email protected] Slovenská republika Medison Pharma s.r.o.

Tel: +421 2 201 109 65 medinfo.slovakia@ medisonpharma .com Italia Alnylam Italy S.r.l.

Tel: 800 90 25 37 (+39 02 89 73 22 91) [email protected] Suomi/Finland Alnylam Sweden AB Puh/Tel: 0800 417 452 (+358 942 727 020) [email protected] Κύπρος Genesis Pharma (Cyprus) Ltd Τηλ: +357 22765715 [email protected] Sverige Alnylam Sweden AB Tel: 020109162 (+46 842002641) [email protected] Latvija Medison Pharma Latvia SIA Tel: +371 67 717 847 medinfo.latvia@m edisonpharma .com

This leaflet was last revised in

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu . ——————————————————————————————- —————————–

🩺 Information intended for healthcare professionals only

Required premedication All patients should receive premedication prior to Onpattro administration to reduce the risk of infusion -related reactions (IRRs). Each of the following medicinal products should be given on the day of Onpattro infusion at least 60 minutes prior to the start of infusion:

• Intravenous corticosteroid (dexamethasone 10 mg, or equivalent)
• Oral paracetamol (500 mg)
• Intravenous H1 blocker (diphenhydramine 50 mg, or equivalent)
• Intravenous H2 blocker ( famotidine 20 mg, or equivalent) 33 For premedications not available or not tolerated intravenously, equivalents may be administered orally.

If clinically indicated, the corticosteroid may be tapered in decrements no greater than 2.5 mg to a minimum dose of 5 mg of dexamethasone (intravenous, IV), or equivalent. The patient should receive at least 3 consecutive infusions of Onpattro without experi encing IRRs before each reduction in corticosteroid premedication.

Additional or higher doses of one or more of the premedications may be administered to reduce the risk of IRRs, if needed.

Preparation of the solution for infusion This medicinal product is for single -use only.

Onpattro must be diluted with sodium chloride 9 mg/mL (0.9%) solution prior to intravenous infusion.

The diluted solution for infusion should be prepared by a healthcare professional using aseptic technique as follows:

• Remove Onpa ttro from the refrigerator. Do not shake or vortex.
• Discard vial if it has been frozen.
• Inspect visually for particulate matter and discolouration. Do not use if discolouration or foreign particles are present. Onpattro is a white to off -white, opalescent, homogeneous solution. A white to off -white coating may be observed on the inner surface of the vial, typically at the liquid -headspace interface. Product quality is not impacted by presence of the white to off -white coating.
• Calculate the required volume of Onpattro based on the recommended weight -based dosage.
• Withdraw the entire contents of one or more vials into a single sterile syringe.
• Filter Onpattro through a sterile 0.45 micron polyethersulfone (PES) syringe filter into a sterile container.
• Withdraw the required volume of filtered Onpattro from the sterile container using a sterile syringe.
• Dilute the required volume of filtered Onpattro into an infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for a total volume of 2 00 mL. Use infusion bags that are free of di(2 – ethylhexyl)phthalate (DEHP).
• Gently invert the bag to mix the solution. Do not shake. Do not mix or dilute with other medicinal products.
• Discard any unused portion of Onpattro. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
• Onpattro does not contain preservatives. The diluted solution should be administered immediately after preparation. If not used immediately, store the diluted solution in the infu sion bag at room temperature (up to 30°C) or at 2°C to 8°C for up to 16 hours (including infusion time). Do not freeze.

Administration Onpattro is for intravenous use.

• Onpattro must be diluted prior to intravenous infusion.
• A dedicated line with an infusion set containing a 1.2 micron PES in -line infusion filter must be used. The infusion sets must be free of di(2 -ethylhexyl)phthalate (DEHP).
• The diluted solution of Onpattro should be infused intravenously over approximately 80 minutes at an initial infusion rate of approximately 1 mL/min for the first 15 minutes, followed by an increase to approximately 3 mL/min for the remainder of the infusion. The duration of infusion may be extended in the event of an IRR.
• Onpattro must be administered through a secure and free -flowing venous access line. The infusion site should be monitored for possible infiltration during administration. Suspected extravasation should be managed according to local standard practice for non -vesicants.

34 • The patient should be obser ved during the infusion and, if clinically indicated, following the infusion.

• After completion of the infusion, the intravenous administration set should be flushed with sodium chloride 9 mg/mL (0.9%) solution to ensure that all medicinal product has been administered.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Onpattro (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/18/1320).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.