Onpattro

Package leaflet: Information for the patient

Onpattro 2 mg/mL concentrate for solution for infusion

patisiran
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Onpattro is and what it is used for

The active substance in Onpattro is patisiran.
Onpattro is a medicine used to treat a disease that is passed down from one generation to the next, called hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis).
hATTR amyloidosis is caused by problems with a protein found in the body called "transthyretin" (TTR).

• This is a protein produced mainly in the liver that transports vitamin A and other substances throughout the body.
• In people affected by this disease, abnormal TTR proteins clump together forming deposits known as "amyloid".
• Amyloid can build up in the nerves, heart and other parts of the body, preventing them from functioning properly. This causes the symptoms characteristic of the disease.

Onpattro works by reducing the amount of TTR protein produced by the liver.

• This leads to lower levels of TTR protein in the blood available to form amyloid.
• This effect may help reduce the effects of this disease.

Onpattro is used only in adults.

2. What you need to know before taking Onpattro

Do not take Onpattro

• if you have previously had a severe allergic reaction to patisiran or to any of the other ingredients of this medicine (listed in section 6). If you are unsure, consult your doctor or nurse before taking Onpattro.

Warnings and precautions
Infusion-related reactions
Onpattro is administered by intravenous infusion into a vein (called “intravenous infusion”).
During treatment with Onpattro, infusion-related reactions may occur. Before each infusion, you will be given medications to help reduce the risk of experiencing infusion-related reactions (see “Medications administered during Onpattro treatment” in section 3).
Immediately inform your doctor or nurse if you experience any signs of an infusion-related reaction. These signs are listed at the beginning of section 4.
If you experience an infusion-related reaction, your doctor or nurse may slow down or stop the infusion, and you may need to take additional medications to control symptoms. Once these reactions have resolved or improved, your doctor or nurse may decide to restart the infusion.
Vitamin A deficiency
Treatment with Onpattro reduces the amount of vitamin A in the blood. Your doctor will monitor your vitamin A levels. If your vitamin A levels are low, your doctor will wait until they return to normal and any symptoms due to vitamin A deficiency have resolved before starting treatment with Onpattro. Symptoms of vitamin A deficiency may include:

• Reduced night vision, dry eyes, poor vision, blurred or hazy vision.

If you experience vision problems or other eye issues while using Onpattro, consult your doctor.
If necessary, your doctor may refer you to an ophthalmologist for an examination.
Your doctor will instruct you to take a daily vitamin A supplement during treatment with Onpattro.
Both excessively high and low levels of vitamin A can harm fetal development. Therefore, women of childbearing potential must not be pregnant when starting treatment with Onpattro and must use effective contraceptive methods (see the section “Pregnancy, breastfeeding and contraception” below).
Inform your doctor if you are planning a pregnancy. Your doctor may instruct you to discontinue Onpattro. Your doctor will ensure that your vitamin A levels have returned to normal before attempting pregnancy.
Inform your doctor if you experience an unplanned pregnancy. Your doctor may instruct you to discontinue Onpattro. During the first 3 months of pregnancy, your doctor may advise you to stop taking vitamin A supplements. During the last 6 months of pregnancy, you must resume vitamin A supplementation if your blood vitamin A levels have not yet returned to normal, due to an increased risk of vitamin A deficiency in the last 3 months of pregnancy.
Children and adolescents
Onpattro is not recommended for children and adolescents under 18 years of age.
Other medicines and Onpattro
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines. It is important that you inform your doctor or nurse if you are taking any of the following medicines, as your doctor may need to adjust their dosage:

• Bupropion, a medicine used to treat depression or to help quit smoking
• Efavirenz, a medicine used to treat HIV infection and AIDS

Pregnancy, breastfeeding and contraception
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, ask your doctor for advice before taking this medicine.
Women of childbearing potential
Onpattro will reduce vitamin A levels in the blood, which is important for normal fetal development. If you are a woman of childbearing potential, you must use an effective contraceptive method during treatment with Onpattro. Discuss appropriate contraceptive methods with your doctor or nurse. Pregnancy must be ruled out before starting treatment with Onpattro.
Pregnancy
You must not take Onpattro if you are pregnant, unless advised by your doctor. If you are of childbearing potential and intend to use Onpattro, you must use an effective contraceptive method.
Breastfeeding
Components of Onpattro may pass into breast milk. Consult your doctor regarding whether to discontinue breastfeeding or Onpattro treatment.
Driving and using machines
Onpattro does not affect or has a negligible effect on the ability to drive vehicles or operate machinery. Your doctor will advise you whether your condition allows you to drive and use machinery safely.
Onpattro contains sodium
This medicine contains 3.99 milligrams (mg) of sodium (a main component of table salt) per milliliter (mL). This amount corresponds to 0.2% of the maximum daily recommended dietary intake of sodium for an adult.

3. How to take Onpattro

What dose of Onpattro will be given

• Your doctor will determine the dose of Onpattro you will receive based on your body weight.
• The usual dose of Onpattro is 300 micrograms per kilogram (kg) of body weight administered once every 3 weeks.

How to take Onpattro

• Onpattro will be administered to you by a doctor or nurse.
• It is given by intravenous infusion (into a vein) over approximately 80 minutes.

If you do not experience problems with infusions at the clinic, your doctor may discuss the possibility of receiving infusions at home administered by a healthcare professional.

Medications administered during Onpattro treatment

Approximately 60 minutes before each Onpattro infusion, you will be given medications to help reduce the risk of infusion-related reactions (see section 4). These include antihistamines, a corticosteroid (a medicine that suppresses inflammation), and a pain reliever.

How long to use Onpattro

Your doctor will inform you how long you should continue taking Onpattro. Do not stop treatment with Onpattro unless instructed by your doctor.

If you receive more Onpattro than you should

This medicine will be administered by your doctor or nurse. In the unlikely event that you receive an excessive amount (overdose), the doctor or nurse will monitor you for any potential adverse effects.

If you miss a dose of Onpattro

If you miss an appointment for Onpattro administration, contact your doctor or nurse to schedule your next treatment.

If you have any questions about the use of this medicine, consult 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 occur in more than 1 in 10 people).
Inform your doctor or nurse immediately if you experience any of the following signs of an infusion-related reaction during treatment. It may be necessary to slow down or stop the infusion, and you may need to take other medicines to manage the reaction.

• Stomach pain
• Feeling unwell (nausea)
• General discomfort and body pain, including back, neck or joint pain
• Headache
• Feeling tired (fatigue)
• Chills
• Dizziness
• Cough, shortness of breath or other breathing problems
• Redness of the face or body (flushing), warm skin, skin rash or itching
• Chest discomfort or chest pain
• Rapid heartbeat
• Low or high blood pressure; some patients have fainted during infusion due to low blood pressure
• Pain, redness, burning sensation or swelling at or near the infusion site
• Facial swelling
• Changes in voice sound or tone (hoarseness)

Other side effects
Inform your doctor or nurse if you notice any of the following side effects:
Very common: may occur in more than 1 in 10 people

• Swelling of arms or legs (peripheral oedema)

Common: may occur in up to 1 in 10 people

• Joint pain (arthralgia)
• Muscle spasms
• Indigestion (dyspepsia)
• Shortness of breath (dyspnoea)
• Skin redness (erythema)
• Feeling dizzy or lightheaded (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 infusion site, resulting in swelling or redness

Inform your doctor or nurse if you notice any of the side effects listed above.
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects can help provide more 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 stated on the carton after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
If refrigeration is not possible, Onpattro may be stored at room temperature (up to 25°C) for a maximum of 14 days.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Onpattro contains

• The active substance is patisiran.
• Each mL contains sodium patisiran equivalent to 2 mg of patisiran.
• Each vial contains sodium patisiran equivalent to 10 mg of patisiran.
• The other components are DLin-MC3-DMA ((6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl-4-(dimethylamino)butanoate), PEG-C-DMG (α-(3’-{[1,2-di(myristyloxy)propoxy]carbonylamino}propyl)-ω-methoxy, polyoxyethylene), DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), cholesterol, dibasic sodium phosphate heptahydrate, monobasic anhydrous potassium phosphate, sodium chloride, and water for injections (see “Onpattro contains sodium” in section 2).

Description of the appearance of Onpattro and contents of the pack

• Onpattro is a sterile, homogeneous, opalescent concentrate, white to off-white in colour, for infusion solution (concentrate).
• Onpattro is supplied in cartons containing one vial each.

Marketing Authorisation Holder and Manufacturer
Alnylam Netherlands B.V.
Antonio Vivaldistraat 150
1083 HP Amsterdam
The Netherlands
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Luxembourg/Luxemburg
Alnylam Netherlands B.V. Alnylam Netherlands B.V.
Tél/Tel: 0800 81 443 (+32 234 208 71) Tél/Tel: 80085235 (+352 203 014 48)
[email protected] [email protected]
България Lietuva
Genesis Pharma Bulgaria EOOD Medison Pharma Lithuania UAB
Teл.: +359 2 969 3227 Tel: +370 37 213824
[email protected] [email protected]
Česká republika Magyarország
Medison Pharma s.r.o. Medison Pharma Hungary Kft
Tel: +420 221 343 336 Tel.: +36 1 293 0955
[email protected] [email protected]
Danmark Malta
Alnylam Sweden AB Genesis Pharma (Cyprus) Ltd
Tlf.: 433 105 15 (+45 787 453 01) Tel: +357 22765715
[email protected] [email protected]
Deutschland Nederland
Alnylam Germany GmbH Alnylam Netherlands B.V.
Tel: 0800 2569526 (+49 89 20190112) Tel: 0800 282 0025 (+31 20 369 7861)
[email protected] [email protected]
Eesti Norge
Medison Pharma Estonia OÜ Alnylam Sweden AB
Tel: +372 679 5085 Tlf: 800 544 00 (+472 1405 657)
[email protected] [email protected]
Ελλάδα Österreich
ΓΕΝΕΣΙΣ ΦΑΡΜΑ Α.Ε Alnylam Austria GmbH
Τηλ: +30 210 87 71 500 Tel: 0800 070 339 (+43 720 778 072)
[email protected] [email protected]
España Polska
Alnylam Pharmaceuticals Spain SL Medison Pharma Sp. z o.o.
Tel: 900810212 (+34 910603753) Tel.: +48 22 152 49 42
[email protected] [email protected]
France Portugal
Alnylam France SAS Alnylam Portugal
Tél: 0805 542 656 (+33 187650921) Tel: 707201512 (+351 21 269 8539)
[email protected] [email protected]
Hrvatska România
Genesis Pharma Adriatic d.o.o Genesis Biopharma Romania SRL
Tel: +385 1 5530 011 Tel: +40 21 403 4074
[email protected] [email protected]
Ireland Slovenija
Alnylam Netherlands B.V. Genesis Biopharma SL d.o.o.
Tel: 1800 924260 (+353 818 882213) Tel: +386 1 292 70 90
[email protected] [email protected]
Ísland Slovenská republika
Alnylam Netherlands B.V. Medison Pharma s.r.o.
Sími: +31 20 369 7861 Tel: +421 2 201 109 65
[email protected] [email protected]
Italia Suomi/Finland
Alnylam Italy S.r.l. Alnylam Sweden AB
Tel: 800 90 25 37 (+39 02 89 73 22 91) Puh/Tel: 0800 417 452 (+358 942 727 020)
[email protected] [email protected]
Κύπρος Sverige
Genesis Pharma (Cyprus) Ltd Alnylam Sweden AB
Τηλ: +357 22765715 Tel: 020109162 (+46 842002641)
[email protected] [email protected]
Latvija
Medison Pharma Latvia SIA
Tel: +371 67 717 847
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:

Premedication required
All patients must receive premedication prior to Onpattro administration to reduce the risk of infusion-related reactions (IRR). Each of the following medications must be administered on the day of Onpattro infusion, at least 60 minutes before the start of the 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)

For premedications not available or not tolerated intravenously, oral equivalents may be administered.
If clinically indicated, the corticosteroid dose may be reduced in increments no greater than 2.5 mg to a minimum dose of 5 mg dexamethasone (IV) or equivalent. The patient must receive at least 3 consecutive IV infusions of Onpattro without experiencing IRR before any reduction in corticosteroid premedication.
Additional or higher doses of one or more premedications may be administered as needed to reduce the risk of IRR.

Preparation of infusion solution
This medicinal product is for single use only.
Onpattro must be diluted with 9 mg/mL (0.9%) sodium chloride solution before intravenous infusion. The diluted infusion solution must be prepared by a healthcare professional using the following aseptic technique:

• Remove Onpattro from the refrigerator. Do not shake or invert.
• Discard the vial if it has been frozen.
• Perform a visual inspection for particulate matter and discoloration. Do not use if discoloration or foreign particles are present. Onpattro is a homogeneous, opalescent solution ranging from white to off-white. A white/whitish layer may be observed on the inner surface of the vial, typically at the liquid-headspace interface. The presence of this white/whitish layer does not affect product quality.
• Calculate the required volume of Onpattro according to the recommended dose based on body weight.
• Withdraw the entire contents of one or more vials into a single sterile syringe.
• Filter Onpattro through a sterile syringe filter made of polyethersulfone (PES) with a pore size of 0.45 micron 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 0.9% sodium chloride solution to a total volume of 200 mL. Use infusion bags 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. Unused product and waste materials derived from this medicinal product must be disposed of in accordance with local regulations.
• Onpattro does not contain preservatives. The diluted solution must be administered immediately after preparation. If not used immediately, the diluted solution in the infusion bag may be stored at room temperature (up to 30°C) or between 2°C and 8°C for up to 16 hours (including infusion time). Do not freeze.

Administration
Onpattro is intended for intravenous use.

• Onpattro must be diluted prior to intravenous infusion.
• A dedicated line with an infusion set containing an in-line filter made of polyethersulfone (PES) with a pore size of 1.2 micron must be used. Infusion sets must be free of di(2-ethylhexyl)phthalate (DEHP).
• The diluted Onpattro solution must be infused over approximately 80 minutes, starting 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 infusion duration may be extended in the event of an IRR.
• Onpattro must be administered through a secure and patent intravenous access line. The infusion site must be monitored for possible infiltration during administration. Suspected extravasation should be managed according to local standard practice for non-vesicants.
• The patient must be monitored during the infusion and, if clinically indicated, after the infusion.
• Upon completion of the infusion, the intravenous administration set must be flushed with a bolus of 0.9% sodium chloride solution to ensure complete delivery of the medicinal product.