Onpattro 2 mg/ml concentrado para solucion para perfusion

Patient Information Leaflet

Onpattro 2mg/ml Concentrate for Solution for Infusion

you will

Read this leaflet carefully before you receive this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, ask your doctor or nurse,even if they do not appear in this leaflet. See section 4.

The active ingredient of Onpattro is patisiran.

Onpattro is a medication that treats a hereditary disease called hereditary transthyretin amyloidosis (ATTRh amyloidosis).

Hereditary ATTRh amyloidosis is caused by problems with a protein in the body called “transtiretina” (TTR).

• This protein is formed mainly in the liver and transports vitamin A and other substances throughout the body.
• In people with this disease, abnormal TTR proteins aggregate to form deposits called “amyloid”.
• Amyloid can accumulate around nerves, the heart, and other parts of the body and prevent them from working normally. This causes the symptoms of the disease.

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

• This way, there is less TTR protein in the blood that can form amyloid.
• This may help reduce the effects of the disease.

Onpattro is only used in adults.

You should not receive Onpattro

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

Warnings and precautions

Perfusion-related reactions

Onpattro is administered as an intravenous infusion. During treatment with Onpattro, you may experience reactions to this infusion. Before each infusion, you will be given medications that reduce the likelihood of experiencing perfusion-related reactions (see "Medications administered during treatment with Onpattro" in section 3).

Inform your doctor or nurse immediately if you experience any signs of a perfusion-related reaction. These signs are listed at the beginning of section 4.

If you experience a perfusion-related reaction, your doctor or nurse may slow down the infusion and have you take other medications to control your symptoms. When these reactions subside or improve, your doctor or nurse may decide to resume the infusion.

Vitamin A deficiency

Treatment with Onpattro reduces the amount of vitamin A in your blood. Your doctor will measure your vitamin A levels. If your vitamin A levels are low, your doctor will wait until they return to normal and any symptoms related to vitamin A deficiency have resolved before you start treatment with Onpattro. Symptoms of vitamin A deficiency may include:

• Decreased night vision, dry eyes, blurred vision, or hazy vision.

If you experience vision problems or any other eye issues while using Onpattro, consult your doctor. Your doctor may refer you to an ophthalmologist for an examination if necessary.

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

Very high or very low levels of vitamin A may harm fetal development. Therefore, women of childbearing age should not become pregnant while starting treatment with Onpattro and should use effective contraceptive methods (see the "Pregnancy, breastfeeding, and contraception" section below).

Inform your doctor if you plan to become pregnant. Your doctor may instruct you to stop taking Onpattro. Your doctor will ensure that your vitamin A levels have returned to normal before attempting to become pregnant.

Inform your doctor if you have an unplanned pregnancy.Your doctor may instruct you to stop taking Onpattro. During the first 3 months of pregnancy, your doctor may instruct you to stop taking the vitamin A supplement. During the last 6 months of pregnancy, you should resume taking the vitamin A supplement if your vitamin A levels in your blood have not yet returned to normal, due to a higher risk of vitamin A deficiency during the last 3 months of pregnancy.

Children and adolescents

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

Other medications and Onpattro

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication. It is essential to inform your doctor or nurse if you are taking any of the following medications, as your doctor may need to adjust the dosage:

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

Pregnancy, breastfeeding, and contraception

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

Women of childbearing age

Onpattro will reduce the level of vitamin A in your blood, which is essential for normal fetal development. If you are a woman of childbearing age, you must use an effective contraceptive method during treatment with Onpattro. Consult your doctor or nurse about suitable contraceptive methods. Pregnancy should be excluded before starting treatment with Onpattro.

Pregnancy

Do not use Onpattro if you are pregnant, unless your doctor has instructed you to do so. If you are of childbearing age and plan to use Onpattro, you must use effective contraceptive methods.

Breastfeeding

The components of Onpattro may pass into breast milk. Consult your doctor about stopping breastfeeding or the treatment with Onpattro.

Driving and operating machinery

It is believed thatthe influence ofOnpattro on your ability to drive or operate machinery is negligible or insignificant. Your doctor will tell you if your condition allows you to drive vehicles and use machinery safely.

Onpattro contains sodium

This medication contains 3.99milligrams (mg) of sodium (the main component of table salt/for cooking) per milliliter (ml). This is equivalent to 0.2% of the recommended daily maximum sodium intake for an adult.

How much Onpattro is administered

• Your doctor will calculate how much Onpattro you 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 Onpattro is administered

• Onpattro will be administered by a doctor or nurse.
• It is administered as an intravenous infusion, usually over a period of 80 minutes.

If you do not have any issues with infusions in the clinic, your doctor may discuss the possibility of a healthcare professional administering the infusions at home.

Medications administered during Onpattro treatment

About 60 minutes before each Onpattro infusion, you will be given medications to reduce the risk of infusion-related reactions (see section 4). These include antihistamines, a corticosteroid (a medication that reduces inflammation), and an analgesic.

How long you should use Onpattro

Your doctor will tell you how long you need to receive Onpattro. Do not stop treatment with Onpattro unless the doctor tells you to.

If you receive more Onpattro than you should

This medication will be administered by your doctor or nurse. In the unlikely event that you receive too much (an overdose), your doctor or nurse will check if you have any adverse effects.

If you forget a dose of Onpattro

If you miss a visit to receive Onpattro, ask your doctor or nurse when to schedule the next treatment.

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

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

Perfusion-related reactions

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

Inform your doctor or nurse immediately if you experience any of the following signs of perfusion-related reaction during treatment. It may be necessary to slow down or stop the infusion and you may need to take other medicines to treat the reaction.

• Abdominal pain
• Nausea
• Muscle pain, such as in the back, neck, or joints
• Headache
• Feeling tired (fatigue)
• Chills
• Dizziness
• Cough, shortness of breath, or other breathing problems
• Redness of the face or body (flushing), warmth in the skin, hives, or itching
• Chest discomfort or pain
• Fast heart rate
• Low or high blood pressure, some patients have fainted during the infusion due to hypotension.
• Pain, redness, warmth, or swelling at the infusion site or near it
• Swelling of the face
• Changes in voice or tone (hoarseness)

Other side effects

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

Very common:may affect more than 1 in 10 people

• Swelling of the arms or legs (peripheral edema)

Common:may affect up to 1 in 10 people

• Joint pain (arthralgia)
• Muscle spasms
• Indigestion (dyspepsia)
• Shortness of breath (dyspnea)
• Redness of the skin (erythema)
• Dizziness or fainting (vertigo)
• Stuffy nose or runny nose (rhinitis)
• Irritation or infection of the respiratory tract (sinusitis, bronchitis)

Rare:may affect up to 1 in 100 people

• Leakage of the medicine into the surrounding tissue of the infusion site, which may cause swelling or redness

Inform your doctor or nurse immediately if you notice any of the side effects listed above.

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse,even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theAppendix Vincluded in thenational notification system. By reporting side effects, you can contribute to providing more information on 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 after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Do not freeze.

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

Medicines should not be disposed of through drains or in the trash. Your healthcare professional will dispose of unused medications. This will help protect the environment.

Composition of Onpattro

• The active ingredient is patisiran.
• Each milliliter contains patisiran sodium equivalent to 2 mg of patisiran.
• Each vial contains patisiran sodium equivalent to 10 mg of patisiran.
• The other components are DLin-MC3-DMA ((6Z,9Z,28Z,31Z)‑heptatriaconta‑6,9,28,31‑tetraen-19‑il‑4‑(dimethylamino) butanoate), PEG 2000‑C-DMG (α-(3’‑{[1,2‑di(miristiloxi)propanoxi]carbonilamino}propil)‑ω‑methoxy, polioxyethylene), DSPC (1,2-distearoyl‑sn‑glycero-3-phosphocholine), cholesterol, dihydrogen phosphate of potassium anhydrous, hydrogen heptahydrate disodium phosphate, sodium chloride, and water for injection (see “Onpattro contains sodium” in section 2).

Appearance of Onpattro and contents of the package

• Onpattro is a homogeneous, opalescent white or off-white concentrate for solution for infusion.
• Onpattro is supplied in carton boxes containing one vial each.

Marketing authorization holder and responsible manufacturer

Alnylam Netherlands B.V.

Antonio Vivaldi Straat 150

1083 HP Amsterdam

Netherlands

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet: 05/2024

Other sources of information

Further information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.

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This information is intended for healthcare professionals only:

Premedication required

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

• Corticosteroid intravenous (10 mg of dexamethasone or equivalent)
• Oral paracetamol (500 mg)
• H1 blocker intravenous (50 mg of diphenhydramine or equivalent)
• H2 blocker intravenous (20 mg of famotidine or equivalent)

In case of premedication not available or not tolerated by intravenous route, an equivalent by oral route may be administered.

If clinically indicated, the corticosteroid may be reduced progressively in decrements not exceeding 2.5 mg to a minimum dose of 5 mg of dexamethasone (intravenous, IV) or equivalent. The patient must receive at least 3 consecutive infusions of Onpattro without experiencing IRR before each reduction in corticosteroid premedication.

Additional or higher doses of one or more premedication medications may be administered to reduce the risk of IRR, if necessary.

Preparation of the infusion solution

This medicinal product is for single use only.

Onpattro must be diluted with a solution of 9 mg/ml (0.9%) of sodium chloride before intravenous infusion. The diluted infusion solution must be prepared by a healthcare professional using aseptic technique as follows:

• Remove Onpattro from the refrigerator. Do not agitate or shake.
• Discard the vial if it has frozen.
• Perform a visual inspection to detect particles and coloration. Do not use if there is coloration or particles present. Onpattro is a homogeneous, opalescent white or off-white solution. A white or off-white coating may be observed on the inner surface of the vial, usually at the surface in contact with the liquid and the empty space. The presence of the white or off-white coating does not affect the quality of the product.
• Calculate the required volume of Onpattro based on the recommended dosage according to the patient's weight.
• Extract the entire contents of one or more vials into a single sterile syringe.
• Filtrate Onpattro through a sterile poliethersulfone (PES) filter of 0.45 micrometers into a sterile container.
• Extract the required volume of filtered Onpattro from the sterile container using a sterile syringe.
• Dilute the required volume of filtered Onpattro in an infusion bag containing a solution of 9 mg/ml of sodium chloride (0.9%) to a total volume of 200 ml. Use infusion bags that do not contain di(2-ethylhexyl) phthalate (DEHP).
• Invert the infusion bag gently to mix the solution. Do not agitate. Do not mix or dilute with other medicinal products.
• Discard any unused parts of Onpattro. The disposal of unused medicinal product and all materials that have come into contact with it will be carried out in accordance with local regulations.
• Onpattro does not contain preservatives. The diluted infusion solution must be administered immediately after preparation. If not used immediately, the diluted infusion solution in the infusion bag should be stored at room temperature (up to 30°C) or between 2°C and 8°C for a maximum of 16 hours (including infusion time). Do not freeze.

Administration

Onpattro is administered intravenously.

• Onpattro must be diluted before intravenous infusion.
• A special infusion set with an integrated infusion filter of PES of 1.2 micrometers must be used. Infusion sets must not contain di(2-ethylhexyl) phthalate (DEHP).
• The diluted Onpattro infusion solution must be infused intravenously over a period of 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 case of IRR.
• Onpattro must be administered through a secure and freely flowing venous access site. The infusion site must be monitored for possible infiltration during administration. If infiltration is suspected, standard local practice for non-vesicant substances must be followed.
• The patient must be observed during infusion and, if clinically indicated, after infusion.
• Once infusion is complete, the intravenous administration equipment must be washed with a solution of 9 mg/ml of sodium chloride (0.9%) to ensure that all medicinal product has been administered.