Waylivra - patient leaflet, side effects, dosage

1. What Waylivra is and what it is used for

Waylivra contains the active substance volanesorsen, which helps to treat a condition called familial chylomicronemia syndrome (FCS). FCS is a genetic disease which gives rise to abnormally high levels of fats called triglycerides in the blood. This can lead to inflammation of your pancreas, causing severe pain. Together with a controlled low-fat diet, Waylivra helps to lower the levels of triglycerides in your blood.

Waylivra may be given after you have already received other medicines used to lower the levels of triglycerides in blood without them having much effect.

You will only be given Waylivra if genetic testing has confirmed you have FCS and your risk for pancreatitis is considered very high..

You should continue the very low-fat diet that your doctor has prescribed during treatment with Waylivra.

This medicine is intended for patients aged 18 years and above.

2. What you need to know before you use Waylivra

Do not use Waylivra:

if you are allergic to volanesorsen or any of the other ingredients in this medicine (listed in section 6).

if you have a condition called thrombocytopenia, which means that you have a very low number of platelets in your blood (less than 140 × 109/L). You may notice this if you have an injury which causes bleeding and it takes a long time to stop (more than 5–6 minutes for a skin scratch). Your doctor will test for this before treatment with this medicine is started. You may not know that you have this condition until this point, or what might have caused it.

If any of the above apply to you, or you are not sure, talk to your doctor, nurse or pharmacist before using Waylivra.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Waylivra if you have or have had any of the following medical problems:

Very high triglyceride levels which are not due to FCS.

A low number of platelets, a type of cell in your blood that clump together to help it clot (thrombocytopenia); your doctor will do a blood test before you start using this medicine to check the number of platelets in your blood.

Any liver or kidney problems.

Blood tests

Your doctor will do a blood test before you start using this medicine to check the number of platelets, and then at regular intervals once you have started using Waylivra to check on platelet levels.

You should see your doctor immediately if you have any signs of low platelet levels, such as unusual or prolonged bleeding, patches of red appearing on the skin (called petechiae), unexplained bruising, bleeding which will not stop, or nosebleeds, or if you get neck stiffness or a severe headache.

Your doctor may also do a blood test every 3 months to check for signs of damage to your liver. You should see your doctor immediately if you have any signs of liver damage, such as yellowing of your skin and eyeballs, pain or swelling in your abdomen, feeling or being sick, confusion or a general feeling of being unwell.

If necessary, your doctor may change how often you use this medicine, or may stop it for a period. It may be necessary to consult a doctor specialising in blood disorders to determine whether you should continue treatment with Waylivra or not.

Urine tests

Your doctor may do a urine and/or blood test every 3 months to check for signs of damage to your kidneys. You should see your doctor immediately if you have any signs of kidney damage, such as swelling in your ankles, legs and feet, passing smaller amounts of urine than usual, shortness of breath, feeling sick, confusion or feeling very tired or drowsy.

Diet

Before starting this medicine, you should be on a diet designed to help lower triglyceride levels in your blood.

It is important that you maintain this triglyceride-lowering diet whilst using Waylivra.

Children and adolescents

Do not use Waylivra if you are under 18 years old. Waylivra has not been studied in patients under 18 years old.

Other medicines and Waylivra

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is important to tell your doctor if you are already being treated with any of the following: Medicines to prevent blood clots, e.g., acetylsalicylic acid, dipyridamol or warfarin.

Other medicines that may change how your blood clots, including non-steroidal anti-inflammatory medicines like ibuprofen, medicines used to prevent heart attacks and strokes such as clopidogrel, ticagrelor and prasugrel, antibiotics such as penicillin, medicines such as ranitidine (used to reduce stomach acid), and quinine (used to treat malaria).

Medicines that may cause problems with your liver, such as paracetamol.

Waylivra with alcohol

The effect of using Waylivra with alcohol is not known. You should avoid alcohol during treatment with this medicine due to risk of liver issues.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. It is preferable to avoid the use of Waylivra during pregnancy.

It is not known if Waylivra passes into breast milk. It is recommended that you discuss breast-feeding with your doctor to see what is best for you and your child.

Driving and using machines

Waylivra is not likely to affect your ability to drive or use machines.

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

3. How to use Waylivra

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Before you are given this medicine other causes of high levels of triglycerides, such as diabetes or problems with your thyroid, will be ruled out by your doctor.

Your doctor will tell you how often you should take this medicine. They may change how often you use it, or may stop it for a period or permanently, depending on the results of your blood and urine tests or occurrence of side effects.

You or your caregiver will be trained on how to use Waylivra according to the instructions in this leaflet. Waylivra should be injected under your skin in the way the doctor, nurse or pharmacist has shown you, and you should make sure you inject all of the liquid in the syringe. Each single-use, prefilled syringe of this medicine gives you a dose of 285 mg in 1.5 ml.

Before using this medicine, it is important that you read, understand, and closely follow the instructions for use.

Instructions for use are provided at the end of this leaflet.

If you use more Waylivra than you should

If you inject too much Waylivra, contact your doctor or pharmacist, or attend a hospital emergency department immediately, even if there are no symptoms.

If you forget to use Waylivra

If you miss a dose, contact your doctor to ask when to take your next dose. If a dose is missed and noticed within 48 hours, you should give the missed dose as soon as possible. If not noticed within 48 hours, then the missed dose should be skipped and the next planned injection given. Do not inject more than one dose within 2 days.

If you stop using Waylivra

Do not stop using Waylivra unless you have discussed stopping your medicine with your doctor.

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

4. Possible side effects

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

Serious side effects

If you get any of the following side effects, contact your doctor immediately:

• – Symptoms that could indicate low counts of platelets in your blood (platelets are cells important for blood clotting). You should see your doctor immediately if you have any signs of low platelet levels, such as unusual or prolonged bleeding, patches of red appearing on the skin (called petechiae), unexplained bruising, bleeding which will not stop, or nosebleeds, or if you get neck stiffness or a severe headache.

Other side effects

Very common (may affect more than 1 in 10 people)

–

• – Injection site reactions (pain, redness, heat, dryness, swelling, itching, tingling, hardening, pimpling, bruising, bleeding, numbness, change in colour or a burning feeling at the injection site). You can reduce the likelihood of having injection site reaction if you wait for Waylivra to reach room temperature before injecting, and by applying ice to the injection site after injecting.

Common (may affect up to 1 in 10 people)

• – Blood tests showing unusually high or low levels of white blood cells in your blood

• – Easy or excessive bruising, or bruising without an obvious cause

• – Bleeding under the skin that appears as a rash, bleeding from the gums or mouth, blood in the urine or stools, nosebleed, or unusually heavy menstrual period

• – An allergic reaction, the symptoms of which include skin rash, joint stiffness or fever

• – Blood or protein in the urine

• – Changes to the results of some blood tests, including:

o an increase in the level of some constituents in your blood: creatinine, urea, transaminases, liver enzymes

o an increase in blood clotting time

o a fall in levels of haemoglobin in your blood

o a fall in the rate of blood passing through the kidneys

• – Diabetes, the symptoms of which include increased thirst, frequent need to pass urine (particularly at night), extreme hunger, severe tiredness, and unexplained weight loss

• – Difficulty sleeping

• – Headaches, numbness, tingling or pins and needles, feeling faint or fainting, dizziness or shaking

• – Visual disturbances, such as flashing lights or brief, temporary blindness in one eye, bleeding under the surface of the eye, or blurred vision

• – High blood pressure

• – Hot flush, increased sweating, night sweats, chills, feeling hot, pain, flu-like illness or a general feeling of being unwell

• – Cough, difficulty breathing, a blocked nose, swelling of the throat, wheezing

• – Feeling or being sick, dry mouth, diarrhoea, swelling of the neck, face or gums, stomach pain

or swelling, indigestion

• – Skin redness, rash, pimples, thickening or scarring, or itchiness of the skin known as ‘hives’ (urticaria)

• – Muscle pain, pain in the hands or feet, joint pain or stiffness, back pain, neck pain, jaw pain, muscle spasms, or other body pains –

• – Severe tiredness (fatigue), weakness or lack of energy, fluid retention, chest pain unrelated to the heart

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Waylivra

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 and syringe label after ‘EXP’. Please note that the expiry date refers to the last day of that month.

Store in a refrigerator (2 ° – 8 °C).

Store in the original carton to protect from light.

Waylivra can be kept at room temperature (up to 30 °C) in the original carton for up to 6 weeks after removing from the refrigerator. During this time this medicine may be kept at either room temperature or put back into the refrigerator, as needed. Record the date you first remove the pack from the refrigerator on the outer carton in the space indicated. If you do not use it within 6 weeks after first removing from the refrigerator, discard the medicine. If the expiry date on the syringe label has passed during the 6 week period at room temperature, do not use the syringe and discard it.

Do not use this medicine if the solution is cloudy or contains particles; it should be clear and colourless to slightly yellow.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Waylivra contains

The active substance is volanesorsen. Each ml contains 200 mg volanesorsen sodium, equivalent to 190 mg volanesorsen. Each single-dose pre-filled syringe contains 285 mg of volanesorsen in 1.5 ml solution.

The other ingredients are water for injections, sodium hydroxide and hydrochloric acid (to adjust acidity level, see section 2 under ‘Sodium’).

What Waylivra looks like and contents of the pack

Waylivra is provided in a carton as a single-dose syringe with needle and needle cap, pre-filled with a clear, colourless to pale yellow solution. It is filled to deliver 1.5 ml of solution upon full depression of the syringe’s plunger.

It is available as either a carton containing 1 pre-filled syringe, or as a multipack of 4 (4 packs of 1-pack cartons) pre-filled syringes.

Marketing Authorisation Holder

Akcea Therapeutics Ireland Ltd.

Regus House, Harcourt Centre,

Harcourt Road, Dublin 2 Ireland

Manufacturer

Almac Pharma Services Ireland Ltd.

Finnabair Industrial Estate

Dundalk

Co. Louth

Ireland

This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:.

Instructions for use

Waylivra is an injection given under the skin with a single-use, disposable, pre-filled syringe.

Do not use Waylivra until you completely understand the procedure described below. If you have any questions about how to use Waylivra, please contact your doctor or pharmacist.

Pre-filled syringe components

Get ready to inject

• 1. Wash hands and gather supplies

Wash your hands thoroughly with soap (for at least 3 minutes) and dry them well. Place the following items on a clean, flat surface in a well-lit area (Figure A).

Figure A

• 2. Allow the injection to reach to room temperature

If the syringe was in the refrigerator, allow the prefilled syringe to reach room temperature by

removing it from the refrigerator at least 30 minutes before the injection.

Injection with cold liquid may cause injection site reactions such as pain, redness, or swelling.

Do not warm syringe in any other way, such as by microwave or warm water.

Figure B

• 3. Check the expiry date

Check the expiry date on the carton.

The expiry date on the package refers to the life of the medicine when refrigerated.

The date you first remove the pack from the refrigerator should be recorded on the outer carton in the space indicated.

Do not use Waylivra if the expiry date has passed or if it was stored for longer than 6 weeks at room temperature. Call your doctor or pharmacist to get a new supply.

• 4. Remove the syringe and inspect the medicine

Open the carton and remove the syringe by grasping the syringe barrel and pulling it straight out (Figure C).

Figure C

Look at the liquid in the syringe. The medicine should be clear to slightly yellow in colour. It is normal to see a large air bubble (Figure D).

Do not try to remove the air bubble before injecting. Injecting the solution with the air bubble is harmless.

Do not use the pre-filled syringe if the liquid is cloudy or has floating particles.

Figure D

• 5. Choose an injection site

If self-injecting:

Stomach – Stomach area as shown, except for 2 inches around the belly button.

7. Remove needle cap

Remove the needle cap by holding the barrel of the syringe with the needle pointing away from you and pulling the needle cap straight off (Figure H).

You may see a drop of liquid at the tip of the needle. This is normal.

Do not hold the plunger rod or the plunger head while removing the needle cap.

Do not use the pre-filled syringe if the needle appears damaged.

Do not use the pre-filled syringe if it is dropped with the needle cap removed.

Insert the needle into the injection site with a quick, firm motion without touching the plunger head. The needle should be inserted at a 45 degree angle to the skin surface (Figure J).

• 10. Inject Waylivra

Inject the liquid by holding the syringe with your thumb on the plunger, and slowly push the plunger down as far as it will go, until the syringe is completely empty (Figure K and L).

• 11. Remove Needle

Remove the needle from the injection site by pulling out at the same angle it was inserted (Figure M).

After the Injection

• 12. Dispose of the Used Syringe into a Sharps Container

Immediately after the injection, dispose of the used syringe as instructed by your healthcare professional, usually into a sharps disposal container (Figure N) by following these steps.

Throw away the needle cap after injecting.

Do not recap the syringe.

If you do not have a sharps disposal container, you may use a household container that is:

• Made of heavy-duty plastic,
• Capable of being closed with a tight-fitting, Puncture-resistant lid, without sharps being able to come out,
• Upright and stable during use,
• Leak-resistant,
• Properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for proper disposal of the sharps container. There may be special local laws regarding how you should throw away used needles and syringes. Ask your pharmacist or see your local public health government website (where available) for more details on how you should dispose of sharps in your location.

Do not dispose of your used sharps disposal container in your household waste.

Do not recycle your used sharps disposal container.

Always keep your sharps container away from children and pets.

• 13. Treat the Injection Site