GIVLAARI 189 mg/mL Injectable Solution

Introduction

Package Leaflet: Information for the User

Givlaari 189 mg/ml Solution for Injection

givosiran

Read all of this leaflet carefully before this medicine is administered to you 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 experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Givlaari and what is it used for
2. What you need to know before you are given Givlaari
3. How to use Givlaari
4. Possible side effects
5. Storage of Givlaari
6. Contents of the pack and other information

1. What is Givlaari and what is it used for

What is Givlaari

Givlaari contains the active substance givosiran.

What Givlaari is used for

Givlaari is used to treat acute hepatic porphyria in adults and adolescents from 12 years of age.

What is acute hepatic porphyria

Acute hepatic porphyria is a rare and inherited disease. It is due to a defect in one of the proteins that make up a molecule called heme produced in the liver. Because there is a problem with one of the proteins that make up heme, the substances used to produce it, namely delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), accumulate. An excess of ALA and PBG can cause nerve damage and lead to crises of pain, nausea, muscle weakness, and changes in mental function. Some people with acute hepatic porphyria may also experience symptoms such as pain and nausea between crises. Long-term complications observed in people with acute hepatic porphyria include hypertension, chronic kidney failure, and liver disease.

How Givlaari works

The medicine works by reducing the amount of an enzyme called "ALAS1", which controls the amount of ALA and PBG produced by the liver. By reducing the amount of ALAS1, the liver produces less ALA and PBG. This may help reduce the effects of the disease.

2. What you need to know before you are given Givlaari

Givlaari must not be given to you:

• if you have ever had a severe allergic reaction to givosiran or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or nurse before you are given Givlaari.

Severe allergic reaction

• Tell your doctor or nurse immediately if you start to experience signs of a severe allergic reaction. The signs are mentioned in "Serious side effects" in section 4.
• If you have a severe allergic reaction, your doctor or nurse will stop using the medicine immediately and you may need to take other medicines to control the symptoms.

Liver problems

Using this medicine may affect your liver. You will have blood tests to check your liver function before starting treatment with Givlaari and these will be repeated periodically during treatment. If these tests show abnormal results, your doctor or nurse will decide whether treatment should be temporarily interrupted or permanently stopped. Abnormalities have been observed in the test results of some patients treated with this medicine, mainly between 3 and 5 months after starting treatment.

Kidney problems

Using this medicine may affect your kidneys, especially if you have already been diagnosed with kidney problems. Your doctor will check that your kidneys are working properly while you are taking this medicine, especially if you already have kidney problems.

Homocysteine level tests

While you are taking this medicine, blood tests may show an increase in homocysteine, a type of amino acid, compared to your homocysteine levels before starting treatment. Your doctor will check your homocysteine levels in the blood before and during treatment. If your homocysteine levels are high, your doctor may give you treatment to reduce homocysteine.

Children

This medicine must not be used in children under 12 years of age because it has not been studied in this age group.

Other medicines and Givlaari

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

When using certain medicines, this medicine may prolong or increase their effect or change their side effects.

Pregnancy

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

Breast-feeding

Animal studies show that this medicine can pass into breast milk. If you are breast-feeding, consult your doctor before using this medicine. Your doctor will help you decide whether to stop breast-feeding or stop treatment with Givlaari after considering the benefit of breast-feeding to your child and the benefit of treatment to you.

Driving and using machines

This medicine is not expected to affect your ability to drive or use machines.

Givlaari contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ml, which is essentially "sodium-free".

3. How to use Givlaari

How much Givlaari is given

Your doctor will decide how much medicine you should be given. The amount will depend on your body weight.

• The recommended dose is 2.5 milligrams per kilogram of body weight
• The medicine will be given to you once a month (every 4 weeks)
• If liver damage is observed in the blood test results, your doctor may interrupt treatment with Givlaari or stop it permanently. Your doctor may consider restarting it at a lower dose.

How to use Givlaari

A doctor or nurse will give you this medicine once a month. It is given by injection under the skin (subcutaneously) in the stomach area (abdominal) or, in some cases, in the arm or thigh. The injection site will be alternated. If the dose is more than 1 ml, more than one vial may be needed and more than one subcutaneous injection may be required.

If you are given too much Givlaari

In the unlikely event that your doctor or nurse gives you too much (overdose), you will be monitored for side effects.

If you miss a dose of Givlaari

If you miss an appointment for an injection, talk to your doctor or nurse as soon as possible.

If you have any other questions about using 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.

Serious side effects

Severe allergic reactions (uncommon: may affect up to 1 in 100 people)

Tell your doctor or nurse immediately if you experience any of the following signs of a severe allergic reaction (anaphylactic reaction); the injection will be stopped and you may need to take other medicines to treat the reaction:

• swelling: mainly of the lips, tongue, or throat, which may make swallowing or breathing difficult
• breathing problems or wheezing
• feeling dizzy or fainting
• rash, hives

• itching

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 people

• Nausea
• Blood tests showing increased transaminases (liver enzymes), which are a sign of possible liver inflammation
• Skin rash, including red, dry, itchy skin, eczema, or hives
• Blood tests showing increased creatinine, a substance that is removed from the body by the kidneys, or decreased glomerular filtration rate (signs of possible kidney damage)
• Redness, pain, itching, or swelling at the injection site (injection site reaction)
• Feeling tired

Common:may affect up to 1 in 10 people

• A type of allergic reaction (hypersensitivity): with symptoms such as hives, skin rash, eye, mouth, or face swelling, difficulty breathing, itching.
• Pancreatitis (inflammation of the pancreas).
• Blood tests showing increased homocysteine (a type of amino acid).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the contact information for your country. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Givlaari

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 is the last day of the month stated.

This medicine is for single use only. Once the product has been opened, use it immediately.

Do not store above 25°C.

Keep the vial in the outer packaging to protect it from light.

Medicines should not be disposed of via wastewater or household waste. Your doctor or nurse will dispose of any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

What Givlaari contains

• The active substance is givosiran.
• Each ml contains givosiran sodium equivalent to 189 mg of givosiran.
• The other ingredients are sodium hydroxide, phosphoric acid, and water for injections. See section 2 "Givlaari contains sodium".

Appearance and packaging

This medicine is a clear, colorless to yellow solution for injection.

Each pack contains one vial of 1 ml solution for injection.

Marketing authorisation holder and manufacturer

Alnylam Netherlands B.V.

Antonio Vivaldistraat 150

1083 HP Amsterdam

Netherlands

For further information about this medicine, contact the local representative of the marketing authorisation holder:

Date of last revision of this leaflet 11/2024

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

Instructions for use

For subcutaneous use only.

• Gather the materials that are not included in the pack and are necessary for administration; these include a sterile syringe (1 ml or 3 ml) with a 21 G (or larger) needle, a 25 G or 27 G needle, and a sharps container.
• Calculate the volume of Givlaari needed based on the recommended dose according to weight. If the dose is more than 1 ml, more than one vial may be needed and more than one subcutaneous injection may be required. The maximum acceptable volume for each individual injection is 1.5 ml.
• To withdraw Givlaari, hold the vial upright or tilt it slightly and ensure that the flat edge of the needle is pointing downwards.
• Withdraw the indicated injection volume with the 21 G (or larger) needle.
• Divide doses that require a volume greater than 1.5 ml into equal parts in multiple syringes; each injection should contain approximately the same volume.
• Point the needle and syringe upwards and gently tap the syringe to move any air bubbles to the top. Once the air bubbles are at the top, gently push the plunger to expel the air bubbles from the syringe. Check that the amount of medicine in the syringe is still correct.
• Once the dose is prepared and in the administration syringe, replace the 21 G (or larger) needle with a 25 G or 27 G needle.
• Note: Do not put the medicine into the 25 G or 27 G needle.
• The injection can be given in the abdomen or, if necessary, in the back or side of the arm or in the thighs. Consider alternating injection sites. The medicine must not be given in scar tissue or on red, inflamed, or swollen surfaces.
• Note: When giving subcutaneous injections in the abdomen, avoid a circle of 5.0 cm in diameter around the navel.
• Clean the surface where you want to give the injection with an alcohol swab and wait for the surface to dry completely.
• Make sure to use the correct injection technique. Do not give the injection into a vein or muscle.

• Pinch and lift the skin at the selected injection site. Insert the needle at a right angle (90 degrees) to give the injection just under the skin. In patients with little subcutaneous tissue or if the needle length is more than 2.5 cm, the needle should be inserted at a 45-degree angle.
• Do not press the plunger while the needle is penetrating the skin. Once the needle is inserted into the skin, release the pinched skin and administer the dose slowly and steadily. After the medicine has been given, count to at least 5 before removing the needle from the skin. Gently press a cotton ball or swab over the injection site as needed. Do not replace the needle cap.
• Note: Do not aspirate after inserting the needle to avoid damaging tissue, causing hematomas, and bruising.
• If more than one injection is needed for a single dose of Givlaari, the injection sites should be at least 2 cm apart from previous injection sites.
• Use the vial only once. After injecting the dose, discard any unused medicine in the vial according to local regulations.
• Use syringes, transfer needles, and injection needles only once. Discard used needles and syringes according to local regulations.