Givlaari 189 mg/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Givlaari 189 mg/ml solution for injection

givosiran

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

Contents of the leaflet

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

1. What Givlaari is and what it is used for

What Givlaari is

Givlaari contains the active substance givosiran.

What Givlaari is used for

Givlaari is used for the treatment of acute hepatic porphyria in adults and adolescents from 12 years of age.

What acute hepatic porphyria is

Acute hepatic porphyria is a rare, inherited disease. It is caused by a defect in one of the proteins that make up a molecule called heme, which is produced in the liver. Due to a problem in one of these proteins, substances used to produce heme—namely aminolevulinic acid (ALA) and porphobilinogen (PBG)—accumulate. Excess ALA and PBG can cause nerve damage and lead to attacks of pain, nausea, muscle weakness, and changes in mental function. Some individuals with acute hepatic porphyria may also experience symptoms such as pain and nausea between attacks. 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 regulates the production of ALA and PBG in 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

Do not take Givlaari:

• if you have ever had a severe allergic reaction to givosiran or to 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

• Inform your doctor or nurse immediately if you start experiencing signs of a severe allergic reaction. The signs are described in “Serious adverse reactions” in section 4.
• If you have a severe allergic reaction, your doctor or nurse will stop the medicine immediately and you may need to take other medicines to control the symptoms.

Liver problems

This medicine may affect the liver. Blood tests will be performed to check your liver function before starting treatment with Givlaari and 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 discontinued. Abnormal test results have been observed in some patients treated with this medicine, mainly between 3 and 5 months after starting treatment.

Kidney problems

This medicine may affect the kidneys, especially if you have already been diagnosed with kidney problems. Your doctor will monitor whether your kidneys are functioning properly while you are taking this medicine, particularly if you already have kidney problems.

Homocysteine level testing

While receiving 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 blood homocysteine levels before and during treatment. If your homocysteine levels are high, your doctor may prescribe a homocysteine-lowering treatment.

Children

This medicine must not be used in children under 12 years of age, as studies with this medicine have not been conducted in this age group.

Other medicines and Givlaari

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

When taking certain medicines, this medicine may prolong or increase their effect or alter their adverse effects.

Pregnancy

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

Breast-feeding

Animal studies have shown that this medicine may pass into breast milk. If you are breast-feeding, consult your doctor before using this medicine. Your doctor will help you decide whether to discontinue breast-feeding or discontinue treatment with Givlaari, taking into account the benefit of breast-feeding for your child and the benefit of treatment for you.

Driving and using machines

The effect of this medicine on the ability to drive and use machines is considered negligible or none.

Givlaari contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ml; that is, essentially “sodium-free”.

3. How to use Givlaari

How much Givlaari is administered

Your doctor will determine the amount of medicine you should receive. The amount will depend on your body weight.

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

How to use Givlaari

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

If you are given too much Givlaari

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

If you miss a dose of Givlaari

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

If you have any further questions about 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 everyone 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 must be stopped and you may need to take other medicines to treat the reaction:

• swelling: mainly in the lips, tongue or throat, which may make swallowing or breathing difficult
• breathing problems or wheezing
• feeling dizzy or faint
• 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), indicating possible liver inflammation
• Skin rashes, including red, dry and itchy skin, eczema or hives
• Blood tests showing increased creatinine, a substance eliminated from the body through the kidneys, or decreased glomerular filtration rate (signs of possible kidney involvement)
• 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 facial swelling, difficulty breathing, itching.
• Inflammation of the pancreas (pancreatitis).
• Blood tests showing increased homocysteine (a type of amino acid).

Reporting of side effects

If you experience any kind of side effect, talk to your doctor or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. 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 stated on the carton after EXP.

The expiry date refers to the last day of the month indicated.

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 medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of Givlaari

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

Nature of the product and pack contents

This medicine is a clear, colourless to yellow, injectable solution.

Each pack contains one vial with 1 ml of injectable solution.

Marketing Authorisation Holder and Manufacturer

Alnylam Netherlands B.V.

Antonio Vivaldistraat 150

1083 HP Amsterdam

The Netherlands

You can request further information about this medicine by contacting the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: 11/2024

Other sources of information

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

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This information is intended for healthcare professionals only:

Instructions for use

For subcutaneous use only.

• Gather the materials not included in the package and required for administration; including a sterile syringe (1 ml or 3 ml) with a 21 gauge (G) or larger needle, a 25 G or 27 G needle, and a sharps container.

• Calculate the required volume of Givlaari based on the recommended dose according to body weight. If the dose exceeds 1 ml, more than one vial will be needed and possibly more than one subcutaneous injection will be required. The maximum acceptable volume per individual injection is 1.5 ml.

• To withdraw Givlaari, hold the vial vertically or slightly tilted and ensure the flat side of the needle bevel is pointing downwards.

• Withdraw the required injection volume using the 21 G or larger needle.

• Divide doses requiring a volume greater than 1.5 ml into equal portions across multiple syringes; each injection should contain approximately the same volume.

• Point the needle and syringe upward and gently tap the syringe to move any air bubbles to the top. Once bubbles have risen, gently push the plunger to expel the air from the syringe. Confirm that the amount of medication in the syringe remains correct.

• Once the dose has been prepared and is in the administration syringe, replace the 21 G or larger needle with a 25 G or 27 G needle.

• Note: Do not prime the 25 G or 27 G needle with medication.

• The injection may be administered in the abdomen or, if necessary, in the upper outer arm or thigh. Consider rotating injection sites. The medication must not be administered into scar tissue or over red, inflamed, or swollen areas.

• Note: When administering subcutaneous injections in the abdomen, avoid a 5.0 cm diameter circle around the umbilicus.

• Clean the intended injection site with an alcohol wipe and wait for the skin to dry completely.

• Ensure proper injection technique is used. Do not inject into a vein or muscle.

• Pinch and lift the skin at the selected injection site. Insert the needle at a 90-degree angle to administer the injection just beneath the skin. In patients with minimal subcutaneous tissue or if the needle length exceeds 2.5 cm, insert the needle at a 45-degree angle.

• Do not press the plunger while penetrating the skin. Once the needle is inserted, release the pinched skin and administer the dose slowly and steadily. After administering the medication, count at least 5 seconds before withdrawing the needle from the skin. Gently press with gauze or a cotton ball over the injection site as needed. Do not recap the needle.

• Note: Do not aspirate after needle insertion, to avoid tissue damage, bruising, and hematoma.

• If more than one injection is required for a single dose of Givlaari, injection sites should be separated by at least 2 cm from previous injection sites.

• Use the vial only once. After injecting the dose, discard any unused medication in the vial according to local regulations.

• Use syringes, transfer needles, and injection needles only once. Dispose of used needles and syringes according to local regulations.