Prospecto: information for the user

Givlaari 189 mg/ml injectable solution

givosiran

Read this prospect carefully before this medicine is administered to you, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

What is Givlaari

Givlaari contains the active ingredient givosiran.

What is Givlaari used for

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

What is acute hepatic porphyria

Acute hepatic porphyria is a rare and inherited disease. It is caused by a defect in one of the proteins that make up a molecule called heme produced in the liver. Due to a problem with one of the proteins to form heme, substances used to produce it accumulate, that is, aminolevulinic acid (ALA) and porphobilinogen (PBG). An excess of ALA and PBG can cause nerve damage and trigger pain crises, nausea, muscle weakness, and changes in mental function. Some people with acute hepatic porphyria may also present symptoms, such as pain and nausea between crises. Long-term complications that can be observed in people with acute hepatic porphyria include hypertension, chronic renal insufficiency, and liver diseases.

How Givlaari works

The medication 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.

You should not be given Givlaari:

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

Warnings and precautions

Consult your doctor or nurse before Givlaari is administered to you.

Severe allergic reaction

• Inform your doctor or nurse immediately if you start experiencing 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 medication immediately and may prescribe other medications to control your symptoms.

Liver problems

The use of this medication 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 to temporarily or permanently stop treatment. Abnormal results have been observed in some patients treated with this medication, mainly between 3 and 5 months after starting treatment.

Kidney problems

The use of this medication may affect the kidneys, especially if you have pre-existing kidney problems. Your doctor will check if your kidneys are functioning correctly while using this medication, especially if you have any kidney problems.

Homocysteine level analysis

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 elevated, your doctor may prescribe a homocysteine-lowering treatment.

Children

This medication should not be used in children under 12 years old, as there have been no clinical trials with this population.

Other medications and Givlaari

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

This medication may prolong or increase the effect of certain medications 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 medication.

Breastfeeding

Studies in animals show that this medication may pass into breast milk. If you are breastfeeding, consult your doctor before using this medication. Your doctor will help you decide whether to stop breastfeeding or stop treatment with Givlaari, considering the benefits of breastfeeding for your child and the benefits of treatment for you.

Driving and operating machinery

It is believed that the effect of this medication on the ability to drive and operate machinery is negligible or insignificant.

Givlaari contains sodium

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

What amount of Givlaari is administered

The doctor will decide the amount of medication to be administered. The amount will depend on the patient's body weight.

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

How to use Givlaari

A doctor or nurse will administer this medication once a month. It is administered via subcutaneous injection in the abdominal area or, in some cases, in the arm or thigh. The injection site will be alternated. If the dose is greater than 1 ml, more than one vial may be needed, and possibly more than one subcutaneous injection.

If too much Givlaari is administered

In the unlikely event that the doctor or nurse administers too much (overdose), the patient will be examined for adverse effects.

If a dose of Givlaari is missed

If a scheduled injection appointment is missed, the patient should contact the doctor or nurse as soon as possible.

If the patient has any other questions about the use of this medication, they should ask their doctor or nurse.

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

Severe side effects

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

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

• Swelling: mainly on the lips, tongue, or throat, which may make it difficult to swallow or breathe
• Respiratory problems or wheezing
• Dizziness or fainting
• Rash, urticaria

• Itching

Other side effects

Inform 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 an increase in transaminases (liver enzymes), which are a sign of possible liver inflammation
• Skin rashes, including red, dry, and itchy skin, eczema, or urticaria
• Blood tests showing an increase in creatinine, a substance that is eliminated from the body through the kidneys, or a decrease in glomerular filtration rate (signs of possible kidney damage)
• Redness, pain, itching, or inflammation 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 urticaria, skin rash, eye, mouth, or face inflammation, difficulty breathing, itching.
• Pancreatitis (inflammation of the pancreas).
• Blood tests showing an increase in homocysteine (a type of amino acid).

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 the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es... 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.

This medication is for single use only. Once the product is opened, use it immediately.

Do not store at a temperature above 25 °C.

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

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

Composition of Givlaari

• The active ingredient is givosiran.
• Each ml contains givosiran sodium equivalent to 189 mg of givosiran.
• The other components are sodium hydroxide, phosphoric acid, and water for injectable preparations. See section 2 “Givlaari contains sodium”.

Appearance of the product and contents of the pack

This medicine is a transparent, colourless to yellowish injectable solution.

Each pack contains a vial of 1 ml of injectable solution.

Marketing authorisation holder and responsible person for manufacturing

Alnylam Netherlands B.V.

Antonio Vivaldistraat 150

1083 HP Amsterdam

Netherlands

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

Last review date of this leaflet 11/2024

Other sources of information

The detailed information about this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

Instructions for use

For subcutaneous use only.

• Collect the materials not included in the pack and required for administration; including a sterile syringe (1 ml or 3 ml) of 21G or a larger gauge, a transfer needle and a sharps container.
• Calculate the required volume of Givlaari based on the recommended dose according to weight. If the dose is greater than 1 ml, more than one vial may be required and possibly more than one subcutaneous injection may be needed. The maximum acceptable volume for each individual injection is 1.5 ml.
• To extract Givlaari, hold the vial in a vertical position or slightly inclined and ensure the flat edge of the needle points downwards.
• Extract the injection volume indicated with the 21G or larger gauge needle.
• Divide doses requiring a volume greater than 1.5 ml into equal parts in several syringes; each injection should contain approximately the same volume.
• Point the needle and syringe upwards and gently tap the syringe to move any bubbles to the top. Once the bubbles are at the top, gently push the plunger to force the bubbles out of the syringe. Check that the amount of medicine within the syringe remains correct.
• Once the dose has been prepared and is in the administration syringe, replace the 21G or larger gauge needle with a 25G or 27G needle.
• Nota: Do not introduce the medicine into the 25G or 27G needle.
• The injection can be applied to the abdomen or, if necessary, to the back or lateral side of the arm or thighs. Consider alternating the injection sites. The medicine should not be administered to scar tissue or to red, inflamed or swollen areas.
• Nota: When applying subcutaneous injections to the abdomen, a circle of 5.0 cm in diameter should be avoided around the navel.
• Clean the surface where you want to apply the injection with an alcohol wipe and wait for the surface to dry completely.
• Ensure you use the correct injection technique. Do not inject 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 administer the injection just below the skin. In patients with little subcutaneous tissue or if the needle length is greater than 2.5 cm, the needle should be inserted at an angle of 45 degrees.
• Do not press the plunger while piercing the skin. Once the needle is inserted into the skin, release the skin you were pinching and administer the dose slowly and steadily. Once the medicine has been administered, count at least 5 seconds before removing the needle from the skin. Press gently with a cotton ball or gauze on the injection site as needed. Do not replace the needle cap.
• Nota: Do not aspirate after inserting the needle, to avoid damage to the tissue, hematomas and ecchymoses.
• If more than one injection is required 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, dispose of the unused medicine in the vial according to local regulations.
• Use the syringes, transfer needles and injection needles only once. Dispose of used needles and syringes according to local regulations.