Leaflet: information for the user

NORMOSANG 25 mg/ml, concentrate for solution for infusion.

Human haemoglobin

Read this leaflet carefully before you start using 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, consult your doctor.

-If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1.What is Normosang and what it is used for

2.What you need to know before you start using Normosang

3.How to use Normosang

4.Possible side effects

5.Storage of Normosang

6.Contents of the pack and additional information

Normosang contains human hemin, which is a substance derived from human blood.

Normosang is used for the treatment of sudden attacks that occur in patients suffering from acute intermittent porphyria, porphyria variegata, and hereditary coproporphyria; the disease is characterized by the hepatic accumulation of compounds (including porphyrins and their toxic precursors). This accumulation gives rise to symptoms of the disease, including pain (mainly in the abdomen, back, and thighs), nausea, vomiting, and constipation.

No use Normosang

• If you are allergic to human hemin or any of the other components of this medication (listed in section 6).

Warnings and precautions

• Before starting treatment with Normosang, your doctor must confirm an attack of hepatic porphyria through a series of clinical and biological criteria:

• Family or personal history indicative;
• Indicative clinical signs;
• Quantitative determination of delta-aminolevulinic acid and porphobilinogen (specific disease markers) in urine.

• The sooner the treatment with Normosang is initiated after the onset of an attack, the greater its efficacy.

• As a result of the Normosang infusions, abdominal pain and other gastrointestinal symptoms usually disappear within 2-4 days. Neurological complications (paralysis and psychological disorders) are less affected by the treatment.

• You will be monitored throughout the treatment cycle as attacks of porphyria are often associated with various effects on the heart and circulation, and the nervous system.

• No:

• Make sudden changes to your usual diet, in particular do not go without food for long periods.
• Take medications or substances such as estrogens (e.g., oral contraceptives), barbiturates (sleeping pills and medications sometimes used to treat epilepsy), or steroids (pseudohormonal medications for the body), as they may trigger an attack or worsen it.

Please consult your doctor or pharmacist to inform you about the medications and substances you should not take (now and in the future).

• To prevent venous irritation, the solution will be administered through infusion in a thick vein of your arm or in a chest vein for a period of at least 30 minutes. After infusion, the vein must be irrigated with saline solution.

• A blood clot (called "venous thrombosis") may block the vein used for infusion.

• If your cannula is placed for a long time, vascular damage may occur, which may lead to involuntary migration of Normosang out of the vein (extravasation). This migration may cause skin discoloration.

• To reduce the risk of extravasation, the nurse/doctor will check your cannula before infusion and check it periodically during infusion.

• The infused solution may cause an unusual color of the blood.

• To reduce the risk of increased iron compound, Normosang should not be used as a preventive treatment for acute attacks.

• Human hemin contains iron. Sometimes, after several years of repeated Normosang infusions, iron may accumulate in the body. Your doctor will be able to perform blood tests from time to time to check the level of iron in your body.

• Standard measures for preventing infections due to the use of medications prepared from human blood or plasma include selecting donors, screening individual donations for specific infection markers, and including effective inactivation and/or elimination steps in the production process. Despite this, when medications prepared from human blood or plasma are administered, the risk of transmission of infectious agents cannot be completely ruled out. This also applies to unknown or emerging viruses and other pathogens.

• The measures taken are considered effective against encapsulated viruses such as HIV, HBV, and HCV.

• It is strongly recommended to register the name and batch number of the product each time Normosang is administered to a patient in order to maintain a link between the patient and the batch of product used.

Other medications and Normosang

Do not take medications or substances such as estrogens (e.g., oral contraceptives), barbiturates (sleeping pills and medications sometimes used to treat epilepsy), or steroids (pseudohormonal medications for the body), as they may trigger an attack or worsen it.

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

Pregnancy and lactation

The safety of using Normosang during pregnancy is unknown. However, mothers treated with Normosang have given birth to normal children.

If you are pregnant, consult your doctor before using this medication. Your doctor will only administer the medication if it is absolutely necessary.

Normosang has not been studied during lactation. However, since numerous substances are excreted in breast milk, you should inform your doctor if you are breastfeeding and consult them before using Normosang. Your doctor will only prescribe Normosang when it is absolutely necessary, or recommend that you stop breastfeeding.

Normosang contains ethanol (alcohol). You should consider this if you are pregnant or breastfeeding. See the title "Important information about some of the components of Normosang"

Driving and operating machines

This medication should not affect your ability to drive or operate machines.

Important information about some of the components of Normosang

Normosang contains 11.78% ethanol (alcohol) by volume, i.e., up to 1000 mg per daily dose (one ampoule), which is equivalent to 23.6 ml of beer or 9.8 ml of wine per daily dose. This may be hazardous for people with alcoholism. This should be taken into account in pregnant women or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.

Consult your doctor before Normosang is administered to you if you suffer from any of the above diseases.

The medication will be administered to you solely in a hospital by qualified hospital staff.

The dose to be administered will be calculated based on your weight, and it is approximately 3 mg per kg of body weight per day, but not more than 250 mg (1 ampule) per day. The calculated amount will be diluted with a saline solution (sodium chloride 0.9%) in a glass bottle and a dark-colored solution will be formed.

The solution will be administered through infusion in a large vein of the arm or in a chest vein for a period of at least 30 minutes. The infused solution may cause an unusual color in your blood.

After the infusion, the vein should be irrigated with a saline solution.

Normally, you will receive an infusion once a day for four days.

If, after the first treatment cycle, your symptoms do not improve, your doctor may decide to initiate an exceptional second treatment cycle.

If you have received more Normosang than you should

If you have received more Normosang than you should, your doctor will treat you to prevent harmful effects.

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

Rare(may affect up to 1 in 1,000 people):

• Severe fever and allergic reactions (hives, tongue swelling), including anaphylactic reactions, may occur rarely.

Anaphylactic reactionsare sudden reactions that are potentially life-threatening. They may occur rarely. If you experience symptoms such as facial swelling, difficulty breathing, chest tightness, rapid heartbeat, low blood pressure, urticaria, spontaneous loss of consciousness (caused by inadequate blood flow to the brain), discontinue the infusion and immediately contact your doctor.

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

• After repeated treatments, access to the veins in the arm may be difficult, which may require placing a catheter in a chest vein.

Common(may affect up to 1 in 10 people):

• If administered in a too small vein, it may cause pain, inflammation, and the formation of blood clots in the vein.

Uncommon(may affect up to 1 in 100 people):

• It may increase the amount of a compound called ferritin in the blood after repeated treatments over several years. To limit the risk of increased iron compounds, Normosang should not be used as a preventive treatment for acute attacks.

Frequency not known(cannot be estimated from available data):

• Headache
• Deep vein thrombosis (formation of blood clots in peripheral or central veins), including thrombosis at the site of administration.
• Perfusion leakage into surrounding tissue (extravasation).
• Skin damage (necrosis).
• Redness of the skin at the injection site (erythema at the injection site).
• Itching of the skin at the injection site (pruritus at the injection site).
• Increased creatinine levels in the blood (substance excreted by the kidneys).
• Skin discoloration.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish 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 ampule and box label after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C).

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

After dilution, the solution must be used within one hour.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need.This will help protect the environment.

Composition of Normosang

• The active principle is human hemin (25 mg/ml). A 10 ml ampoule contains 250 mg of human hemin. After diluting a 10 ml ampoule in 100 ml of 0.9 % NaCl solution, the diluted solution contains 2273 micrograms per ml of human hemin.
• The other components are arginine, ethanol (96 %), propylene glycol, and water for injection.

Appearance of the product and content of the container

NORMOSANG is presented as a concentrate for solution for infusion (10 ml ampoules – boxes of 4). NORMOSANG is a dark-colored solution even after diluting the concentrate for solution for infusion.

Holder of the marketing authorization

Recordati Rare Diseases

Tour Hekla

52, avenue du Général de Gaulle

F-92800 Puteaux

France

Responsible for manufacturing

Recordati Rare Diseases

Tour Hekla

52, avenue du Général de Gaulle

F-92800 Puteaux

France

or

Recordati Rare Diseases

Eco River Parc

30, rue des Peupliers

F-92000 Nanterre

France

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Recordati Rare Diseases Spain, S.L.U.

Autovía de Logroño, km. 13,300

50180 Utebo (Zaragoza) – Spain

Phone: +34 91 659 28 90

This medication is authorized in the member states of the European Economic Area with the following names:

Normosang – Germany / Austria / Belgium / Cyprus / Denmark / Slovakia / Slovenia / Spain / Estonia / France / Finland / Greece / Hungary / Ireland / Iceland / Italy / Latvia / Lithuania / Luxembourg / Malta / Norway / Netherlands / Portugal / United Kingdom / Czech Republic / Sweden

Human Hemin Orphan Europe – Poland

Last review date of this leaflet:

The detailed and updated information about this medication is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.