NORMOSANG 25 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

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

Human hemin

Read all of this leaflet carefully before you start using this medicine 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 pharmacist.

-If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

1. What is Normosang and what is it used for

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 who suffer from acute hepatic porphyria; the disease is characterized by the accumulation of compounds (including porphyrins and their toxic precursors) in the liver. There are three types of hepatic porphyria whose medical names are: acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria. This accumulation leads to symptoms of the disease, including pain (mainly in the abdomen, back, and thighs), nausea, vomiting, and constipation.

2. What you need to know before you use Normosang

Do not use Normosang

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

Warnings and precautions

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

• family or personal history indicating;
• indicative clinical signs;
• quantitative determination of delta-aminolevulinic acid and porphobilinogen (specific markers of the disease) in urine.

• The sooner treatment with Normosang is started after the onset of an attack, the more effective it will be.

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

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

• Do not:

• make sudden changes to your usual diet, in particular, do not go without eating 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 (pseudo-hormonal 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 by infusion into a large vein (blood vessel) in your arm or in a vein in your chest over a period of at least 30 minutes. After the infusion, the vein should be flushed with saline solution.

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

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

• In order to reduce the risk of extravasation, the nurse/doctor will check your cannula before infusion and 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 preventive treatment for acute attacks.

• Human hemin contains iron. It may happen that, after several years of treatment with repeated infusions of Normosang, iron accumulates in the body. Your doctor may perform blood tests from time to time to check the iron level in your body.

• The standard measures for preventing infections due to the use of medicines prepared from human blood or plasma include donor selection, screening of individual donations for specific infection markers, and the inclusion in the production process of effective stages for virus inactivation and/or removal. Despite this, when medicines prepared from human blood or plasma are administered, the risk of transmission of infectious agents cannot be completely excluded. This also applies to unknown or emerging viruses and other pathogens.

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

• It is strongly recommended to record 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 medicines 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 (pseudo-hormonal medications for the body), as they may trigger an attack or worsen it.

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

Pregnancy and breastfeeding

It is not known if there is any risk in using Normosang during pregnancy. However, mothers treated with Normosang have given birth to normal children.

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

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

Normosang contains ethanol (alcohol). This should be taken into consideration if you are pregnant or breastfeeding. See the section "Important information about some of the components of Normosang".

Driving and using machines

This medicine should not affect your ability to drive or use 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 suffering from alcoholism. This should be taken into consideration in pregnant 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-mentioned diseases.

3. How to use Normosang

This medicine will be administered to you only in a hospital by qualified hospital staff.

The dose to be administered will be calculated according to your weight, and is approximately 3 mg per kg of body weight per day, but no more than 250 mg (1 ampoule) per day. The calculated amount will be diluted with saline solution (0.9% sodium chloride) in a glass vial and will form a dark-colored solution.

The solution will be administered by infusion into a large vein (blood vessel) in your arm or in a vein in your chest over a period of at least 30 minutes. The infused solution may cause an unusual color of the blood.

After the infusion, the vein should be flushed with saline solution.

Normally, you will receive one infusion per day for four days.

If after this first treatment cycle, the symptoms do not improve, your doctor may decide to start a second treatment cycle exceptionally.

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.

4. Possible side effects

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

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

• Fever and severe allergic reactions (rash, swelling of the tongue), including anaphylactoid reaction, may occur rarely.

Anaphylactoid reactions are reactions that occur suddenly and are potentially life-threatening. They may occur rarely. If you experience symptoms such as swelling of the face, difficulty breathing, chest tightness, rapid heart rate, low blood pressure, hives, spontaneous loss of consciousness (caused by insufficient blood flow to the brain), the administration of the infusion should be stopped and the doctor should be called immediately.

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 make it necessary to place a cannula in a vein in the chest.

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

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

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

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

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

• Headache
• Venous thrombosis (formation of blood clots in peripheral or central veins), including thrombosis at the infusion site.
• Infusion leakage into the 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 level in the blood (substance excreted by the kidneys).
• Discoloration of the skin.

Reporting of side effects

If you experience 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 Spanish Medicines Surveillance System for Human Use:www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Normosang

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 label of the ampoule and carton after EXP. The expiry date is the last day of the month shown.

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

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

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Normosang

• The active substance is human hemin (25 mg/ml). One 10 ml ampoule contains 250 mg of human hemin. After dilution of one 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 injections.

Appearance and packaging

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

Marketing authorisation holder

Recordati Rare Diseases

Tour Hekla

52, avenue du Général de Gaulle

F-92800 Puteaux

France

Manufacturer

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 obtain further information on this medicine from the representative of the marketing authorisation holder:

Recordati Rare Diseases Spain, S.L.U.

Autovía de Logroño, km. 13,300

50180 Utebo (Zaragoza) – Spain

Tel.: +34 91 659 28 90

This medicine is authorised in the Member States of the European Economic Area under 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

Date of last revision of this leaflet:

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.