Normosang 25 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

Human haematin

Read the entire 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 questions, ask your doctor.

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

Leaflet contents:

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

1. What Normosang is and what it is used for

Normosang contains human heme, a substance derived from human blood.

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

2. What you need to know before using Normosang

Do not use Normosang

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

Warnings and precautions

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

• indicative personal or family history;

• indicative clinical signs;

• quantitative determination of delta-aminolevulinic acid and porphobilinogen (specific markers of the disease) in urine.

• The earlier treatment with Normosang is started after the onset of an attack, the greater its effectiveness.

• As a result of 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 porphyria attacks are frequently associated with various effects on the heart, circulation, and nervous system.

• Do not:

• make sudden changes to your usual diet, in particular avoid prolonged fasting;

• take medications or substances such as estrogens (e.g., oral contraceptives), barbiturates (sleeping pills and medications sometimes used to treat epilepsy), or steroids (hormone-like medications for the body), as they may trigger or worsen an attack.

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

• To prevent venous irritation, the solution will be administered by infusion into a large vein in your arm or into 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”) may block the vein used for the infusion.

• If your cannula remains in place for a long time, vascular damage may occur, which could lead to involuntary leakage of Normosang outside the vein (extravasation). This leakage may cause skin discoloration.

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

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

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

• Human heme contains iron. Sometimes, after several years of repeated Normosang infusions, iron may accumulate in the body. Your doctor may perform blood tests from time to time to monitor your iron levels.

• Standard infection prevention measures related to medicines prepared from human blood or plasma include donor selection, screening of individual donations for specific infection markers, and inclusion in the manufacturing process of effective steps for virus inactivation and/or removal. Nevertheless, when medicines prepared from human blood or plasma are administered, the risk of transmitting infectious agents cannot be completely excluded. This applies also 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 product name and batch number each time Normosang is administered to a patient, in order to maintain a traceability link between the patient and the product batch 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 (hormone-like medications for the body), as they may trigger or worsen an attack.

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

Pregnancy and breastfeeding

It is unknown whether 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 administer the medicine only if it is absolutely necessary.

Normosang has not been studied during breastfeeding. However, since many substances are excreted in breast milk, you must inform your doctor if you are breastfeeding and consult with them before using Normosang. Your doctor will prescribe Normosang only if absolutely necessary, or may recommend that you discontinue breastfeeding.

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

Driving and use of machines

This medicine should not affect your ability to drive or operate machinery.

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 vial), equivalent to 23.6 ml of beer or 9.8 ml of wine per daily dose. This may be dangerous for individuals with alcoholism. This should be taken into account 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 have any of the above conditions.

3. How to use Normosang

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

The dose to be administered will be calculated according to your body weight, and is approximately 3 mg per kg of body weight per day, but not 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 to form a dark-colored solution.

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

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

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

If, after this first treatment cycle, your symptoms have not improved, your doctor may exceptionally decide to start a second treatment cycle.

If you have been given more Normosang than you should

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

4. Possible adverse effects

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

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

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

Anaphylactoid reactions are sudden-onset reactions that can be potentially life-threatening. They may occur on rare occasions. If you experience symptoms such as facial swelling, difficulty breathing, chest tightness, tachycardia, low blood pressure, urticaria, or spontaneous loss of consciousness (caused by insufficient blood flow to the brain), the infusion must be stopped immediately and a doctor should be contacted urgently.

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

• After repeated treatments, access to arm veins may become difficult, which might necessitate placement of a catheter into a vein in the chest.

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

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

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

• Repeated treatments over several years may increase blood levels of an iron compound (called ferritin). To limit the risk of iron compound accumulation, Normosang must not be used as a preventive treatment for acute attacks.

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

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse 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 stated on the ampoule and carton after EXP. The expiry date refers to the last day of the month indicated.

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

Keep 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 and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Normosang

• The active substance is human heme (25 mg/ml). A 10 ml vial contains 250 mg of human heme. After dilution of one 10 ml vial in 100 ml of 0.9% sodium chloride solution, the diluted solution contains 2273 micrograms per ml of human heme.
• The other components are arginine, ethanol (96%), propylene glycol and water for injections.

Appearance of the product and contents of the pack

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

Marketing Authorization 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

For further information about this medicinal product, please contact 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

Tel.: +34 91 659 28 90

This medicinal product is authorized in the European Economic Area member states 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 the most recent review of this summary:

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.