NORMOSANG Concentrate for solution for infusion Ref.[9643] Active ingredients: Hemin

Before treatment is started, it is necessary to confirm an attack of hepatic porphyria by series of clinical and biological criteria:

• suggestive family or personal history,
• suggestive clinical signs,
• quantitative determination of urinary delta-amino-laevulinic acid and porphobilinogen (in preference to the classical WATSON-SCHWARZ or HOESCH tests, which are considered to be less reliable).

The sooner NORMOSANG treatment is started after the onset of an attack, the greater its efficacy.

As a result of NORMOSANG infusions, abdominal pain and other gastro-intestinal symptoms generally disappear within 2 – 4 days. Neurological complications (paralysis and psychological disorders) are less affected by the treatment.

As porphyric attacks are often associated with various cardiovascular and neurological manifestations, appropriate monitoring should be ensured.

It is also important to warn patients of the risk of attacks being worsened or triggered by fasting or taking certain medicinal products (particularly oestrogens, barbiturates and steroids), because by increasing the haem demand of the liver they are capable of indirectly inducing the delta-aminolaevulinic acid synthase activity.

As the diluted solution is hypertonic, it should be administered by very slow intravenous infusion only.

To prevent vein irritation, the infusion should be administered in at least 30 minutes in a large vein of the forearm or in a central vein.

Venous thrombosis in the vein used for infusion may potentially occur following administration of NORMOSANG. There are few cases describing thrombosis at the caval vessels and their major tributaries (iliac and subclavian veins). The risk of thrombosis at the caval vessels cannot be excluded.

Peripheral venous alterations have been reported after repeated infusions and can prevent the use of the affected veins for further infusions, necessitating the use of a central venous line. It is therefore recommended to rinse the vein with 100 ml of 0.9 % NaCl after the infusion.

If intravenous cannula is in place for too long, due to mechanical irritation and also due to irritation by the injection fluid, vascular damage may occur which may lead to extravasation.

Test the cannula before infusing NORMOSANG and also check it regularly during the infusion.

In case of extravasation, skin discoloration may occur.

Increased serum ferritin concentrations have been reported after repeated infusions. It is therefore recommended that serum ferritin be measured at regular intervals to monitor body iron stores. If necessary other investigation methods and therapeutic measures should be undertaken.

The dark NORMOSANG colour may give the plasma an unusual colouring.

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations for specific markers of infections and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

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

It is strongly recommended that every time that NORMOSANG is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

NORMOSANG contains 1 g of ethanol (96 %) per ampoule of 10 ml. This may be harmful for those suffering from liver disease, alcoholism, epilepsy, brain injury or disease as well as for pregnant woman and children. The ethanol content of NORMOSANG may modify or increase the effect of other medicines.

NORMOSANG should not be used as a preventive treatment since available data is too limited and long term administration of regular infusions carries the risk of iron overload (see section 4.8. Undesirable effects).

In addition to treatment with NORMOSANG and other necessary measures such as the elimination of triggering factors, ensuring a sufficient supply of carbohydrates is recommended.

During treatment with NORMOSANG the enzyme activity of the P450 enzymes increases. The metabolism of concomitantly administered drugs that are metabolised by cytochrome P450 enzymes (such as oestrogens, barbiturates and steroids) may increase during administration of NORMOSANG, leading to lower systemic exposure.

Pregnancy

In the absence of specific experimental and clinical data, the risks during pregnancy are not defined; to date, however, no after-effects have been observed in new-born babies whose mothers were treated with NORMOSANG during their pregnancy.

Breast-feeding

NORMOSANG has not been studied during breast-feeding. However, since numerous substances are excreted in breast milk, it is appropriate to be cautious when administering NORMOSANG during lactation.

Due to limited data the use of NORMOSANG can not be recommended unless clearly necessary during pregnancy and breast-feeding.

There is no evidence to suggest that NORMOSANG affects adversely the ability to drive or use machines.

The most commonly reported ADRs are infusion site reactions especially occurring if infusion takes place into veins which are too small (see section 4.4. Special warnings and precautions for use).

Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Immune system disorders

Rare: anaphylactoid reaction, hypersensitivity (such as dermatitis medicamentosa and tongue oedema).

Nervous system disorders:

Not known: headache

Vascular disorders

Very common: poor venous access

Not known: injection site thrombosis, venous thrombosis

General disorders and administration site conditions

Common: infusion site phlebitis, infusion site pain, infusion site swelling

Rare: pyrexia

Not known: injection site erythema, injection site pruritus, extravasation, injection site necrosis

Investigations

Uncommon: serum ferritin increased

Not known: blood creatinine increase

Increased serum ferritin concentrations have been reported after several years of treatment with repeated infusions, which may indicate an iron overload (see section 4.4. Special warnings and precautions for use).

Skin disorders

Not known: skin discoloration

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

United Kingdom, Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard

Ireland, Health Products Regulatory Authority, Pharmacovigilance Section, Earlsfort Terrace, Dublin 2, Ireland, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, e-mail: medsafety@hpra.ie.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.