NORMOSANG

9% sodium chloride in a glass bottle and infused intravenously over at least 30 minutes into a large antebrachial or central vein using an inline filter. The dose should not exceed 250 mg (1 ampoule) per day. Exceptionally, the course of the treatment may be repeated under strict biochemical surveillance if there is inadequate response after the first course of treatment.

Elderly patients No dose adjustment is required. Children and adolescents Attacks of porphyria are rare in children but limited experience in tyrosinaemia suggests that it is safe to use a dose of not more than 3 mg/kg daily for 4 days, administered with the same precautions as for adults.

Method of administration The infusions should be administered in a large antebrachial or central vein over a period of at least 30 minutes. 9 % NaCl. 9 % NaCl after which the remaining volume of saline can be infused for 10 - 15 minutes.

6.

). • 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. 5 Interaction with other medicinal products and other forms of interaction 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.

6 Fertility, pregnancy and lactation 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.

7 Effects on ability to drive and use machines There is no evidence to suggest that NORMOSANG affects adversely the ability to drive or use machines. 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).

• 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 repeated 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.

1.