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

Posology

The recommended daily dose is 3 mg/kg once daily for four days, diluted in 100 ml of 0.9% 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. After the infusion, the vein should be rinsed with 100 ml of 0.9 % NaCl. It is recommended to flush the vein initially with 3 to 4 bolus injections of 10 ml 0.9 % NaCl after which the remaining volume of saline can be infused for 10 – 15 minutes.

For instructions for the preparation of the solution, see section 6.6.

In animal experiments with NORMOSANG the acute toxic effects after high dosage were directed to the liver. Ten times higher total doses than the recommended human posology also decreased blood pressure in rats. High doses may cause disturbances in hemostasis.

NORMOSANG contains 4000 mg of propylene glycol per ampoule of 10 ml. Propylene glycol in high doses may cause central nervous system side-effects, lactic acidosis, kidney and liver toxicity, increase in plasma osmolarity, and haemolytic reactions.

Cases of overdosage with Normosang have been reported. For example, one patient had slight vomiting, pain and tenderness over the forearm (at the site of infusion) and made uneventful recovery. One other patient who received 10 ampoules of Normosang (2500 mg of human hemin) in a single infusion developed fulminant hepatic failure and one patient with a medical history of chronic hepatic failure who received 4 ampoules of Normosang (1000 mg of human hemin) experienced acute liver failure requiring liver transplantation. One patient received 12 ampoules of Normosang (3000 mg of human hemin) over 2 days which resulted in hyperbilirubinemia, anemia and a generalised haemorrhagic diathesis. The effects lasted for several days after administration, but the patient then improved without consequences.

Also, a high dose (1000 mg) of haematin, another form of haem, has been reported to have caused transitory renal failure in one patient.

Blood coagulation parameters, hepatic, renal and pancreatic functions should be carefully monitored until their normalisation.

Cardiovascular monitoring should also be performed (possibility of arrythmias).

Therapeutic measures:

• Albumin infusions should be administered to fix the freely-circulating and potentially reactive hemin.
• The administration of activated charcoal will enable the enterohepatic recirculation of the haem to be interrupted.
• Haemodialysis is necessary to eliminate the propylene glycol.

Shelf life: 2 years.

After dilution, the solution should be used within 1 hour.

Store in a refrigerator (2°C–8°C).

Keep the ampoule in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

10 ml of solution in ampoule (type I glass) - pack of 4.

Preparation of the solution

NORMOSANG, presented in ampoules, should be diluted immediately prior to administration in 100 ml of 0.9% NaCl solution in a glass bottle; the amount of product required, calculated according to the patient’s weight, is transferred from the ampoule to the glass bottle. The dilution should be prepared in a glass bottle because of slightly faster degradation of hemin in PVC plastic container.

Do not prepare more than one ampoule a day.

The solution should be used within the hour following dilution.

As the NORMOSANG solution is dark coloured even after dilution, it is difficult to verify visually the absence of particles in suspension. It is therefore recommended to use an infusion set with a filter.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.