אינפוזיות ברזל - מחקר 1

אינפוזיות ברזל – מחקר 1

Physician Information Leaflet

VENOFER

Intravenous Iron Therapy

COMPOSITION
Each 5 ml ampoule contains 100 mg of Fe (III) as iron sucrose complex

ACTION
The iron contained in Venofer is bound in a ferric complex and transported as such in the blood, from where it is absorbed by tissue partly for storage as depot iron, and partly for utilization for the synthesis of haemoglobin, myoglobin and iron-containing enzymes.  Blood haemoglobin levels increase more rapidly and more reliably under Venofer than under oral bivalent iron therapy.  In particular, Venofer rules out any complications affecting the gastro-intestinal tract.

PHARMOCOKINETICS
After administration of 50 mg of iron in the form of Venofer, a maximum serum iron concentration of 3.6 μg/ml is found.  The half life of the α-elimination phase from the serum is 30 minutes, and of the β-phase is 9 hours.  The volume of distribution is 25 L.  The majority of the iron passes to the intra-cellular fluid, from where the iron is utilized for haemoglobin production via liver metabolism.

INDICATIONS
Severe iron deficiency only when oral administration has been found impossible; in cases of gastro-intestinal malabsorption which rules out oral iron therapy; patients on dialysis treated with Erythropoietin.

CONTRAINDICATIONS
– known hypersensitivity to iron polysaccharide complexes.
– anaemia not caused by iron deficiency (eg. haemachromatosis, haemosiderosis, haemolytic anaemias, thalassemia).
– decompensated liver cirrhosis, epidemic hepatitis, asthma, progressive chronic polyarthritis, acute renal infection.

PRECAUTIONS
As with all parenteral iron preparations, Venofer should not be administered in conjunction with oral iron preparations.

Use in Pregnancy and Lactation:
Animal studies with iron sucrose have shown no mutagenicity nor undesired effects on the foetus in contrast to iron-dextran complexes.  There are, however, no controlled studies on pregnant women.

Venofer should only be administered in pregnancy where the potential benefit outweighs the risk.

Unmodified iron-sucrose does not pass into the breast milk.  The iron is bound to the naturally occurring lactoferrin and therefore the iron-sucrose complex should not present a risk to the suckling baby.

ADVERSE REACTIONS
Parenterally administered iron preparations can cause allergic and hypersensitivity reactions (skin rash or hives, trouble in breathing).

Patients with asthma are particularly at risk as are patients with low iron binding capacity and/or folic acid deficiency.  Unlike iron dextran complexes no dextran – induced anaphylactic reactions occur.  Anaphylactic reactions occur within the first several minutes of administration and have been characterized by sudden onset of respiratory difficulties and/or cardiovascular collapse.
Therefore, adrenalin should be kept near the patient in case of emergency.

A test dose (see Dosage and Administration) is recommended and facilities for resuscitation should be available.  In the case of mild allergic reactions, antihistamines should be administered.

Occasionally the following undesired reactions can occur: joint, backache or muscle pains, swelling of the lymph glands, fever with increased sweating, headaches, dizziness, abdominal disorders, nausea, vomiting and in the region of the punctured vein phlebitis and venous spasm.  Hypotonic episodes may occur if injection into the vein is carried out too quickly.  In children parenteral iron therapy may have adverse influence on existing infections.

Brown discoloration of skin – usually fading within several weeks or months.

Iron taste in the mouth.

DOSAGE AND ADMINISTRATION
In all patients it is recommended that before administering the first therapeutic dose a slow intravenous test injection should be made (1/4 to ½ ampoule in adults; half the calculated daily dose in children) in order to check for tolerance.  If no reactions are observed, the full dose can be administered no sooner than fifteen minutes later.

Administer by slow injection into a suitable arm vein (1 ml per minute).  Extend the patients arm after injecting.

VENOFER SHOULD NOT BE INJECTED INT PERIVENOUS TISSUES AVOID EXTRAVASATION.

Venofer can also be administered as infusion.  For this, add the contents of one ampoule of Venofer to 100 ml of sodium chloride 0.9% immediately before starting the infusion; mix before infusion.  Infuse within 15 to 30 minutes.

Individual dosage should be calculated from the table below.

Adults:
Dosage in cases of Iron Deficiency:
Day 1: 2.5 ml (50 mg Fe {III}), day 3: 5ml (100 mg Fe {III}), then twice a week 5 ml as required according to the haemoglobin level.
Total number of ampoules as below.  In sensitive patients Venofer can be diluted by blood aspiration.

The following table provides a guideline for the determination of the total dose (number of ampoules) required for the correction of iron deficiency.

If no response in hematological parameters is seen after 1-2 months then the original diagnosis should be reconsidered.

Dosage in cases of blood loss:
In patients who have suffered blood loss, Venofer can be used to replace the quantity of iron proportionate to the blood lost.  An initial quantitative assessment of the volume of blood lost must be made in this case, in order to calculate the required dosage of iron.

The formula for determining the quantity to be administered are based on the following assumptions.

– administering 150 mg Fe III to a patient of body weight 60 kg normally brings about a rise in haemogloblin of 1g/dl.

– administering 200 mg Fe III normally results in an increase in haemoglobin which is sufficient to replace 400 ml (1 unit) of blood lost or removed, providing that this unit of blood has a haemoglobin content of 150 g/l.

The formula therefore is:

Quantity of iron (in mg) to be replaced at approximately body weight of 60 kg.
= 150 X (target haemoglobin minus actual haemoglobin level)

or

Quantity of iron (in mg) to be replaced.
= 200 X number of 400 ml blood units of 150 g haemoglobin per liter.

The maximum daily dose for adults is 500 mg iron (5 ampoules) as an infusion given in 500 ml 0.9% sodium chloride over an infusion period of 3-4 hours.  There are recorded cases of total doses of 1500 to 2000 mg iron given over a period of 3 days.

Children:
Dosage instruction same as for adults.

Maximum daily dose for children:
Up to 5 kg  1.25 ml = ¼ ampoule
5 to 10 kg  2.5   ml = ½ ampoule
10 to 20 kg  3.75 ml = ¾ ampoule
more than 20 kg 5.0   ml =  1 ampoule

Elderly:
Dosage  as for adults.

OVERDOSAGE
Overdose can cause acute iron overloading which may mainifest itself as haemosiderosis.  Particular caution should be exercised to avoid iron overload where anaemia unresponsive to treatment has been incorrectly diagnosed as iron deficiency anaemia.

PHARMACEUTICAL PRECAUTIONS
Venofer must not be mixed with other medications for simultaneous administration.  Sodium chloride 0.9% is the only recommended diluent where infusion is required.

Store between 4 and 25ºC.
Inappropriate storing can result in sedimentation.
Always check for sedimentation (bottom and point of the ampoule).
Only clean and sediment free solution should be used.

PRESENTATION
5 and 50 ampoules

MANUFACTURER
Vifor (International) Inc.
P.O.Box CH-0—1 St., Gallen, Switzerland
Phone ++44-71-29-84-84

MANUFACTURER’S AGENT
C.T.S. Ltd.,
100 Jabotinsky St., Petach Tikva, Israel.