Venofer

Venofer

iron sucrose

Manufacturer:

Vifor

Distributor:

DKSH

Marketer:

Fresenius Kabi
Full Prescribing Info
Contents
Fe(OH)3 sucrose complex.
Description
Each 5 ml ampoule of Venofer contains 100 mg iron as iron sucrose [iron(III)-hydroxide sucrose complex] corresponding to 20 mg iron per ml.
Excipients/Inactive Ingredients: Water for injection, sodium hydroxide.
Action
Pharmacology: The polynuclear iron(III)-hydroxide cores are superficially surrounded by a large number of non-covalently bound sucrose molecules resulting in a complex whose molecular mass Mw is approx. 43 kDa. This is sufficiently large to prohibit renal elimination. The resulting complex is stable and does not release ionic iron under physiological conditions. The iron in the polynuclear cores is bound in a similar structure as in the case of physiologically occurring ferritin.
Pharmacodynamics: The ferrokinetics of Venofer labelled with 59Fe and 52Fe were assessed in 6 patients with anaemia and chronic renal failure. Plasma clearance of 52Fe was in the range of 60 to 100 minutes. 52Fe was distributed to the liver, spleen and bone marrow. At two to four weeks after administration, the maximum red blood cell utilisation of 59Fe ranged from 68% to 97%.
Pharmacokinetics: Following intravenous injection of a single dose of Venofer containing 100 mg iron in healthy volunteers, maximum iron levels, averaging 538 µmol/L, were obtained 10 min after injection. The volume of distribution of the central compartment corresponded well to the volume of plasma (approximately 3 litres).
The iron injected was rapidly cleared from the plasma, the terminal half-life being approx. 6 h. The volume of distribution at steady state was about 8 litres, indicating a low iron distribution in the body fluid. Due to the lower stability of iron sucrose in comparison to transferrin, a competitive exchange of iron to transferrin was observed. This resulted in iron transport of approx. 31 mg iron/ 24 h.
Renal elimination of iron, occurring in the first 4 h after injection, corresponds to less than 5% of the total body clearance. After 24 h the plasma levels of iron were reduced to the pre-dose iron level and about 75% of the dosage of sucrose was excreted.
Toxicology: Preclinical safety data: Preclinical data showed no special hazards based on conventional studies of repeated toxicity, genotoxicity and toxicity to reproduction in animals.
Indications/Uses
Venofer is indicated for the treatment of iron deficiency anaemia in the following indications: Where there is a clinical need for a rapid iron supply; in patients who cannot tolerate oral iron therapy or who are non-compliant; in active inflammatory bowel disease where oral iron preparations are ineffective.
Venofer should only be administered where the indication is confirmed by appropriate investigations (e.g. Hb, serum ferritin, serum iron).
Dosage/Direction for Use
Calculation of dosage: The total cumulative dose of Venofer, equivalent to the total iron deficit (mg), is determined by the haemoglobin level and body weight. The dose of Venofer must be individually determined for each patient according to the total iron deficit calculated with the following formula: (See Equation 1.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

If the total necessary dose exceeds the maximum allowed single dose, then the administration has to be split, please see Administration in the following text.
Calculation of dosage for iron replacement secondary to blood loss and to support autologous blood donation: The required Venofer dose to compensate the iron deficit is calculated according the following formulas: (See Equations 2 and 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Normal posology: Adults and the elderly: 5-10 ml Venofer (100-200 mg iron) one to three times a week depending on the haemoglobin level.
Children: There is limited data on children under study conditions. If there is a clinical need, it is recommended not to exceed 0.15 ml Venofer (3 mg iron) per kg body weight one to three times per week depending on the haemoglobin level.
Maximum tolerated dose: As injection, maximum tolerated dose per day, given not more than three times per week: 200 mg iron (10 ml Venofer) injected over at least 10 minutes.
As infusion, maximum tolerated single dose per day given not more than once per week: Patients above 70 kg: 500 mg iron (25 ml Venofer) in at least 3 ½ hours.
Patients of 70 kg and below: 7 mg iron / kg body weight in at least 3 ½ hours.
The maximum tolerated single dose is 7 mg iron per kg body weight given once per week, but not exceeding 500 mg iron. Administration time and dilution ratio see Administration. The infusion times given in Administration must be strictly adhered to, even if the patient does not receive the maximum tolerated single dose.
Administration:
Venofer must only be administered by the intravenous route. This may be by a slow intravenous injection or by an intravenous drip infusion.
Venofer must not be used for intramuscular injection.
Before administration of the first therapeutic dose, a test dose should be given. If any allergic reactions or intolerance occurs during administration, the therapy must be stopped immediately.
Intravenous drip infusion: Venofer must be diluted only in sterile 0.9% m/V sodium chloride solution: 100 mg iron (5 ml Venofer) in maximum 100 ml sterile 0.9% m/V sodium chloride solution.
500 mg iron (25 ml Venofer) in maximum 500 ml sterile 0.9% m/V sodium chloride solution.
For stability reasons, dilutions to lower Venofer concentrations are not permissible.
As infusion, maximum tolerated single dose per day given not more than once per week: Patients above 70 kg: 500 mg iron (25 ml Venofer) in at least 3 ½ hours.
Patients of 70 kg and below: 7 mg iron / kg body weight in at least 3 ½ hours.
Dilution must take place immediately prior to infusion and the solution should be administered as follows: 100 mg iron (5 ml Venofer) in at least 15 minutes.
200 mg iron (10 ml Venofer) in at least 30 minutes.
300 mg iron (15 ml Venofer) in at least 1 ½ hours.
400 mg iron (20 ml Venofer) in at least 2 ½ hours.
Before administration of the therapeutic dose in a new patient the first 20 mg iron in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg iron/kg) in children with a body weight less than 14 kg should be infused over 15 minutes as a test dose. If no adverse reactions occur, the remaining portion of the infusion can be administered at recommended speed.
Intravenous injection: Venofercan be administered undiluted by slow intravenous injection as follows: 100 mg iron (5 ml Venofer) in at least 5 minutes.
200 mg iron (10 ml Venofer) in at least 10 minutes.
Before administration of the therapeutic dose in a new patient a test dose of 1 ml Venofer (20 mg iron) in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg iron/kg) in children with a body weight less than 14 kg should be injected over 1 to 2 minutes. If no adverse reactions occur within a waiting period of 15 minutes, the remaining portion of the injection can be administered at recommended speed.
Injection into dialyser: Venofer may be administered during a haemodialysis session directly into the venous limb of the dialyser under the same conditions as for intravenous injection.
Overdosage
Overdosage can cause acute iron overloading which may manifest itself as haemosiderosis. Overdosage should be treated, if required, with an iron chelating agent.
Contraindications
The use of Venofer is contra-indicated in cases of: Anaemia not caused by iron deficiency; iron overload or disturbances in utilisation of iron; known hypersensitivity to Venofer or any of its inactive components; Pregnancy first trimester.
Special Precautions
Parenterally administered iron preparations can cause allergic or anaphylactoid reactions, which can be potentially fatal. Therefore, antiallergic treatment should be in place with the established cardio-pulmonary resuscitation procedures.
In patients with a history of asthma, eczema, other atopic allergies or allergic reactions to other parenteral iron preparations, Venofer should be administered with care as they are particularly at risk of an allergic reaction. However it was shown in a study with a limited number of iron dextran sensitive patients that Venofer could be administered with no complications.
Venofer should be administered with care in patients with liver dysfunction.
Venofer must be used with care in patients with acute or chronic infection who have excessive ferritin values as parenterally administered iron can unfavourably influence a bacterial or viral infection.
Hypotensive episodes may occur if the injection is administered too rapidly.
Paravenous leakage must be avoided because leakage of Venofer at the injection site may lead to pain, inflammation, tissue necrosis and brown discoloration of the skin.
Effects on Ability to Drive and Use Machines: It is unlikely that Venofer has an influence on the ability to drive and use machines.
Use In Pregnancy & Lactation
Data on a limited number of exposed pregnancies indicated no adverse effects of Venofer on pregnancy or on the health of the foetus/newborn child. No well-controlled studies in pregnant women are available to date. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Nevertheless, risk/benefit evaluation is required.
Non metabolised Venofer is unlikely to pass into the mother's milk. No well-controlled clinical studies are available to date. Animal studies do not indicate direct or indirect harmful effects to the nursing child.
Adverse Reactions
The most frequently reported adverse drug reactions (ADRs) of Venofer in clinical trials were transient taste perversion, hypotension, fever and shivering, injection site reactions and nausea, occurring in 0.5 to 1.5% of the patients. Non-serious anaphylactoid reactions occurred rarely.
In general anaphylactoid reactions are potentially the most serious adverse reactions (see Precautions).
In clinical trials, the following adverse drug reactions have been reported in temporal relationship with the administration of Venofer, with at least a possible causal relationship:
Nervous system disorders: Common (greater than or equal to 1% and less than 10%): Transient taste perversions (in particular metallic taste).
Uncommon (greater than or equal to 0.1% and less than 1%): Headache, dizziness.
Rare (greater than or equal to 0.01% and less than 0.1%):
Paraesthesia, syncope, loss of consciousness, burning sensation.
Cardio-vascular disorders: Uncommon: Hypotension and collapse, tachycardia and palpitations.
Rare: Hypertension.
Respiratory, thoracic and mediastinal disorders: Uncommon: Bronchospasm, dyspnoea.
Gastrointestinal disorders: Uncommon: Nausea, vomiting, abdominal pain, diarrhoea.
Skin and subcutaneous tissue disorders: Uncommon: Pruritus; urticaria, rash, exanthema, erythema.
Musculoskeletal, connective tissue and bone disorders: Uncommon: Muscle cramps, myalgia.
General disorders and administration site disorders: Uncommon: Fever, shivering, flushing, chest pain and tightness. Injection site disorders such as superficial phlebitis, burning, swelling.
Rare: Arthralgia, peripheral oedema, fatigue, asthenia, malaise, feeling hot, oedema.
Immune system disorders: Rare: Anaphylactoid reactions.
Moreover, in spontaneous reports the following adverse reactions have been reported: Isolated cases: Reduced level of consciousness, light-headed feeling, confusion, angio­ oedema, and swelling of joints, hyperhidrosis, back pain, bradycardia, chromaturia.
Drug Interactions
As with all parenteral iron preparations, Venofer should not be administered concomitantly with oral iron preparations since the absorption of oral iron is reduced. Therefore an oral iron therapy should at least be started 5 days after the last injection of Venofer.
Caution For Usage
Instructions for use/handling: Ampoules should be visually inspected for sediment and damage before use. Only those with sediment free and homogenous solution must be used.
The diluted solution must appear as brown and clear.
See Shelf-life under Storage.
Incompatibilities: Venofer must only be mixed with sterile 0.9% m/V sodium chloride solution. No other solutions and therapeutic agent should be used as there is the potential for precipitation and/or interaction. The compatibility with containers other than glass, polyethylene and PVC is not known.
Storage
Store in original carton. Do not store above 25°C. Do not freeze.
Shelf-Life: Shelf-life in the product as packaged for sale: 3 years.
Shelf-life after first opening the container: From a microbiological point of view, the product should be used immediately.
Shelf-life after dilution with sterile 0.9% m/V sodium chloride solution: From a microbiological point of view, the product should be used immediately after dilution with sterile 0.9% m/V sodium chloride.
ATC Classification
B03AC - Iron, parenteral preparations ; Used in the treatment of anemia
Presentation/Packing
Inj (amp) 100 mg/5 mL (dark brown, nontransparent, aqueous solution) x 5's.
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