Avofer

Avofer

iron sucrose

Manufacturer:

Abio

Distributor:

Apex
Full Prescribing Info
Contents
Iron (III) hydroxide sucrose complex.
Description
Each 5 mL contains 100 mg (20 mg/mL) of elemental iron as an iron (111)-hydroxide sucrose complex in water for injection.
AVOFER (iron (III) hydroxide sucrose complex injection, USP), an iron replacement product, is a sterile, brown, aqueous, complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use. Iron (III) hydroxide sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula: [Na2Fe5O8(OH) · 3(H2O)]n · m(C12H22O11).
where: n is the degree of iron polymerization and m is the number of sucrose molecules associated with the iron (111)-hydroxide. Each mL contains 20 mg elemental iron as iron (III) hydroxide sucrose in water for injection. A VOFER is available in 5 mL single-use vials (100 mg elemental iron per 5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 1 L 1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.
Excipients/Inactive Ingredients: Each vial contains: Water for injection Sodium hydroxide.
Action
ATC code: B03AC02 (Iron, parenteral preparations).
Pharmacology: Pharmacodynamics: Following intravenous administration of iron (III) hydroxide sucrose complex injection, iron (III) hydroxide sucrose is dissociated by the reticulo-endothelial system into iron and sucrose leading to increases in serum iron and serum ferritin and decrease in total iron binding.
Pharmacokinetics: The following data are based on the innovator product (Venofer 20mg iron/ml, solution for injection or concentrate for solution for in.fusion) summary of product characteristics from UK.
Following intravenous injection of a single dose of Iron (III) hydroxide Sucrose Injection containing 100 mg iron, maximum iron levels, averaging 538 μmol/i were obtained 10 minutes 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 (III) hydroxide 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.
The ferrokinetics of Iron (III)-hydroxide sucrose complex injection labelled with 59Fe and 52Fe were assessed in 5 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 weeks after administration, the maximum red blood cell utilisation of 59Fe ranged from 62% to 97%.
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.
Indications/Uses
Iron (III) hydroxide Sucrose Injection is indicated in the treatment of iron deficiency in the following indications: where there is a clinical need to deliver iron rapidly to iron stores.
in patients who cannot tolerate oral iron therapy or who are non-compliant,
in active inflammatory bowel disease where oral iron preparations are ineffective.
Avofer Injection 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 Avofer, equivalent to the total iron deficit (mg) is determined by the haemoglobin level and body weight. The dose for the Avofer must be individually determined for each patient according to the total iron deficit calculated with the formula as follows: (See Equation 1.)

Click on icon to see table/diagram/image

Below 35 kg body weight: target Hb ~ 130 g/1 and depot iron - 15 mg/kg body weight.
35 kg body weight and above: target Hb ~ 150 g/1 and depot iron= 500mg.
* Factor 0.24 - 0.0034 x 0.07 x l000.
(Iron content of haemoglobin ~0.34%; Blood volume ~7% of body weight; Factor 1000 = conversion from g/1 to mg/I). (See Equation 2.)

Click on icon to see table/diagram/image

Alternatively, the total amount of Avofer Injection required in ml is determined from the following formula or dosage table. (See table.)

Click on icon to see table/diagram/image

To convert Hb (mM) to Hb (g/l), multiply the former by 16.1145.
Example: For a patient of 60 kg body weight with an actual Hb of 60 g/190 ml should be administered. (Alternatively 18 vials of5 ml should be administered.)
Normal Posology: Adults and the elderly: 5-10ml of Avofer (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 clinical need, it is recommended not to exceed 0.15ml Avofer (3mg iron) per kg body weight one to three times per week depending on the haemoglobin level.
Method of Administration: Monitor carefully patients for signs and symptoms of hypersensitivity reactions during and following each administration of Avofer Injection.
Avofer Injection should only be administered when staff trained to evaluate and manage anaphylactic reactions is immediately available, in an environment where full resuscitation facilities can be assured. The patient should be observed for adverse effects for at least 30 minutes following each Avofer Injection.
Avofer Injection must only be administered by the intravenous route. This may be by a slow intravenous injection or by an intravenous drip infusion. Avofer Injection 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: Iron (III) hydroxide Sucrose Injection must be diluted only in sterile 0.9% m/v sodium chloride solution: 5 ml Avofer lnjection (100mg iron) in maximum 100 ml sterile 0.9% m/v sodium chloride solution.
25 ml Avofer Injection (500 mg iron) in maximum 500 ml sterile 0.9% m/v sodium chloride solution.
For stability reasons, dilutions to lower Avofer Injection concentrations are not permissible.
Dilution must take place immediately prior to infusion and the solution should be administered as follow: 100 mg iron (5ml Avofer) in at least 15 minutes.
200 mg iron (10ml Avofer) in at least 30 minutes.
300 mg iron (15ml Avofer) in at least 1 ½ hours.
400 mg iron (20ml Avofer) in at least 2 ½ hours.
500mg iron (25ml Avofer) in at least 3 ½ hours.
As intravenous infusion, maximum tolerated single dose per day given not more than once per week: Patient above 70kg : 500mg iron (25ml Avofer) in at least 3 ½ hours.
Patient of 70kg and below: 7mg 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.
Intravenous Injection: Avofer can be administered undiluted by slow intravenous injection as follow: 100 mg iron (5ml Avofer) in at least 5 minutes.
200 mg iron (10ml Avofer) in at least 10 minutes.
As intravenous injection, the maximum tolerated single dose per day is 200mg, given not more than three times per week at injection rate of 1 ml undiluted solution per minute.
200mg iron (10 ml Avofer) injected over at least 10 minutes.
Injection into dialyzer: Avofer may be administered during haemodialysis session directly into the venous limb of the dialyzer under the same condition 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 Avofer injection is contraindicated in cases of: hypersensitivity to the active substance, to Avofer injection or any of its excipients; known serious hypersensitivity to other parenteral iron products; anaemias not attributable to iron deficiency; iron overload or disturbances in utilisation of iron.
Special Precautions
Parenterally administered iron preparations can cause hypersensitivity reactions serious and potentially fatal anaphylactic/anaphylactoid reactions. Hypersensitivity reactions have also been reported after previously uneventful doses of parenteral iron complexes.
The risk is enhanced for patients with known allergies including drug allergies, including patients with a history of severe asthma, eczema or other atopic allergy.
There is also an increased risk of hypersensitivity reactions to parenteral iron complexes in patients with immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis).
Iron (III) hydroxide Hydroxide Sucrose Injection should only be administered when staff trained to evaluate and manage anaphylactic reactions is immediately available, in an environment where full resuscitation facilities can be assured. Each patient should be observed for adverse effects for at least 30 minutes following each Iron (III) hydroxide Hydroxide Sucrose Injection. If hypersensitivity reactions or signs of intolerance occur during administration, the treatment must be stopped immediately. Facilities for cardio respiratory resuscitation and equipment for handling acute anaphylactic/anaphylactoid reactions should be available, including an injectable 1: 1000 adrenaline solution. Additional treatment with antihistamines and/or corticosteroids should be given as appropriate.
In patients with liver dysfunction, parenteral iron should only be administered after careful risk/benefit assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction where iron overload is a precipitating factor, in particular Porphyria Cutanea Tarda (PC1). Careful monitoring of iron status is recommended to avoid iron overload.
Parenteral iron must be used with caution in cases of acute or chronic infection. It is recommended that the administration of iron (III) hydroxide sucrose is stopped in patients with ongoing bacteraemia. In patients with chronic infection a risk/benefit evaluation has to be performed, taking into account the suppression of erythropoiesis.
Hypotensive episodes may occur if the injection is administered too rapidly. Allergic reactions, sometimes involving arthralgia, have been more commonly observed when the recommended dose is exceeded.
Paravenous leakage must be avoided because leakage of Iron (III) hydroxide Sucrose Injection 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: In the case of symptoms of dizziness, confusion or light headedness following the administration of Iron (III) Hydroxide Sucrose Complex Injection, patients should not drive or use machinery until the symptoms have ceased.
Use In Pregnancy & Lactation
There are no adequate and well-controlled trials of Iron (III) Hydroxide Sucrose Complex Injection in pregnant women. A careful risk/benefit evaluation is therefore required before use during pregnancy and Iron (III) Hydroxide Sucrose Complex Injection should not be used during pregnancy unless clearly necessary.
Iron deficiency anaemia occurring in the first trimester of pregnancy can in many cases be treated with oral iron. Treatment with Iron (III) hydroxide Sucrose Complex Injection should be confined to second and third trimester if the benefit is judged to outweigh the potential risk for both the mother and the foetus.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Data on a limited number of exposed human pregnancies indicated no adverse effects of Iron (III) hydroxide Sucrose Complex Injection on pregnancy or on the health of the foetus/newborn child.
Non metabolised Iron (III) hydroxide Sucrose Complex Injection 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.
Side Effects
The following data are based on the innovator product (Venofer 20mg iron/ml, solution for injection or concentrate for solution for infusion) summary of product characteristics from UK.
The most frequently reported adverse drug reactions (ADRs) of Iron (III) Hydroxide Sucrose Complex Injection 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.
The following adverse drug reactions have been reported with the administration of Iron (ID) Hydroxide Sucrose Complex Injection, with at least a possible causal relationship: Nervous system disorders: Common (≥ 1/100, < 1/10): transient taste perversions (in particular metallic taste). Uncommon (≥ 1/1000, < 1/100): headache, dizziness. Rare (≥ 1/10000, < 1/1000): paraesthesia, syncope, loss of consciousness, burning sensation.
Cardio-vascular disorders: Uncommon (≥ 1/1000, < 1/100): hypotension and collapse, tachycardia and palpitations. Rare (≥ 1/10000, < 1/1000): hypertension.
Respiratory, thoracic and mediastinal disorders: Uncommon (≥ 1/1000, < 1/100): bronchospasm, dyspnoea.
Gastrointestinal disorders: Uncommon (≥ 1/1000, < 1/100): nausea; vomiting, abdominal pain, diarrhoea.
Skin and subcutaneous tissue disorders: Uncommon (≥ 1/1000, < 1/100): pruritus, urticaria, rash, exanthema, erythema.
Musculoskeletal, connective tissue and bone disorders: Uncommon (≥ 1/1000, < 1/100): muscle cramps, myalgia.
General disorders and administration site disorders:
Uncommon (≥ 1/1000, < 1/100): fever, shivering, flushing, chest pain and tightness. Injection site disorders such as superficial phlebitis, burning, swelling. Rare (≥ 1/10000, < 1/1000): arthralgia, peripheral oedema, fatigue, asthenia, malaise, feeling hot, oedema.
Immune system disorders: Rare (≥ 1/10000, < 1/1000): 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, swelling of joints, hyperhidrosis, back pain, bradycardia, chromaturia.
Drug Interactions
As with all parenteral iron preparations, Iron (III) Hydroxide Sucrose Complex Injection should not be administered concomitantly with oral iron preparations since the absorption of oral iron is reduced. Therefore, oral iron therapy should be started at least 5 days after the last injection of Iron (III) Hydroxide Sucrose Complex Injection.
Caution For Usage
Special Precautions for Disposal and Other Handling: Vials 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.
Incompatibilities: Iron (III) Hydroxide Sucrose Complex must only be mixed with sterile 0.9% mN sodium chloride solution. No other solutions and therapeutic agents 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
For unopened vials: store below 30°C. Protect from light and moisture. Do not freeze.
Shelf-Life: 3 years.
Each vial of Iron (III) hydroxide. Hydroxide Sucrose Complex is intended for single use only. Discard any remaining contents after first use.
Shelf life of the product as packaged for sale: 36 months.
Shelf life after first opening of the container: Once opened, the product should be used immediately.
Specific for preparation for infusion or injection: Chemical and physical in-use stability has been demonstrated for 13 hours at 25°C and 4°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user.
ATC Classification
B03AC - Iron, parenteral preparations ; Used in the treatment of anemia
Presentation/Packing
Inj (sterile, brown, aqueous in vial) 100 mg/5 mL x 1's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in