Data Sheet
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`Page 1 of 6
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`Data Sheet
`
`Ferrosig
`Iron polymaltose 50 mg/ml
`
`Presentation
`
`A slightly viscous, dark reddish brown liquid. Odour faintly malt-like. Each ampoule of FERROSIG contains the
`equivalent of 100mg of iron.
`
`Uses
`
`Actions
`
`FERROSIG is complexed in an aqueous, approximately isotonic solution for intramuscular injection. The complex
`is stable over a wide pH range (1-14) and each ampoule contains the equivalent of 50mg iron per ml.
`Pharmacological tests have shown that the complex has a low toxicity with a LD50 (intravenous) of 400mg iron
`per kg in white mice.
`
`Pharmacokinetics
`
`After an infusion of 100mg iron as FERROSIG in 48ml 0.9% sodium chloride, at a rate of 1.7ml/min, a Cmax (in
`serum) of 25.1mcg/ml iron was observed. The terminal half-life was 22.4 hours. The MRT 20.2 hours and the VD
`(distribution volume) 2.93 litres. Renal elimination is less than 1% of the total dosage.
`
`Iron polymaltose shows a high structural homogeneity and thus steady delivery of the complexed iron to
`endogenous iron binding proteins. Taken up from plasma by the reticuloendothelial system (RES), the iron is split
`off, binds to transferrin and partially re-enters the plasma from where it reaches the bone marrow for haemoglobin
`synthesis.
`
`Indications
`
`For the prevention and treatment of iron deficiency anaemia in the following circumstances:
`
` When oral therapy is contraindicated
` When enteric absorption of iron is defective
` When patient non-compliance or persistent gastrointestinal intolerance makes oral therapy impractical
` Treating iron deficiency anaemia of prematurity and that occurring in geriatric patients
` Treating iron deficiency states discovered in the third trimester of pregnancy
` Anaemia resulting from excessive blood loss
` Where contact between the doctor and patient occurs at irregular intervals
`
`http://www.medsafe.govt.nz/Profs/Datasheet/f/Ferrosiginj.htm
`
`2/16/2010
`
`Luitpold Pharmaceuticals, Inc., Ex. 2003, p. 1
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01495
`
`

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`Data Sheet
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`Page 2 of 6
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`Dosage and Administration
`
`Intramuscular Use
`
`Technique of Injection
`
`The technique of injection is of crucial importance. FERROSIG should never be injected into the arm or other
`exposed areas. The wrong method may result in pain and discolouration of the skin.
`
`The following method of ventro-gluteal injection according to HOCHSTETTER is recommended instead of the
`normal method of injection in the top outer quadrant of the gluteus maximus muscle:
`
` The length of the needle should be at least 5-6cm. The lumen of the needle should not be too wide.
` According to HOCHSTETTER, the site of injection is determined as follows: First point A is found,
`corresponding to the ventral iliac spine. If the patient lies on the right side, for instance, the middle finger of
`the left hand is placed on point A. The index finger is extended away from the middle finger, so that it
`comes to lie below the iliac crest, at point B. The triangle lying between the proximal phalanges of the
`middle and index fingers represents the site of injection. This is disinfected in the usual way.
` Before the needle is inserted, the skin over the site of injection is pulled down, about 2cm, to give an S-
`shaped puncture channel. This prevents the injected solution from running back into the subcutaneous
`tissues and discolouring the skin.
` The needle is introduced more or less vertically to the skin surface, angled to point towards the iliac crest
`rather than the hip joint.
` After the injection, the needle is slowly withdrawn and pressure from a finger applied beside the puncture
`site. This pressure is maintained for about one minute.
` The patient should move about after the injection.
`
`Intravenous Use
`
`Total dose infusion of iron polymaltose complex is recommended only when the intramuscular route is impractical
`or unacceptable and when bone marrow shows no stored iron. It is suitable for use in hospitals only.
`
`The total dose to be administered, calculated from the dosage table, is aseptically added to 500ml of sterile,
`normal saline (up to 2500mg may be given in 500ml).
`
`Notes
`
` Do not inject the iron into the tube of the administration set.
` The first 50ml should be infused slowly (5-10 drops/minute) and the patient observed carefully. If this is
`well tolerated, the rate may be increased to 30 drops/minute (based on a drop volume of 0.067ml).
` To avoid nausea and epigastric troubles the infusion rate should not be excessive.
` The infusion should not be mixed with any other therapeutic agents. If mixed with acidic substances or
`other substances with a strong reducing effect toxic iron compounds may be liberated from the compound.
` Use the diluted solution within 12 hours.
`
`Calculation of Required Dose
`
`The figures in the accompanying dosage table have been calculated using the following formula taken from
`GANZONI (Wchweiz. Med. Wschr. 100, 301-619, 1970):
`
`Note: factor 0.24 = 0.0034 x 0.07 x 1000 (for the purposes of this calculation iron content of the haemoglobin =
`
`
`
`http://www.medsafe.govt.nz/Profs/Datasheet/f/Ferrosiginj.htm
`
`2/16/2010
`
`Luitpold Pharmaceuticals, Inc., Ex. 2003, p. 2
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01495
`
`

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`Data Sheet
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`Page 3 of 6
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`0.34%, blood volume = 7% of the body weight, 1000 is the conversion from grams to milligrams).
`
`The above formula can also be used to calculate the total iron deficit.
`
`Example of Calculation
`Assuming patient weighing 60kg, normal Hb 150g/L, actual Hb 60g/L then
`HB-iron deficiency = 60 x (150-60) x 0.24 = 1296mg + 500mg = 1800mg iron
`Therefore patient requires 1800mg iron or 18 ampoules.
`
`The requirements of iron reserves (stored iron) (ca. 15mg per kg up to a weight of about 34kg, total of 500mg
`about 34kg body weight).
`
`
`Normal Hb
`
`Body weight <34kg Body weight >34kg
`130g/L
`150g/L
`
`
`Dosage Table
`Dosage table for the determination of the total millilitres of FERROSIG injection required.
`
`Body weight
`kg
`
`5
`10
`15
`20
`25
`30
`35
`40
`45
`50
`55
`60
`65
`70
`75
`80
`85
`90
`
`Hb 105g/L
`Hb 90g/L
`Hb 75g/L
`Hb 60g/L
`mL ampoules mL ampoules mL ampoules mL ampoules
`3
`1.5
`3
`1.5
`3
`1.5
`2
`1
`6
`3
`6
`3
`5
`2.5
`4
`2
`10
`5
`9
`4.5
`7
`3.5
`6
`3
`13
`6.5
`11
`5.5
`10
`5
`8
`4
`16
`8
`14
`7
`12
`6
`11
`5.5
`19
`9.5
`17
`8.5
`15
`7.5
`13
`6.5
`25
`12.5
`23
`11.5
`20
`10
`18
`9
`27
`13.5
`24
`12.
`22
`11
`19
`9.5
`30
`15
`26
`13
`23
`11.5
`20
`10
`32
`16
`28
`14
`24
`12
`21
`10.5
`34
`17
`30
`15
`26
`13
`22
`11
`36
`18
`32
`16
`27
`13.5
`23
`11.5
`38
`19
`33
`16.5
`29
`14.5
`24
`12
`40
`20
`35
`17.5
`30
`15
`25
`12.5
`42
`21
`37
`18.5
`32
`16
`26
`13
`45
`22.5
`39
`19.5
`33
`16.5
`27
`13.5
`47
`23.5
`41
`20.5
`34
`17
`28
`14
`49
`24.5
`43
`21.5
`36
`18
`29
`14.5
`
`
`Administer 2ml by intramuscular injection every second day until the total dose is attained or administer 4ml at
`longer intervals. Regular determination of Hb level is recommended.
`
`Maximum Single Daily Dose by Intramuscular Injection
`Infants up to 5kg body weight: 0.5ml
`Children of 5-10kg body weight: 1ml
`Patients weighing >10kg to 45kg: 2ml
`
`http://www.medsafe.govt.nz/Profs/Datasheet/f/Ferrosiginj.htm
`
`2/16/2010
`
`Luitpold Pharmaceuticals, Inc., Ex. 2003, p. 3
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01495
`
`

`
`Data Sheet
`
`Adults: 4ml
`
`Contraindications
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`Page 4 of 6
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`FERROSIG should not be given to patients presenting with any of the following conditions:
`
` Hypersensitivity to iron(III) hydroxide polymaltose complex
` Anaemia not caused by simple iron deficiency (e.g. haemolytic anaemia, megablastic anaemia caused by
`Vitamin B12 deficiency, disturbances in erythropoesis, hypoplasia of the marrow)
` Iron overload (e.g. haemochromatosis, haemosiderosis)
` Ostler-Rendu-Weber syndrome
` Chronic polyarthritis
` Bronchial asthma
` Infectious renal complaints in acute phase
` Uncontrolled hyperparathyroidism
` Decompensated hepatic cirrhosis
` Infectious hepatitis
` During the first trimester of pregnancy
`
`As elemental iron tends to accumulate in inflamed tissues parenteral iron should not be given to patients with
`severe inflammation or infection of the kidney or liver.
`
`Warnings and Precautions
`
`Parentally administered iron preparations can cause allergic or anaphylactoid reactions. In the case of a mild
`allergic reaction, antihistamines should be administered immediately. Facilities for cardiopulmonary resuscitation
`must be available. Caution is recommended in patients with allergies and hepatic and renal insufficiency. The
`incidence of undesirable side effects in patients with angiocardiopathy may increase the related cardiovascular
`complications.
`
`Patients with bronchial asthma, with low iron binding capacity and/or folic acid deficiency are particularly at risk of
`an allergic or anaphylactoid reaction. Parenterally administered iron preparations can unfavourably influence the
`course of infections in children.
`
`Some cases of anaphylactic reactions after parenteral administration of iron having been described, it is
`recommended to initiate the treatment with a test dose to test the sensitivity of the patient.
`
`Use in pregnancy and lactation
`
`FERROSIG should not be administered in the first trimester of pregnancy. FERROSIG should only be
`administered in the second and third trimester of pregnancy if the benefits of treatment outweigh the potential risk
`to the foetus. No controlled studies are available on animals or on pregnant women.
`
`Adverse Effects
`
`Adverse reactions to parenteral FERROSIG have only been reported infrequently. However, the following
`reactions are known to have occurred after parenteral iron therapy:
`
`Intramuscular Injection
`
`Local reactions may include pain at the site of injection, local inflammation with inguinal lymphadenopathy, and
`lower quadrant abdominal pain. Systemic reactions after this form of administration are rare but may include
`anaphylaxis. (Reference is made to the following paragraph describing delayed systemic reactions).
`
`http://www.medsafe.govt.nz/Profs/Datasheet/f/Ferrosiginj.htm
`
`2/16/2010
`
`Luitpold Pharmaceuticals, Inc., Ex. 2003, p. 4
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01495
`
`

`
`Data Sheet
`
`Intravenous Drip Therapy
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`Page 5 of 6
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`Systemic reactions may include headache, nausea, vomiting, joint and muscle pains, faintness, tachycardia,
`flushing, sweating, bronchospasm with dyspnoea, hypotension, dizziness and circulatory collapse.
`
`Delayed systemic reactions
`
`Delayed systemic reactions may include dizziness, syncope, a sensation of stiffening of the arms, legs or face,
`chest and back pain, arthralgia, chills, fever, rash, urticaria, angioneurotic oedema and generalised
`lymphadenopathy.
`
`Interactions
`
`As with all parenteral iron preparations, FERROSIG ampoules should not be administered concomitantly with oral
`iron preparations as the absorption of oral iron is reduced. Oral iron therapy should not commence until at least
`one week after the last iron injection.
`
`Concomitant administration of ACE inhibitors can increase the systemic effect of parenteral iron preparations.
`
`Overdosage
`
`Not available.
`
`Pharmaceutical Precautions
`
`The ampoules should be stored below 25°C. Do not freeze. Protect from light. When diluted in saline the solution
`should be used within 12 hours.
`
`Medicine Classification
`
`Prescription Medicine.
`
`Package Quantities
`
`Cartons of 5 x 2ml ampoules, each ampoule containing 100mg Fe as iron polymaltose.
`
`Further Information
`
`FERROSIG contains a macromolecular spherocolloidal complex of iron(III) hydroxide and the carbohydrate ligand
`polymaltose. The complex has a molecular weight of about 462,000.
`
`The aqueous colloidal solution is sterile, pyrogen-free and approximates the pH and tonicity of the tissues.
`
`Excipients
`
`Water - purified, sodium hydroxide (for pH adjustment).
`
`http://www.medsafe.govt.nz/Profs/Datasheet/f/Ferrosiginj.htm
`
`2/16/2010
`
`Luitpold Pharmaceuticals, Inc., Ex. 2003, p. 5
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01495
`
`

`
`Data Sheet
`
`Page 6 of 6
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`Name and Address
`
`Zuellig Pharma Limited
`54 Carbine Road
`Mt Wellington
`Auckland
`
`Telephone: (09) 570 1080
`
`Date of Preparation
`
`10 July 2003
`
`http://www.medsafe.govt.nz/Profs/Datasheet/f/Ferrosiginj.htm
`
`2/16/2010
`
`Luitpold Pharmaceuticals, Inc., Ex. 2003, p. 6
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01495