Prescription Information

(Product Monograph)

English PDF



PART 1: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Does not contain gluten or lactose.

INDICATION AND CLINICAL USE

FeraMAX® 150 (polysaccharide-iron complex) is indicated for:

  • The treatment of iron deficiency and iron deficiency anaemia
  • Iron is required for the formation of hemoglobin, myoglobin, cytochromes and peroxidase
  • Iron is a factor in the maintenance of good health and helps to form red blood cells

CONTRAINDICATIONS

FeraMAX® 150 (polysaccharide-iron complex) is contraindicated in:

  • Hemosiderosis
  • Hemochromatosis
  • Known hypersensitivity to any of the components of this product

WARNINGS AND PRECAUTIONS

When a diagnosis of iron deficiency or iron deficiency anaemia has been made, its nature should be established and underlying causes determined.

Keep out of reach of children. There is enough drug in this in this package to seriously harm a child. In case of accidental over dosage, seek professional assistance or contact a Poison Control Centre immediately.

ADVERSE REACTIONS

Some people may experience gastrointestinal side effects.

DRUG INTERACTIONS

If an interaction is suspected, take a few hours before or after taking other medications.

Listed below is a recap of associated of drugs and medical conditions from clinical trials using polysaccharide-iron complex.

DOSAGE AND ADMINISTRATION

Usual adult dose of FeraMAX® 150 is one capsule daily or as directed by a health care practitioner. FeraMAX® 150 allows for once a day dosing for patients who require a higher dose of elemental iron. For patients who may have difficulty swallowing capsules, the capsule can be opened and the powder can be diluted in liquid or sprinkled on food.

Dose Equivalent – Oral Formulations

SAFETY / OVERDOSAGE17,19,20

No human toxicity data on polysaccharide-iron complex (PIC) is available. The American Association of Poison Control Centres (AAPCC) suggests that there is reduced toxicity for PIC relative to other forms of iron.

A retrospective analysis of potential toxic exposures to PIC reported to the AAPCC Toxic Exposure Surveillance System from 1990 to 1998 was undertaken. The majority of outcomes (95.6%) were no effect, minor effect, unrelated effect, not followed since nontoxic, or not followed since only minimal toxicity possible. There were no serious adverse events following PIC exposure reported to the AAPCC.

The oral LD50 of PIC was estimated to be greater than 5000 mg iron/kg in rats. Chronic toxicity studies in rats and dogs administered PIC (polysaccharide-iron complex) showed that a daily dosage of 250 mg iron/kg for three months had no adverse effects.

From 1983-1991 in the United States, iron caused over 30% of the deaths from accidental ingestion of drug products by children. The recommendations of the panel concluded that: paediatric or adult patients with a known ingestion of 40 mg/kg or greater of elemental iron in the form of adult ferrous salt formulations or who have severe or persistent symptoms related to iron ingestion should be referred to a healthcare facility for medical evaluation. Patients with unintentional ingestions of PIC formulations should be observed at home with appropriate follow-up.

In comparison to other iron formulations, the FeraMAX® 150 PIC is non-ionic, tasteless, and clinically non-toxic.

ACTION AND CLINICAL PHARMCOLOGY

Mechanism of Action1,3

Iron is an essential component in the formation of hemoglobin. Iron deficiency generally develops slowly and is not clinically apparent until anaemia is present as a severe stage of iron deficiency.

FeraMAX® 150 PIC is derived by chemical complexation of elemental iron with polysaccharides formed by partial acid hydrolysis of starch under controlled conditions. It is unique because of its low molecular weight of approximately 600 g/mol and its straight-chained molecular configuration.

The chemical structure of PIC differs substantially from conventional oral iron products (ferrous sulfate, gluconate, and fumarate). PIC is a non-ionic, low molecular weight complex composed of spheres which range in diameter from 3 to 10 nm. The spheres are composed of iron atoms interspersed among tightly packed oxygen atoms. These spheres are surrounded by a polysaccharide coat. PIC contains no free iron ions and is capable of maintaining relatively high concentrations of iron in a soluble, nontoxic form at physiological pH.

Pharmacokinetics

Standard approaches are not appropriate when assessing pharmacokinetics of iron supplements due to the ubiquity of endogenous iron, its compartmentalized sites of action, and the complexity of iron metabolism. The primary site of action of iron is the erythrocyte, and in contrast to conventional drugs, no drug-receptor interaction takes place. Notably, the process of erythropoiesis, i.e. formation of new erythrocytes, takes 3−4 weeks. Accordingly, serum iron concentration and area under the curve (AUC) are clinically irrelevant for assessing iron utilization.

Absorption

PIC (polysaccharide-iron complex) is a synthetic complex of ferric iron and carbohydrate. It does not suffer from some of the disadvantages of ferrous iron supplements in that it does not readily ionize and combine with inhibiting substances in the gut, while it remains soluble enough to cross the mucosal barrier of the intestinal lumen. PIC is believed to be absorbed via an active transport mechanism wherein iron at the surface of the intestinal mucosa in bound to a carrier (transferrin) for transport into the blood stream.

The amount absorbed is dependent upon the degree of iron deficiency or iron deficiency anaemia and is monitored by changes in factors such as hemoglobin and hematocrit.

Excretion

There is no physiological mechanism to increase or reduce the excretion of iron. Small losses occur in the feces, from hemoglobin, bile, and by shedding cells of endothelial cells. A small amount of iron is also lost via the urine, sweat, tears, and the sloughing off of skin cells. Iron depletion can also occur through acute or chronic loss of blood, which is a common cause of iron deficiency.

STORAGE AND STABILITY

Store at controlled room temperature 15◦C - 30◦C. FeraMAX® 150 Carton of 30 has a 2 years and 5 months shelf life and FeraMAX® 150 Bottle of 100 has a 4 year shelf life.

DOSAGE FORMS, COMPOSITION AND PACKAGING

FeraMAX® 150 is a dark brown powder which dissolves in water to form a very dark brown solution. It is virtually tasteless and odorless. Because it is an organic complex, it contains no free ions. PIC is capable of maintaining relatively high concentrations of iron in a soluble, nontoxic form at physiological pH.

The Polysaccharide-Iron Complex (PIC) in FeraMAX® 150 is an ionized iron delivery system that allows the ionic iron to be delivered to the bloodstream, without coming into contact with the stomach or upper GI tract. FeraMAX® 150 is absorbed intact through the small intestine where it is then delivered to the bloodstream. There, the polysaccharide starch is broken away from the ionic iron by an enzymatic process. This process can occur because of the unique polarity of the PIC. Once free from the PIC, the ionized iron can be used by the body to make hemoglobin.

FeraMAX® 150 capsules are supplied as capsular-shaped, biconvex capsules imprinted with “FMX 150” in child resistant bottles of 100 and blister packs of 30.

Oral Iron Comparison

Iron supplementation requirements will vary by patient and may require dosing options that become impractical in the treatment of iron deficiency. Other factors to consider are associated diseases and the number of additional medications that are prescribed. FeraMAX® 150 may allow for a reduction in the number of doses per day especially for patients requiring high amounts of elemental iron. Considerations should be given to patients who are taking numerous medications to reduce their overall pill burden (i.e. chronic kidney disease).

PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Proper name: polysaccharide-iron complex

AHFS classification: 20:04.04 Iron Preparations

Active ingredient group number: 0108536027

Anatomical Therapeutical Chemical (ATC): B03AB02 SACCHARATED IRON OXIDE

NAPRA Schedule: Schedule II

NPN Number: 80013210

Physicochemical Properties: FeraMAX® 150 is based upon a unique and proprietary formulation of polysaccharide-iron complex formulated to deliver 150mg of elemental iron per capsule. PIC differs from typical iron salt formulations. The PIC is a non-ionic iron hematinic whereby the polar oxygen groups in the polysaccharide form coordination complex with the iron atoms. The well- hydrated microspheres of polysaccharide iron remain in solution over a wide pH range

CLINICAL TRIALS

Formulated by a proprietary process, PIC was first introduced by Central Pharmaceuticals in the United States and sold under the brand name Niferex. Now known as JLM Pharmatech, PIC is manufactured from raw material to finished dosage forms using the same formulation as the original brand and currently sold under the brand name FeraMAX®, exclusively sold to BioSyent Pharm Inc.

Additional formulations of PIC include FeraMAX® Powder (120 x 15 mg of elemental iron doses). PIC formulations from the same manufacturer have included: PIC as part of a multi-vitamin, PIC as part of a pre-natal vitamin and PIC combined with folic acid for pregnancy.

Listed below in the Table is a review of publications including date and patient characteristics of studies using PIC.

Dosage and Administration during Clinical Trials (PIC has been evaluated over a wide range of dosing)

Clinical Efficacy

PIC has been evaluated in a wide variety of patient groups resulting in an increase in hemoglobin and where applicable, hematocrit in all studies.

Side Effects

The side effects associated with polysaccharide-iron complex are shown in the table below. PIC is generally well tolerated in a variety of patients. Of note in the Feagan study, only 2% of patients experienced side effects which necessitated in a reduction in dose or discontinuation of therapy.

Clinical Efficacy in Renal Dialysis Patients

In patients with renal disease who require iron supplementation, PIC may have a role to play. Recommendations state that a minimum of 200 mg of elemental iron be used and to continue to monitor the effects and adjust the dose accordingly. Shown below in the two tables are the results from 2 studies within this patient group.

Hefferman10 – Hematologic Results (means ± deviation)

Johnson11 – Laboratory values before and after PIC

Side Effects in Renal Dialysis Patients

Side effects associated with iron supplementation are of major importance. To increase absorption, ferrous salts are typically prescribed on an empty stomach, which increases side effects. To compensate, they are given with food, which decreases absorption.

Also in this patient population, additional medicines are prescribed which also cause and add to the potential for gastrointestinal side effects.

The major limitation with oral iron supplementation is compliance due to gastrointestinal upset (both diarrhea and constipation.) Hence it is also not possible to achieve the necessary oral iron dosages that are required in some patients.

Hefferman10 – Gastrointestinal symptom scores at baseline and 12 weeks

Johnson11 – Results of Adverse Effects Questionnaire

 

REFERENCES

1. Bereman, Robert D, Berg KA: The structure, size and solution chemistry of a polysaccharide iron complex (Niferex®). Inorganica Chimica Acta 1989; 155: 183-189.

2. Mohie-Eldin: A comparison of the magnetic properties of polysaccharide iron complex (PIC) and ferritin. Journal of Magnetism and Magnetic Materials 135(1994) 65-81.

3. Coe, Emma M: The re-characterization of a polysaccharide iron complex. Journal of Inorganic Biochemistry, 58, 269-278(1995).

4. Andrews, N: Disorders of Iron metabolism, The New England Journal of Medicine. Vol. 341, no 26.pp 1986-1995

5. Sanders J: Clinical response to iron-polysaccharide complex in geriatric patients with iron-deficient anemia, Michigan Medicine, 1968 ;67(11): 726-27

6. Crawford OW: Oral treatment of iron deficiency anemia. Illinois Med J,1970; 137: 60-63

7. Bonchil, G Treatment of iron deficiency anaemia with polysaccharide-iron complex,1975 Translation of a clinical report

8. Newton R.W. Prophylaxis of iron-deficiency anemia of prematurity. Oral and intramuscular iron in preterm infants. Clin Tri J 1980,Vol.17 No.3:106-111

9. Piccinni L, Ricciotti M: Therapeutic effectiveness of an iron-polysaccharide complex in comparison with iron fumarate in the treatment of iron deficiency anaemia. Pan Minerva Medica 1982;Vol24-No.3;213-220

10. Heffernan, Patrick J. Polysaccharide-iron complex use in chronic dialysis patients receiving erythropoietin. American Society of Hospital Pharmacists Midyear Clinical Meeting, Dec,1991,1-22

11. Johnson CA, Rosowski E, Zimmerman SW: A prospective open-label study evaluating the efficacy and adverse reactions of the use of Niferex-150 in ESRD patients receiving EPOGEN. Adv Perit Dial 1992;8:444-447

12. Naude S, Clijsen S. Naulaers G, Daniels H, Vanhole C, Devlieger H: Iron supplementation in preterm infants: A study comparing the effect and tolerance of a Fe2+ and a non-ionic FeIII compound. J Clin Pharmacol 2000; 40: 1447-1451.

13. Feagan, Brian G et al: Erythropoietin with iron supplementation to prevent allogeneic blood transfusion in total hip joint arthroplasty. Ann Intern Med 2000;133: 845-854

14. Gelone, Daniele K: Lack of an effect of oral administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients. Pharmacotherapy 2007; 27(9):1272-1278.

15. Kaufman, James S: Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. NEJM, Aug 27,1998,pp 578-583

16. McCluskey. S Treatment of Post-Operative Anemia: Intravenous Iron Compound Compared to Intravenous Iron and Erythropoietin .Anesthesiology 2005; 103: A454

17. Klein-Schwartz W: Toxicity of polysaccharide-iron complex exposures reported to poison control centers. The Annals of Pharmacology 2000, February, Vol. 34; 165-169.

18. Finkelstein. Y: Universal versus Selective Iron Supplementation for Infants and the Risk of Unintentional Poisoning in Young Children: A Comparative of Two Populations. The Annals of Pharmacotherapy 2007 March, Volume 41.pp 414-419

19. Merriman, Todd N: An acute oral toxicity study in rats with polysaccharide iron complex – Final Report. Springborn Laboratories Inc., Spencerville Ohio, 1994,1-40

20. Manoguerra, Anthony et al: Iron Ingestion: an evidence–based consensus guideline for out-of-hospital management. Clinical Toxicology,43:553-570,2005

21. Coe, Emma M. Comparison of polysaccharide iron complexes used as iron supplements. Journal of inorganic biochemistry,57,287-292(1995)

PART III: CONSUMER INFORMATION

FeraMAX® 150

Polysaccharide-iron complex

This leaflet is part III of a three-part "Product Monograph" produced when FeraMAX® 150 was approved for sale in Canada and is designed specifically for Consumers. This leaflet is a summary and will not tell you everything about FeraMAX® 150.

Contact your doctor or pharmacist if you have any questions about the drug.

ABOUT THIS MEDICATION

What the medication is used for:

FeraMAX® 150 is used in the treatment of iron deficiency and/or iron deficiency anaemia.

What it does:

Iron is a mineral needed by our bodies as it is a part of all cells. Iron deficiency is a condition resulting from too little iron in the body. There are times when you cannot obtain the required amount of iron from diet alone and your health care practitioner may then suggest a product like FeraMAX® 150 to help with your deficiency.

When it should not be used:

Do not use FeraMAX® 150 if:

  • You know you are allergic (hypersensitive) to the active substance or to any of the ingredients of FeraMAX® 150
  • You have not been diagnosed as being iron deficient
  • The product has expired (taken past the date on the label)

What the medicinal ingredient is:

Polysaccharide-iron complex

What the nonmedicinal ingredients are:

D&C Red # 28, D&C Yellow # 10, FDC Blue # 1, FDC Red # 40, gelatin, magnesium stearate, microcrystalline cellulose and titanium dioxide

What the product does not contain:

FeraMAX® 150 does not contain any gluten or lactose.

What dosage forms it comes in:

FeraMAX® 150 is supplied in a capsular-shaped, biconvex capsule that contains 150 mg of elemental iron. FeraMAX® 150 is available in a Carton of 30 capsules and Bottle of 100 capsules.

WARNINGS AND PRECAUTIONS

Keep out of reach of children. There is enough drug in this package to seriously harm a child.

INTERACTIONS WITH THIS MEDICATION

It is best to take FeraMAX® 150 if possible a few hours before or after taking other medications.

PROPER USE OF THIS MEDICATION

Use FeraMAX® 150 only as prescribed or ordered by your health care practitioner. Do not change the amount you take or how often you take it unless directed to do so by a health care practitioner.

FeraMAX® 150 can be taken with or without food. As an option, the capsules can be broken open and mixed with water or sprinkled on food which will not affect the efficacy or tolerability of the product.

Usual dose:

The dose of FeraMAX® 150 will be determined by your health care practitioner depending upon the degree of iron deficiency. It is best to take FeraMAX® 150 at the same time every day.

Missed dose:

If you forgot to take your dose do not take your missed dose with the next dose. To help remember, take the dose at the same time each day (for example before bed.)

Overdose:

In case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Like all medicines, FeraMAX® 150 can cause side effects, although not everybody gets them. These could include things like constipation and diarrhea. These side effects have been shown to be lower than other commonly used iron supplements.

HOW TO STORE THIS MEDICATION

Keep FeraMAX® 150 and other medications out of the reach of children. FeraMAX® 150 should be stored at temperatures between 15ºC - 30ºC. Like all medications, FeraMAX® 150 should not be stored in the bathroom cabinet.

MORE INFORMATION

Additional information is available online at www.feramax.com or by contacting BioSyent Pharma Inc. at: 1-888-439-0013

This leaflet was prepared by BioSyent Pharma Inc. Toronto, ON.

Last revised: May 28th, 2013.