MONOFERRIC (Iron Isomaltoside 1000 for Injection) 7 Warnings and Precautions

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Excessive therapy with parenteral iron can lead to excess storage of iron and possible iatrogenic hemosiderosis. Do not administer MONOFERRIC to patients with iron overload (see 2 CONTRAINDICATIONS).

Carcinogenesis and Mutagenesis

Carcinogenicity studies have not been conducted. MONOFERRIC showed no evidence of genotoxicity or mutagenicity in a standard battery of tests. These included an in vitro Ames test with and without metabolic activation, an in vitro human lymphocyte chromosome aberration test with and without metabolic activation and an in vivo mouse micronucleus test.


In clinical studies hypotension was reported in 0.7 % (29/3922) of patients, including serious events in 0.03 % (1/3922) of patients who received MONOFERRIC. Hypotension has also been reported in the post-marketing experience. Hypotensive episodes may occur if intravenous injection is administered too rapidly. Observe patients for signs and symptoms of hypersensitivity including hypotension during and for at least 30 minutes following each administration.


MONOFERRIC is contraindicated in patients with decompensated liver cirrhosis or active hepatitis (see 2 CONTRAINDICATIONS). In patients with compensated liver dysfunction, parenteral iron should only be administered after careful benefit/risk assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction (alanine aminotransferase and/or aspartate aminotransferase > 3 times upper limit of normal) where iron overload is a precipitating factor, in particular Porphyria Cutanea Tarda (PCT). Careful monitoring of iron status is recommended to avoid iron overload.



Parenterally administered iron preparations can cause hypersensitivity reactions including serious and potentially fatal anaphylactic/anaphylactoid reactions. Hypersensitivity reactions have also been reported after previously uneventful doses of parenteral iron complexes. MONOFERRIC is contraindicated in patients with known serious hypersensitivity to other parenteral iron products (see 2 CONTRAINDICATIONS).

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).

MONOFERRIC may cause life-threatening and fatal hypersensitivity reactions, including anaphylaxis and/or anaphylactoid reactions. In clinical trials, severe or serious hypersensitivity reactions were reported in 0.7% (28/3922) of patients who received MONOFERRIC and 0.2 % (8/3922) of these patients reported a severe or serious hypersensitivity reaction within 1 day of dosing. Hypersensitivity reactions have been seen in spontaneously reported adverse events from post-marketing experience (see 8 ADVERSE REACTIONS, Post-market Adverse Reactions).

Fishbane reaction is an infusion reaction characterised by flushing in the face, acute chest and/or back pain and tightness sometimes with dyspnoea that may occur with IV iron treatment (frequency uncommon). This may mimic the early symptoms of an anaphylactoid/anaphylactic reaction. The infusion should be stopped and the patient's vital signs should be assessed. These symptoms disappear shortly after the iron administration is stopped. They typically do not reoccur if the administration is restarted at a lower infusion rate.

Delayed reactions may also occur with parenteral iron preparations and can be severe. They are characterised by arthralgia, myalgia and sometimes fever. The onset varies from several hours up to four days after administration. Symptoms usually last two to four days and settle spontaneously or following the use of simple analgesics.

MONOFERRIC should only be administered when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitive reactions. Observe patients for signs and symptoms of hypersensitivity during and for at least 30 minutes following each administration of MONOFERRIC. If hypersensitivity reactions or signs of intolerance occur during administration, the treatment must be stopped immediately.


There is a risk that iron preparations enhance bacterial growth and inhibit leucocyte function and phagocytosis. Parenteral iron should be used with caution in case of severe acute or chronic infection. In patients with chronic infection a risk/benefit evaluation has to be performed, taking into account the suppression of erythropoiesis. MONOFERRIC should not be used in patients with ongoing bacteraemia.

Monitoring and Laboratory Tests

Patients must have confirmed iron deficiency anemia (IDA) based on appropriate laboratory tests before treatment (see 7 WARNINGS AND PRECAUTIONS, General). 

Regularly monitor the haematologic response and iron parameters, such as serum ferritin and transferrin saturation, during parenteral iron therapy. Monitoring of iron parameters such as serum ferritin may assist in recognizing iron accumulation. 

Monitor patient’s blood pressure and heart rate for signs and symptoms of hypotension before, during and for 30 minutes after each MONOFERRIC administration. Each patient should be observed for adverse effects, including signs and symptoms of hypersensitivity reactions (e.g., urticaria, oedema, bronchospasm, hypotension, cardiorespiratory arrest, syncope, unresponsiveness, or loss of consciousness) during administration and for at least 30 minutes following each MONOFERRIC administration. If hypersensitivity reactions or signs of intolerance occur during administration, the treatment must be stopped immediately.  


In clinical trials the frequencies of a transient drop in phosphate below 2 mg/dL have been 5 20 % in patients treated with MONOFERRIC from the studies in patients with iron deficiency anemia (IDA) of various aetiologies and 1-2 % in studies with chronic kidney disease (CKD) patients. Nadir was in the first weeks. No clinical symptoms were reported. One of the risks with profound hypophosphataemia is osteomalacia which has been reported after repeated use of IV iron. No cases of osteomalacia after MONOFERRIC use have been received.

Reproductive Health: Female and Male Potential

  • Fertility

MONOFERRIC did not affect fertility in male or female rats when administered intravenous (IV) at up to 19 mg/kg/day in males and 32 mg/kg/day in females (3 and 2.5 times the maximum recommended human (2000 mg in a 70 kg human) exposure from a single course of MONOFERRIC). Degenerative changes of the male reproductive system of unknown reversibility were observed in male rats at 80 mg/kg/day thrice weekly (5 times the maximum recommended human exposure from a single course of MONOFERRIC) (see 16 NON-CLINICAL TOXICOLOGY).


MONOFERRIC should be administered with caution to avoid paravenous leakage during administration. Paravenous leakage may lead to irritation of the skin and long-lasting brown discoloration at the injection site. In case of paravenous leakage, the administration of MONOFERRIC must be stopped immediately. Distant skin discolouration has also been reported.

7.1 Special Populations

7.1.1 Pregnant Women

There are no studies of MONOFERRIC in pregnant women.

Based on findings in nonclinical studies, MONOFERRIC should not be used during pregnancy; if pregnancy occurs, the patients should be informed of the potential risk. MONOFERRIC should not be used in women of childbearing potential not using adequate contraception.

Administration of ferric derisomaltose in pregnant rats at IV doses of 11 and 32 mg Fe/kg/day for 14 days prior to cohabitation and 17 days during gestation (2 and 6 times the maximum recommended human (2000 mg in a 70 kg human) exposure from a single course of MONOFERRIC) resulted in an increase in the incidence of skeletal developmental delays (see 16 NON-CLINICAL TOXICOLOGY). 

In pregnant rabbits, administration of 43 mg Fe/kg/day ferric derisomaltose for 14 days (7 times the maximum recommended human exposure from a single course of MONOFERRIC) resulted in an increased mortality, abortion, and/or premature delivery, a higher mean litter proportion of postimplantation loss, a corresponding lower mean number and litter proportion of viable fetuses, and lower mean fetal weights. Fetal malformations indicating teratogenicity were noted in the 25 and 43 mg Fe/kg/day groups (4 and 7 times the maximum recommended human exposure from a single course of MONOFERRIC, respectively), and fetal developmental variations were noted in the 43 mg Fe/kg/day (see 16 NON-CLINICAL TOXICOLOGY). 

Fetal bradycardia may occur following administration of parenteral irons. It is usually transient and a consequence of a hypersensitivity reaction in the mother. Patients should be advised of the potential risk to the fetus. If intravenous administration of MONOFERRIC to a pregnant woman occurs, the unborn baby should be carefully monitored.

7.1.2 Breast-feeding 

The available data on the use of MONOFERRIC in lactating women demonstrate that iron is present in breast milk. However, the data do not inform the potential exposure of iron for the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for MONOFERRIC in addition to any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition (see 10 CLINICAL PHARMACOLOGY). Monitor breastfed children for gastrointestinal toxicity (constipation, diarrhea).

7.1.3 Pediatrics 

Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

7.1.4 Geriatrics 

Clinical studies with MONOFERRIC have not identified differences in adverse reactions between elderly and younger adult patients, but there was a higher percentage of patients experiencing serious adverse events (SAEs) and adverse events (AEs) leading to fatal outcome in patients ≥ 65 years (SAEs: < 65 years at 5 %, ≥ 65 years at 11 %; AEs leading to fatal outcome: < 65 years at < 1 %, ≥ 65 years at 1 %). A careful risk benefit assessment is required before MONOFERRIC is used in patients aged > 65 years and close monitoring for adverse events is required.