Last Updated on eMC 09-06-2017 View medicine  | Pharmacosmos UK Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:19-05-2017

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



In section 4.2 Posology and method of administration

Addition to wording under ‘simplified table’, wording added:

The treatment effect should be monitored by blood tests. To reach the target Hb-level, the cumulative iron dose may need adjustment.

 

In section 4.3 Contraindications

Change to wording

From:

Decompensated liver cirrhosis and hepatitis

To:

Decompensated liver disease

 

In section 4.4 Special warnings and precautions for use

Additional wording added:

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.

 

Caution should be exercised to avoid paravenous leakage when administrating Monofer. Paravenous leakage of Monofer at the injection site may lead to irritation of the skin and potentially long lasting brown discolouration at the site of injection. In case of paravenous leakage, the administration of Monofer must be stopped immediately.

 

In section 4.6 Fertility, pregnancy and lactation

Sub heading added in first paragraph: Pregnancy

 

Removal of wording in first paragraph: (see section 4.4)

 

Addition of wording in second paragraph, wording added: 

In rare cases, foetal bradycardia has been observed in pregnant women with hypersensitivity reactions (see section 4.8).

 

Change to wording

From:

There is no information available on the excretion of Monofer in human breast milk.

To:

Breast-feeding

A clinical study showed that transfer of iron from Monofer to human milk was very low. At therapeutic doses of Monofer no effects on the breastfeed newborns/infants are anticipated.

 

Additional wording added:

Fertility

There are no data on the effect of Monofer on human fertility. Fertility was unaffected following Monofer treatment in animal studies (see section 5.3).

 

In section 4.8 Undesirable effects

Additional wording added:

The table presents the adverse drug reactions (ADRs) reported during Monofer treatment in clinical trials and in-market experience.

Acute severe hypersensitivity reactions may occur with parenteral iron preparations. They usually occur within the first few minutes of administration and are generally characterised by the sudden onset of respiratory difficulty and/or cardiovascular collapse; fatalities have been reported. Other less severe manifestations of immediate hypersensitivity, such as urticaria and itching may also occur. In pregnancy, associated foetal bradycardia may occur with parenteral iron preparations.

Flushing in the face, acute chest and/or back pain and tightness sometimes with dyspnea in association with IV iron treatment may occur (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.

 

Change to adverse event reaction overview:

From:

Due to limited clinical data on Monofer the mentioned undesirable effects are primarily based on safety data for other parenteral iron solutions.

More than 1% of patients may be expected to experience adverse reactions.

Acute, severe anaphylactoid reactions may occur with parenteral iron preparations, although they are uncommon. They usually occur within the first few minutes of administration and are generally characterised by the sudden onset of respiratory difficulty and / or cardiovascular collapse; fatalities have been reported. Other less severe manifestations of immediate hypersensitivity are also uncommon and include urticaria, rashes, itching, nausea and shivering. Administration must be stopped immediately if signs of an anaphylactoid reaction are observed.

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. In addition, exacerbation of joint pain in rheumatoid arthritis can occur and local reactions may cause pain and inflammation at or near injection site and a local phlebitic reaction.

 

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very Rare (<1/10,000)

Not known (cannot be estimated with the available data)

 
Cardiac disorders

Rare: Arrhythmia, tachycardia

Very rare: Foetal bradycardia, palpitations

 
Blood and lymphatic system disorders

Very rare: Haemolysis

 
Nervous system disorders

Uncommon: Blurred vision, numbness, dysphonia

Rare: Loss of consciousness, seizure, dizziness, restlessness, tremor, fatigue, altered mental status

Very rare: Headache, paresthesia

 
Ear and labyrinth disorders

Very rare: Transient deafness

 
Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Rare: Chest pain

 
Gastrointestinal disorders

Uncommon: Nausea, emesis, abdominal pain, constipation

Rare: Diarrhoea

 
Skin and subcutaneous tissue disorders

Uncommon: Flushing, pruritus, rash

Rare: Angioedema, sweating

 
Musculoskeletal and connective tissue disorders

Uncommon: Cramps

Rare: Myalgias, arthralgia

 
Vascular disorders

Rare: Hypotension

Very rare: Hypertension

 
General disorders and administration site conditions

Uncommon: Anaphylactoid reactions, feeling hot, fever, soreness, inflammation near the injection site, local phlebitic reaction

Rare: Fatigue

Very rare: Acute severe anaphylactic reactions

 

To:

Adverse drug reactions observed during clinical trials and post-marketing experience

 

System Organ Class

Common (≥1/100 to <1/10)

Uncommon (≥1/1000 to <1/100)

Rare (≥1/10000 to <1/1000)

Immune system disorders

 

Hypersensitivity, including severe reactions

Anaphylactoid/

anaphylactic reactions

Nervous system disorders

Headache, paraesthesia, dysgeusia, blurred vision,

loss of consciousness, dizziness, fatigue

Dysphonia, seizure,

tremor, altered mental status

Cardiac disorders

 

Tachycardia

Arrhythmia

Vascular disorders

Hypotension, hypertension

Respiratory, thoracic and mediastinal disorders

 

Chest pain, dyspnoea, bronchospasm

Gastrointestinal disorders

Nausea

Abdominal pain, vomiting, dyspepsia, constipation, diarrhoea

Skin and subcutaneous tissue disorders

 

Pruritus, urticaria, rash, flushing, sweating, dermatitis

Angioedema

Metabolism and nutritional disorders

 

Hypophosphataemia

 

 

Musculoskeletal and connective tissue disorders

 

Back pain, myalgia, arthralgia, muscle spasms

 

General disorders and administration site conditions

Injection site reactions*

Pyrexia, chills/shivering, infection, local phlebitic reaction

Malaise, influenza like symptoms

Investigations

 

Hepatic enzyme increased

 

* Includes the following preferred terms, i.e. injection site erythema, -swelling, -burning, -pain, -bruising, -discolouration, -extravasation, -irritation, -reaction.

 

Description of selected adverse reactions

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.

In section 5.1 Pharmacodynamic properties

Change to and addition of wording:

From:

Monofer solution for injection is a colloid with strongly bound iron in spheroidal iron-carbohydrate particles. Each particle consists of an iron(III) core and a carbohydrate shell of isomaltosides that surrounds and stabilises the core. The chelation of iron(III) with a carbohydrate shell confers to the particles a structure resembling ferritin that is suggested to protect against the toxicity of unbound inorganic iron(III).

The iron is available in a non-ionic water-soluble form in an aqueous solution with pH between 5.0 and 7.0. The toxicity is low and Monofer can therefore be administered in large doses.

Evidence of a therapeutic response can be seen within a few days of administration of Monofer as an increase in the reticulocyte count.

Serum ferritin peaks approximately 7 to 9 days after an intravenous dose of Monofer and slowly returns to baseline after about 3 weeks.

 

To:

The Monofer formulation contains iron in a complex that enables a controlled and slow release of bioavailable iron to iron-binding proteins with little risk of free iron.

Each particle consists of a matrix of iron(III) atoms andisomaltoside pentamers. The chelation of iron(III) with carbohydrate confers to the particles a structure resembling ferritin that is suggested to protect against the toxicity of unbound inorganic iron(III).

The iron is available in a non-ionic water-soluble form in an aqueous solution with pH between 5.0 and 7.0.

Evidence of a therapeutic response can be seen within a few days of administration of Monofer as an increase in the reticulocyte count. Due to the slow release of bioavailable iron serum ferritin peaks within days after an intravenous dose of Monofer and slowly returns to baseline after weeks.

 

Additional section added on Clinical efficacy:

Clinical efficacy

The efficacy of Monofer has been studied in the different therapeutic areas necessitating IV iron to correct iron deficiency. The main trials are described in more detail below.

 

Iron deficiency anaemia outside CKD

The P-Monofer-IDA-01 trial was an open-label, comparative, randomised, multi-centre, non-inferiority trial conducted in 511 patients with IDA randomised 2:1 to either Monofer or iron sucrose.  90 % of recruited patients were females. The dosing of Monofer was performed according to the Simplified Table as described in section 4.2 above and dosing of iron sucrose was calculated according to Ganzoni and administered as 200 mg infusions. The primary endpoint was the proportion of patients with an Hb increase ≥2 g/dL from baseline at any time between weeks 1 to 5. A higher proportion of patients treated with Monofer compared to iron sucrose reached the primary endpoint, 68.5% vs 51.6%, respectively.(FAS, p < 0.0001).

 

Nephrology

Non-dialysis-dependent chronic kidney disease

The P-Monofer-CKD-02 trial was an open-label, comparative, randomised, multi-centre, non-inferiority trial conducted in 351 iron deficient non-dialysis dependent (NDD) chronic kidney disease (CKD) patients, randomised 2:1 to either Monofer or oral iron sulphate administered as 100 mg elemental oral iron twice daily (200 mg daily) for 8 weeks. The patients in the Monofer group were randomized to infusion of 1000 mg single dose or bolus injections of 500 mg.Monofer was both non-inferior to oral iron at week 4 (p<0.001) and  also sustained a superior increase in Hb compared to oral iron from week 3 until the end of trial at week 8 (p=0.009 at week 3).

 

Haemodialysis-dependent chronic kidney disease

The P-Monofer-CKD-03 trial was an open-label, comparative, randomised, multi-centre, non-inferiority trial conducted in 351 haemodialysis patients randomised 2:1 to either Monofer or iron sucrose. Patients were randomised to either a single injection of 500 mg or 500 mg in split doses of Monofer or 500 mg iron sucrose in split doses. Both treatments showed similar efficacy with more than 82% of patients with Hb in the target range (non-inferiority, p=0.01).

 

Oncology

Cancer related anaemia

The P-Monofer-CIA-01 trial was an open-label, comparative, randomised, multi-centre, non-inferiority trial conducted in 350 cancer patients with anaemia randomised 2:1 to either Monofer or oral iron sulphate administered as 100 mg elemental oral iron twice daily (200 mg daily) for 12 weeks. The patients in the Monofer group were randomised to either an infusion of max 1000 mg single doses over 15 min or bolus injections of 500 mg over 2 min. The primary endpoint was change in Hb concentrations from baseline to week 4. Monofer was non-inferior to oral iron at week 4 (p<0.001) and a faster onset of the Hb response was observed with infusion of Monofer.

 

Gastroenterology

Inflammatory bowel disease

The P-Monofer-IBD-01 trial was an open-label, comparative, randomised, multi-centre, non-inferiority trial conducted in 338 inflammatory bowel disease (IBD) patients randomised 2:1 to receive either Monofer or oral iron sulphate administered as 100 mg elemental oral iron twice daily for 8 weeks (200 mg daily). The patients in the Monofer group were randomised to either an infusion of max 1000 mg single doses over 15 min or bolus injections of 500 mg over 2 min. A modified Ganzoni formula was used to calculate the IV iron need with a target Hb of only 13 g/dL resulting in an average iron dose of 884 mg elemental iron compared to oral iron administered as 200 mg oral iron sulfate once daily for 8 weeks (11,200 mg elemental

oral iron in total). The primary endpoint was change in Hb concentrations from baseline to week 8. The patients had mild to moderate disease activity. Non-inferiority in change of Hb to week 8 could not be demonstrated. The dose-response relationship observed with Monofer suggests that the true iron demand of IV iron was underestimated by the modified Ganzoni formula. The Hb response rate was 93% for patients receiving > 1000 mg Monofer.

 

Women's health

Postpartum

The P-Monofer-PP-01 trial was an open-label, comparative, randomised, single-centre, non-inferiority trial conducted in 200 healthy women with  postpartum haemorrhage exceeding 700 mL within 48 hours after delivery. The women were randomised 1:1 to receive either a single dose of 1200 mg Monofer or standard medical care. The primary endpoint was the aggregated change in physical fatigue within 12 weeks postpartum. The difference in aggregated change in physical fatigue score within 12 weeks postpartum was -0.97 (p=0.006), in favour of Monofer.

 

In section 5.2 Pharmacokinetic properties

Change to and addition of wording in first paragraph:

 

From:

 

The Monofer formulation contains iron in a strongly bound complex that enables a controlled and slow release of bioavailable iron to iron-binding proteins with little risk of free iron.

 

To:

The Monofer formulation contains iron in a strongly bound complex that enables a controlled and slow release of bioavailable iron to iron-binding proteins with little risk of free iron toxicity. After administration of a single dose of Monofer of 100 to 1000 mg of iron in pharmacokinetic studies, the iron injected or infused was cleared from the plasma with a half-life that ranged from 1 to 4 days. Renal elimination of iron was negligible.

 

Removal of wording in second paragraph:

The plasma half-life is 5 hours for circulating iron and 20 hours for total iron (bound and circulating).

 

In section 5.3 Preclinical safety data

Change to wording:

 

From:

Iron complexes have been reported to be teratogenic and embryocidal in non-anaemic pregnant animals at high single doses above 125 mg iron/kg body weight. The highest recommended dose in clinical use is 20 mg iron/kg body weight.

There are no other additional preclinical data of relevance to the prescriber than those already included in other sections of the SPC.

 

To:

Iron complexes have been reported to be teratogenic and embryocidal in non-anaemic pregnant animals at high single doses above 125 mg iron/kg body weight. The highest recommended dose in clinical use is 20 mg iron/kg body weight.

In a fertility study with Monofer in rats no effects on male reproductive performance and spermatogenic parameters were found at dose level tested.

 

In section 10. DATE OF REVISION OF THE TEXT, change of date:

From:

2015-10-15

To:

2017-05-19

 

 

 

 

 

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:15-10-2015

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

$0In section 4.1, Therapeutic indications$0$0 $0$0Change of wording $0$0From:$0$0Monofer is indicated for the treatment of iron deficiency anaemia in the following conditions:$0$0•           When oral iron preparations are ineffective or cannot be used$0$0•           Where there is a clinical need to deliver iron rapidly         $0$0The diagnosis of iron deficiency anaemia should be based on appropriate laboratory tests (e.g. serum ferritin, serum iron, transferrin saturation or hypochromic red cells).$0$0To:$0$0Monofer is indicated for the treatment of iron deficiency in the following conditions:$0$0•           When oral iron preparations are ineffective or cannot be used$0$0•           Where there is a clinical need to deliver iron rapidly         $0$0The diagnosis must be based on laboratory tests.$0$0 $0$0In section 4.2, Posology and method of administration$0$0 $0$0Changes to sub heading and wording under ‘Calculation of the cumulative iron dose:’$0$0 $0$0From:$0$0Calculation of the cumulative iron dose:$0$0Iron replacement in patients with iron deficiency anaemia:$0$0The dose and dosage schedule for Monofer must be individually established for each patient. The optimal haemoglobin target level and iron stores may vary in different patient groups and between patients. Please refer to official guidelines. The dose of Monofer is expressed in mg of elemental iron.$0$0To:$0$0Calculation of the cumulative iron need:$0$0Iron replacement in patients with iron deficiency:$0$0The dose of Monofer is expressed in mg of elemental iron. The iron need and the administration schedule for Monofer must be individually established for each patient. The optimal haemoglobin target level and iron stores may vary in different patient groups and between patients. Please refer to official guidelines. $0$0 $0$0From:$0$0The cumulative iron dose can be determined using either the Ganzoni formula (1) or the dosing table below (2).$0$0 $0$0To:$0$0The cumulative iron need can be determined using either the Ganzoni formula (1) or the Table below (2)$0$0 $0$0Change to wording under ‘Ganzoni Formula’:$0$0 $0$0From:$0$0Iron dose  =  Body weight(A)  x  (Target Hb – Actual Hb)(B)  x  2.4(C)  +  Iron for iron stores(D)$0[mg iron]             [kg]                                [g/dl]                                                         [mg iron] $0$0 $0$0(A)       It is recommended to use the patient’s ideal body weight or pre-pregnancy weight$0$0(B)       To convert Hb [mM] to Hb [g/dl] you should multiply Hb [mM] by factor 1.61145$0$0(C)       Factor 2.4 = 0.0034 x 0.07 x 10,000$0$0            0.0034: Iron content of haemoglobin is 0.34%$0$0            0.07: Blood volume 70 ml/kg of body weight » 7% of body weight$0$0            10,000: The conversion factor 1 g/dl = 10,000 mg/l$0$0(D)       For a person with a body weight above 35 kg, the iron stores are 500 mg or above$0$0 $0$0To:$0$0Iron need  =  Body weight(A)  x  (Target Hb(E) – Actual Hb)(B)  x  2.4(C)  +  Iron for iron stores(D)$0[mg iron]             [kg]                                [g/dl]                                                         [mg iron] $0$0 $0$0(A)       It is recommended to use the patient’s ideal body weight for obese patients or pre-pregnancy weight for pregnant women. Ideal body weight may be calculated in a number of ways e.g. by calculating weight at BMI 25 i.e. ideal body weight = 25 * (height in m)2 $0$0(B)       To convert Hb [mM] to Hb [g/dl] you should multiply Hb [mM] by factor 1.61145$0$0(C)       Factor 2.4 = 0.0034 x 0.07 x 10,000$0$0            0.0034: Iron content of haemoglobin is 0.34%$0$0            0.07: Blood volume 70 ml/kg of body weight » 7% of body weight$0$0            10,000: The conversion factor 1 g/dl = 10,000 mg/l$0$0(D)       For a person with a body weight above 35 kg, the iron stores are 500 mg or above. Iron stores of 500 mg are at the lower limit normal for small women. Some guidelines suggest using 10-15 mg iron /kg body weight. $0$0(E)       Default Hb target is 15 g/dl in the Ganzoni formula. In special cases such as pregnancy consider using a lower haemoglobin target.$0$0 $0$0Change to wording under ‘Dosing table’:$0$0 $0$0From:$0$02.         Dosing table:$0$0Cumulative iron dose$0$0To:$0$02.         Simplified Table:$0$0Iron need$0$0 $0$0Change to wording under ‘iron replacement for blood loss’:$0$0 $0$0From:$0$0Iron therapy in patients with blood loss should supply an amount of iron equivalent to the amount of iron represented in the blood loss.$0$0·         If the Hb level is reduced: Use the Ganzoni formula considering that the depot iron does not need to be restored: $0$0 $0$0Cumulative iron dose  =  Body weight  x  (Target Hb – Actual Hb)  x  2.4$0[mg iron]                         [kg]                             [g/dl]$0$0To:$0$0Iron therapy in patients with blood loss should supply an amount of iron equivalent to the amount of iron represented in the blood loss.$0$0·         If the Hb level is reduced: Use the Ganzoni formula considering that the depot iron does not need to be restored: $0$0 $0$0Iron need  =  Body weight  x  (Target Hb – Actual Hb)  x  2.4$0[mg iron]            [kg]                            [g/dl]$0$0 $0$0Addition of wording under ‘Administration’, wording added:$0$0Each IV iron administration is associated with a risk of a hypersensitivity reaction. Thus, to minimise risk the number of single IV iron administrations should be kept to a minimum. $0$0 $0$0Change of wording under ‘Intravenous bolus infusion’:$0$0 $0$0From:$0$0Monofer may be administered as an intravenous bolus injection up to 500 mg up to three times a week at an administration rate of up to 50 mg iron/minute.$0$0To:$0$0Monofer may be administered as an intravenous bolus injection up to 500 mg up to three times a week at an administration rate of up to 250 mg iron/minute.$0$0 $0$0 $0$0Change of wording under ‘Intravenous drip infusion’:$0$0 $0$0From:$0$0If the cumulative iron dose exceeds 20 mg iron/kg body weight, the dose must be split in two administrations with an interval of at least one week.$0$0Doses up to 1000 mg must be infused over 30 min.$0$0Doses exceeding 1000 mg must be infused over 60 min.$0$0To:$0$0If the cumulative iron dose exceeds 20 mg iron/kg body weight, the dose must be split in two administrations with an interval of at least one week. It is recommended whenever possible to give 20 mg iron/kg body weight in the first administration. Dependent on clinical judgement the second administration could await follow-up laboratory tests.$0$0Doses up to 1000 mg must be administered over more than 15 minutes.$0$0Doses exceeding 1000 mg must be administered over 30 minutes or more.$0$0 $0$0In section 6.3, Shelf life, removal of wording:$0$0 $0$0From:$0$0Shelf life after dilution with sterile 0.9% sodium chloride:$0$0Chemical and physical in-use stability has been demonstrated for 48 hours at 30°C in dilutions up to 1:250 with sterile 0.9% sodium chloride.$0$0From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.$0$0 $0$0To:$0$0Shelf life after dilution with sterile 0.9% sodium chloride:$0$0Chemical and physical in-use stability has been demonstrated for 48 hours at 30°C in dilutions up to 1:250 with sterile 0.9% sodium chloride.$0$0From a microbiological point of view, the product should be used immediately. $0$0 $0$0In section 10, Date of revision of the text, change of date:$0$0From: 2015-04-15 $0$0To: 15/10/2015 $0

Reasons for adding or updating:

  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:15-04-2015

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

$0In section 9 DATE OF FIRST AUTHORISATION/RENEWAL OFTHE AUTHORISATION$0$0The date of latest renewal has been added:$0$0Date of firstauthorisation: 18/01/2010$0$0Date of latestrenewal: 26/11/2014 $0$0In section 10 DATEOF REVISION OF THE TEXT$0$0The date has been amended to:$0$0 2015-04-15$0

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text
  • Change to extra statutory information

Date of revision of text on the SPC:10-03-2014

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

$0Addition of blacktriangle wording:$0$0'▼This medicinal product is subject toadditional monitoring. This will allow quick identification of new safetyinformation. Healthcare professionals are asked to report any suspected adversereactions. See section 4.8 for how to report adverse reactions.'$0$0In Section 2 QUALITATIVE ANDQUANTITATIVE COMPOSITION, change of wording:$0$0From:$0$0'For a full list of excipients, see6.1.'$0$0To:$0$0'For the full list of excipients, seesection 6.1.'$0$0 $0$0In 4.2 Posology and method ofadministration$0$0Change of wording under‘Administration’$0$0From:$0$0Anaphylactoidreactions to parenteral iron are usually evident within a few minutes, andclose observation is necessary to ensure recognition. If at any time during theintravenous administration of Monofer, any signs of a hypersensitivity reactionor intolerance are detected, administration must be stopped immediately.$0$0Resuscitativemedication and personnel trained to evaluate and handle anaphylactoid reactionsshould be available whenever a dose of parenteral iron is administered.$0$0To:$0$0Monitorcarefully patients for signs and symptoms of hypersensitivity reactions duringand following each administration of Monofer.$0$0Monofershould only be administered when staff trained to evaluate and manageanaphylactic reactions is immediately available, in an environment where full resuscitationfacilities can be assured. The patient should be observed for adverse effectsfor at least 30 minutes following each Monofer injection (see section 4.4).$0$0 $0$0In 4.3 Contraindications, amendment tothe list (asthma, allergic eczema, atopic allergy,rheumatoid arthritis moved to Section 4.4 Special warnings and precautionsfor use):$0$0Change of wording$0$0From:$0$0Non-iron deficiency anaemia (e.g. haemolytic anaemia)$0$0Iron overload or disturbances in utilisation of iron (e.g.haemochromatosis, haemosiderosis)$0$0Hypersensitivity to the active substance or to any of the excipients.$0$0Patients with a history of asthma, allergic eczema or other atopicallergy$0$0Decompensated liver cirrhosis and hepatitis$0$0Rheumatoid arthritis with symptoms or signs of active inflammation$0$0 $0$0To: $0$0 $0$0Hypersensitivity to the active substance, to Monofer or any of itsexcipients listed in section 6.1.$0$0Known serious hypersensitivity to other parenteral iron products.$0$0Non-iron deficiency anaemia (e.g. haemolytic anaemia)$0$0Iron overload or disturbances in utilisation of iron (e.g.haemochromatosis, haemosiderosis)$0$0Decompensated liver cirrhosis and hepatitis$0$0 $0$0In 4.4    Special warnings and precautions for use$0$0Change of wording $0$0From:$0$0Parenteraladministration of all iron complexes may cause immediate severe and potentiallylethal hypersensitivity reactions. $0$0Therisk is enhanced for patients with known (medical) allergies. Resuscitativemedication and personnel trained to evaluate and handle anaphylactoid reactionsshould therefore be available.$0$0Thereis particularly increased risk of allergic reactions to parenteral ironcomplexes in patients with immune or inflammatory conditions (e.g. systemiclupus erythematosus, rheumathoid arthritis).$0$0 $0$0To:$0$0Parenterallyadministered iron preparations can cause hypersensitivity reactions includingserious and potentially fatal anaphylactic/anaphylactoid reactions.Hypersensitivity reactions have also been reported after previously uneventfuldoses of parenteral iron complexes.$0$0Therisk is enhanced for patients with known allergies including drug allergies,including patients with a history of severe asthma, eczema or other atopicallergy.$0$0Thereis also an increased risk of hypersensitivity reactions to parenteral ironcomplexes in patients with immune or inflammatory conditions (e.g. systemiclupus erythematosus, rheumatoid arthritis).$0$0Monofershould only be administered when staff trained to evaluate and manageanaphylactic reactions is immediately available, in an environment where fullresuscitation facilities can be assured. Each patient should be observed foradverse effects for at least 30 minutes following each Monofer injection. Ifhypersensitivity reactions or signs of intolerance occur during administration,the treatment must be stopped immediately. Facilities for cardio respiratoryresuscitation and equipment for handling acute anaphylactic/anaphylactoidreactions should be available, including an injectable 1:1000 adrenalinesolution. Additional treatment with antihistamines and/or corticosteroidsshould be given as appropriate.$0$0 $0$0In 4.6    Fertility, pregnancy and lactation$0$0Change of wording$0$0From:$0$0Thereare no adequate and well-controlled trials of Monofer in pregnant women. Acareful risk/benefit evaluation is therefore required before use duringpregnancy and Monofer should not be used during pregnancy unless clearlynecessary.$0$0Irondeficiency anaemia occurring in the first trimester of pregnancy can in manycases be treated with oral iron. If the benefit of Monofer treatment is judgedto outweigh the potential risk to the foetus, the treatment should be confinedto second and third trimester.$0$0 $0$0To:$0$0Thereare no adequate and well-controlled trials of Monofer in pregnant women. Acareful risk/benefit evaluation is therefore required before use duringpregnancy and Monofer should not be used during pregnancy unless clearlynecessary (see section 4.4).$0$0Irondeficiency anaemia occurring in the first trimester of pregnancy can in manycases be treated with oral iron. Treatment with Monofer should be confined tosecond and third trimester if the benefit is judged to outweigh the potentialrisk for both the mother and the foetus.$0$0 $0$0In 4.8    Undesirable effects, addition of wording regarding reporting ofside effects:$0$0Reporting of suspected adverse reactions$0$0Reportingsuspected adverse reactions after authorisation of the medicinal product isimportant. It allows continued monitoring of the benefit/risk balance of themedicinal product. Healthcare professionals are asked to report any suspectedadverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard$0$0 $0$0In 5.1    Pharmacodynamic properties$0$0Change of wording and ATC Code:$0$0From:$0$0Pharmacotherapeuticgroup: Iron trivalent parenteral preparation, ATC code: B03A C06$0$0 $0$0To:$0$0Pharmacotherapeuticgroup: Iron parenteral preparation, ATC code: B03AC$0$0 $0$0In 6.4    Special precautions for storage$0$0Change of wording$0$0From:$0$0Thismedicinal product does not require any special storage conditions.$0$0Forstorage conditions of the reconstituted and diluted solution see 6.3.$0$0 $0$0To:$0$0Thismedicinal product does not require any special storage conditions.$0$0Forstorage conditions of the reconstituted and diluted solution see section 6.3.$0$0In 9 Dateof First Authorisation/renewal of the authorisation (change from centralapproval date to local country approval date)$0$0From:$0$02009-11-26 /$0$0To:$0$018/01/2010$0$0 $0$0In 10 DATEOF REVISION OF THE TEXT, revision of date:$0$02014-03-10$0$0 $0$0 $0

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:01-07-2013

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



In Section 4.2:

 

Change of wording from total iron dose to cumulative iron dose.

 

Inclusion of a fixed dose table option in addition to the Ganzoni calculation for estimation of the iron need.

 

Under Iron replacement for blood loss:  Correction of an error in previous SPC – unknown blood loss changed to known blood loss.

 

Under Administration:  Reference to Total Dose Infusion (TDI) has been removed.

 

Under Intravenous Bolus Injection:  the injectable dose is increased to up to 500 mg at 50 mg/min up to 3 times weekly.

 

Under Intravenous Drip Infusion:  doses ≤ 1000 mg may be infused over 30 minutes - higher doses still require 60 minutes infusion time

 

Section 4.6  Change of title to Fertility, pregnancy and lactation.

 

Section 10  Date of revision changed to July 1, 2013.

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications

Date of revision of text on the SPC:01-06-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

In section 4.3 a typo has been corrected.


·          Non-iron deficiency anaemia (e.g. haemolytic anaemia)

·          Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis,

·          haemosiderosis)

·          Hypersensitivity to the active substance or to any of the excipients.

has been corrected to read:

·          Non-iron deficiency anaemia (e.g. haemolytic anaemia)

·          Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis)

·          Hypersensitivity to the active substance or to any of the excipients.

Reasons for adding or updating:

  • Addition of black triangle

Date of revision of text on the SPC:01-06-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Black triangle still applicable to this product.

Reasons for adding or updating:

  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 5 - Nature and Contents of Container
  • Removal of Black Triangle

Date of revision of text on the SPC:01-06-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

The black triangle has been removed.
In Section 6.3 the shelf-life of vials has been extended to 3 years.
In section 6.5 1 x 1ml, 1 x 5ml and 1 x 10ml packs have been introduced, although not all may be marketed.

Reasons for adding or updating:

  • Addition of Black Triangle

Date of revision of text on the SPC:18-01-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Addition of Black Triangle

Reasons for adding or updating:

  • New SPC for new product

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): NO