Active ingredients: Ferric carboxymaltose
Ferinject 50 mg iron / ml solution for injection / infusion
Indications Why is Ferinject used? What is it for?
Ferinject is an anti-anemic preparation, a medicine used for the treatment of anemia. It contains iron in the form of an iron carbohydrate. Iron is an essential element for the oxygen-carrying capacity of hemoglobin in red blood cells and on the other. of myoglobin in muscle tissues. Iron is also involved in many other vital functions for the human organism. Ferinject is used to treat patients with iron deficiency, when oral iron preparations are ineffective or cannot be used. The goal of therapy is to replenish the body's iron stores and correct anemia, a lack of red blood cells due to iron deficiency.
Before administration, your doctor will carry out a blood test to determine the dose of Ferinject that you need.
Contraindications When Ferinject should not be used
Do not take Ferinject
- If you are allergic (hypersensitive) to the product or any of the other ingredients of this medicine (listed in section 6).
- If you have experienced severe allergic (hypersensitivity) reactions to other iron injectable preparations.
- If you have anemia not caused by iron deficiency.
- If you have iron overload (excess iron in the body) or disturbances in the use of iron.
Precautions for use What you need to know before taking Ferinject
Talk to your doctor or nurse before taking Ferinject
- if you have previously had allergies to medicines
- if you have systemic lupus erythematosus
- if you have rheumatoid arthritis
- if you have severe asthma, eczema or other allergies
- if you have an infection - if you have liver problems.
- Ferinject should not be given to children under 14 years of age.
- Incorrect administration of Ferinject may cause leakage of the product at the injection site, which can lead to skin irritation and potentially long-lasting brown discoloration at the injection site. Administration should be stopped as soon as this occurs.
How Ferinject is given
Your doctor or nurse will give you undiluted Ferinject by injection, during dialysis, or diluted by infusion. Ferinject will be given in a facility where immune allergic events can receive immediate and appropriate treatment.
You will be observed for at least 30 minutes by your doctor or nurse after each administration.
Interactions Which drugs or foods can modify the effect of Ferinject
Tell your doctor if you are using, have recently used or might use any other medicines, including medicines you can buy without a prescription. If Ferinject is given together with oral iron preparations, these oral preparations may be less effective.
Warnings It is important to know that:
Pregnancy
Ferinject has not been evaluated in pregnant women. It is important to tell your doctor if you are pregnant, suspect or plan to become pregnant.
If you become pregnant during treatment you should ask your doctor for advice. Your doctor will decide whether or not you should take this medicine.
Feeding time
If you are breast-feeding, ask your doctor for advice before taking Ferinject. Ferinject is unlikely to pose a risk to the infant.
Driving and using machines
Ferinject is unlikely to affect the ability to drive or use machines.
Important information about some of the ingredients of Ferinject
This medicinal product contains 0.24 mmol (or 5.5 mg) sodium per milliliter of undiluted solution.This should be considered in patients on a controlled sodium diet.
Dosage and method of use How to use Ferinject: Dosage
The doctor can administer Ferinject in three ways: undiluted by injection, during dialysis or diluted by infusion.
- By injection, you can receive up to 20 ml of Ferinject, corresponding to 1,000 mg of iron once a week directly into a vein.
- If you are on dialysis, you can receive Ferinject during a hemodialysis session through the dialysis machine.
- By infusion, you can receive up to 20 ml of Ferinject, corresponding to 1,000 mg of iron, once a week directly into a vein. Since Ferinject is diluted with sodium chloride solution for infusion, it can have a volume up to 250 ml and appear as a brown solution.
Overdose What to do if you have taken too much Ferinject
It will be the physician's responsibility to determine the appropriate dose and to choose the route of administration, frequency and duration of treatment.
Overdose can cause iron accumulation at storage sites. The doctor will monitor the iron parameters, such as serum ferritin and transferrin, in order to avoid an accumulation of iron.
Side Effects What are the side effects of Ferinject
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects:
Tell your doctor right away if you have any of the following signs and symptoms which may indicate a serious allergic reaction: rash (e.g. hives), itchy feeling, difficulty breathing, wheezing and / or swelling of the lips, swollen tongue, swelling throat or body.
In some patients these allergic reactions (occurring in less than 1 in 1,000 patients) can become serious or life-threatening (anaphylactoid reactions) and can be associated with heart and circulatory problems and loss of consciousness.
Your doctor is aware of these possible side effects and will monitor you during and after you are given Ferinject.
Other side effects that the doctor should be aware of if they get serious:
Common side effects (may affect up to 1 in 10 patients): headache, dizziness, high blood pressure, nausea and injection site reaction (see also section 2).
Uncommon side effects (may affect up to 1 in 100 people): numbness, tingling or tingling sensation on the skin, taste changes, high heart rate, low blood pressure, flushing of the face, difficulty breathing, vomiting, indigestion, pain in the stomach, constipation, diarrhea, itching sensation, hives, red skin, rash, muscle pain, joint pain and / or back pain, muscle spasms, fever, tiredness, chest pain, swelling of the hands and / or feet and chills .
Rare side effects (may affect up to 1 in 1,000 people): inflammation of a vein, shaking and discomfort, loss of consciousness, anxiety, fainting, feeling faint, wheezing, excess abdominal gas (flatulence), rapid swelling of the deep layers of skin, paleness and swelling of the face and flu-like symptoms such as fever, headache and / or feeling sick (flu-like illness).
Some blood parameters may be temporarily altered, as can be seen in laboratory tests.
The following changes in blood parameters are common: decrease in the level of phosphorus in the blood and increase in a liver enzyme called alanine aminotransferase.
The following changes in blood parameters are uncommon: increase in certain liver enzymes called aspartate aminotransferase, gamma glutamyl transferase and alkaline phosphatase, and increase in an enzyme called lactate dehydrogenase.
For more information, ask your doctor.
Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov. .it / en / responsible By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep Ferinject out of the sight and reach of children.
Do not use Ferinject after the expiry date which is stated on the label. The expiry date refers to the last day of that month.
Store in the original package to protect from light. Do not store above 30 ° C. Do not freeze.
Once opened, Ferinject vials should be used immediately. After dilution with sodium chloride solution, the diluted solution should be used immediately.
Ferinject is usually kept by the doctor or hospital.
Deadline "> Other information
What Ferinject contains
The active ingredient is iron (as ferric carboxymaltose, an iron carbohydrate compound). The iron concentration present in the product is 50 mg per milliliter. The other ingredients are sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment) and water for injections.
Description of what Ferinject looks like and contents of the pack
Ferinject is a dark brown, non-transparent solution for injection / infusion.
Ferinject is supplied in glass vials containing:
- 2 mL of solution corresponding to 100 mg of iron. Available in packs of 1 and 5 vials.
- 10 mL of solution corresponding to 500 mg of iron. Available in packs of 1 and 5 vials.
- 20 mL of solution corresponding to 1000 mg of iron. Available in packs of 1 vial.
Not all pack sizes may be marketed.
Deadline "> Information for healthcare professionals
The following information is intended for healthcare professionals only:
Monitor patients closely for signs and symptoms of hypersensitivity reactions during and after each administration of Ferinject. Ferinject should only be administered if qualified personnel are immediately available to evaluate and manage anaphylactic reactions, in a facility where resuscitation equipment can be guaranteed. The patient should be observed for adverse reactions for at least 30 minutes after each injection of Ferinject.
Determination of the need for iron
The individual iron requirement for recovery with the help of Ferinject is determined on the basis of the patient's body weight and hemoglobin level (see Table 1):
Table 1: Determination of the iron requirement
Iron deficiency must be confirmed by laboratory tests.
Calculation and administration of the maximum individual dose (s) of iron
Based on the iron requirement determined above, the appropriate dose (s) of Ferinject should be administered taking into account the following:
A single administration of Ferinject should not exceed:
- 15 mg iron / kg body weight (intravenous injection) or 20 mg iron / kg body weight (intravenous infusion)
- 1,000 mg of iron (20 mL of Ferinject)
The maximum recommended cumulative dose of Ferinject is 1,000 mg of iron (20 mL of Ferinject) per week.
In hemodialysis-dependent chronic kidney disease patients a maximum single daily injectable dose of 200 mg of iron should not be exceeded. The use of Ferinject has not been studied in children, therefore this medicine is not recommended in children below 14 years.
Method of administration
Ferinject should only be administered intravenously: by injection, infusion or during an undiluted hemodialysis session directly into the venous inlet of the dialyzer. Ferinject should not be administered subcutaneously or intramuscularly.
When administering Ferinject, care must be taken to avoid paravenous extravasation. Paravenous extravasation of Ferinject at the injection site may cause skin irritation and potentially long-lasting dark discoloration at the injection site. In case of paravenous extravasation, the administration of Ferinject must be stopped immediately.
Intravenous injection
Ferinject can be administered by intravenous injection using an undiluted solution. The maximum single dose is 15 mg of iron / kg body weight but should not exceed 1,000 mg of iron. The rates of administration are shown in Table 2:
Table 2: Rate of administration of Ferinject by intravenous injection
Intravenous infusion
Ferinject can be administered by intravenous infusion; in this case it must be diluted. The maximum single dose is 20 mg of iron / kg body weight but should not exceed 1,000 mg of iron. Ferinject must only be diluted in sterile 0.9% m / V sodium chloride solution as shown in Table 3. Note: For stability reasons, Ferinject must not be diluted to concentrations below 2 mg iron / mL (excluding the volume of the ferric carboxymaltose solution).
Table 3: Ferinject dilution plan for intravenous infusion
Monitoring measures
The physician should re-evaluate based on the individual patient's condition. The Hb level should be re-evaluated at least 4 weeks after the last administration of Ferinject to allow sufficient time for erythropoiesis and iron utilization. the requirement using Table 1, above.
Incompatibility
Oral iron absorption is reduced when concomitant parenteral iron preparations are administered. Therefore, if required, oral iron therapy should not be initiated for at least 5 days after treatment. last injection of Ferinject.
Overdose
Administering Ferinject in quantities greater than those needed to correct iron deficiency at the time of administration may result in an accumulation of iron at the storage sites, eventually leading to hemosiderosis. Monitoring of iron parameters, such as serum ferritin and transferrin saturation, can facilitate the detection of iron accumulation. If iron accumulation occurs, treat it according to standard medical practice, for example consider the use of an iron chelator.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
FERINJECT 50 MG IRON / ML SOLUTION FOR INJECTION / FOR INFUSION
▼ Medicinal product subject to additional monitoring. This will allow the rapid identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for information on how to report adverse reactions.
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
One ml of solution contains 50 mg of iron as ferric carboxymaltose.
Each 2 mL vial contains 100 mg of iron as ferric carboxymaltose.
Each 10 mL vial contains 500 mg of iron as ferric carboxymaltose.
Each 20 mL vial contains 1,000 mg of iron as ferric carboxymaltose.
One ml of solution contains up to 5.5 mg (0.24 mmol) sodium, see section 4.4.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Solution for injection / infusion. Aqueous, non-transparent, dark brown solution.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Ferinject is indicated for the treatment of iron deficiency, when oral iron preparations are ineffective or cannot be used.
Diagnosis of iron deficiency should be made on the basis of laboratory tests.
04.2 Posology and method of administration -
Monitor patients closely for signs and symptoms of hypersensitivity reactions during and after each administration of Ferinject.
Ferinject should only be administered if personnel trained to assess and manage anaphylactic reactions are immediately available, in a facility where complete resuscitation equipment can be guaranteed. The patient should be observed for adverse reactions for at least 30 minutes after each injection of Ferinject (see section 4.4).
Dosage
Ferinject dosing follows a step-by-step approach: [1] determination of individual iron requirements, [2] calculation and administration of iron dose (s) and [3] post-restoration assessments of iron values. These steps are illustrated below:
Step 1: Determining Your Iron Need
The individual iron requirement for recovery with the help of Ferinject is determined on the basis of the patient's body weight and hemoglobin (Hb) level. For the determination of iron requirements, refer to Table 1:
Table 1: Determination of the iron requirement
Iron deficiency must be confirmed by laboratory tests, as indicated in section 4.1.
Step 2: Calculation and administration of the maximum individual dose (s) of iron
Based on the iron requirement determined above, the appropriate dose (s) of Ferinject should be administered taking into account the following:
A single administration of Ferinject should not exceed:
• 15 mg iron / kg body weight (for administration by intravenous injection) or 20 mg iron / kg body weight (for administration by intravenous infusion)
• 1,000 mg of iron (20 mL of Ferinject)
The maximum recommended cumulative dose of Ferinject is 1,000 mg of iron (20 mL of Ferinject) per week.
Step 3: Post-Restoration Assessments of Iron Values
The physician should re-evaluate based on the individual patient's condition. The Hb level should be re-evaluated at least 4 weeks after the last administration of Ferinject to allow sufficient time for erythropoiesis and iron utilization. the requirement using Table 1, above (see section 5.1).
Special population - Patients with hemodialysis-dependent chronic kidney disease
In patients with hemodialysis-dependent chronic kidney disease a single maximum daily injectable dose of 200 mg of iron should not be exceeded (see also section 4.4).
Pediatric population
The use of Ferinject has not been studied in children, therefore this medicine is not recommended in children below 14 years.
Method of administration
Ferinject should only be administered intravenously:
• by injection or
• by infusion or
• during a hemodialysis session injected undiluted directly into the venous inlet of the dialyzer
Ferinject must not be administered subcutaneously or intramuscularly.
Intravenous injection
Ferinject can be administered by intravenous injection using an undiluted solution. The maximum single dose is 15 mg of iron / kg body weight but should not exceed 1,000 mg of iron. The rates of administration are shown in Table 2:
Table 2: Rate of administration of Ferinject by intravenous injection
Intravenous infusion
Ferinject can be administered by intravenous infusion; in this case it must be diluted. The maximum single dose is 20 mg of iron / kg body weight but should not exceed 1,000 mg of iron.
For infusion, Ferinject must only be diluted in sterile 0.9% m / V sodium chloride solution as shown in Table 3. Note: For stability reasons, Ferinject must not be diluted to concentrations below 2 mg of iron / mL (excluding volume of ferric carboxymaltose solution).
Table 3: Ferinject dilution plan for intravenous infusion
04.3 Contraindications -
The use of Ferinject is contraindicated in case of:
• Hypersensitivity to the active substance, to Ferinject or to any of the excipients listed in section 6.1.
• Known severe hypersensitivity to other parenteral iron products.
• Anemia not attributable to iron deficiency, eg. other microcytic anemia.
• Evidence of iron overload or disturbances in iron use.
04.4 Special warnings and appropriate precautions for use -
Hypersensitivity reactions
Parenterally administered iron preparations can cause hypersensitivity reactions including severe and life-threatening anaphylactic / anaphylactoid reactions. Hypersensitivity reactions have also been reported after previously administered doses of parenteral iron complexes without incident.
The risk is increased for patients with known allergies which include drug allergies, including patients with a history of severe asthma, eczema, or other atopic allergies.
There is also an increased risk of hypersensitivity reactions to parenteral iron complexes in patients with inflammatory or immune conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis).
Ferinject should only be administered if personnel trained to assess and manage anaphylactic reactions are immediately available, in a facility where complete resuscitation equipment can be guaranteed. Each patient should be observed for adverse reactions for at least 30 minutes after each injection of Ferinject.
If hypersensitivity reactions or signs of intolerance occur during administration, treatment should be stopped immediately Cardiorespiratory resuscitation equipment and equipment to manage acute anaphylactic / anaphylactoid reactions, including 1: 1000 solution for injection of adrenaline should be available. Additional treatment with antihistamines and / or corticosteroids should be given as appropriate.
Hepatic impairment or kidney damage
In patients with hepatic dysfunction, parenteral iron should only be administered after a "careful benefit / risk assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction in whom iron overload is a factor. precipitating, particularly in the case of porphyria cutanea tarda (PCT) It is recommended to keep the martial state under careful control in order to avoid iron overload.
There are no data on the safety of single doses greater than 200 mg of iron in patients with chronic kidney disease dependent on hemodialysis.
Infection
Parenteral iron should be used with caution in case of acute or chronic infection, asthma, eczema or atopic allergies. It is recommended that Ferinject treatment be discontinued in patients with ongoing bacteraemia. Therefore, a benefit / risk assessment should be performed in patients with chronic infection, taking into account the suppression of erythropoiesis.
Extravasation
Caution should be exercised when administering Ferinject to avoid extravasation. Extravasation of Ferinject at the injection site may result in skin irritation and potentially long-lasting brown discoloration at the injection site. In case of extravasation, the administration of Ferinject must be stopped immediately.
Excipients
One ml of undiluted Ferinject contains up to 5.5 mg (0.24 mmol) of sodium. This should be taken into consideration in patients on a controlled sodium diet.
Pediatric population
The use of Ferinject has not been studied in children.
04.5 Interactions with other medicinal products and other forms of interaction -
The absorption of oral iron is reduced in case of concomitant administration of parenteral iron preparations. Therefore, if required, oral martial therapy should not be started for at least 5 days after the last injection of Ferinject.
04.6 Pregnancy and breastfeeding -
Pregnancy
There is no adequate and well-controlled study of Ferinject in pregnant women. Therefore, a careful risk / benefit assessment is required before use in pregnancy and Ferinject should not be used in pregnancy unless clearly necessary.
Iron deficiency anemia occurring in the first trimester of pregnancy can in many cases be treated with oral iron. Treatment with Ferinject should be limited to the second and third trimesters if the benefit is judged to outweigh the potential risk. for both mother and fetus.
Animal data indicate that iron released by Ferinject can cross the placental barrier and that use during pregnancy may affect the skeletal development of the fetus (see section 5.3).
Feeding time
Clinical studies have shown that iron transfer from Ferinject into breast milk is negligible (≥ 1%). Based on the limited data available in breastfeeding women, Ferinject is unlikely to pose a risk to the infant.
Fertility
There are no data on the effects of Ferinject on human fertility. Fertility was not affected following Ferinject therapy in animal studies (see section 5.3).
04.7 Effects on ability to drive and use machines -
Ferinject is unlikely to affect the ability to drive or use machines.
04.8 Undesirable effects -
Table 4 presents adverse drug reactions (ADRs) reported during clinical trials in which 6,755 patients received Ferinject as well as those reported from post-marketing experience (see table notes for details).
The most often reported ADR is nausea (present in 3.1% of patients), followed by headache, dizziness and hypertension. Injection site reactions classified as common in Table 4 include several ADRs that have been individually reported with one frequency uncommon or rare Hypophosphataemia (common) may occur. In clinical trials, troughs were reached after approximately 2 weeks, and after 4-12 weeks of treatment with Ferinject the values had returned to within the range of baseline. The most severe ADR is anaphylactoid reactions with a rare frequency.
Table 4: Adverse drug reactions observed during clinical trials and post-marketing experience
1 Includes the following preferred terms: rash (frequency of single ADR determined as uncommon) and rash erythematous, generalized, macular, maculo-papular, pruritic (all single ADRs have frequencies determined as rare).
2 Includes the following preferred terms: burning, pain, contusion, discoloration, extravasation, irritation, infusion site reaction (all individual ADRs have frequencies determined as uncommon) and paraesthesia (all individual ADRs have frequencies determined as rare ).
3 ADRs reported exclusively in the post-marketing setting.
4 ADRs reported in the post-marketing setting were also observed in the clinical setting.
Note: ADR = adverse drug reaction.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "Street address
www.aifa.gov.it/responsabili
04.9 Overdose -
Administering Ferinject in excess of what is needed to correct iron deficiency at the time of administration may result in an accumulation of iron at the storage sites, eventually leading to hemosiderosis. Monitoring of martial parameters, such as serum ferritin and transferrin saturation, may be helpful in detecting iron accumulation. If iron accumulation occurs, treat according to standard medical practice, for example, consider use. of an iron chelator.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: trivalent iron, parenteral preparation, ATC code: B03AC
Ferinject solution for injection / infusion is a colloidal solution of ferric carboxymaltose, an iron complex.
The complex is formulated to provide usable iron in a controlled manner by the iron transport and storage proteins in the body (transferrin and ferritin, respectively).
The use of radioactively labeled 59Fe from Ferinject by red blood cells ranged from 91% to 99% in patients with iron deficiency (ID) and from 61% to 84% in patients with renal anemia at 24 days post-dose.
Treatment of patients with ID anemia with Ferinject results in an increase in the reticulocyte count and serum ferritin levels within the normal ranges.
Clinical efficacy and safety
The efficacy and safety of Ferinject have been studied in several therapeutic areas where intravenous administration of iron was required to correct an iron deficiency. The main studies are described in more detail below.
Nephrology
Chronic kidney disease dependent on hemodialysis
Study VIT-IV-CL-015 was a randomized, parallel group, open label study comparing Ferinject (n = 97) and iron sucrose (n = 86) in subjects with ID anemia undergoing hemodialysis. Subjects received Ferinject or iron sucrose 2-3 times per week in single doses of 200 mg of iron directly into the dialyzer until the individually calculated cumulative iron dose was reached (mean cumulative iron dose as Ferinject: 1,700 mg). The primary efficacy endpoint was the proportion of patients who achieved an increase in Hb of ≥1.0 g / dL at 4 weeks of study initiation. At 4 weeks from the start of the study, 44.1% responded to treatment with Ferinject (Hb increase ≥1.0 g / dL) compared with 35.3% for iron sucrose (p = 0.2254).
Chronic kidney disease not dependent on dialysis
Study 1VIT04004 was a randomized, active-controlled, open-label study evaluating the safety and efficacy of Ferinject (n = 147) vs oral iron (n = 103). Subjects in the Ferinject group received 1,000 mg of iron at the start of the and 500 mg of iron on days 14 and 28, if TSAT was oral iron arm they received 65 mg of iron TID as ferrous sulfate from study initiation on day 56. Subjects were followed up to day 56. The primary efficacy endpoint was the proportion of subjects who achieved an increase in Hb of ≥1.0 g / dL at any time between the start and end of the study or the time of intervention. This was achieved by the 60, 54% of subjects receiving Ferinject vs 34.7% of subjects in the oral iron group (p
Gastroenterology
Inflammatory bowel disease
Study VIT-CL-IV-008 was an open-label randomized study comparing the efficacy of Ferinject vs. oral ferrous sulfate in reducing ID anemia in subjects with inflammatory bowel disease (IBD). Subjects received Ferinject (n = 111) in single doses of up to 1,000 mg of iron once weekly until the individually calculated iron dose (using the Ganzoni formula), (mean cumulative iron dose: 1,490 mg) or 100 mg of iron BID as ferrous sulfate (n = 49) for 12 weeks. At week 12, subjects receiving Ferinject had an average increase in Hb from the start of the study of 3.83 g / dl, no less than that obtained with 12 weeks of BID therapy with ferrous sulphate (3.75 g / dl). dl, p = 0.8016).
Study FER-IBD-07-COR was an open-label randomized study comparing the efficacy of Ferinject vs iron sucrose in subjects with remission or mild IBD. The dosage of subjects receiving Ferinject was determined based on a dosing grid. simplified using the initial Hb value and body weight (see section 4.2) in single doses up to 1,000 mg of iron while in subjects receiving iron sucrose the iron doses were calculated individually using the Ganzoni formula in doses of 200 mg of iron until cumulative iron dose was reached. Patient follow-up was performed for 12 weeks. 65.8% of patients receiving Ferinject (n = 240; mean cumulative iron dose: 1,414 mg) vs 53, 6% receiving iron sucrose (n = 235; mean cumulative dose 1,207 mg; p = 0.004) had shown a response at week 12 (defined as an increase in Hb ≥2 g / dL). L "83.8% of patients treated with Ferinject vs 75.9% d and patients treated with iron sucrose achieved an increase in Hb ≥2 g / dL or had an Hb within normal limits at week 12 (p = 0.019).
Women's health
Postpartum
Study VIT-IV-CL-009 was a randomized, open-label, non-inferiority study comparing the efficacy of Ferinject (n = 227) vs ferrous sulfate (n = 117) in women with postpartum anemia. Subjects had received Ferinject in single doses up to 1,000 mg of iron until the individually calculated cumulative iron dose (according to Ganzoni's formula) or 100 mg of iron as oral ferrous sulfate BID for 12 weeks was reached. Patient follow-up was performed for 12 weeks. The mean change in Hb from baseline at week 12 was 3.37 g / dl in the Ferinject group (n = 179; mean cumulative iron dose: 1,347 mg) vs 3.29 g / dl in the ferrous sulphate group (n = 89), showing non-inferiority between treatments.
Ferritin monitoring after integrative therapy
Study VIT-IV-CL-008 provided limited data demonstrating that ferritin levels decline rapidly 2-4 weeks after supplementation and more slowly thereafter. During the 12-week follow-up of the study levels ferritin averages had not fallen to values that would prompt retreatment to be considered. Therefore the available data did not clearly indicate an optimal period for ferritin reevaluation, however ferritin level assessment prior to 4 weeks post integrative therapy appears premature, so it is advisable for the physician to reevaluate the ferritin based on the individual patient's condition.
05.2 "Pharmacokinetic properties -
Positron emission tomography has shown that 59Fe and 52Fe derived from Ferinject are rapidly cleared from the blood, transferred to the bone marrow and deposited in the liver and spleen.
After administration of a single dose of Ferinject of 100 to 1,000 mg of iron in ID patients, maximum total serum iron levels of 37 mcg / ml up to 333 mcg / ml are obtained after 15 minutes and 1.21 hours, respectively. The volume of the central compartment corresponds well to the plasma volume (approximately 3 liters).
Iron injected or infused was rapidly cleared from plasma, terminal half-life ranged from 7 to 12 hours, and mean residence time (MRT) from 11 to 18 hours. Renal elimination of iron was negligible.
05.3 Preclinical safety data -
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity. Preclinical studies indicate that the iron released by Ferinject crosses the placental barrier and is excreted in milk in limited and controlled quantities. In reproductive toxicity studies in rabbits with high iron levels, Ferinject was associated with minor skeletal abnormalities in the fetus. In a fertility study in rats, no effects on fertility were recorded in either males or females. Long-term animal studies have not been conducted to evaluate the carcinogenic potential of Ferinject. No evidence of allergic or immunotoxic potential was observed. A test in vivo controlled demonstrated the absence of cross-reactivity of Ferinject with anti-dextran antibodies. No local irritation or intolerance was observed after intravenous administration.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)
Water for injections
06.2 Incompatibility "-
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
The compatibility of the medicinal product with containers other than polyethylene and glass is not known.
06.3 Period of validity "-
Shelf life of the medicinal product as packaged for sale:
3 years.
Shelf life after first opening the container:
From a microbiological point of view, preparations for parenteral administration should be used immediately.
Shelf life after dilution with sterile 0.9% m / V sodium chloride solution:
From a microbiological point of view, preparations for parenteral administration should be used immediately after dilution with sterile 0.9% m / V sodium chloride solution.
06.4 Special precautions for storage -
Store in the original package to protect from light. Do not store above 30 ° C. Do not freeze.
06.5 Nature of the immediate packaging and contents of the package -
Ferinject is supplied in a vial (type I glass) with a bromobutyl rubber stopper and an aluminum cap containing:
2 mL of solution corresponding to 100 mg of iron. Available in packs of 1 and 5 vials.
10 mL of solution corresponding to 500 mg of iron. Available in packs of 1 and 5 vials.
20 mL of solution corresponding to 1000 mg of iron. Available in packs of 1 vial.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
Before use, visually inspect the vials for sediment or damage. Use only vials that contain a homogeneous, sediment-free solution.
Each vial of Ferinject is for single use only. Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
Ferinject must only be mixed with sterile 0.9% m / V sodium chloride solution. Other solutions or therapeutic agents for intravenous dilution should not be used due to the possibility of precipitation and / or interaction. For instructions on dilution, see section 4.2.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Vifor France
100-101 Terrasse Boieldieu
Franklin La Défense Tour 8
92042 Paris La Défense Cedex
France
08.0 MARKETING AUTHORIZATION NUMBER -
AIC n. 040251011 - "50 MG / ML SOLUTION FOR INJECTION / FOR INFUSION" 1 GLASS VIAL OF 2 ML
AIC n. 040251023 - "50 MG / ML SOLUTION FOR INJECTION / FOR INFUSION" 5 GLASS VIALS OF 2 ML
AIC n. 040251035 - "50 MG / ML SOLUTION FOR INJECTION / FOR INFUSION" 1 GLASS VIAL OF 10 ML
AIC n. 040251047 - "50 MG / ML SOLUTION FOR INJECTION / FOR INFUSION" 5 GLASS VIALS OF 10 ML
AIC n. 040251074 - "50 MG / ML SOLUTION FOR INJECTION / FOR INFUSION" 1 GLASS VIAL OF 20 ML
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 05 October 2011
Date of most recent renewal: June 18, 2012
10.0 DATE OF REVISION OF THE TEXT -
July 2016
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