Igamad

Package leaflet: Information for the patient

Igamad 1500 IU/2 ml solution for injection in pre-filled syringe for intramuscular use

Human anti-D immunoglobulin
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Igamad is and what it is used for
2. What you need to know before using Igamad
3. How to use Igamad
4. Possible side effects
5. How to store Igamad
6. Package contents and other information

1. What Igamad is and what it is used for

Igamad is an injectable solution for intramuscular use. It is supplied in a pre-filled syringe
containing human anti-D (Rh) immunoglobulins, which are antibodies specifically directed against the D (Rh)
antigen of human red blood cells.
The medicine belongs to the pharmacotherapeutic group: immune sera and immunoglobulins.
Administration of Igamad is indicated for:
Prophylaxis of Rh(D) immunization in Rh(D)-negative women.

• Antenatal prophylaxis
• Planned antenatal prophylaxis.
• Antenatal prophylaxis following pregnancy complications, including:

Spontaneous abortion/threatened abortion, ectopic pregnancy or hydatidiform mole, intrauterine fetal death, transplacental haemorrhage due to antepartum haemorrhage, amniocentesis, chorionic biopsy, obstetric manipulative procedures (e.g.: external cephalic version, invasive procedures, cordocentesis, blunt abdominal trauma or therapeutic intervention on the fetus).

• Postnatal prophylaxis
• Delivery of an Rh(D)-positive infant (D, D , D ).

Treatment of Rh(D)-negative individuals following transfusion of incompatible Rh(D)-positive blood or other
products containing Rh(D)-positive red blood cells, such as platelet concentrates.

2. What you need to know before using Igamad

Do not use Igamad
If you are allergic to human immunoglobulin or to any of the other ingredients of this
medicinal product (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Igamad.

• Ensure that Igamad is not administered intravenously, as it may cause shock.
• Injections must be given intramuscularly, taking care to aspirate with the syringe before injection to confirm that the needle is not inside a blood vessel.
• In postpartum use, the product must be administered to the mother. It must not be administered to the newborn.
• The product must not be administered to Rh(D)-positive women or women previously immunized against the Rh(D) antigen.
• Your doctor will monitor you for at least 20 minutes after administration.
• Hypersensitivity reactions, up to anaphylactic shock, are rare and include urticaria, generalized urticaria, chest tightness, wheezing, and low blood pressure (hypotension). However, allergic-type reactions to anti-D immunoglobulins may occur.
• Igamad contains a small amount of IgA. If you are IgA-deficient, you may develop antibodies against IgA and may experience anaphylactic reactions after administration of plasma-derived medicinal products containing IgA. Your doctor will evaluate the benefit of treatment with Igamad versus the potential risk of hypersensitivity reactions.
• Rarely, human anti-D (Rh) immunoglobulin may induce a drop in blood pressure with anaphylactic reaction (hypovolemic shock), even in patients who have previously tolerated treatment with human immunoglobulin well.
• If symptoms of allergic or anaphylactic reactions occur, your doctor will immediately stop administration of the medicinal product and initiate appropriate treatment, depending on the type and severity of the reaction.
• If you receive an incompatible transfusion and high doses of human anti-D (Rh) immunoglobulin, your doctor will monitor your clinical and laboratory parameters due to the risk of hemolytic reaction.

Viral safety
When medicinal products are manufactured from human blood or plasma, specific safety measures are applied to prevent transmission of infectious agents to patients. These measures include:

• careful selection of blood and plasma donors to exclude potential carriers of infections;
• testing of each individual donation and plasma pool for signs of virus/infection;
• inclusion of processing steps capable of inactivating or removing viruses during blood or plasma manufacturing.

Despite these measures, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infections cannot be completely excluded. This also applies to viruses of unknown nature or emerging viruses, or other types of infections.

The measures adopted are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and against the non-enveloped hepatitis A virus (HAV). The measures adopted may have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Immunoglobulins have not been associated with transmission of hepatitis A or parvovirus B19 infections, probably because the antibodies against these infections contained in the product exert a protective effect.
It is strongly recommended that each time Igamad is administered, the name and batch number of the product be recorded, in order to maintain traceability between the patient and the batch of product used.

Children and adolescents
The same warnings mentioned for adults are expected to apply to the pediatric population.

Other medicines and Igamad
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

Interference with vaccinations
Igamad may reduce the efficacy of certain types of vaccines, such as live attenuated virus vaccines (e.g., measles, mumps, rubella, and varicella vaccines). Administration of such vaccines should be performed 3 months after the last dose of Igamad.
In the case of measles vaccination, this interference may last up to one year. Therefore, patients receiving the measles vaccine should have their antibody levels monitored.
If human anti-D (Rh) immunoglobulin must be administered within 2–4 weeks of a live attenuated virus vaccination, the efficacy of such vaccination may be reduced.

Interference with blood tests
Inform your doctor or nurse if you undergo blood tests after receiving Igamad.
After administration of human anti-D (Rh) immunoglobulins, a transient increase in various antibodies in your blood may occur, which may alter laboratory test results, including the Coombs test or blood and antibody typing.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before using this medicinal product.

Pregnancy
Igamad is intended for use during pregnancy.

Breastfeeding
Igamad may be used during breastfeeding.

Fertility
No fertility studies have been conducted in animals using Igamad. Based on clinical experience with human anti-D (Rh) immunoglobulin, no harmful effects on fertility are expected.

Driving and using machines
No effects on the ability to drive or use machines have been observed.

Igamad contains sodium
This medicinal product contains less than 23 mg (1 mmol) of sodium per dose, i.e., it is practically "sodium-free".

3. How to use Igamad

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
Igamad must be administered by slow intramuscular injection.
If a high dose is required (> 2 ml for children or > 5 ml for adults), it will be given to you in divided doses at different anatomical sites.
If intramuscular administration is contraindicated (e.g. due to coagulation disorders), alternative products will be administered.
After the injection, firm manual pressure must be applied to the injection site using a gauze pad.
Igamad must not be mixed with other medicines.
The recommended dose of Igamad should be determined based on the level of exposure to Rh(D)-positive red blood cells, and is based on the fact that 0.5 ml of concentrated Rh(D)-positive red blood cells or 1 ml of Rh(D)-positive whole blood is neutralized by approximately 10 micrograms (50 IU) of human anti-D (Rh) immunoglobulin.
For further information, refer to the section at the end of this leaflet entitled “The following information is intended exclusively for physicians or healthcare professionals”.
If you use more Igamad than you should
Data regarding overdose are not available.
If you administer a higher dose than recommended, inform your doctor or pharmacist immediately.
If you forget to use Igamad
Do not use a double dose to make up for the missed dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
As with all normal human immunoglobulins administered intramuscularly, the following reactions may occur:

• Pain and local hypersensitivity (swelling, erythema, redness, hardening, itching, skin rash, and sensation of warmth) may occur at the injection site; this can be avoided by administering higher doses at different injection sites.
• Occasionally, fever, malaise, headache, nausea, vomiting, skin reactions, chills, and joint pain may occur.
• In rare cases, the following have been reported: hypotension and allergic or anaphylactic reactions, including difficulty in breathing (dyspnea) and shock, even in patients who did not show hypersensitivity to previous administrations. From post-marketing experience with the use of Igamad, the following adverse reactions have been reported: hypersensitivity, erythema, arthralgia, pruritus, and urticaria, with frequencies not known.

Additionally, following administration of anti-D human immunoglobulins by intramuscular route, the following adverse effects have also been reported: tachycardia and malaise.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via
http://www.agenziafarmaco.gov.it/it/responsabili . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Igamad

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label after "Exp".
The expiry date refers to the last day of that month.
The expiry date applies to the product in its original packaging and stored as recommended.
Store in the refrigerator (2 °C–8 °C) in the outer packaging. Do not freeze.
The solution may vary in colour from colourless to pale yellow or light brown.
Slight opalescence or a small amount of particulate matter may occur during storage.
The solution should be visually inspected before administration.
Do not use Igamad if the solution appears cloudy or contains deposits.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Igamad contains

• The active substance is: Human anti-D (Rh) immunoglobulin 1500 IU (300 micrograms *) * 100 micrograms of human anti-D (Rh) immunoglobulin correspond to 500 International Units (IU).

The total human protein content is 320 mg, of which at least 95% are immunoglobulins G (IgG).
The IgA content is less than 1 mg/ml.

• The other components are: glycine, sodium chloride and water for injections.

(See section 2 for further information on excipients).
Description of the appearance of Igamad and package contents
IGAMAD “1500 IU/2 ml solution for injection for intramuscular use” pre-filled syringe.
Pack: one 1500 IU/2 ml pre-filled syringe.
Igamad is an injectable solution intended for intramuscular use. The solution is clear and ranges from pale yellow to light brown. During storage, it may show slight opalescence or a small amount of particulate precipitate.
Marketing Authorization Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - SPAIN

The following information is intended exclusively for physicians or healthcare professionals:
Dosage
The recommended dose of Igamad must be determined based on the level of exposure to Rh(D)-positive red blood cells and is based on the fact that 0.5 ml of concentrated Rh(D)-positive red blood cells or 1 ml of Rh(D)-positive whole blood is neutralized by approximately 10 micrograms (50 IU) of human anti-D (Rh) immunoglobulin.
Prevention of Rh(D) immunization in Rh(D)-negative women

• Prenatal prophylaxis: according to general recommendations, the administered dose ranges between 50–330 micrograms or 250–1650 IU.
• Planned prenatal prophylaxis: A single dose between the 28th and 30th week of gestation or two doses at the 28th and 34th week.
• Prenatal prophylaxis following pregnancy complications:

A single dose should be administered as soon as possible and in any case within 72 hours, and if necessary repeated at intervals of 6–12 weeks during pregnancy.

• Postnatal prophylaxis: according to general recommendations, the administered dose ranges between 100–300 micrograms or 500–1500 IU. If the lower dose (100 micrograms or 500 IU) is administered, maternal-fetal hemorrhage must be quantified.

For postnatal use, the product must be administered to the mother as soon as possible and in any case within 72 hours after delivery of an Rh-positive infant (D, D , D ). If more than 72 hours have elapsed, administration should still occur as soon as possible.
The postnatal dose must be administered even when prenatal prophylaxis has been performed and even if residual activity from prenatal prophylaxis is still present in maternal serum.
If massive maternal-fetal hemorrhage (> 4 ml (0.7%–0.8% of women)) is suspected, for example in cases of fetal/neonatal anemia or intrauterine fetal death, its extent must be quantified using an appropriate method, such as the acid elution test of Kleihauer-Betke for determination of fetal hemoglobin (HbF) levels or flow cytometry specifically identifying Rh(D)-positive cells. Additional doses of human anti-D (Rh) immunoglobulin must be administered as determined (10 micrograms or 50 IU for every 0.5 ml of fetal erythrocytes).
Transfusion of Rh-incompatible red blood cells
The recommended dose is 20 micrograms (100 IU) of human anti-D (Rh) immunoglobulin for every 2 ml of transfused Rh(D)-positive whole blood, or for every 1 ml of packed red blood cells. The appropriate dose must be determined in consultation with a blood transfusion specialist. Monitoring tests (follow-up) must be performed every 48 hours to detect Rh(D)-positive erythrocytes, and administration of human anti-D (Rh) immunoglobulin must continue until complete disappearance of Rh(D)-positive erythrocytes from the bloodstream. In case of larger incompatible transfusions, a maximum dose of 3000 micrograms (15000 IU) is sufficient, regardless of whether the volume of transfused Rh(D)-positive erythrocytes exceeds 300 ml.
The use of an alternative intravenous product is recommended, which will allow immediate achievement of adequate plasma levels. If no intravenous product is available, the high volume required must be administered intramuscularly over several days in divided doses.
Method of administration
For intramuscular use only.
The product should be brought to room temperature or body temperature before use.
If administration of a high dose (> 2 ml in children or > 5 ml in adults) is required, it is recommended to administer it in divided doses at different anatomical sites.
If intramuscular administration is contraindicated (e.g., due to coagulation disorders), the patient must be treated with alternative products.
After injection, firm manual pressure should be applied to the injection site using a gauze pad.