Prospect: Information for the Patient

Rhophylac 300 micrograms/2 ml of injectable solution in pre-filled syringe

Human Anti-D Immunoglobulin

Read this prospect carefully before starting to use this medicine, as it contains important information for you.

Follow exactly the administration instructions of the medicine contained in this prospect or those indicated by your doctor, pharmacist or nurse.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect. See section 4.

1. What isRhophylac 300and for what it is used

2. What you need to know before using Rhophylac 300

3. How to use Rhophylac 300

4. Possible adverse effects

5. Storage ofRhophylac 300

6. Contents of the package and additional information

What is Rhophylac 300

This medication is a ready-to-use injectable solution, presented in a preloaded syringe. The solution contains special proteins, isolated from human plasma. These proteins belong to the class called “immunoglobulins”, also known as antibodies. The active ingredient of Rhophylac 300 is a specific antibody called “anti-D (Rh) immunoglobulin”. This antibody acts against the Rh factor type D.

What is the Rh factor type D

The Rh factors are special characteristics of human red blood cells. Approximately 85% of the population has the Rh factor type D (abbreviated “Rh(D)”). These people are calledRh(D) positive. People who do not have the Rh factor type D are calledRh(D) negative.

What is anti-D (Rh) immunoglobulin

Anti-D (Rh) immunoglobulin is an antibody that acts against the Rh factor type D, and is produced by the human immune system. When a Rh(D) negative person receives Rh(D) positive blood, their immune system will recognize the Rh(D) positive red blood cells as “foreign” to their body and attempt to destroy them. For this purpose, their immune system will manufacture a specific antibody against the Rh factor type D. This process is called “immunization” and usually takes some time (2-3 weeks). Therefore, Rh(D) positive red blood cells will not be destroyed after the first contact, and no signs or symptoms are usually observed. However, when the same Rh(D) negative person receives Rh(D) positive blood again, the antibodies will be “available” and their immune system will destroy the foreign red blood cells immediately.

How Rhophylac 300 works

If a Rh(D) negative person receives a sufficient dose of human anti-D (Rh) immunoglobulin, they can prevent the isoinmunization against the Rh factor type D. To achieve this, the treatment with Rhophylac 300 must begin before or as soon as possible after the first contact with Rh(D) positive red blood cells. The anti-D (Rh) immunoglobulin contained in this medication will immediately destroy the foreign Rh(D) positive red blood cells. Thus, the person's immune system will not manufacture its own antibodies.

When to use Rhophylac 300

This medication is used in two different situations:

A) If you are a Rh(D) negative woman, pregnant and carrying a Rh(D) positive fetus

In this special situation, you may be immunized by the Rh(D) positive red blood cells of your fetus that have passed into your bloodstream. If this occurs, the first baby, usually, is not affected and is completely healthy. However, in your next Rh(D) positive baby, your maternal antibodies will destroy the Rh(D) positive red blood cells of the baby during pregnancy. This would produce complications in the development of your next baby, including its possible death.

Therefore, you must receive Rhophylac 300:

?when you are carrying, or have just had, a Rh(D) positive baby;

?when you have lost a Rh(D) positive baby (fetal intrauterine death, abortion, or threatened abortion);

?when your pregnancy is especially complicated (ectopic pregnancy or pregnancy with a non-viable fertilized egg (hydatidiform mole));

?when it is probable that the Rh(D) positive red blood cells of your baby have passed into your bloodstream (transplacental hemorrhageas a consequence ofprepartum hemorrhage). This can occur, for example, when you suffer vaginal bleeding during pregnancy.

?when your doctor needs to perform tests to detect fetal malformations (amniocentesis, chorionic villus sampling, cordocentesis);

?when your doctor or midwife need to attempt to manipulate your baby from the outside (e.g. external version of the baby or other obstetric manipulations);

?when you suffer an accident that damages your stomach or abdomen (abdominal trauma).

This medication is also used if you are a Rh(D) negative woman, pregnant and it is not known if your baby is Rh(D) positive.

(B) You are an adult, child, or adolescent (0 – 18 years) Rh(D) negative, who has received accidentally Rh(D) positive transfusions or other preparations containing Rh(D) positive red blood cells as a “platelet concentrate” (wrong transfusion).

Read this section carefully. The information contained must be taken into account by you and your doctor before this medication is administered.

Do not use Rhophylac 300:

• If you are allergic (hypersensitive) to human immunoglobulins or to any of the other components of this medication (including those listed in section 6).

• Inform your doctor, pharmacist, or nurse before treatment about any medication that you have not tolerated well previously.

• You should not receive intramuscular injections if you have a severe reduction in the number of platelets (thrombocytopenia) or any other coagulation disorder.

• Inform your doctor, pharmacist, or nurse before treatment if this applies to you. In that case, this medication may only be administered as an intravenous injection.

Warnings and precautions

Consult your doctor or nurse before starting to use Rhophylac 300.

• To protect Rh(D) negative women after the birth of an Rh(D) positive baby, this medication must always be administered to the mother, not the newborn.
• This medication is not indicated for Rh(D) positive individuals or for individuals immunized against the Rh(D) antigen.

Stopping treatment may be necessary

• Rhophylac 300 may cause hypersensitivity reactions (allergic reactions). In rare cases, allergic reactions such as sudden blood pressure drop or shock (see also section “4. Possible adverse effects”) may occur even if you have previously received human immunoglobulins and have tolerated them well.

Please inform your doctor or nurse immediately if these reactions occur.They will discontinue the product administration and initiate appropriate treatment, depending on the nature and severity of the adverse effect.

Your doctor or nurse will take special care

If you have low levels of IgA immunoglobulins, you have a higher risk of presenting hypersensitivity reactions.

Please inform your doctor or nurse if you have low levels of IgA immunoglobulins. They will carefully weigh the benefits of treatment with this medication against the increased risk of hypersensitivity reactions.

• If you are being treated with this medication, after receiving an incompatible transfusion, you may be administered a large amount of the product (up to 3,000 micrograms, equivalent to 20 ml or 10 syringes). In this case, a so-called hemolytic reaction occurs, which is a consequence of the destruction of the Rh(D) positive red blood cells foreign to your body. For this reason, your doctor or healthcare professional will monitor you closely and may need to perform special blood tests.
• If your body mass index (BMI) is 30 or higher (calculated by dividing your body weight by the square of your height), the intramuscular injection of Rhophylac may not be fully effective. In this case, your doctor or nurse must inject this medication into a vein.

Information on safety regarding infections

This medication is obtained from human plasma (the liquid part of the blood).

When medications are manufactured from blood or human plasma, certain measures are taken to prevent infections that can be transmitted to patients. These include:

• a careful selection of blood and plasma donors to ensure that carriers who are at risk of transmitting infections are excluded,

• analysis of each donation and plasma mixture to detect signs of viruses/infection,
• the inclusion of steps in the blood or plasma processing that can inactivate or eliminate viruses.

Despite these measures, when medications obtained from blood or human plasma are administered, the possibility of transmission of infectious agents cannot be completely ruled out. This also applies to any unknown or emerging viruses or other types of infection.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV, the virus that causes AIDS), hepatitis B virus, and hepatitis C virus.

The measures may have limited value against non-enveloped viruses such as hepatitis A virus and parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections present in the product are protective.

It is strongly recommended that each time you receive a dose of Rhophylac 300, you record the name and batch number of the product to maintain a record of the batches used.

Blood tests

Please inform your doctor or nurse that you have been treated with Rhophylac 300 if you are to undergo a blood test (serological test) or if your newborn is to undergo a blood test.

After administration of this medication, the results of certain blood tests may be altered for a certain time. If you are a mother who received this medication before delivery, the results of certain blood tests in your newborn may also be affected.

Use of Rhophylac with other medications

Please inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription.

Vaccinations

If you have been vaccinated in the last 2-4 weeks, please inform your doctor or nurse before treatment.

Please also inform the doctor administering the vaccines after treatment. This way, they can check the effectiveness of your vaccination.

This medication may interfere with the effectiveness of live virus vaccines, such as those against measles, mumps, rubella, or varicella. Therefore, such vaccines should not be given until 3 months after the last administration of Rhophylac 300.

Pregnancy and breastfeeding

This medication is used during pregnancy or shortly after delivery.

Immunoglobulins are excreted in breast milk. In clinical studies in which 432 mothers received this medication before delivery and 256 of them again after delivery, no adverse effects were detected in their babies.

Driving and operating machinery

No effects of Rhophylac 300 on the ability to drive or operate machinery are expected.

Rhophylac contains sodium

This medication contains less than 1 mmol (23 mg) of sodium per syringe; it is essentially “sodium-free”.

This medication will be administered by your doctor or nurse intramuscularly, or directly into a vein. Your doctor will decide how much Rhophylac 300 you should receive and the appropriate route of administration. For example, if your body mass index (BMI) is 30 or higher, your doctor will administer this medication directly into a vein (see also section 2).

The syringe should be brought to room temperature (25 °C) before administration.

One syringemust be used forone patientonly (even if there is leftover product).

You should remain under observation for at least 20 minutes after administration of Rhophylac.

If you use more Rhophylac 300 than you should

The consequences of an overdose are unknown.

In case of overdose or accidental ingestion, contact the Toxicology Information Service at

telephone 91 562 04 20.

If you forgot to use Rhophylac 300

Do not use a double dose to make up for the missed dose.

If you interrupt treatment with Rhophylac 300

If you interrupt treatment with Rhophylac 300, consult your doctor.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can have side effects, although not everyone will experience them. These side effects can occur even if you have previously received human immunoglobulins and tolerated them well.

Rarely (between 1 and 10 users in every 10,000) allergic reactions (hypersensitivity reactions) have been observed. Early signs can be small, itchy blisters (hives) on your skin all over your body (generalized urticaria). They can evolve into severe hypersensitivity / anaphylactic reactions such as sudden drop in blood pressure or shock (e.g. you may feel dizzy, disoriented, faint when standing up, feel cold in hands and feet, feel an abnormal heartbeat or chest pain, chest tightness, shortness of breath or blurred vision) even if you have not shown hypersensitivity in previous administrations.

?Inform your doctor, pharmacist or nurse immediately if you detect these symptoms during the administration of Rhophylac. They can decide whether to stop the administration and start the appropriate treatment.

If you have been administered this medicine intramuscularly, you may feel local pain and sensitivity at theinjection site.

The following side effects wereinfrequent(affects 1 to 10 users in 1,000):

?fever and chills (shivering),

?general discomfort (discomfort),

?headache,

?skin reactions, redness of the skin (erythema), itching (pruritus)

The following side effects wererare(affects 1 to 10 users in 10,000):

• allergic reactions, anaphylactic shock,

?nausea and/or vomiting,

?low blood pressure (hypotension),

?rapid heartbeats, or accelerated heart rate (tachycardia),

?joint pain (arthralgia),

• difficulty breathing (dyspnea),

?reactions at the injection site.

Reporting of side effects

?If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can alsoreport them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep out of sight and reach of children.

• Store in refrigerator (between 2 °C and 8 °C).
• Do not freeze.
• Maintain the syringe in its case (in its plastic container) in order to protect it from light.
• Do not use this medication if you observe that the solution is cloudy or presents sediment.
• Do not use this medication after the expiration date that appears on the case and on the syringe label after EXP. The expiration date is the last day of the month indicated.
• Medicines should not be disposed of through drains or in the trash. Deposit the containers and medicines that you do not need in the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines that you do not need. In this way, you will help to protect the environment.

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Composition of Rhophylac 300

?The active principle is human anti-D (Rh) immunoglobulin (IgG antibodies against the Rhesus D factor).

?The other components are human albumin, glycine, sodium chloride, and water for injections.

?The product contains a maximum of 30 mg of human plasma protein/ml, of which 10 mg/ml is human albumin acting as a stabilizer. At least 95% of the other plasma proteins are human immunoglobulins (antibodies) of type IgG.Rhophylac300 contains a maximum of 5 micrograms/ml of human immunoglobulins (antibodies) of type IgA.

• Rhophylac does not contain preservatives.

Appearance of the product and contents of the package

This medication is a clear or slightly opalescent, colorless or pale yellow injectable solution. Rhophylac 300 is provided in a pre-filled glass syringe with 2 ml of sterile solution ready for use containing 1,500 UI (300 micrograms) of anti-D immunoglobulin.

Rhophylac 300 is available in single-unit packs containing 1 pre-filled syringe and 1 injection needle, both packaged in a transparent plastic blister sealed with aluminum foil, or in multipack packs containing 5 single-unit packs. Some sizes may only be marketed.

Marketing authorization holder and manufacturer responsible

CSL Behring GmbH

Emil von Behring Strasse, 76

35041 – Marburg

Germany

For more information about this medication, please contact the local representative of the marketing authorization holder:

CSL Behring, S.A.

c/ Tarragona 157, 18th floor

08014 Barcelona. Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Rhophylac 300 Mikrogramm / 2 ml

Injektionslösung in einer FertigspritzeAustria

Rhophylac 300 microgram / 2 ml

oplossing voor injectie in een voorgevulde spuitBélgica

Rhophylac 300 μικρογραμμ?ρια/2 ml

εν?σιμο δι?λυμα σε προγεμισμ?νη σ?ριγγαChipre, Grecia

Rhophylac 300 mikrogramu / 2 mlRepública Checa

RhophylacDinamarca, Finlandia, Islandia, Italia, Noruega, Suecia

Rhophylac 300 microgrammes/2 ml,

solution injectableen seringue préremplieFrancia

Rhophylac 300Alemania, Polonia, Portugal

Rhophylac 300 mikrogramm/2 ml oldatos

injekció eloretöltött fecskendobenHungría

Rhophylac 1500 UILuxemburgo

Rhophylac 300 microgram / 2 ml

oplossing voor injectie in een voorgevulde spuitPaíses Bajos

Rhophylac 300 micrograme/2 ml

solutie injectabila în seringa preumplutaRumania

Rhophylac 300 mikrogramov / 2 mlEslovaquia

Rhophylac 300 mikrogramov/2 ml raztopina

za injiciranje v napolnjeni injekcijski brizgiEslovenia

Rhophylac 300 microgramos/2 ml de

solución inyectable en jeringa precargadaEspaña

Rhophylac 300 micrograms / 2 ml,

solution for injection in pre-filled syringeReino Unido, Irlanda, Malta

Last review date of this leaflet: June 2019

For detailed and updated information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es