RHOPHYLAC 300 micrograms / 2ml PRE-FILLED SYRINGE SOLUTION FOR INJECTION

Introduction

Package Leaflet: Information for the Patient

Rhophylac 300 micrograms/2 ml solution for injection in a pre-filled syringe

Human Anti-D Immunoglobulin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Follow the instructions for administration of the medicine contained in this leaflet or as indicated by your doctor, pharmacist, or nurse.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What Rhophylac 300 is and what it is used for
2. What you need to know before you use Rhophylac 300
3. How to use Rhophylac 300
4. Possible side effects
5. Storage of Rhophylac 300
6. Contents of the pack and other information

1. What Rhophylac 300 is and what it is used for

What Rhophylac 300 is

This medicine is a ready-to-use solution for injection, which comes in a pre-filled syringe. The solution contains special proteins, isolated from human plasma. These proteins belong to a class called "immunoglobulins", also known as antibodies. The active substance of Rhophylac 300 is a specific antibody called "anti-D (Rh) immunoglobulin". This antibody acts against the Rhesus D factor.

What the Rhesus D factor is

Rhesus factors are special characteristics of human red blood cells. About 85% of the population has the so-called Rhesus D factor (abbreviated "Rh(D)"). These people are called Rh(D) positive. People who do not have the Rhesus D factor are called Rh(D) negative.

What anti-D (Rh) immunoglobulin is

Anti-D (Rh) immunoglobulin is an antibody that acts against the Rhesus D factor and is produced by the human immune system. When an Rh(D) negative person receives Rh(D) positive blood, their immune system recognizes the Rh(D) positive red blood cells as "foreign" to their body and tries to destroy them. To do this, the immune system produces a specific antibody against the Rhesus D factor. This process is called "immunization" and usually takes some time (2-3 weeks). Therefore, the Rh(D) positive red blood cells will not be destroyed after the first contact, and no signs or symptoms are normally seen. But when the same Rh(D) negative person receives Rh(D) positive blood a second time, the antibodies will be "available" and their immune system will destroy the foreign red blood cells immediately.

How Rhophylac 300 works

If an Rh(D) negative person receives a sufficient dose of human anti-D (Rh) immunoglobulin, immunization against the Rhesus D factor can be prevented. To achieve this, treatment with Rhophylac 300 must start 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 medicine will destroy the foreign Rh(D) positive red blood cells immediately. Thus, the person's immune system will not produce its own antibodies.

What Rhophylac 300 is used for

This medicine is used in two different situations:

• If you are an Rh(D) negative woman, pregnant with an Rh(D) positive baby

In this special situation, you may be immunized by the Rh(D) positive red blood cells of your baby that have passed into your bloodstream. If this happens, your first baby will usually not be affected and will be 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 can cause complications in the development of your next baby, including possible death.

For this reason, you must receive Rhophylac 300:

? when you are pregnant with, or have just given birth to, an Rh(D) positive baby;

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

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

? when it is likely that your baby's Rh(D) positive red blood cells have passed into your bloodstream (transplacental hemorrhageas a result of antepartum hemorrhage). This can happen, for example, when you experience 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 needs to try 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 medicine is also used if you are an Rh(D) negative woman who is pregnant and it is not known if your baby is Rh(D) positive.

(B) You are an adult, child, or adolescent (0-18 years) who is Rh(D) negative and has accidentally received Rh(D) positive blood transfusions or other preparations that contain Rh(D) positive red blood cells, such as "platelet concentrate" (wrong transfusion).

2. What you need to know before you use Rhophylac 300

?Read this section carefully. The information contained must be taken into account by both you and your doctor before you are given this medicine.

Do not use Rhophylac 300:

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

• Please inform your doctor, pharmacist, or nurse before treatment about any medicine that you have not tolerated well in the past.

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

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

Warnings and precautions

? Consult your doctor or nurse before starting treatment with Rhophylac 300.

• To protect Rh(D) negative women after giving birth to an Rh(D) positive baby, this medicine must always be administered to the mother, not the newborn.
• This medicine is not indicated in Rh(D) positive individuals or in individuals who have been immunized against the Rh(D) antigen.

When stopping treatment may be necessary

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

? Please inform your doctor or nurse immediately if these reactions occur. They will stop the administration of the product and start the appropriate treatment, depending on the nature and severity of the side effect.

Your doctor or nurse will be particularly careful

? 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 medicine against the increased risk of hypersensitivity reactions.

• If you are being treated with this medicine after receiving an incompatible transfusion, you may be given 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 may occur. This is a consequence of the destruction of the foreign Rh(D) positive red blood cells in your body. For this reason, your doctor or healthcare professional will closely monitor you 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), intramuscular injection of Rhophylac may not be fully effective. In this case, your doctor or nurse should inject this medicine into a vein.

Safety information regarding infections

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

When medicines are manufactured from human blood or plasma, certain measures are taken to prevent infections from being passed on to patients. These include:

• careful selection of blood and plasma donors to ensure that those who may be at risk of transmitting infections are excluded,

• testing of each donation and plasma pool for signs of virus/infection.
• inclusion of steps in the processing of blood or plasma that can inactivate or remove viruses.

Despite these measures, when medicines obtained from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be totally excluded. This also applies to any unknown or emerging virus or other types of infection.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the AIDS virus), 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, the name and batch number of the product should be recorded to maintain a record of the batches used.

Blood tests

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

After administration of this medicine, the results of certain blood tests may be altered for some time. If you are a mother who was given this medicine before birth, the results of certain blood tests in your newborn may also be affected.

Using Rhophylac with other medicines

? Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription.

Vaccinations

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

Also, inform the doctor who administers the vaccines after treatment. This way, they can check the effectiveness of your vaccination.

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

Pregnancy and breastfeeding

This medicine is used during pregnancy or shortly after birth.

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

Driving and using machines

No effects of Rhophylac 300 on the ability to drive or use machines are expected.

Rhophylac contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per syringe; this is, essentially "sodium-free".

3. How to use Rhophylac 300

This medicine will be administered to you 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, they will administer this medicine directly into a vein (see also section 2).

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

One syringeshould be used for one patientonly (even if product remains).

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 not known.

In case of overdose or accidental ingestion, consult the Toxicology Information Service at telephone 91 562 04 20.

If you forget to use Rhophylac 300

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

If you stop treatment with Rhophylac 300

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Such side effects may 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 may be small blisters that itch (hives) on the skin all over your body (generalized urticaria). They can evolve into severe hypersensitivity/granulomatous reactions such as a sudden drop in blood pressure or shock (e.g., you may feel dizzy, faint, pass out when standing up, feel cold in hands and feet, feel an abnormal heartbeat or chest pain, tightness in the chest, shortness of breath, or blurred vision) even when you have not shown hypersensitivity in previous administrations.

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

If you have been given this medicine by intramuscular injection, you may feel pain and sensitivity at the injection site.

The following side effects were uncommon(affect 1 to 10 users in every 1,000):

? fever and chills (shivering),

? general malaise (malaise),

? headache,

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

The following side effects were rare(affect 1 to 10 users in every 10,000):

• allergic reactions, anaphylactic shock,

? nausea and/or vomiting,

? low blood pressure (hypotension),

? rapid heartbeat, or accelerated pulse rate (tachycardia),

? joint pain (arthralgia),

• difficulty breathing (dyspnea),

? reactions at the injection site.

Reporting of side effects

? If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Rhophylac 300

• Keep out of sight and reach of children.

• Store in a refrigerator (between 2°C and 8°C).
• Do not freeze.
• Keep the syringe in its case (in its plastic container) to protect it from light.
• Do not use this medicine if you notice that the solution is cloudy or contains sediment.
• Do not use this medicine after the expiry date that appears on the case and on the label of the syringe after EXP. The expiry date is the last day of the month indicated.
• Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicine in the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

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6. Container Content and Additional Information

Composition of Rhophylac 300

? The active ingredientis human anti-D (Rh) immunoglobulin (antibodies of type IgG against the Rhesus type D factor).

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

? The product contains a maximum of 30 mg of human plasma protein /ml, of which 10 mg/ml is human albumin that acts as a stabilizer. At least 95% of other plasma proteins are human immunoglobulins (antibodies) of type IgG. Rhophylac 300 contains a maximum of 5 micrograms/ml of human immunoglobulin (antibodies) of type IgA.

• Rhophylac does not contain preservatives.

Appearance of the Product and Container Content

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

Rhophylac 300 is available in single-unit containers containing 1 pre-filled syringe and an injection needle, both packaged in a blister (sealed transparent plastic container with aluminum paper) or in multipack containers that contain 5 single-unit containers. Only some sizes may be marketed.

Marketing Authorization Holder and Manufacturer

CSL Behring GmbH

Emil von Behring Strasse, 76

35041 – Marburg

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

CSL Behring, S.A.

c/ Tarragona 157, planta 18

08014 Barcelona, Spain

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

Rhophylac 300 Mikrogramm / 2 ml

Injektionslösung in einer Fertigspritze Austria

Rhophylac 300 microgram / 2 ml

oplossing voor injectie in een voorgevulde spuit Belgium

Rhophylac 300 μικρογραμμ?ρια/2 ml

εν?σιμο δι?λυμα σε προγεμισμ?νη σ?ριγγα Cyprus, Greece

Rhophylac 300 mikrogramu / 2 ml Czech Republic

Rhophylac Denmark, Finland, Iceland, Italy, Norway, Sweden

Rhophylac 300 microgrammes/2 ml,

solution injectable en seringue préremplie France

Rhophylac 300 Germany, Poland, Portugal

Rhophylac 300 mikrogramm/2 ml oldatos

injekció eloretöltött fecskendoben Hungary

Rhophylac 1500 UI Luxembourg

Rhophylac 300 microgram / 2 ml

oplossing voor injectie in een voorgevulde spuit Netherlands

Rhophylac 300 micrograme/2 ml

solutie injectabila în seringa preumpluta Romania

Rhophylac 300 mikrogramov / 2 ml Slovakia

Rhophylac 300 mikrogramov/2 ml raztopina

za injiciranje v napolnjeni injekcijski brizgi Slovenia

Rhophylac 300 microgramos/2 ml de

solución inyectable en jeringa precargada Spain

Rhophylac 300 micrograms / 2 ml,

solution for injection in pre-filled syringe United Kingdom, Ireland, Malta

Date of the Last Revision of this Prospectus: June 2019

Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es