RHOPHYLAC 300 mcg/2 ml Solution

Contents of the leaflet

1. PATIENT INFORMATION LEAFLET: USER INFORMATION
2. Rhophylac 300, 300 micrograms / 2 ml
3. Solution for injection in a pre-filled syringe
   1. Before using the medicine, read this leaflet carefully.
   2. Table of contents of the leaflet:
4. WHAT IS RHOPHYLAC 300 AND WHAT IS IT USED FOR
   1. What is Rhophylac 300
   2. What is the Rhesus D factor
   3. What is anti-D immunoglobulin
   4. How Rhophylac 300 works
   5. What Rhophylac 300 is used for
5. IMPORTANT INFORMATION BEFORE USING RHOPHYLAC 300
   1. Read this section carefully. The information provided should be taken into account by the patient and doctor before using this medicine.
   2. When not to use Rhophylac 300
   3. Warnings and precautions
   4. Rhophylac 300 and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Rhophylac 300 contains sodium
6. HOW TO USE RHOPHYLAC 300
   1. After receiving Rhophylac 300, the patient should be monitored for at least 20 minutes.
   2. Using a higher dose of Rhophylac 300 than recommended
7. POSSIBLE SIDE EFFECTS
   1. Reporting side effects
8. HOW TO STORE RHOPHYLAC 300
9. CONTENTS OF THE PACK AND OTHER INFORMATION
   1. What the medicine contains
   2. What Rhophylac 300 looks like and what the pack contains
   3. Marketing authorization holder and manufacturer
   4. This medicinal product is authorized in the Member States of the European Economic Area under the following names:

PATIENT INFORMATION LEAFLET: USER INFORMATION

Rhophylac 300, 300 micrograms / 2 ml

Solution for injection in a pre-filled syringe

Human anti-D immunoglobulin

Before using the medicine, read this leaflet carefully.

• Keep this leaflet, you may need to read it again.
• Ask your doctor or pharmacist if you need advice or more information.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Rhophylac 300 and what is it used for
• 2. Important information before using Rhophylac 300
• 3. How to use Rhophylac 300
• 4. Possible side effects
• 5. How to store Rhophylac 300
• 6. Contents of the pack and other information

1. WHAT IS RHOPHYLAC 300 AND WHAT IS IT USED FOR

What is Rhophylac 300

This medicine is a ready-to-use solution for injection in a pre-filled syringe. The solution contains special proteins isolated from human blood plasma. These proteins belong to the class of "immunoglobulins", also called antibodies. The active ingredient of Rhophylac 300 is a specific antibody called "anti-D immunoglobulin". This antibody neutralizes the Rhesus D factor.

What is the Rhesus D factor

Rhesus factors are specific characteristics of human red blood cells. The so-called Rhesus D factor (abbreviated as "Rh(D)") occurs in about 85% of the population. People with this factor are referred to as Rh(D) positive. People without the Rhesus D factor are referred to as Rh(D) negative.

What is anti-D immunoglobulin

Anti-D immunoglobulin is an antibody directed against the Rhesus D antigen produced by the human immune system. When an Rh(D) negative person receives blood with the Rh(D) positive factor, their immune system recognizes the Rh(D) positive red blood cells as "foreign" and tries to destroy them. This process is called "immunization" and usually takes some time (2-3 weeks). Therefore, the destruction of Rh(D) positive red blood cells does not occur after the first contact, and no symptoms are usually observed at that time. However, if the same Rh(D) negative person receives Rh(D) positive blood again, the antibodies will be "ready to act immediately" and their immune system will immediately destroy the foreign Rh(D) positive red blood cells.

How Rhophylac 300 works

If an Rh(D) negative person receives a sufficient dose of human anti-D immunoglobulin, it may prevent immunization against the Rhesus D factor. To achieve this effect, treatment with Rhophylac 300 should be started before or shortly after the first contact with Rh(D) positive red blood cells. The anti-D immunoglobulins contained in this medicine will immediately destroy the foreign Rh(D) positive red blood cells. As a result, the patient's immune system will not be stimulated to produce its own antibodies.

What Rhophylac 300 is used for

This medicine is used in two different situations:

A) In Rh(D) negative pregnant women who are carrying an Rh(D) positive child

In this special situation, immunization may occur through Rh(D) positive red blood cells of the child that enter the mother's bloodstream. If this happens during the first pregnancy, it usually does not affect the fetus, and the child is born healthy. However, during a second pregnancy, when the fetus is Rh(D) positive, the antibodies may damage the Rh(D) positive red blood cells of the child during pregnancy. This can lead to serious complications in the child, even death.

Rhophylac 300 can be administered in the following cases:

• during pregnancy or immediately after childbirth of an Rh(D) positive child;
• after a miscarriage of an Rh(D) positive child (intrauterine death, miscarriage, threatened miscarriage, or abortion);
• if there are serious complications during pregnancy (ectopic pregnancy or molar pregnancy);
• if it is suspected that Rh(D) positive red blood cells of the child have entered the mother's bloodstream (hemorrhage due to antepartum hemorrhage);
• if the doctor decides that there is a need for tests to detect fetal abnormalities (amniocentesis, chorionic villus sampling, cordocentesis);
• if the doctor or midwife needs to perform an obstetric procedure during childbirth (e.g., external rotation of the child or other obstetric procedures);
• if the mother's abdomen or intestines are injured in an accident.

This medicine is also used if the pregnant woman is Rh(D) negative and it is not possible to determine if her child will be Rh(D) positive.

B) In Rh(D) negative adults, children, and adolescents (0-18 years) who have accidentally received Rh(D) positive blood transfusions or other products containing Rh(D) positive red blood cells, such as "platelet concentrate" (mismatched blood transfusion).

2. IMPORTANT INFORMATION BEFORE USING RHOPHYLAC 300

Read this section carefully. The information provided should be taken into account by the patient and doctor before using this medicine.

When not to use Rhophylac 300

• if the patient is allergic (hypersensitive) to human immunoglobulins or other components of this medicine (listed in section 6 of this leaflet). Before using the medicine, inform your doctor or nurse about any cases of adverse reactions to other medicines.
• The medicine should not be administered by intramuscular injection in patients with severe thrombocytopenia or other severe coagulation disorders.

Before using the medicine, inform your doctor or nurse about the above-mentioned conditions. In such cases, the medicine may only be administered intravenously.

Warnings and precautions

Before starting treatment with Rhophylac 300, discuss it with your doctor or medical staff.

• to protect Rh(D) negative women after childbirth of an Rh(D) positive child, this medicine is always administered to the mother, not the newborn. This medicine is not intended for use in Rh(D) positive individuals or patients already immunized against the Rh(D) antigen.

When it may be necessary to stop using the medicine

• Rhophylac 300 may cause allergic reactions (anaphylactic type). 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 human immunoglobulins were previously well tolerated. If such symptoms occur, inform your doctor or nurse immediately. The administration of the medicine will be stopped, and treatment will be initiated according to the type and severity of the side effects.

Doctors and medical staff should pay special attention to

• patients with low levels of IgA immunoglobulins, who may be more likely to experience allergic reactions. Inform your doctor or medical staff if you have a low IgA level. Then, the doctor will carefully weigh the benefits of treatment with this medicine against the increased risk of allergic reactions.
• during treatment with this medicine, large amounts of the product (up to 3,000 micrograms, equivalent to 20 ml or 10 syringes) are administered after mismatched blood transfusion. In such cases, a hemolytic reaction may occur, which is the result of the destruction of foreign Rh(D) positive red blood cells. Therefore, close monitoring by a doctor or nurse is recommended, and special blood tests may be necessary.

Information on safety, including the possibility of transmitting infectious agents

This medicine is obtained from human plasma (the liquid part of blood). When medicines are obtained from human blood or plasma, certain methods are used to prevent the transmission of infectious agents to patients. These include

• careful selection of blood and plasma donors to exclude individuals who may be carriers of infectious agents,
• testing each donation and plasma pool for the presence of viruses/infectious agents.
• including steps in the processing of blood or plasma that can inactivate or remove viruses. Despite these precautions, the use of medicines prepared from human blood or plasma does not completely eliminate the risk of transmitting infectious agents. This also applies to unknown or newly discovered viruses or other types of infectious agents.

The methods used are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the virus that causes AIDS), hepatitis B virus, and hepatitis C virus. The methods used may have limited effectiveness against non-enveloped viruses, such as hepatitis A virus and parvovirus B19. The use of immunoglobulins is not associated with the transmission of hepatitis A or parvovirus B19. The protective effect is likely due to the presence of antibodies against these infections in the product. It is strongly recommended that the name and batch number of the medicine Rhophylac 300 be recorded after each administration to identify the batch used. Blood tests

Inform your doctor or medical staff if you have been treated with Rhophylac 300 and have had any blood tests (serological tests) performed on you or your newborn. After treatment with this medicine, the results of some blood tests may be altered for a period of time. If you received this medicine before childbirth, the results of some blood tests in your newborn may also be disrupted.

Rhophylac 300 and other medicines

Always inform your doctor or nurse about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. This also applies to medicines sold without a prescription. Vaccinations

Before treatment, inform your doctor or medical staff about any vaccinations you have received in the last 2-4 weeks. After treatment, also inform the doctor who performs vaccinations. They may plan to check the effectiveness of the vaccinations performed. This medicine may reduce the effectiveness of live virus vaccines, such as measles, mumps, rubella (German measles), or chickenpox vaccines. Therefore, you should not be vaccinated before 3 months have passed since the last dose of Rhophylac 300.

Pregnancy and breastfeeding

This medicinal product is used during pregnancy or shortly after childbirth. Immunoglobulins are excreted in breast milk. In clinical trials, 432 mothers received 300 micrograms of this medicine before childbirth, and 256 of them received it again after childbirth. No adverse reactions were observed in their children.

Driving and using machines

No effects of Rhophylac 300 treatment on the ability to drive and use machines have been observed.

Rhophylac 300 contains sodium

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

3. HOW TO USE RHOPHYLAC 300

This medicine is injected by a doctor or nurse into a muscle or directly into a vein. The dose of Rhophylac 300 and the route of administration are determined by the doctor. For example, if the patient's body mass index (BMI) is 30 or higher, the medicine should be administered intravenously (see also section 2). Before use, the syringe should be warmed to room temperature or body temperature (25°C). One syringe can only be used for one patient (even if some medicine remains unused after administration).

After receiving Rhophylac 300, the patient should be monitored for at least 20 minutes.

Using a higher dose of Rhophylac 300 than recommended

The consequences of overdose are not known.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Rhophylac 300 can cause side effects, although not everybody gets them. Side effects may occur even if the patient has previously taken immunoglobulins and tolerated them well. Allergic reactions (hypersensitivity reactions) that have been observed rarely (affecting 1 to 10 people per 10,000 treated)

Early symptoms may appear as small, itchy blisters on the skin (hives) or on the entire body surface (generalized rash). They can develop into severe hypersensitivity/anaphylactic reactions, such as a sudden drop in blood pressure or shock (e.g., you may feel improved mood, dizziness, fainting when standing, cold feet or hands, abnormal heart rhythm, chest pain, tightness in the chest, wheezing, or double vision) even if the patient has not shown hypersensitivity during previous administrations. If such symptoms occur during treatment with Rhophylac 300, inform your doctor or nurse immediately. They will decide whether to stop the administration and start appropriate treatment. When this medicine is administered intramuscularly, pain and pressure sensitivity at the injection site may occur. The following side effects have been reported not very often (affecting 1 to 10 people per 1,000 treated):

• fever and chills (shivering),
• malaise (feeling unwell),
• headache,
• skin reactions, redness of the skin (erythema), itching (pruritus).

The following side effects have been reported rarely (affecting 1 to 10 people per 10,000 treated):

• allergic reactions, anaphylactic shock,
• nausea and/or vomiting,
• low blood pressure (hypotension),
• rapid heart rate or tachycardia,
• joint pain (arthralgia),
• difficulty breathing (dyspnea)
• reactions at the injection site

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, inform your doctor or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products

Al. Jerozolimskie 181C

02-222 Warsaw

Phone: +48 22 49 21 301

Fax: +48 22 49 21 309

Website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE RHOPHYLAC 300

Keep out of sight and reach of children.

Store in a refrigerator (2°C to 8°C).

Do not freeze.

The syringe should be stored in a plastic, tightly closed container and in the outer packaging (carton) to protect it from light.

Do not use this medicine if the solution is cloudy or contains sediment.

Do not use this medicine after the expiry date. The expiry date is stated on the outer packaging and on the label of the pre-filled syringe after EXP. The expiry date refers to the last day of the month stated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What the medicine contains

• The active substance is human anti-D immunoglobulin (anti-D antibodies of the IgG type).
• The other ingredients are human albumin, glycine, sodium chloride, and water for injections.
• The product contains a maximum of 30 mg/ml of human plasma proteins, of which 10 mg/ml is human albumin as a stabilizer. At least 95% of the other plasma proteins are immunoglobulins (antibodies) of the IgG type. Rhophylac 300 contains no more than 5 micrograms/ml of human immunoglobulins (antibodies) of the IgA type.
• Rhophylac 300 does not contain preservatives.

What Rhophylac 300 looks like and what the pack contains

This medicine is a clear or slightly opalescent, colorless or pale yellow solution for injection. Rhophylac 300 is supplied in a glass pre-filled syringe with 2 ml of ready-to-use sterile solution containing 300 micrograms (1,500 IU) of anti-D immunoglobulin. Rhophylac 300 is available in single packs containing 1 pre-filled syringe and 1 injection needle, packed in one blister (transparent plastic packaging closed with paper foil) or in multipacks containing 5 single packs. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76

35041 Marburg

Germany

This medicinal product 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 ______ Belgia

Rhophylac 300 μικρογραμμάρια/2 ml ενέσιμο διάλυμα σε προγεμισμένη σύριγγα ___________ Cyprus, Greece

Rhophylac 300 mikrogramů / 2 ml Injekční roztok v předplněné injekční stříkačce ________ Czech Republic

Rhophylac 1500 IE (300 mikrogram) / 2 ml injektionsvæske, opløsning fyldt injektionssprøjte _____ Denmark

Rhophylac 1500 IU (300 mikrog) / 2 ml injektioneste, liuos esitäytetyssä ruiskussa ____________ Finland

Rhophylac 300 microgrammes/2 ml, solution injectable en seringue préremplie ____________ France

Rhophylac 300 Mikrogramm/2 ml, Injektionslösung in Fertigspritze ____________________ Germany, Luxembourg

Rhophylac 300 mikrogramm/2 ml oldatos injekció előretöltött fecskendőben ___________________ Hungary

Rhophylac 300 míkrógrömm / 2 ml stungulyf, lausn, í áfylltri sprautu ___________________ Iceland

Rhophylac 300 microgrammi/2 ml Soluzione iniettabile in siringa pre-riempita ___________ Italy

Rhophylac 300 microgram / 2 ml Oplossing voor injectie in voorgevulde spuit __________ Holand

Rhophylac 1500 IU (300 mikrogram) / 2 ml injeksjonsvæske, oppløsning, i ferdigfylt sprøyte _______ Norway

Rhophylac 300, 300 mikrogramów / 2 ml Roztwór do wstrzykiwań w ampułko-strzykawce _______ Poland

Rhophylac 300 microgramas /2 ml solução injetável em seringa pré-cheia _______________ Portugal

Rhophylac 300 micrograme/2 ml soluţie injectabilă în seringă preumplută ______________ Romania

Rhophylac 300 mikrogramov / 2 ml Injekčný roztok naplnený v injekčnej striekačke _______ 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 1500 IE (300 mikrogram) / 2 ml injektionsvätska, lösning i förfylld spruta _____________ Sweden

Rhophylac 300 micrograms / 2 ml, solution for injection in pre-filled syringe _____________ United Kingdom, Ireland, Malta

Date of leaflet approval: September 2021