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

Package leaflet: Information for the user

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 the entire leaflet carefully before you start using this medicine, because it contains important information for you.

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

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

Leaflet contents

1. What Rhophylac 300 is and what it is used for
2. What you need to know before using Rhophylac 300
3. How to use Rhophylac 300
4. Possible adverse 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 injectable solution presented in a pre-filled syringe. The solution contains special proteins isolated from human plasma. These proteins belong to a class known as “immunoglobulins”, also called antibodies. The active substance in Rhophylac 300 is a specific antibody called “anti-D (Rh) immunoglobulin”. This antibody acts against the Rhesus factor type D.

What is Rhesus factor type D

Rhesus factors are special characteristics of human red blood cells. Approximately 85% of the population has what is known as Rhesus factor type D (abbreviated as “Rh(D)”). These individuals are referred to as Rh(D) positive. People who do not have the Rhesus factor type D are referred to as Rh(D) negative.

What is anti-D (Rh) immunoglobulin

Anti-D (Rh) immunoglobulin is an antibody that acts against the Rhesus factor type D and is produced by the human immune system. When an Rh(D) negative individual receives Rh(D) positive blood, their immune system will recognize the Rh(D) positive red blood cells as “foreign” and will attempt to destroy them. To achieve this, the immune system will produce a specific antibody against the Rhesus factor type D. This process is known as “immunization” and usually takes some time (2–3 weeks). Therefore, Rh(D) positive red blood cells are not destroyed upon first exposure, and no signs or symptoms are typically observed. However, when the same Rh(D) negative individual receives Rh(D) positive blood a second time, the antibodies will already be “available”, and their immune system will immediately destroy the foreign red blood cells.

How Rhophylac 300 works

If an Rh(D) negative individual receives a sufficient dose of human anti-D (Rh) immunoglobulin, immunization against the Rhesus factor type D can be prevented. To achieve this, treatment with Rhophylac 300 must begin before or as soon as possible after the first exposure to Rh(D) positive red blood cells. The anti-D (Rh) immunoglobulin contained in this medicine will immediately destroy the foreign Rh(D) positive red blood cells. Thus, the individual’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 become immunized by Rh(D) positive red blood cells from your baby that have passed into your bloodstream. If this occurs, the first baby is usually unaffected and completely healthy. However, in a subsequent pregnancy with an Rh(D) positive baby, your maternal antibodies would destroy the baby’s Rh(D) positive red blood cells during pregnancy. This could lead to complications in the development of the unborn baby, including possible death.

For this reason, you should 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 (intrauterine fetal death, miscarriage, or threatened miscarriage);

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

? when it is likely that Rh(D) positive red blood cells from your baby have entered your bloodstream (transplacental haemorrhage) as a result of antepartum haemorrhage. This may occur, for example, if you experience vaginal bleeding during pregnancy;

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

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

? when you have suffered an accident causing injury to your abdomen or stomach (abdominal trauma).

This medicine is also used if you are an Rh(D) negative pregnant woman and it is unknown whether 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 infusions (blood transfusions) or other blood products containing Rh(D) positive red blood cells, such as a “platelet concentrate” (incorrect transfusion).

2. What you need to know before using Rhophylac 300

? Read this section carefully. The information contained herein must be considered by both you and your doctor before this medicine is administered.

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 you have previously not tolerated well.

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

• Please inform your doctor, pharmacist, or nurse before treatment if this applies to you. In that case, this medicine 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 delivery of an Rh(D)-positive baby, this medicine must always be given to the mother, not to the newborn.
• This medicine is not indicated in Rh(D)-positive individuals or in individuals already immunized against the Rh(D) antigen.

Interrupting administration may be necessary

• Rhophylac 300 may cause hypersensitivity reactions (allergy-type reactions). Rarely, allergic reactions such as a sudden drop in blood pressure or shock may occur (see also section “4. Possible side effects”), 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 interrupt administration of the product 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-type immunoglobulins, you have an increased risk of developing hypersensitivity reactions.

? Please inform your doctor or nurse if you have low levels of IgA-type 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 results from the destruction of foreign Rh(D)-positive red blood cells. For this reason, your doctor or healthcare professional will monitor you closely and you may need to undergo special blood tests.
• If your body mass index (BMI) is greater than or equal to 30 (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 derived from human plasma (which is the liquid part of blood).

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

• careful selection of blood and plasma donors to ensure that carriers at risk of transmitting infections are excluded,
• testing of each donation and pooled plasma 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 derived from human blood or 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 against enveloped viruses such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus, and hepatitis C virus.

The measures may have limited effectiveness 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 be recorded in order 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 or your newborn child are to undergo a blood test (serological testing).

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

Use of Rhophylac with other medicines

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

Vaccinations

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

Also inform the doctor administering vaccines after treatment. This will allow them to check the effectiveness of your vaccination.

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

Pregnancy and breastfeeding

This medicine is used during pregnancy or shortly after delivery.

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

Driving and using machines

Effects of Rhophylac 300 on the ability to drive or use machines are not 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 either 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 greater than or equal to 30, your doctor 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 syringe must be used for one patient only (even if there is product remaining).

You should remain under observation for at least 20 minutes after receiving 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, contact the Toxicology Information Service at telephone number 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 interrupt 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 adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. Such adverse effects may occur even if you have previously received human immunoglobulins and tolerated them well.

Allergic reactions (hypersensitivity reactions) have been observed rarely (in between 1 and 10 users per 10,000). Early signs may include itchy small blisters (wheals) on the skin throughout the body (generalized urticaria). These may progress to severe hypersensitivity / anaphylactic reactions such as sudden drop in blood pressure or shock (e.g. you may feel dizzy, lightheaded, faint upon standing, feel cold in hands and feet, experience abnormal heartbeat or chest pain, chest tightness, shortness of breath or blurred vision), even if you did not show hypersensitivity during previous administrations.

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

If you have been administered this medicine intramuscularly, you may experience local pain and tenderness at the injection site.

The following adverse effects were uncommon (affects 1 to 10 users per 1,000):

? fever and chills (shivering),
? general malaise (malaise),
? headache,
? skin reactions, skin redness (erythema), itching (pruritus)

The following adverse effects were rare (affects 1 to 10 users per 10,000):

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

Reporting of adverse effects

? If you experience any type of adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse 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 particles or sediments.

• Do not use this medicine after the expiry date stated on the case and on the syringe label following EXP. The expiry date refers to the last day of the month indicated.

• Medicines must not be disposed of via wastewater drains or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If in doubt, please consult your pharmacist on how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the package and other information

Composition of Rhophylac 300

• The active substance is human anti-D (Rh) immunoglobulin (IgG antibodies against Rhesus factor D).

• 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 IgG type. Rhophylac 300 contains a maximum of 5 micrograms/ml of human immunoglobulin (antibodies) of IgA type.

• Rhophylac does not contain preservatives.

Appearance of the medicine and contents of the pack

This medicine is a clear or slightly opalescent, colourless or pale yellow injectable solution. Rhophylac 300 is supplied in a glass pre-filled syringe containing 2 ml of sterile ready-to-use solution with 1,500 IU (300 micrograms) of anti-D immunoglobulin.

Rhophylac 300 is available in single packs containing one pre-filled syringe and one injection needle, both packed in a blister (a sealed transparent plastic container with aluminium backing) or in multipacks containing 5 single packs. Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

CSL Behring GmbH
Emil von Behring Strasse, 76
35041 – Marburg
Germany

For further information about this medicine, please contact the local representative of the Marketing Authorization Holder:

CSL Behring, S.A.
Tarragona 157, 18th floor
08014 Barcelona, Spain

This medicine 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 előretöltött fecskendőben Hungary

Rhophylac 1500 IU Luxembourg

Rhophylac 300 microgram / 2 ml
oplossing voor injectie in een voorgevulde spuit Netherlands

Rhophylac 300 micrograme/2 ml
solutie injectabilă în seringă preumplută 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 most recent revision of this leaflet: June 2019

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es