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RHOPHYLAC 300 MICROGRAMS / 2 ML SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE

Active substance(s): ANTI-D (RHO) IMMUNOGLOBULIN

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uk_ie_rhophylac_300_insert_MBR 14.06.2016 07:55 Seite 1

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&

Package leaflet: Information for the user

Rhophylac® 300 micrograms / 2 ml,
solution for injection in pre-filled syringe
Human anti-D immunoglobulin
Please read all of this leaflet carefully before you are
given this medicine because it contains important
information for you.
– Keep this leaflet. You may need to read it again.
– If you have further questions, please ask your doctor or
healthcare professional.
– If you get any side effects, talk to your doctor or healthcare
professional. This includes any possible side effects not listed
in this leaflet. See section 4.
What is in this leaflet:
1. What Rhophylac is and what it is used for
2. What you need to know before you are given Rhophylac
3. How to use Rhophylac
4. Possible side effects
5. How to store Rhophylac
6. Contents of the pack and other information

1. What Rhophylac is and what it is
used for



What Rhophylac 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 blood plasma. These proteins belong to the class of
“immunoglobulins”, also called antibodies. The active ingredient of
Rhophylac is a specific antibody called “anti-D (Rh) immunoglobulin”.
This antibody works against Rhesus factor type D.
What Rhesus factor type D is
Rhesus factors are special characteristics of human red blood cells.
About 85% of the population carry the so called Rhesus factor type
D (abbreviated “Rh(D)”). These people are called Rh(D) positive.
People who do not carry Rhesus factor type D are called Rh(D)
negative.
What anti-D (Rh) immunoglobulin is
Anti-D (Rh) immunoglobulin is an antibody, which works against
Rhesus 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 recognise the Rh(D) positive red blood cells as
“foreign” to their body, and will attempt to destroy them. For this

purpose, the immune system will build specific antibodies against
Rhesus factor type D. This process is called “immunisation” and it
usually takes some time (2– 3 weeks). Therefore, the Rh(D) positive
red blood cells will not be destroyed upon the first contact, and no
signs or symptoms are usually seen then. But when the same Rh(D)
negative person receives Rh(D) positive blood a second time, the
antibodies will be “ready at hand” and their immune system will
destroy the foreign red blood cells immediately.
How Rhophylac works
If a Rh(D) negative person is given a sufficient amount of human
anti-D (Rh) immunoglobulin, isoimmunisation against Rhesus factor
type D can be prevented. To achieve this, treatment with Rhophylac
should commence before or early enough after the first contact to
Rh(D) positive red blood cells. The anti-D (Rh) immunoglobulins
contained in this medicine will then destroy the foreign Rh(D) positive
red blood cells immediately. Thus, the person’s immune system will
not be prompted to build-up its own antibodies.
What Rhophylac is used for
This medicine is used in two distinct situations:
A) You are a Rh(D) negative pregnant woman, who carries a Rh(D)
positive baby.
In this special situation you may be immunised by red blood cells
from your baby passing over into your own blood circulation. If
this happens, the first baby is not usually affected and fully
healthy. But in the next Rh(D) positive baby, the mother’s
antibodies would destroy the baby’s red blood cells already during
pregnancy. This may lead to complications with the baby, including
their possible death.
This medicine is also used if you are a Rh(D) negative pregnant
woman and it is not known if your baby is Rh(D) positive.
As a Rh(D) negative pregnant woman, you may receive anti-D
(Rh) immunoglobulins in the following situations:
• when you carry or have just delivered a Rh(D) positive baby;
• when you lose a Rh(D) positive baby (miscarriage, threatened
miscarriage or abortion);
• when your pregnancy is severely complicated (ectopic
pregnancy or hydatidiform mole);
• when it is likely that your baby’s red blood cells have passed
over into your own blood circulation (transplacental
haemorrhage resulting from antepartum haemorrhage). This
may, for example, happen when you experience vaginal
bleedings during pregnancy;
• when your doctor needs to perform testing methods for foetal
deformities (amniocentesis, chorionic biopsy);
• when your doctor or midwife needs to try moving the baby
from outside (e.g., external version of the baby or other
obstetric manipulative procedures);
• when you have an accident hurting your stomach or gut
(abdominal trauma).

B) You are a Rh(D) negative adult, child or adolescent (0 –18 years)
who has accidentally received infusions (transfusions) of Rh(D)
positive blood (mismatched transfusion). This also applies to any
blood products containing Rh(D) positive red blood cells.

2. What you need to know before you are
given Rhophylac

t Read this section carefully. The information given should be
taken into consideration by you and your doctor before you are
given this medicine.

Do not take Rhophylac:
• If you are allergic (hypersensitive) to human immunoglobulins or
any of the other ingredients of this medicine (listed in section 6).
t Tell your doctor or healthcare professional prior to treatment
about any medicine which you have not well tolerated earlier.
• You must not receive injections into a muscle, if you suffer from a
severe reduction in the number of platelets (thrombocytopenia) or
any other severe blood clotting disorder.
t Tell your doctor or healthcare professional prior to treatment
if this applies to you. In this case this medicine may be given
to you only by injection into a vein.
Warnings and Precautions

t Talk to your doctor or healthcare professional before you are
given Rhophylac.

• For protecting Rh(D) negative women after delivery of a Rh(D)
positive baby, this medicine is always given to the mother, not to
the new-born baby.
• This medicine is not intended for use in Rh(D) positive persons.
When stopping the administration may be required
• Rhophylac may trigger hypersensitivity reactions (allergic-type). In
rare cases, allergic reactions such as a sudden fall 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.
t Tell your doctor or healthcare professional immediately if such
reactions occur. He or she will then stop the administration of
the product and treat you depending on the nature and
severity of the side effect.
Your doctor or healthcare professional will take special care
• if you have low levels of the IgA type immunoglobulins you are
more likely to experience a hypersensitivity reaction.
t Tell your doctor or healthcare professional if you have low
levels of IgA. He or she will then very thoroughly weigh the
benefit of treatment with this medicine against the increased
risk of hypersensitivity reactions.

• if you are treated with this medicine after a mismatched
transfusion, you may receive quite a large amount of the product
(up to 3000 micrograms, equivalent to 20 ml or 10 syringes). In
this case a so called haemolytic reaction occurs. This results from
the intended destruction of the foreign Rh(D)-positive red blood
cells. For this reason your doctor or healthcare professional will
monitor you closely and may need to do special blood tests.
• if your body mass index (BMI) is greater or equal to 30 (calculated
by dividing your body mass by the square of your height), the
injection of Rhophylac into a muscle may not be fully effective. In
this case, your doctor or healthcare professional may inject this
medicine into a vein.
Information on safety with respect to infections
This medicine is made from human blood plasma (this is the liquid
part of the blood).
When medicines are made from human blood or plasma, certain
measures are put in place to prevent infections being passed on to
patients. These include:
• careful selection of blood and plasma donors to make sure those
at risk of carrying infections are excluded,
• the testing of each donation and pools of plasma for signs of
virus/infections,
• the inclusion of steps in the processing of the blood or plasma
that can inactivate or remove viruses.
Despite these measures, when medicines prepared from human
blood or plasma are administered, the possibility of passing on
infection cannot be totally excluded. This also applies to any
unknown or emerging viruses or other types of infections.
The measures taken are considered effective for enveloped viruses
such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis
B virus and hepatitis C virus.
The measures taken may be of limited value against non-enveloped
viruses such as hepatitis A virus and parvovirus B19.

Tear here

FOR HEALTHCARE PROFESSIONALS ONLY

SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Rhophylac 300 micrograms / 2 ml, solution for injection in
pre-filled syringe
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each pre-filled syringe contains 1500 IU (300 micrograms)
human anti-D immunoglobulin*.
One ml contains 750 IU (150 micrograms) human anti-D
immunoglobulin.
The product contains a maximum of 30 mg/ml of human plasma
proteins of which 10 mg/ml is human albumin as stabiliser. At
least 95 % of the other plasma proteins are IgG.
Distribution of the IgG subclasses (approximate values):
84.1%
IgG1
7.6%
IgG2
8.1%
IgG3
1.0%
IgG4
The content of immunoglobin A (IgA) is not more than
5 micrograms/ml.
*Produced from the plasma of human donors.
Excipient with known effect:
The maximal sodium content is 11.5 mg (0.5 mmol) per syringe.
Rhophylac contains no preservatives.
For the full list of excipients, see section 6.1.

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

3. PHARMACEUTICAL FORM
Solution for injection.
The solution is clear or slightly opalescent and colourless or pale
yellow.
Rhophylac has an osmolality of at least 240 mosmol/kg.

It is strongly recommended that every time you receive a dose of
Rhophylac, the name and batch number of the product are recorded
in order to maintain a record of the batches used.

4. CLINICAL PARTICULARS

Blood tests
t Tell your doctor or healthcare professional that you were treated
with Rhophylac if you or your new-born baby have any blood
tests (serological testing).
After you were given this medicine, the results of some blood tests
may be altered for a certain period of time. If you are a mother having
received this medicine before delivery, the results of some blood tests
in your new-born baby may also be affected.

4.1 Therapeutic indications
Prevention of Rh(D) isoimmunisation in Rh(D) negative women
• Antepartum prophylaxis
– Planned antepartum prophylaxis
– Antepartum prophylaxis following complications of
pregnancy including:
Abortion/threatened abortion, ectopic pregnancy or
hydatidiform mole, intrauterine foetal death, transplacental
haemorrhage resulting from antepartum haemorrhage,
amniocentesis, chorionic biopsy, obstetric manipulative
procedures e.g. external version, invasive interventions,

cordocentesis, blunt abdominal trauma or foetal
therapeutic intervention.
• Postpartum prophylaxis
– Delivery of a Rh(D) positive (D, Dweak, Dpartial) baby
An Rh(D) incompatible pregnancy is assumed if the foetus/baby
is either Rh(D) positive or Rh(D) unknown or if the father is
either Rh(D) positive or Rh(D) unknown.
Treatment of Rh(D) negative adults, children and adolescents
(0 –18 years) after incompatible transfusions of Rh(D) positive
blood or other products containing red blood cells e.g. platelet
concentrate.
4.2 Posology and method of administration
Posology
The dose of anti-D immunoglobulin should be determined
according to the level of exposure to Rh(D) positive red blood
cells (RBCs) and based on the knowledge that 0.5 ml of packed
Rh(D) positive RBCs or 1 ml of Rh(D) positive blood is
neutralised by approximately 10 micrograms (50 IU) of anti-D
immunoglobulin.
The following doses are recommended based on the clinical
studies performed with Rhophylac. For specific study details see
section 5.1.
Consideration should also be given to dose and dose schedules
for human anti-D immunoglobulin for intramuscular and
intravenous use recommended in other official guidance.
Prevention of Rh(D) isoimmunisation in Rh(D) negative women
• Antepartum prophylaxis: The recommended dose is a single
dose of 300 micrograms (1500 IU) administered by
intravenous or intramuscular injection.
– Planned antepartum prophylaxis:
A single dose of 300 micrograms at 28 –30 weeks of
gestation.
– Antepartum prophylaxis following complications of
pregnancy:
A single dose of 300 micrograms should be administered
as soon as possible and within 72 hours. If necessary, the
dose may be repeated at 6–12 week intervals throughout
the pregnancy.
• Postpartum prophylaxis: The recommended dose is a single
dose of 300 micrograms (1500 IU), administered by
intravenous or intramuscular injection. When administered
intravenously, a minimum dose of 200 micrograms may be
sufficient provided large foeto-maternal haemorrhage can be
excluded.
For postpartum use, the product should be administered to the
mother as soon as possible within 72 hours of delivery of an
Rh(D) positive (D, Dweak, Dpartial) infant. If more than 72 hours

have elapsed, the product should not be withheld but
administered as soon as possible.
The postpartum dose must still be given even when antepartum
prophylaxis has been administered and even if residual activity
from antepartum prophylaxis can be demonstrated in maternal
serum.
If a large foeto-maternal haemorrhage (> 4 ml (0.7%– 0.8% of
women)) is suspected, e.g. in the event of foetal/neonatal
anaemia or intrauterine foetal death, its extent should be
determined by a suitable method, e.g. Kleihauer-Betke acid
elution test to detect foetal HbF or flow cytometry which
specifically identifies Rh(D) positive cells.
Additional doses of anti-D immunoglobulin should be
administered accordingly (10 micrograms or 50 IU) per 0.5 ml
foetal RBCs.
Incompatible transfusions of RBCs in Rh(D) negative patients
The recommended dose is 20 micrograms (100 IU) anti-D
immunoglobulin per 2 ml of transfused Rh(D) positive blood or
per 1 ml of RBC concentrate.
The appropriate dose should be determined in consultation with
a specialist in blood transfusion. Follow-up tests for Rh(D)
positive RBCs should be done every 48 hours and further anti-D
administered until all Rh(D) positive RBCs have cleared from the
circulation.
A maximum dose of 3000 micrograms (15,000 IU) is sufficient
even if more than 300 ml of Rh(D) positive blood or 150 ml of
erythrocyte concentrate was transfused.
Intravenous use is recommended as it will achieve adequate
plasma levels immediately.
If given by intramuscular injection the large volume should be
administered over a period of several days.

Paediatric population
As the posology in case of incompatible transfusion depends on
the volume of Rh(D) positive blood or RBC concentrate
transfused, the recommended dose in children and adolescents
(0 –18 years) is not considered to be different to that of adults.
However, the appropriate dose should be determined in
consultation with a specialist in blood transfusion.
Use in the elderly
As the posology in case incompatible transfusion depends on
the volume of Rh(D)-positive blood or RBC concentrate
transfused, the recommended dose in elderly patients (≥ 65
years of age) is not considered to be different to that of adults.
The appropriate dose should be determined in consultation with
a specialist in blood transfusion.
Method of administration
As with all blood products, patients should be observed for at
least 20 minutes following administration of Rhophylac.

For intravenous or intramuscular use, to be administered by slow
injection.
If a large volume (> 2 ml for children or > 5 ml for adults) is
required and intramuscular injection is chosen, it is
recommended to administer this in divided doses at different
sites.
If intramuscular administration is contraindicated (bleeding
disorders), Rhophylac should be administered intravenously.

Overweight patients
In patients with a body mass index (BMI) ≥ 30 intravenous
administration should be considered (see section 4.4).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the
excipients of Rhophylac listed in section 6.1.
Hypersensitivity to human immunoglobulins.
The intramuscular route is contraindicated in persons with
severe thrombocytopenia or other disorders of haemostasis.
4.4 Special warnings and precautions for use
In the case of postpartum use, anti-D immunoglobulin is
intended for maternal administration. It should not be given to
the new-born infant.
The product is neither intended for use in Rh(D) positive
individuals, nor for individuals already immunised to Rh(D)
antigen.
Hypersensitivity
Allergic reactions to anti-D immunoglobulin may occur even in
patients who have tolerated previous administrations. Patients
should be informed of the early signs of hypersensitivity
reactions including hives, generalised urticaria, tightness of the
chest, wheezing, hypotension and anaphylaxis. The treatment
required depends on the nature and severity of the side effect.
In case of shock, the current medical standards for treatment of
shock should be observed. If symptoms of allergic or
anaphylactic type reactions occur, immediate discontinuation of
the administration is required.
The concentration of IgA in Rhophylac was found to be below
the detection limit of 5 micrograms/ml. Nevertheless, the
product may contain trace amounts of IgA. Although anti-D
immunoglobulin has been used successfully to treat selected
IgA-deficient patients, individuals who are deficient in IgA have
the potential for developing IgA antibodies and may have
anaphylactic reactions after administration of blood components
containing IgA. The physician must therefore weigh the benefit
of treatment with Rhophylac against the potential risks of
hypersensitivity reactions.

Haemolytic reactions
Patients in receipt of incompatible transfusion, who receive very
large doses of anti-D immunoglobulin, should be monitored
clinically and by biological parameters, because of the risk of
haemolytic reaction.
Obesity
There have been reports that the intramuscular administration
of Rhophylac in patients with a body mass index (BMI) ≥ 30 is
associated with an increased risk of lack of effect. Therefore, in
patients with a BMI ≥ 30, intravenous administration should be
considered.
Rhophylac contains up to 11.5 mg (0.5 mmol) sodium per
syringe. That should be taken into consideration for patients on
a controlled sodium diet.
Information on safety with respect to transmissible agents
Standard measures to prevent infections resulting from the use
of medicinal products prepared from human blood or plasma
include selection of donors, screening of individual donations
and plasma pools for specific markers of infection and the
inclusion of effective manufacturing steps for the inactivation/
removal of viruses. Despite this, when medicinal products
prepared from human blood or plasma are administered, the
possibility of transmitting infective agents cannot be totally
excluded. This also applies to unknown or emerging viruses and
other pathogens.
The measures taken are considered effective for enveloped
viruses such as human immunodeficiency virus (HIV), hepatitis
B virus (HBV) and hepatitis C virus (HCV). They may be of limited
value against non-enveloped viruses such as hepatitis A (HAV)
and parvovirus B19.
There is reassuring clinical experience regarding the lack of
hepatitis A or parvovirus B19 transmission with immunoglobulins
and it is also assumed that the antibody content makes an
important contribution to the viral safety.
It is strongly recommended that every time that Rhophylac is
administered to a patient, the name and batch number of the
product are recorded in order to maintain a link between the
patient and the batch of the product.
4.5 Interaction with other medicinal products and other
forms of interaction
Live attenuated virus vaccines
Active immunisation with live virus vaccines (e.g. measles,
mumps, rubella or varicella) should be postponed until 3 months
after the last administration of anti-D immunoglobulin, as the
efficacy of the live virus vaccine may be impaired.

If anti-D immunoglobulin needs to be administered within
2 to 4 weeks of a live virus vaccination, then the efficacy of such
a vaccination may be impaired.
Interference with serological testing
After injection of immunoglobulin, the transitory rise of the
various passively transferred antibodies in the patient’s blood
may result in misleading positive results in serological testing.
Passive transmission of antibodies to erythrocyte antigens, e.g.
blood group A or B, Rh (C), Rh (D) may interfere with some
serological tests for red cell antibodies, for example the
antiglobulin test (Coombs’ test) particularly in Rh(D) positive
neonates whose mothers have received antepartum prophylaxis.
4.6 Fertility, pregnancy and lactation
Fertility
No animal fertility studies have been conducted with Rhophylac.
Nevertheless, clinical experience with human anti-D
immunoglobulin suggests that no harmful effects on fertility are
to be expected.
Pregnancy
This medicinal product is intended for use in pregnancy.
No study drug-related adverse events were reported in children
delivered of 432 women who received antepartum
administration of Rhophylac 300 micrograms.
Breastfeeding
This medicinal product can be used during breastfeeding.
Immunoglobulins are excreted in human milk. No study
drug-related adverse events were reported in children delivered
of 256 women who received postpartum administration of
Rhophylac 300 micrograms, nor in children delivered of
139 women who received postpartum administration of
Rhophylac 200 micrograms.
4.7 Effects on ability to drive and use machines
Rhophylac has no influence on the ability to drive and use
machines.
4.8 Undesirable effects
Summary of the safety profile
The most serious adverse reactions observed during the
treatment are hypersensitivity or allergic reactions which may
in rare cases progress to a sudden fall in blood pressure and
anaphylactic shock even when the patient has shown no
hypersensitivity to previous administration. When anti-D
immunoglobulins are administered by the intramuscular route,
local pain and tenderness may be observed at the injection site.
Tabulated list of adverse reactions
The following adverse reactions have been reported from
592 patients in clinical studies and from post-marketing
experience. The summary table presented below is according to

uk_ie_rhophylac_300_insert_MBR 14.06.2016 07:55 Seite 2

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the MedDRA system organ classification (SOC and Preferred
Term Level).
Frequency has been evaluated using the following criteria: very
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon
(≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare
(<1/10,000).
System Organ Adverse
Class (SOC,
Reaction
MedDRA)
(MedDRA
Preferred Term (PT)
Immune system
disorders

Hypersensitivity,
anaphylactic shock

Frequency
of ADR

rare

Nervous system Headache
disorders

uncommon

Cardiac
disorders

Tachycardia

rare

Vascular
disorders

Hypotension

rare

Respiratory,
thoracic and
mediastinal
disorders

Dyspnoea

rare

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the
medicinal product is important. It allows continued monitoring
of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse
reactions via:
UK:
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Ireland:
HPRA Pharmacovigilance
Earlsfort Terrace, IRL − Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
E-mail: medsafety@hpra.ie
4.9 Overdose
No data are available on overdosage. Consequences of an
overdose are not known.
5. PHARMACOLOGICAL PROPERTIES

Gastrointestinal Nausea, vomiting
disorders

rare

Skin and
subcutaneous
tissue disorders

uncommon

Skin reaction,
erythema, pruritus

Musculoskeletal Arthralgia
and connective
tissue disorders

rare

General
disorders and
administration
site conditions

uncommon

Fever, malaise,
chills

At injection site:
rare
swelling, pain,
erythema,
induration, warmth,
pruritus, rash

There have been spontaneous reports of severe intravascular
haemolysis when anti-D has been administered intravenously
to Rh(D) positive patients with primary immune
thrombocytopenia (ITP). Haemolysis resulting in death has been
reported. The exact frequency of this adverse event is not
known.
For safety information with respect to transmissible agents, see
section 4.4.

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: immune sera and immunoglobulins:
Anti-D (Rh) immunoglobulin. ATC Code: J06BB01.
Mechanism of action
Rhophylac contains specific antibodies (IgG) against the Rh(D)
antigen of human erythrocytes. It can also contain antibodies
to other Rh antigens, e.g. anti-Rh C antibodies.
During pregnancy, and especially at the time of childbirth, foetal
RBCs may enter the maternal circulation. When the woman is
Rh(D) negative and the foetus Rh(D) positive, the woman may
become immunised to the Rh(D) antigen and produce anti-Rh(D)
antibodies which cross the placenta and may cause haemolytic
disease of the new-born.
Passive immunisation with anti-D immunoglobulin prevents
Rh(D) immunisation in more than 99 % of cases provided that
a sufficient dose of anti-D immunoglobulin is administered soon
enough after exposure to Rh(D) positive foetal RBCs.
The mechanism by which anti-D immunoglobulin suppresses
immunisation to Rh(D) positive red cells is not known.
Suppression may be related to the clearance of the red cells from
the circulation before they reach immunocompetent sites or, it
may be due to more complex mechanisms involving recognition
of foreign antigen and antigen presentation by the appropriate
cells at the appropriate sites in the presence or absence of
antibody.

Pharmacodynamic effects
Prevention of Rh(D) isoimmunisation
In Rh(D) negative healthy male volunteers, both the intravenous
and intramuscular administration of 200 micrograms (1000 IU)
of Rhophylac at 48 hours after injection of 5 ml of Rh(D) positive
RBCs resulted in an almost complete clearance of Rh(D) positive
RBCs within 24 hours.
While the intravenous administration of Rhophylac caused an
instant onset of RBC disappearance, the onset of elimination of
RBCs following intramuscular administration was delayed as
anti-D IgG had to be first absorbed from the injection site.
On an average, 70 % of injected red cells were cleared
2 hours after intravenous administration of Rhophylac.

5.3 Preclinical safety data
Due to induction of and interference with antibodies, there are
limited preclinical data of relevance for anti-D immunoglobulin.
Repeated dose testing and embryo-foetal toxicity studies have
not been conducted and are impracticable to conduct.

After intramuscular administration, a similar degree of red cell
clearance was measured after 12 hours.

The potential for mutagenic effects of immunoglobulins have
not been studied.

Furthermore, the efficacy, safety and pharmacokinetics of
Rhophylac are supported by the results of three clinical studies
in patients. In one clinical study, Rhophylac
200 micrograms(1000 IU) was administered postpartum in 139
per protocol patients.
In the other two clinical studies, Rhophylac 300 micrograms
(1500 IU) was administered antepartum in 446 per protocol
patients and in addition postpartum in 256 who gave birth to
an Rh(D) positive baby.
None of the patients included in these studies developed
antibodies against the Rh(D) antigen.
In the clinical studies with Rhophylac 300, 222 women were
given the antepartum dose of Rhophylac 300 intravenously, and
224 women were given it intramuscularly. In more than 99% of
cases, the method of post- and antepartum administration was
the same.
Clinical studies with Rhophylac at doses below 200 micrograms
(1000 IU) have not been conducted.
Paediatric population
The safety and effectiveness of Rhophylac have not been
established in paediatric subjects after incompatible transfusion
of Rh(D) positive blood or other products containing RBCs.
5.2 Pharmacokinetic properties
Absorption and Distribution
The bioavailability of human anti-D immunoglobulin for
intravenous use is complete and immediate. IgG is quickly
distributed between plasma and extravascular fluid.
Human anti-D immunoglobulin for intramuscular administration
is slowly absorbed into the recipient’s circulation and reaches a
maximum after a delay of 2 to 3 days.

Elimination
Human anti-D immunoglobulin has a half-life of about 3 to
4 weeks. This half-life may vary individually from patient to
patient.
IgG and IgG-complexes are broken down in cells of the
reticuloendothelial system.

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Human albumin
Glycine
Sodium chloride
Water for Injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product
must not be mixed with other medicinal products.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in a refrigerator (+2 °C to +8 °C). Do not freeze.
The product must not be used after the expiry date (EXP) printed
on the outer carton.
Keep the syringe originally blistered in the outer carton in order
to protect from light.
6.5 Nature and contents of containers
2 ml solution in a pre-filled syringe (type I glass) with
1 injection needle in a pack size of 1 or in a multi-pack
consisting of 5 single packs.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Rhophylac should be brought to room or body temperature
before use.
Rhophylac should be inspected visually for particulate matter
and discolouration prior to administration.
Do not use solutions which are cloudy or have deposits.

Rhophylac is for single use only (one syringe – one patient).
Any unused product or waste material should be disposed of in
accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
8. MARKETING AUTHORISATION NUMBER(S)
UK: PL 15036/0019
IE: PA 800/6/2
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
UK: 01 June 2006
IE: 17 October 2003 / 20 February 2006
10. DATE OF REVISION OF THE TEXT
11 June 2016

Other medicines and Rhophylac
t Tell your doctor or healthcare professional if you are taking, have
recently taken or might take any other medicines. This also
applies to medicines obtained without a prescription.
Vaccinations

t Tell your doctor or healthcare professional prior to treatment if

you have just had a vaccination within the last 2 to 4 weeks.
Also inform your vaccinating doctor after the treatment. He or
she can then plan to check the efficacy of your vaccination.

This medicine may impair the efficacy of vaccinations with live virus
vaccines, for example against measles, mumps, rubella (German
measles) or varicella. Such vaccinations should therefore not be given
for 3 months after you were last given Rhophylac.
Pregnancy and breast-feeding
This medicinal product is used in pregnancy or early after delivery.
Immunoglobulins are excreted in human milk. In clinical studies,
432 mothers received this medicine before delivery and 256 of them
again after delivery, and no side effects were seen in their children.
Driving and using machines
No effects of Rhophylac on the ability to drive and use machines are
expected.
Rhophylac contains sodium
This medicine contains up to 11.5 mg (0.5 mmol) sodium per syringe.
Your doctor or healthcare professional will take that into
consideration if you are on a controlled sodium diet.

3. How to use Rhophylac
This medicine will be injected by your doctor or healthcare
professional into a muscle or directly into a vein. Your doctor will
decide how much Rhophylac you should receive, and which is the
appropriate route of administration. For example, if your body mass
index (BMI) is greater or equal to 30, he or she may inject this
medicine directly into a vein (see also section 2).
The syringe should be brought to room or body temperature before
use.
One syringe should be used for one patient only (even if product
is left over then).
You should be observed for at least 20 minutes after having received
Rhophylac.
If you receive more Rhophylac than you should
Consequences of an overdosage are not known.

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
previously received human immunoglobulins and tolerated them
well.
Allergic reactions (hypersensitivity reactions) have been observed
rarely (affects 1 to 10 users in 10,000). Early signs may appear as
small itching bubbles on your skin (hives) or all over your body
(generalised urticaria). They may progress to severe hypersensitivity/
anaphylactic reactions such as a sudden fall in blood pressure or
shock (e.g. you may feel light-headed, dizzy, faint on standing, cold
in the hands and feet, sense an abnormal heart beat or chest pain,
tightness of the chest, wheezing or have blurred vision) even when
you have shown no hypersensitivity on previous administrations.
t Tell your doctor or healthcare professional immediately if you
notice such signs during the administration of Rhophylac. He or
she will decide to stop the administration completely and start
the appropriate treatment.
If you are given this medicine into a muscle, you may feel local pain
and tenderness at the injection site.
The following side effects were uncommon (affects 1 to 10 users
in 1000):
• fever and chills (shivering),
• generally feeling unwell (malaise),
• headache,
• skin reactions, redness of the skin (erythema), itching (pruritis).
The following side effects were rare (affects 1 to 10 users in 10,000):
• allergic reactions, anaphylactic shock
• nausea and/or vomiting,
• low blood pressure (hypotension),
• rapid heartbeat or pulse rate (tachycardia),
• joint pain (arthralgia),
• difficulty in breathing (dyspnoea),
• reactions at the injection site.
Reporting of side effects
If you get any side effects, talk to your doctor or healthcare
professional. This includes any possible side effects not listed in this
leaflet. You can also report side effects directly (see details below).
By reporting side effects, you can help provide more information on
the safety of this medicine.
UK:
Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard

Ireland:
HPRA Pharmacovigilance Section
Earlsfort Terrace
IRL – Dublin 2
Tel: +353 1 676 4971
Fax: +353 1 676 2517
Website: www.hpra.ie
E-mail: medsafety@hpra.ie

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041, Marburg
Germany
This leaflet was last revised in: 04/2016
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5. How to store Rhophylac





Keep out of the sight and reach of children.
Store in a refrigerator (+2 to +8 °C).
Do not freeze.
Keep the syringe in the outer carton (in its sealed plastic pack) in
order to protect from light.
• Do not use this medicine if you notice that the solution is cloudy
or has deposits.
• Do not use this medicine after the expiry date which is stated on
the outer carton and the syringe label after EXP. The expiry date
refers to the last day of that month.
• Do not throw away any medicines via wastewater or household
waste. Ask your pharmacist how to throw away medicines you no
longer use. These measures will help protect the environment.

6. Contents of the pack and other
information
What this medicine contains
• The active substance is human anti-D (Rh) immunoglobulin
(antibodies of the IgG type against the so called Rhesus factor
type D).
• The other ingredients are human albumin, glycine, sodium chloride
and water for injections.
• This product contains a maximum of 30 mg/ml of human plasma
proteins of which 10 mg/ml is human albumin as stabiliser. At
least 95 % of the other plasma proteins are human
immunoglobulins (antibodies) of the IgG type. Rhophylac contains
not more than 5 micrograms/ml human immunoglobulins
(antibodies) of the IgA type.
• Rhophylac contains no preservatives.
What Rhophylac looks like and contents of the pack
This medicine is a clear or slightly pearly and colourless or pale yellow
solution for injection. It comes in a glass syringe pre-filled with
2 ml of solution containing 1500 IU (300 micrograms) of anti-D
immunoglobulin.
Rhophylac is available in single packs containing 1 pre-filled syringe
and 1 injection needle, both packed in one blister pack (a clear plastic
container sealed with a paper foil) or in multipacks comprising
5 single packs. Not all pack sizes may be marketed.

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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