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

Active substance: ANTI-D (RHO) IMMUNOGLOBULIN

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Perforation

&

Package leaflet: Information for the user

Rhophylac® 300 micrograms / 2 ml
solution for injection in pre-filled syringe
Human anti-D immunoglobulin
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 is Rhophylac?
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 is Rhesus factor type D?
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 is anti-D (Rh) immunoglobulin?
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, immunisation 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.
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 should rather
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.
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.
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.
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.
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 2–4 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). 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
appropriateroute of administration. For example, if your body mass
index (BMI) is greater or equal to 30, he or she should rather 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).
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

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

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.

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.

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 and based on the knowledge that 0.5 ml of packed Rh(D)
positive red blood cells or 1 ml of Rh(D) positive blood is
neutralised by approximately 10 micrograms (50 IU) of 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.

The following doses are recommended based on the clinical
studies performed with Rhophylac. For specific study details see
section 5.1.

Distribution of the IgG subclasses (mean values):
84.1%
IgG1
7.6%
IgG2
8.1%
IgG3
1.0%
IgG4

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.

The content of IgA is not more than 5 micrograms/ml.
Excipient with known effect:
The maximal sodium content is 11.5 mg (0.5 mmol) per syringe.
For the full list of excipients, see section 6.1.
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.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Prevention of Rh(D) immunisation 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 (IUFD),
transplacental haemorrhage (TPH) resulting from
antepartum haemorrhage (APH), 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

Prevention of Rh(D) immunisation 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 and if necessary
repeated at 6 –12 week intervals throughout the
pregnancy.
• Postpartum prophylaxis: For intravenous administration,
200 micrograms (1000 IU) is a sufficient dose. If administered
intramuscularly, 200 micrograms (1000 IU) to 300 micrograms
(1500 IU) is recommended.
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 (50 IU) per 0.5 ml
foetal red blood cells).
Incompatible transfusions of red blood cells (RBCs)
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
in the case of larger incompatible transfusions independent of
whether the transfusion volume is greater than 300 ml of Rh(D)
positive blood.
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.
Method of administration
For intravenous use, 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 advisable 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 is recommended (see section 4.4).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the
excipients 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, the product 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.
True allergic reactions are rare, but allergic-type responses to
anti-D immunoglobulin may occur.
Rhophylac contains a small quantity of IgA. Although anti-D
immunoglobulin has been used successfully to treat selected
IgA-deficient individuals, individuals who are deficient in IgA
have the potential for developing IgA antibodies and may have
anaphylactic reactions after administration of plasma-derived
medicinal products containing IgA. The physician must therefore
weigh the benefit of treatment with Rhophylac against the
potential risks of hypersensitivity reactions.
Rarely, human anti-D immunoglobulin can induce a fall in blood
pressure with anaphylactic reaction, even in patients who have
tolerated previous treatment with human immunoglobulin.
Suspicion of allergic or anaphylactic-type reactions requires
immediate discontinuation of the injection. In case of shock,
standard medical treatment for shock should be implemented.
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.
There have been reports that the intramuscular administration
of Rhophylac in patients with a body mass index (BMI) ≥ 30 is
associated with a risk of lack of efficacy. Therefore, in patients
with a BMI ≥ 30 intravenous administration is recommended.
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 product.
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.
A, B, C, 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.
4.5 Interaction with other medicinal products and other
forms of interaction
Live attenuated virus vaccines
Active immunisation with live virus vaccines (e.g. measles,
mumps or rubella) should be postponed for 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– 4 weeks of a live virus vaccination, then the efficacy of such
a vaccination may be impaired.
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.

Perforation

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.
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
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, < 1/10), uncommon
(≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare
(<1/10,000).
System Organ Adverse
Class (SOC,
Reaction
MedDRA)

Frequency
of ADR
(MedDRA
Preferred Term (PT)

Immune system
disorders

Hypersensitivity,
anaphylactic shock

rare

Nervous system
disorders

Headache

uncommon

Cardiac
disorders

Tachycardia

rare

Vascular
disorders

Hypotension

rare

Respiratory,
thoracic and
mediastinal
disorders

Dyspnoea

rare

Gastrointestinal Nausea, vomiting
disorders

rare

System Organ Adverse
Class (SOC,
Reaction
MedDRA)

Frequency
of ADR
(MedDRA
Preferred Term (PT)

Skin and
subcutaneous
tissue disorders

For safety information with respect to transmissible agents, see
section 4.4.

uncommon

Skin reaction,
erythema, pruritus

5. PHARMACOLOGICAL PROPERTIES

Musculoskeletal Arthralgia
and connective
tissue disorders

rare

General
disorders and
administration
site conditions

uncommon

Fever, malaise,
chills

4.9 Overdose
Consequences of an overdose are not known.

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 immune thrombocytopenic purpura (ITP)
patients. Haemolysis resulting in death has been reported. The
exact frequency of this adverse event is not known.
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.
UK: via the MHRA Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard
IRELAND: preferably through the online reporting option
accessible from the IMB homepage. A downloadable report form
is also accessible from the IMB website, which may be
completed manually and submitted to the IMB via ‘freepost’.
Alternatively, the traditional post-paid ‘yellow card’ option may
also continue to be used.
FREEPOST
Pharmacovigilance Section
Irish Medicines Board
Kevin O’Malley House
Earlsfort Centre
Earlsfort Terrace
IRL – Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.imb.ie
e-mail: imbpharmacovigilance@imb.ie

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: immune sera and immunoglobulins:
Anti-D (Rh) immunoglobulin. ATC Code: J06B B01.
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
red blood cells 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 red blood cells.
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.

in patients. Rhophylac 200 micrograms (1000 IU) were
administered postpartum in 139 per protocol patients.
Rhophylac 300 micrograms (1500 IU) were administered
antepartum as well as postpartum in 446 and 256 per protocol
patients, respectively.
None of the patients included in these studies developed
antibodies against the Rh(D) antigen.
Clinical studies with Rhophylac at doses below 200 micrograms
(1000 IU) have not been performed.
5.2 Pharmacokinetic properties
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 recipients’s circulation and reaches
a maximum after a delay of 2 –3 days.
Human anti-D immunoglobulin has a half-life of about
3 – 4 weeks. This half-life may vary from patient to patient.
IgG and IgG-complexes are broken down in cells of the
reticuloendothelial system.
5.3 Preclinical safety data
There are no preclinical data of relevance for anti-D
immunoglobulin.
Repeated dose testing and embryo-foetal toxicity studies have
not been conducted and are impracticable due to induction of,
and interference with antibodies.
The potential for mutagenic effects of immunoglobulins have
not been studied.

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
red blood cells resulted in an almost complete clearance of
Rh(D) positive red blood cells within 24 hours. While the
intravenous administration of Rhophylac caused an instant
onset of red blood cell disappearance, the onset of elimination
of red blood cells 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.

6.3 Shelf life
3 years

Furthermore, the efficacy, safety and pharmacokinetics of
Rhophylac are supported by the results of three clinical studies

6.4 Special precautions for storage
Store in a refrigerator (+2 °C to +8 °C). Do not freeze.

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.
Do not use solutions which are cloudy or have deposits.
Use only once (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
03 December 2013

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):
• 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.

6. PHARMACEUTICAL PARTICULARS

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

Keep the syringe (originally blistered) in the outer carton in order
to protect from light.

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.

UK:
Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard
Ireland:
FREEPOST
Pharmacovigilance Section
Irish Medicines Board
Kevin O’Malley House
Earlsfort Centre
Earlsfort Terrace
Dublin 2
Ireland.
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.imb.ie
e-mail: imbpharmacovigilance@imb.ie

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.
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 multi packs comprising
5 single packs. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041, Marburg
Germany
This leaflet was last revised in: 12/2013
E9864 /663

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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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