A) Prophylaxis of Rh(D) immunisation in Rh(D) negative women:
Anti-D immunoglobulin is used to prevent haemolytic disease of the newborn caused by Rh(D)
antibodies. In Rh(D) negative women, sensitisation may be due to fetal Rh(D) positive red blood
cells entering the maternal circulation.
Rhophylac is administered with the following constellations:
a) Routine antepartum prophylaxis
In Rh(D) negative women (including partial D) for routine antepartum prophylaxis in the
28th to the 30th week of pregnancy for the prevention of Rh(D) immunisation as a result
of fetomaternal transfusions occurring spontaneously in the last trimester ( fetomaternal
haemorrhage (FMH)).

In the event of complications during pregnancy in Rh(D) negative women (including partial
D):
􀁸 Procedures during pregnancy, for example invasive prenatal diagnostic investigations
(such as amniocentesis, chorionic villus sampling, cordocentesis/fetal blood sampling)
or intrauterine procedures (such as insertion of shunts, embryo reduction), external
cephalic version, and therapeutic abortion.
􀁸 Incidents during pregnancy, such as antepartum haemorrhage, spontaneous abortion,
ruptured fallopian tube pregnancy, ectopic pregnancy, stillbirth, intrauterine death and
abdominal trauma.
b) For postpartum prophylaxis if the mother is Rh(D) negative (including partial D) and the
child is Rh(D) positive.

B) Prophylaxis of Rh(D) immunisation in Rh(D) negative persons after incompatible transfusions
of Rh(D) positive blood or blood products containing Rh(D) positive red blood cells.

5 Dosage / Administration
Rhophylac may be administered both intravenously and intramuscularly.
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 mcg (50 IU) of
anti-D immunoglobulin.
The following recommended dosages are based on the clinical studies performed with
Rhophylac. For specific study details, see section “Pharmacodynamics”. The recommended
dosages and official guidelines for the intramuscular and intravenous use of human anti-D
immunoglobulin should be followed.
To ensure traceability of biological medicinal products, it is recommended that the trade name
and batch number should be documented for each treatment.

Dosage
A) Prophylaxis of Rh(D) immunisation in Rh(D) negative women (including partial D):
a) Routine antepartum prophylaxis:
A dose of 300 mcg (1500 IU), administered in the 28th to the 30th week of pregnancy by
intravenous or intramuscular injection, is recommended.
CSL Behring
Rhopylac®
MMM/MEA/EN, Rev.: December 2020 / CCDS update V2.0 & 3.0
Should the need for antepartum prophylaxis not be established until after the 30th week of
pregnancy, Rhophylac should not be withheld but administered as quickly as possible.
Prophylaxis after complications during pregnancy:
􀁸 Procedures and incidents: 300 mcg (1500 IU) should be given intravenously or
intramuscularly as soon as possible and no later than 72 hours after the complication
has occurred. Rhophylac should still be administered as quickly as possible even if
more than 72 hours have elapsed. The dose of anti-D IgG should then be repeated
every 12 weeks until the birth.
􀁸 Invasive prenatal diagnostic investigations: Irrespective of the time of the procedure,
300 mcg (1500 IU) should be given intravenously or intramuscularly as soon as
possible and no later than 72 hours after the procedure.

b) Postpartum prophylaxis:
300 mcg (1500 IU) should be given intravenously or intramuscularly as soon as possible
and no later than 72 hours after the birth. Rhophylac should be administered as quickly as
possible even if the 72 hours have elapsed.
In cases of known or suspected excessive FMH, the number of fetal red blood cells in the
mother’s circulation should be determined using the Kleihauer-Betke test or by another suitable
test method (e.g. by flow cytometry). If excessive transplacental FMH5(>4 mL Rh(D) positive fetal
red blood cells) is detected, additional Rhophylac (10 mcg (50 IU) per 0.5 mL Rh(D) positive fetal
red blood cellsor per 1 mL RhD positive fetal whole blood) should be injected, preferably
intravenously. If no test is available and excessive FMH cannot be excluded, an additional dose
of 300 mcg (1500 IU) should be injected.
B) Incompatible transfusions:
The dose is 10 mcg (50 IU) anti-D Immunoglobulin per 0.5 mL (RhD) positive packed red blood
cells or 1 mL transfused Rh(D) positive whole blood. Intravenous administration is recommended
in order to achieve immediate plasma availability. In the event of intramuscular use, large doses
should be given in divided doses over several days. A total dose of 3000 mcg (15,000 IU) will be
sufficient, even if more than 300 mL Rh(D) positive whole blood or 150 mL Rh(D) positive packed
red blood cells have been transfused. Given the possible risk of haemolysis, it is generally
recommended not to exceed a dose of 3000 mcg (15,000 IU).
The dose recommendations for prevention of Rh(D) isoimmunisation are summarised in the
following table:

Indication Timing of Administration Dose
Routine antepartum prophylaxis:
At 28 to 30 weeks of
pregnancy
300 mcg (1500 IU) as single
dose
Antepartum prophylaxis
following complications of
pregnancy
Procedures and incidents:
Invasive prenatal diagnostic
investigations:
Within 72 h of complication
Within 72 h of procedure
300 mcg (1500 IU) as single
dose
300 mcg (1500 IU) as single
dose
Postpartum prophylaxis: Within 72 h of birth 300 mcg (1500 IU) as single
dose
Massive fetomaternal
haemorrhage (>4 mL) Within 72 h of complication
300 mcg (1500 IU) as single
dose plus:
• 10 mcg (50 IU) per
0.5 mL transfused Rh(D)
positive fetal red blood cells
or
• 10 mcg (50 IU) per 1 mL
transfused Rh(D) positive fetal
whole blood
Incompatible transfusions Within 72 h of exposure
• 10 mcg (50 IU) per 0.5 mL
Rh(D) positive packed red
blood cells or
• 10 mcg (50 IU) per 1 mL
Rh(D) transfused Rh(D)

Children and adolescents
Since the dosage in the event of incompatible transfusions depends on the volume of the Rh(D)
positive blood or Rh(D) positive red blood cells, the recommended dose for children and
adolescents (0-18 years) is no different to that for adults. The appropriate dose should, however,
be determined in consultation with a transfusion specialist.
Mode of administration
Rhophylac 300 is ready for use and should be at room or body temperature when administered.
Rhophylac 300 can be given either by slow intravenous or by slow intramuscular injection. In
patients with coagulation disorders in whom intramuscular administration is contraindicated,
Rhophylac 300 should be injected intravenously. If large doses (> 5 mL) are to be administered
intramuscularly, it is advisable to give them in divided doses at different administration sites.
It is recommended that patients are observated for a period of at least 20 minutes after
administration.
Overweight patients
Intravenous administration is recommended for patients with a body mass index (BMI) of 􀂕 30
(see also section “Warnings and precautions”).

Postpartum prophylaxis is given to the mother. Anti-D immunoglobulin should not be given to the
neonate.
The product is not intended for administration to Rh(D) positive individuals or for persons who
have already been immunised against Rh(D) antigen.
Rhophylac contains less than 1 mmol sodium (23 mg) per pre-filled syringe, that is to say
essentially “sodium free”.
The maximum recommended dose is 3000 mcg (15,000 IU). This corresponds to 20 mL
Rhophylac and thus 5 mmol or 115 mg sodium, equivalent to 6% of the WHO recommended
maximum daily dietary intake of 2 g sodium for an adult.

Hypersensitivity
Anti-D immunoglobulin may cause allergic reactions even in patients who have tolerated earlier
administrations. It is therefore recommended that patients are informed about the early signs of a
hypersensitivity reaction. Such signs may be hives, generalized urticaria, tightness in the chest,
dyspnoea, drop in blood pressure, and anaphylaxis. The treatment needed should be tailored to
the type and severity of the adverse reaction. If symptoms of shock occur, the current medical
guidelines on the treatment of shock should be followed. Administration should be stopped
immediately if allergic or anaphylactic reactions occur.
The concentration of IgA in Rhophylac 300 is below the detection limit of 5 mcg/mL. However, it
cannot be ruled out that the product contains traces of IgA. Persons with IgA deficiency may
develop antibodies to IgA and may react to the administration of blood components containing
IgA with anaphylactic symptoms. It is the doctor’s responsibility to weigh up the benefit of
treatment with Rhophylac 300 against the possible risk of a hypersensitivity reaction.
Haemolytic reactions
Patients treated with large doses of anti-D immunoglobulin after an incompatible transfusion
should be monitored on the basis of clinical and laboratory parameters because of the risk of a
haemolytic reaction.
Obesity (adiposity)
There are reports that there is a risk of a lack of effectiveness with the intramuscular
administration of Rhophylac to patients with a body mass index (BMI) of 􀂕􀀖􀀓􀀑􀀃For this reason,
intravenous administration is recommended for patients with a BMI of 􀂕􀀖􀀓􀀑
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 the selection of donors, screening of individual donations
and plasma pools for specific infection markers, and in inclusion of effective manufacturing steps
for the inactivation/ elimination of viruses. Nevertheless, when medicinal products prepared from
human blood or plasma are administered, the possibility of transmitting infectious agents cannot
be totally excluded. This also applies to previously unknown or emerging viruses and other
pathogens.
The procedures used are regarded as effective against enveloped viruses such as human
immunodeficiency virus (HIV), hepatitis B virus (HBV) and heptatitis C virus (HCV). They may be
of limited value with non-enveloped viruses such as hepatitits A virus (HAV) and parvovirus B19.
Clinical experience shows that hepatitis A or parvovirus B19 infections are not transmitted by
immunoglobulins, and it is also assumed that the antibody content makes an important
contribution to viral safety.

Live-attenuated virus vaccines
After the administration of anti-D immunoglobulin, an interval of at least 3 months must elapse
before vaccination with live virus vaccines (for example, against measles, mumps, rubella or
varicella) since otherwise the vaccination might not be successful. If anti-D immunoglobulin is
administered within 2-4 weeks after vaccination with a live virus vaccine, it may impair the
effectiveness of the vaccination.
Interference with serological determinations
With serological testing after the administration of immunoglobulins, it must be borne in mind that
the transient rise in various passively transmitted antibodies in the patient’s blood may result in
false positive results.
Determinations of blood group and antibodies in neonates, including the Coombs’ or antiglobulin
test, are substantially affected by the administration of anti-D immunoglobulin, i.e. the
administration of anti-D immunoglobulin may give a positive direct Coombs’ test in the neonate.
However, such a result does not indicate the presence of rhesus incompatibility.
Rhophylac 300 may contain antibodies of other red blood cell antigens, such as anti-A, anti-B,
Rh(C), and Rh€ antibodies that can be detected by sensitive serological test methods.

This product is used during pregnancy and postpartum period. There are no known negative
effects on the course of pregnancy and/or the neonate.
This medicinal product can be used during lactation.

There is no evidence of any adverse effects on the ability to drive or to operate machines.

The following adverse drug reactions have been reported from clinical studies with 592 patients
and are based on analyses of post-marketing data. The list below is presented according to the
MedDRA system organ classes (SOC and Preferred Term (PT)). The following frequency
convention is used: very common 􀀋􀂕􀀃􀀔􀀒􀀔􀀓􀀌􀀏􀀃common 􀀋􀂕􀀃􀀔􀀒􀀔􀀓􀀓􀀃and <1/10), uncommon 􀀋􀂕􀀃􀀔􀀒􀀔􀀓􀀓􀀓􀀃
and <1/100), rare 􀀋􀂕􀀃􀀔􀀒􀀔􀀓,000 and <1/1000), very rare (< 1/10,000).

Immune system disorders:

Rare: Hypersensitivity reaction, anaphylactic shock
Nervous system disorders:
Uncommon: Headache
Cardiac disorders:
Rare: Tachycardia
Vascular disorders:
Rare: Drop in blood pressure
Respiratory, thoracic and mediastinal disorders:
Rare: Dyspnoea
Gastrointestinal disorders:
Rare: Nausea, vomiting
Skin and subcutaneous tissue disorders:
Uncommon: Skin reaction, erythema, pruritus
Musculoskeletal and connective tissue disorders:
Rare: Arthralgia
General disorders and administration site conditions:
Uncommon: Fever, malaise, chills
Rare: At the injection site: swelling, pain, erythema, induration, warmth, pruritus, rash
There are spontaneous reports of severe intravascular haemolysis after the intravenous use of
anti-D in Rh(D) positive patients with primary immune thrombocytopenia (ITP) (off label use).
Cases of haemolysis resulting in death have been reported. The exact frequency of this adverse
effect is not known.
If anti-D immunoglobulins are administered intramuscularly, local pain and sensitivity may occur
at the injection site.
CSL Behring
Rhopylac®
MMM/MEA/EN, Rev.: December 2020 / CCDS update V2.0 & 3.0
Information about virus safety: see section “Warnings and precautions”.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is very
important. It allows continued monitoring of the benefit/risk ratio of the medicinal product.
Healthcare professionals are requested to report any suspected new or serious adverse reaction
through.
Saudi Arabia:
The National Pharmacovigilance Centre (NPC):
SFDA Call Center: 19999
E-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa
Sultanate of Oman:
Department of Pharmacovigilance & Drug Information
Directorate General of Pharmaceutical Affairs & Drug Control
Ministry of Health, Sultanate of Oman
Phone Nos. 22357687 / 22357686
Fax: 22358489
Email: dg-padc@moh.gov.om
Website: www.moh.gov.om
United Arab Emirates:
Pharmacovigilance & Medical Device section
P.O.Box: 1853
Tel: 80011111
Email: pv@mohap.gov.ae
Drug Department
Ministry of Health & Prevention
Dubai, UAE
Other GCC States:
Please contact the relevant competent authority.
Algeria:
http://www.cnpm.org.dz/index.php
Tunisia:
effets.indesirables@rns.tn or www.pharmacovigilance.rns.tn
CSL Behring
Rhopylac®
MMM/MEA/EN, Rev.: December 2020 / CCDS update V2.0 & 3.0
Egypt:
The Egyptian Pharmaceutical Vigilance Center (EPVC)
Email: pv.followup@edaegypt.gov.eg
Website: www.edaegypt.gov.eg
Hotline:15301
Jordan:
Email: jpc@jfda.jo
JFDA reporting link on JFDA website www.jfda.com: https://primaryreporting.who-umc.org/JO
Tel: +962-6-5632000
Iraq
Please Contact The Iraqi Pharmacovigilance center
Mobile: 07807820490
E-mail: iraqiphvc@moh.gov.iq
Website: http://tec-moh-com/

No data on overdose are available. The consequences of overdose are not known.

ATC code: J06B B01
Pharmacotherapeutic group: immune sera and immunoglobulins: anti-D (Rh) immunoglobulin
Rhophylac 300 contains specific IgG antibodies to the Rh(D) antigen of human red blood cells.
Rhophylac 300 is prepared from pooled human plasma. The starting material is the plasma of
Rh(D) negative persons who have been immunised in the past through a specific incompatible
pregnancy (women) or with Rh(D) positive red blood cells.
The immunoglobulin contained in Rhophylac 300 is obtained by ion-exchange chromatography.
The method is extremely gentle and prevents spontaneous complement activation; for this
reason, the product is suitable for intravenous use. This process does not alter the binding
properties of the immunoglobulin; when binding to the Rh(D) antigen it therefore retains all its
biological functions.
The particular isolation method leads to the specific concentration of the desired anti-D
immunoglobulins.
Mechanism of action
CSL Behring
Rhopylac®
MMM/MEA/EN, Rev.: December 2020 / CCDS update V2.0 & 3.0
In Rh(D) negative mothers, anti-D immunoglobulin prevents the formation of antibodies to fetal
Rh(D) positive red blood cells that have entered the circulation. The mechanism probably via
binding of the anti-D antibodies to the Rh(D) antigen of Rh(D) positive red blood cells and
subsequent degradation of the resulting complex by cells of the monocytic phagocyte system,
mainly in the spleen.
Standard doses of 300 mcg administered postpartum prevent 90% of all cases of sensitisation in
the Rh(D) system. The protective effect of postpartum prophylaxis is increased to 99% by
additional antepartum prophylaxis.
Pharmacodynamics properties
In clinical studies in healthy male Rh(D) negative test subjects have shown that both the
intravenous and the intramuscular administration of Rhophylac 300 leads to the efficient removal
of Rh(D) positive red blood cells from the circulation. Compared with intravenous administration,
the elimination of Rh(D) positive red blood cells is delayed on intramuscular administration, since
the anti-D immunoglobulin first has to be absorbed from the injection site.
Clinical efficacy
It has shown in clinical studies that the ante- and postpartum administration of Rhophylac 300
effectively prevents Rh(D) immunisation in Rh(D) negative women.
In two clinical studies, Rhophylac 300 was administered to Rh(D) negative women in the 28th
week of pregnancy and within 72 hours after the birth of an Rh(D) positive child. 206 per-protocol
subjects received the antepartum dose of Rhophylac 300 intravenously and 202 per-protocol
subjects received it intramuscularly. The post- and antepartum method of administration was the
same In more than 99% of cases.
6-11 months after the birth, 256 of the 278 women who gave birth to an Rh(D) positive child were
available for follow-up. Anti-D antibodies could not be detected in any of the women, which
suggest that no Rh(D) immunisation occurred.

Absorption
Anti-D immunoglobulin is available immediately, after intravenous injection, whereas measurable
serum anti-D IgG levels are achieved only after about 4 hours following intramuscular injection.
Distribution
The maximum serum anti-D IgG concentration is reached after 5 days on average. After 2-3
weeks, the serum levels converge, so that there is no longer any difference between the two
routes of administration.
Metabolism

IgG and IgG complexes are broken down in the cells of the reticuloendothelial system.
Elimination
The average half-life of anti-D IgG in pregnant women is 17 days.
Kinetics in special patient groups
To date there is no evidence that the pharmacokinetic properties of anti-D IgG are altered in
kidney disease or with increasing age.
The biological half-life depends on the plasma level of IgG, i.e. in patients with
hypogammaglobulinaemia it may increase to 70 days, in those with hypergammaglobulinaemia it
may be reduced to 11 days.

Immunoglobulins are normal constituents of the human body. Single-dose toxicity studies are not
valid, since higher doses lead to protein overloading in animals. Repeated-dose toxicity tests and
embryofetal studies cannot be carried out, since they lead to the development of and interference
with antibodies. This product’s effects on the immune system of the neonate have not been
investigated.
Since there is no clinical evidence of oncogenic or mutagenic effects of immunoglobulins,
experimental studies are not necessary, particularly in heterologous species.

NA

Incompatibilities
Rhophylac 300 must not be mixed with other medicinal products.

Special precautions for storage
Store in a refrigerator at +2 to +8 C. Do not freeze. Keep out of the reach of children. Keep the
pre-filled syringe (with the blister unopened) in the outer carton in order to protect the contents
from light.

NA

Instructions for handling
The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or
contain deposits.
CSL Behring
Rhopylac®
MMM/MEA/EN, Rev.: December 2020 / CCDS update V2.0 & 3.0
Rhophylac 300 is intended to be single use only; unused product or surplus material should be
disposed of in accordance with local regulations.
17 Marketing authorization number:
Saudi Arabia: 0606222136
Egypt: EGY/BP/October.2016/00122/01
Algeria: 14/12J 171/485
Tunisia: 13813011
Lebanon: 23859/07
Kuwait: 4932/Jul 03
UAE: 4537-5684-3
Oman: D04800A
Yemen: 0010436
Jordan: 15/ 􀤐 􀤟- B.P/2021
Iraq: 17-564

18 Packs
2 ml (300 􀈝􀁊􀀌􀀃solution in a pre-filled syringe with an injection needle (B)
ListI – Prescription only medicines