Rhophylac 300 Micrograms / 2 Ml Solution For Injection In Pre-Filled Syringe
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CSL Behring
Package leaflet: Information for the user
Rhophylac® 300 micrograms / 2 ml solution for injection in pre-filled syringe
Human anti-D immunoglobulin
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 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
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.
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.
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.
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.
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
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 (mean values):
IgG1 84.1%
IgG2 7.6%
IgG3 8.1%
IgG4 1.0%
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
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 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 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) 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.
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.
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.
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.
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.
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.
|
System Organ Class (SOC, MedDRA) |
Adverse Reaction |
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 disorders |
Nausea, vomiting |
rare |
|
System Organ Class (SOC, MedDRA) |
Adverse Reaction |
Frequency of ADR (MedDRA Preferred Term (PT) |
|
Skin and subcutaneous tissue disorders |
Skin reaction, erythema, pruritus |
uncommon |
|
Musculoskeletal and connective tissue disorders |
Arthralgia |
rare |
|
General disorders and administration site conditions |
Fever, malaise, chills |
uncommon |
|
At injection site: swelling, pain, erythema, induration, warmth, pruritus, rash |
rare |
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).
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
For safety information with respect to transmissible agents, see section 4.4.
4.9 Overdose
Consequences of an overdose are not known. 5. PHARMACOLOGICAL PROPERTIES
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 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.
After intramuscular administration, a similar degree of red cell clearance was measured after 12 hours.
Furthermore, the efficacy, safety and pharmacokinetics of Rhophylac are supported by the results of three clinical studies
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.
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.
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.
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.
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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