INFORMATION FOR HEALTH PROFESSIONALS
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600 IU (120 (g)
Powder for Injection
Passive Immunising Agent
WinRho SDF™, Anti-D (Rho) Immunoglobulin (Human), is a sterile freeze-dried gamma globulin (IgG) fraction containing antibodies to Rho (D). WinRho SDF™ is prepared from human plasma by an anion-exchange column chromatography method. Standard measures to minimize a possible transmission of infectious agent, resulting fromt he use of human plasma-derived products, have been applied during the manufacturing process of WinRho SDFTM. These measures include selection of the plasma donors and screening of individual donations and pooled plasma for specific markers of viral infections. Additionally, the isolated Anti-D (Rho) fraction eluded from the anion exchange procedure is subjected to solvent detergent treatment for viral inactivation of lipid enveloped viruses and Planova (20N) viral filtration for removal of lipid and some non-lipid enveloped viruses (for details see SPECIAL WARNING).
The product is stabilised with 0.1 M glycine, 0.04 M sodium chloride, and 0.01 % polysorbate 80. It contains no preservative.
SPECIAL WARNING
This product is made from human plasma. Products made from human plasma may
contain infectious agents such as viruses and theoretically Creutzfeldt-Jakob
Disease (CJD) agents, that can cause disease. The risk that such products will
transmit an infectious agent has been reduced by screening plasma donors for
prior exposure to certain infectious agents and by testing for the presence of
certain virus markers.
In addition, virus removal and inactivation procedures are included in the
manufacturing process. The current procedures applied in the manufacture of this
product are effective against enveloped viruses such as HIV (human
immunodeficiency virus), hepatitis B and hepatitis C viruses, and the
non-enveloped viruses, hepatitis A and human parvovirus B19.
Despite these measures, such products may still potentially transmit disease.
There is also the possibility that other unknown infectious agents may be
present in such products.
Vaccination for patients in receipt of medicinal products from human plasma
should be considered where appropriate.
Pharmacodynamics
WinRho SDF™, Anti-D (Rho) Immunoglobulin (Human), is used to suppress the immune response of non-sensitised Rho (D)-negative individuals who receive Rho (D)-positive blood either by fetomaternal hemorrhage during delivery of an Rho (D)-positive infant, abortion (either spontaneous or induced), following amniocentesis, abdominal trauma or transfusion. Administration of anti- Rho (D) antibody to the Rho (D)-negative mother prevents an immune response with subsequent anti- Rho (D) antibody formation. The exact mechanism of action has yet to be determined.
WinRho SDF™, when administered within 72 hours of a full-term delivery of an Rho (D)-positive infant by an Rho (D)-negative mother, will reduce the incidence of Rh alloimmunisation from 12-13% to 1-2%. The 1-2% is, for the most part, due to alloimmunisation during the last trimester of pregnancy. When treatment is given both antenatally at 28 weeks gestation and postpartum the Rh immunization rate drops to about 0.1%.
A clinical study was conducted with ten Rho (D)-negative volunteers. All subjects were administered an IV infusion of Rho (D)-positive foetal red cells. Two days after injection of the red cells, five subjects were given an IM injection of 600 IU Win Rho™ (an earlier formulation of WinRho SDF™). Approximately 3mL of foetal red cells were cleared from the circulation of the subjects within eight hours of IV administration of the drug or within 24 hours of IM administration of the drug. None of the subjects had evidence of Rh alloimmunisation either by screening for anti- Rho (D) (two stage papain, indirect Coombs saline and low ionic Autoanalyser techniques) or by challenge of the subjects with Rho (D) foetal cells six months after first clearance of the red cells with WinRho™.
The half-life of anti-D is significantly shortened in pregnant women compared to non-pregnant subjects. When only 600 IU of drug is administered to pregnant women, passive anti- Rho (D) antibodies are not detectable in the circulation for more than six weeks and therefore a dose of 1,500 IU should be used for antenatal administration.
A retrospective survey of WinRho SDF™ use in Rh-negative pregnant women was conducted. Two hundred and twenty-six at-risk women were included in the survey, 225 of whom delivered an Rh-positive baby; the remaining patient had a spontaneous abortion with the Rh status of the foetus unknown. The women received an antenatal dose of 1,500 IU, either at 28-weeks gestation or after a potentially sensitising event, and at 12 week intervals thereafter throughout the pregnancy, and a post-partum dose of 600 IU. There was no seroconversion at delivery versus an expected rate of 4/225 or 1.8% in the absence of effective prophylaxis.
Pharmacokinetics
There have been no pharmacokinetic studies conducted with WinRho SDF™.
In a clinical study with four non-pregnant Rho (D)-negative volunteers, two subjects received 600 IU WinRho™, Anti-D (Rho) Immunoglobulin (Human) via an intravenous (IV) route while two subjects were administered this dose via an intramuscular (IM) route. Peak levels of about 40 ng/mL were reached within two hours of IV administration while peak levels of about 20 ng/mL were reached at 5-10 days after IM administration. The calculated Areas Under the Plasma concentration-time Curve (AUC) were the same in this study regardless of the route of administration of drug. The t½ for anti- Rho (D) was about 24 days in this study.
WinRho SDF™ is indicated for the prevention of Rh sensitisation in Rho (D)-negative females at or below child bearing age.
Prevention of Rh Immunisation
When WinRho SDF™ is used to prevent Rh alloimmunisation, it should not be administered to:
General
As is the case with all drugs of this nature, there is a remote chance of an idiosyncratic or anaphylactoid reaction with WinRho SDF™ in individuals with hypersensitivity to blood products. In the event of an immediate reaction (anaphylaxis) characterised by collapse, rapid pulse, shallow respiration, pallor, cyanosis, edema or generalized urticaria, subcutaneous injection of adrenaline hydrochloride 0.3 mL 1:1000 aqueous solution should be instituted followed by intravenous administration of hydrocortisone 50 to 100 mg if necessary.
WinRho SDF™ contains trace quantities of IgA. Although WinRho ™ has been used successfully to treat selected IgA deficient individuals, the physician must weigh the potential benefit of treatment with WinRho SDF™ against the potential for hypersensitivity reactions. Individuals deficient in IgA have a potential for development of IgA antibodies and anaphylactic reactions after administration of blood components containing IgA. Individuals known to have had an anaphylactic or severe systemic reaction to human globulin should not receive WinRho SDF™ or any other Immunoglobulin (Human).
Administration of WinRho SDF™ with other drugs has not been evaluated. It is recommended that WinRho SDF™ be administered separately from other drugs.
Live attenuated virus vaccines: Passively acquired antibody can interfere with the response to live, attenuated virus vaccines. Therefore, administration of such vaccines, e.g. poliomyelitis or measles, should be deferred until approximately three months after passive immunisation. By the same token, immunoglobulins should not be administered for at least two weeks after such a vaccine has been given.
Animal reproduction studies have not been conducted with WinRho SDF™. It is not known whether WinRho SDF™ can cause foetal harm when administered to a pregnant woman. WinRho SDF™ should be given to a pregnant woman only if clearly needed.
Immunoglobulins are excreted into breast milk and may contribute to the transfer of protective antibodies to the neonate within the first few days of birth. However, it is not known whether passively administered anti-D (Rho) immunoglobulin is excreted into the milk.
No mutagenicity, carcinogenicity or reproductive toxicity studies have been conducted with WinRho SDF™.
In addition to anti-D, WinRho SDF™ contains trace amounts of anti-A, B, C, and E. These antibodies may be detected by laboratory screening tests.
In the prevention of Rh immunisation, the presence of passively administered Rh antibody in maternal or foetal blood can lead to a positive direct antiglobulin (Coombs) test. In case of doubt as to the individual's Rh group or immune status, WinRho SDF™ should be administered.
The Table below lists adverse reactions from post-marketing experience with WinRho®/ WinRho SD® in Rho (D)-negative women.
| BODY SYSTEM | FREQUENCY | ADVERSE REACTION |
|---|---|---|
| BODY AS A WHOLE | Common (≥1% and < 10%) | Headache Chills Fever Discomfort and slight swelling at the site of injection |
| DIGESTIVE SYSTEM | Nausea Vomiting | |
| MUSCULOSKELETAL SYSTEM | Myalgia | |
| BODY AS A WHOLE | Uncommon (≥ 0.1% and < 1%) | Asthenia Abdominal or Back Pain Sweating Increased LDH |
| CARDIOVASCULAR SYSTEM | Vasodilation | |
| MUSCULOSKELETAL SYSTEM | Arthralgia | |
| NERVOUS SYSTEM | Hypotension Dizziness |
|
| SKIN AND APPENDAGES | Pallor | |
| BODY AS A WHOLE | Rare (≥0.01% and < 0.1%) | Anaphylaxis |
| NERVOUS SYSTEM | Somnolence | |
| SKIN AND APPENDAGES | Allergic Reactions (erythema, pruritus, rash) |
In a clinical study with five healthy Rho (D)-negative male
volunteers, Rho (D)-positive foetal red cells were administered by IV
infusion and then 1-2 days later the foetal red cells were cleared by IV
administration of 600 IU WinRho SD®. At 6-8 hours after
administration of WinRho SD® to these subjects, there was an
elevation in mean levels of granulocytes from 4.25 to 7.88 x 109/L (p
<0.01) and monocytes from 0.38 to 0.64 x 109/L (p<0.02). Levels of
phagocytic leucocytes returned to pretreatment levels by 24 hours after WinRho
SD® treatment. This effect of WinRho SD® is believed to
result from the anti- Rho (D) mediated clearance of Rho
(D)-positive foetal red cells as it was not observed at much higher dosages of
WinRho SD® when no Rho (D)-positive red cells were present
in the circulation.
Non-anaphylactic reactions are the most common type of reaction to intravenous immunoglobulin, being reported in up to 10% of patients receiving products in this class. The reactions are characterized by back or abdominal pain, nausea or vomiting within the first 30 minutes of the infusion. Usually there is no dyspnea or other changes in vital signs. Chills, fever, headache, myalgia and fatigue may begin at the end of the infusion and continue for several hours.
There are no reports of known overdoses in patients being treated for Rh isoimmunisation.
Anti-D immunoglobulin may be administered intramuscularly or intravenously. Prophylaxis is effective if anti-D immunoglobulin is given within 72 hours of a sensitising event. The recommended doses for various situations are given in the Table below.
Anti-D (Rho) Immunoglobulin (WinRho SDF™) Dose
| Indication | Dose |
|---|---|
| At 28 weeks gestation in Rho(D)-negative women | 1,500 IU |
| During Pregnancy, in Rho(D)-negative women who experience a sensitising event in which there is a risk of foetal blood crossing in to the maternal circulation, unless the blood type of the foetus is confirmed to be Rho(D)-negative. Such events include spontaneous or induced abortion, amniocentesis, chorion villus sampling, ruptured tubal pregnancy, abdominal trauma or transplacental haemorrhage. | <34 weeks gestation: 1,500 IU repeated every 12 weeks ≥ 34 weeks gestation: 600 IU For massive foeto-maternal haemorrhage, see During Transfusion. |
| Post-partum in Rho(D)-negative women who deliver Rho(D)-positive babies or Rh status of the baby is unknown | 600 IU |
| Post-abortion, in Rho(D)-negative women, unless the blood type of the foetus is confirmed to be Rho(D)-negative | 600 IU |
| During transfusion, in Rho(D)-negative females at or below child-bearing age who are transfused with Rho(D)-positive red blood cells or blood components containing red blood cells, provided the transfused blood represents less than 20% of total circulating red cells. | If exposed to Rho(D)-positive whole blood: 45 IU/mL blood IV or 60 IU/mL blood IM If exposed to Rho(D)-positive red blood cells: 90 IU/mL cells IV or 120 IU/mL cells IM Max 3,000 IU q8h IV and 6,000 IU q12h IM |
WinRho SDF™ should be reconstituted only with the accompanying vial of 0.9% Sodium Chloride Injection. Use aseptic technique throughout.
| Vial Size | Volume of Diluent to be Added to Vial | Nominal Concentration per mL |
|---|---|---|
| Intravenous Injection | ||
| 600 IU | 1.25 mL - 2.5 mL | 480 IU/mL - 240 IU/mL |
| Intramuscular Injection | ||
| 600 IU | 1.25 mL | 480 IU/mL |
Inspect the product for particulate matter and discoloration prior to injection.
Intravenous. Inject into a suitable vein at a rate of 1,500 IU over 5 to 15 seconds.
Intramuscular. Inject into the deltoid muscle of the upper arm or the anterolateral aspect of the upper thigh.
WinRho SDF™ is FOR SINGLE USE ONLY. Discard any unused portion appropriately. If the product is not used immediately following reconstitution, it can be stored at room temperature for up to 4 hours.
WinRho SDF™ is available in a single dose vial containing 600 IU of anti- Rho(D). Each single pack contains one single dose vial of product and one single dose vial of saline, 0.9% Sodium Chloride Injection, BP, sterile non-pyrogenic for reconstitution of WinRho SDF™.
Store WinRho SDF™, Anti-D (Rho) Immunoglobulin (Human) at 2-8°C. Do not freeze. Do not use after expiration date. Discard any unused portion.
MANUFACTURER:
Cangene Corporation
Winnipeg, Canada R3T 5Y3
SPONSOR:
Baxter Healthcare Pty. Ltd.
1 Baxter Drive
Old Toongabbie, N.S.W. 2146
AUSTRALIA
Baxter Healthcare Ltd
33 Vesty Drive
Mt Wellington
Auckland
New Zealand
15 June 2007
™ Trademark of Cangene Corporation.