Browse WinRho® SDF WinRho Home Patients and Families Healthcare Professionals Plasma Safety Common Questions WinRho®SDF Canadian Product Monograph & Canadian Package Insert

Standard: In-house standard against WHO 1st Reference Preparation 1976 (anti-D immunoglobulin, human)

The following information has been obtained from the Canadian package insert and therefore is only applicable in Canada.

Prevention of Rh Immunization
WinRho® SDF, Rho (D) Immune Globulin (Human), is used to suppress the immune response of non-sensitized Rho (D) negative individuals who receive Rho (D) positive RBCs either by fetomaternal haemorrhage during delivery of an Rho (D) positive infant, abortion (either spontaneous or induced), following amniocentesis, abdominal trauma or accidental 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 alloimmunization from 12 - 13% to 1 - 2%. The 1 - 2% is, for the most part, due to alloimmunization 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%.

Treatment of Immune Thrombocytopenic Purpura (ITP)
WinRho® SDF is used to increase platelet counts in nonsplenectomized Rho (D) positive patients with ITP and to alleviate clinical signs of bleeding in this patient population. The mechanism of action is not completely understood, but is thought to be due to the production of anti-Rho (D)-(anti-D) coated RBC complexes resulting in Fc receptor blockade, thus sparing antibody- coated platelets. In a clinical study of WinRho® therapy of children with chronic ITP (duration of ITP > 6 months), administration of anti-Rho (D) increased platelet counts from 36 ± 14 x 109/L to 263 ± 138 x 10 /L; peak platelet levels were recorded at about one week after WinRho® therapy; the effect of WinRho® on platelet levels lasted a median of 29 days from the start of therapy. Comparable results were obtained in a clinical study of both adult and children with ITP of varying etiologies including ITP secondary to HIV infection. However, larger increases in platelet levels were seen in children than in adults.

Pharmacology
When administered by an intravenous route, peak levels are achieved within two hours, while the mean time to peak is 5 - 10 days when drug is administered by an intramuscular route. When 600 IU (120 µg) of product was administered to nonpregnant volunteers, the peak levels of passive anti-Rho (D) antibody that were achieved were about 40 ng/mL when the drug was administered by an intravenous route and about 20 ng/mL when the product was administered by an intramuscular route. In clinical studies with Rho (D) negative volunteers, Rho (D) positive red cells were completely cleared from the circulation within eight hours of intravenous administration of WinRho SD®.

When only 600 IU (120 µg) 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 (300 µg) should be used for antenatal administration.

WinRho SD®, Rho (D) Immune Globulin (Human), has been shown to increase platelets in ITP patients. Platelet counts usually rise within one to two days and peak within seven to 14 days after initiation of therapy. The duration of response is variable; however, the average duration is approximately 30 days.

Pregnancy and Other Obstetric Conditions
WinRho® SDF, Rho (D) Immune Globulin (Human) is recommended for prevention of Rh immunization of Rho (D) negative women at risk of developing Rh antibodies. Rho (D) Immune Globulin (Human) prevents the development of Rh antibodies in the Rho (D) negative and previously not sensitized mother carrying a Rho (D) positive fetus, thus preventing the occurrence of haemolytic disease in the fetus or the newborn.

WinRho® SDF is indicated for the prevention of Rh immunization in Rho January 10, 2007en previously sensitized to the Rho (D) factor.

The administration of WinRho® SDF to women satisfying the above conditions should be done at about 28 weeks gestation when the child’s father is either Rho (D) positive or unknown. WinRho® SDF should be administered within 72 hours after delivery if the baby is Rho (D) positive or unknown.

WinRho® SDF administration is also recommended in these same women within 72 hours after spontaneous or induced abortion, amniocentesis, chorion villus sampling, ruptured tubal pregnancy, abdominal trauma or transplacental haemorrhage, unless the blood type of the fetus or father are confirmed to be Rho (D) negative. It should be administered as soon as possible in the case of maternal bleeding due to threatened abortion.

Transfusion
WinRho® SDF is recommended to prevent alloimmunization in Rho (D) negative individuals transfused with Rho (D) positive RBCs or blood components with Rho (D) positive RBCs. Treatment is indicated if the individual who has received the transfusion is a female child or adult in her child bearing years. Treatment should only then be carried out (without preceding exchange transfusion), if the transfused Rho (D) positive blood represents less than 20% of the total circulating red cells.

Immune Thrombocytopenic Purpura (ITP)
WinRho® SDF, Rho (D) Immune Globulin (Human) is recommended in the treatment of destructive thrombocytopenia of an immune etiology in situations where platelet counts must be increased to control bleeding. Clinical studies have shown that the peak platelet counts occur about seven days after IV anti-Rho (D) treatment. The effect is not curative but is transient; platelet counts are usually elevated from several days to several weeks. For individuals with chronic ITP, a maintenance dosage is recommended with the dosage schedule determined on an individual basis.

WinRho® SDF, Rho (D) Immune Globulin (Human), is recommended for the treatment of nonsplenectomized Rho (D) positive 1) children with chronic or acute ITP, 2) adults with chronic ITP, or 3) children and adults with ITP secondary to HIV infection in clinical situations requiring an increase in platelet count to prevent excessive haemorrhage. The safety and efficacy of WinRho have not been evaluated in clinical trials for patients with non-ITP causes of thrombocytopenia or in previously splenectomized patients.

Childhood Chronic ITP
In an open-label, single arm, multicenter study, 24 non-splenectomized, Rho (D) positive children with ITP of greater than six months duration were treated initially with 250 IU/kg (50 µg/kg) Rho (D) Immune Globulin (Human) (125 IU/kg [25 µg/kg] on days 1 and 2), with subsequent doses ranging from 125 to 275 IU/kg (25 to 55 µg/kg). Response was defined as a platelet increase to at least 50,000/mm3 and a doubling of the baseline. Nineteen of 24 patients responded for an overall response rate of 79%, an overall mean peak platelet count of 229,400/mm3(range 43,300 to 456,000), and a mean duration of response of 36.5 days (range 6 to 84).

Childhood Acute ITP
A multicenter, randomized, controlled trial comparing Rho (D) IGIV to high dose and low dose Immune Globulin (Human) and prednisone was conducted in 146 non-splenectomized, Rho (D) positive children with acute ITP and platelet counts less than 20,000/mm3. Of 38 patients receiving Rho (D) IGIV (125 IU/kg [25 µg/kg] on days 1 and 2), 32 patients (84%) responded (platelet count = 50,000/mm3) with a mean peak platelet count of 319,500/mm3 (range 61,000 to 892,000), with no statistically significant differences compared to other treatment arms. The mean times to achieving = 20,000/mm3 or = 50,000/mm3 platelets for patients receiving Rho (D) IGIV were 1.9 and 2.8 days, respectively. When comparing the different therapies for time to platelet count = 20,000/mm3 or = 50,000/mm3, no statistically significant differences among treatment groups were detected, with a range of 1.3 to 1.9 days and 2.0 to 3.2 days, respectively.

Adult Chronic ITP
Twenty-four non-splenectomized, Rho (D) positive adults with ITP of greater than six months duration and platelet counts < 30,000/mm3 or requiring therapy were enrolled in a single-arm, open-label trial and treated with 100 to 375 IU/kg (20 to 75 µg/kg) Rho (D) IGIV (mean dose 231 IU/kg [46.2 µg/kg]). Twenty-one of 24 patients responded (increase = 20,000/mm3) during the first two courses of therapy for an overall response rate of 88% with a mean peak platelet count of 92,300/mm3 (range 8,000 to 229,000).

ITP Secondary to HIV Infection
Eleven children and 52 adults who were non-splenectomized, Rho (D) positive with all Walter Reed classes of HIV infection and ITP, with initial platelet counts of = 30,000/mm3 or requiring therapy, were treated with 100 to 375 IU/kg (20 to 75 µg/kg) Rho (D) IGIV in an open-label trial. Rho (D) IGIV was administered for an average of 7.3 courses (range 1 to 57) over a mean period of 407 days (range 6 to 1,952). Fifty-seven of 63 patients responded (increase = 20,000/mm3) during the first six courses of therapy for an overall response rate of 90%. The overall mean change in platelet count for six courses was 60,900/mm3 (range -2,000 to 565,000), and the mean peak platelet count was 81,700/mm3 (range 16,000 to 593,000).

Prevention of Rh Immunization
When WinRho® SDF, Rho (D) Immune Globulin (Human) is used to prevent Rh alloimmunization, it should not be administered to:

1. Rho (D) positive individuals including babies;
2. Rho (D) negative women who are Rh immunized as evidenced by standard manual Rh antibody screening tests.
3. Individuals with a history of anaphylactic or other severe systemic reaction to immune globulins.

Immune Thrombocytopenic Purpura
When WinRho® SDF is used to treat patients with ITP, it should not be administered to:

1. Rho (D) negative individuals,
2. Splenectomized individuals,
3. Individuals with known hypersensitivity to plasma products.

WinRho® SDF, Rho (D) Immune Globulin (Human) 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; Burks et al. (1986) have reported that as little as 15 µg IgA/mL of blood product has elicited an anaphylactic reaction in IgA deficient individuals. Individuals known to have had an anaphylactic or severe systemic reaction to human globulin should not receive WinRho® SDF or any other Immune Globulin (Human).

WinRho® SDF must be administered via the intravenous route for the treatment of ITP as its efficacy has not been established by the intramuscular or subcutaneous routes.

WinRho® SDF should not be administered to Rho (D) negative or splenectomized individuals as its efficacy in these patients has not been demonstrated.

General
Plasma used in manufacturing has been tested in accordance with regulations and has been treated to inactivate lipid and nonlipid enveloped viruses, however, the possibility of transmission of infectious disease cannot be excluded.

Prevention of Rh Immunization
A large fetomaternal haemorrhage late in pregnancy or following delivery may cause a weak mixed field positive Du test result. Such an individual should be screened for a large fetomaternal haemorrhage and the WinRho® SDF, Rho (D) Immune Globulin (Human), adjusted accordingly. WinRho® SDF should be administered if there is any doubt about the mother’s blood type.

Treatment of ITP
Following administration of WinRho® SDF, Rho (D) positive ITP patients should be monitored for signs and/or symptoms of intravascular hemolysis (IVH), clinically compromising anemia, and renal insufficiency.

If patients are to be transfused, Rho (D) negative red blood cells (PRBCs) should be used so as not to exacerbate ongoing IVH. Platelet products may contain up to 5.0 mL of RBCs, thus caution should likewise be exercised if platelets from Rho (D) positive donors are transfused.

If the patient has a lower than normal haemoglobin level (less than 10 g/dL), a reduced dose of 125 to 200 IU/kg (25 to 40 µg/kg) body weight should be given to minimize the risk of increasing the severity of anaemia in the patient. WinRho® SDF, Rho (D) Immune Globulin (Human), must be used with extreme caution in patients with a haemoglobin level that is less than 8 g/dL due to the risk of increasing the severity of the anaemia. (See DOSAGE AND ADMINISTRATION, Immune Thrombocytopenic Purpura)

Drug Interactions
Administration of WinRho® SDF, Rho (D) Immune Globulin (Human) concomitantly with other drugs has not been evaluated. It is recommended that WinRho® SDF be administered separately from other drugs. Refer to Dosage and Administration section for information on drug compatibility.

Pregnancy Category C
Animal reproduction studies have not been conducted with Win- Rho SDF™. It is not known whether WinRho® SDF can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. WinRho® SDF should be given to a pregnant woman only if clearly needed.

Laboratory Tests
In addition to anti-D antibody, WinRho® SDF contains trace amounts of anti-C, E, A and B. These antibodies may be detected by laboratory screening tests.

Prevention of Rh Immunization
The presence of passively administered Rh antibody in maternal or fetal 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, Rho (D) Immune Globulin (Human), should be administered.

Treatment of ITP
The presence of passively administered anti-Rho (D) can lead to positive direct antiglobulin and indirect antiglobulin (Coombs’) test. Interpretation of direct and indirect antiglobulin tests must be made in the context of the patient’s underlying clinical condition and supporting laboratory data.

Prevention of Rh Immunization
Reactions to Rho (D) Immune Globulin (Human) are rare in Rho (D) negative individuals. Discomfort and light swelling at the site of injection and slight elevation in temperature have been reported in a small number of cases.

In a clinical study with five healthy Rho (D) negative males, Rho (D) positive fetal red cells were administered to volunteers by IV infusion and then 1 - 2 days later the fetal red cells were cleared by IV administration of 600 IU (120 µg) 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 1O9/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 fetal 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.

Treatment of ITP
WinRho® SDF, Rho (D) Immune Globulin (Human), is administered to Rho (D) positive patients with ITP. Therefore, side effects related to the destruction of Rho (D) positive red blood cells, most notably a decreased haemoglobin, can be expected. In four clinical trials of patients treated with the recommended initial intravenous dose of 250 IU/kg (50 µg/kg), the mean maximum decrease in haemoglobin was 1.70 g/dL (range +0.40 to -6.1 g/dL). At a reduced dose, ranging from 125 to 200 IU/kg (25 to 40 µg/kg), the mean maximum decrease in haemoglobin was 0.81 g/dL (range +0.65 to -1.9 g/dL). Only 5/137 (3.7%) of patients had a maximum decrease in haemoglobin of greater than 4 g/dL (range 4.2 to 6.1 g/dL). In most cases, the RBC destruction is believed to occur in the spleen. However, signs and symptoms consistent with IVH, including back pain, shaking chills, and/or hemoglobinuria, have been reported, occurring within minutes and up to a few days after WinRho administration.

IVH-related complications that have been reported include death (four cases reported between January 1996 and November 2000), acute onset or exacerbation of anemia, and acute onset or exacerbation of renal insufficiency. One patient died from complications secondary to IVH-induced exacerbation of anemia after administration of WinRho for treatment of ITP. Although the primary cause of death in the other three ITP patients treated with Win- Rho was related to underlying disease, the extent to which IVHrelated clinical complications exacerbated their conditions and contributed to their deaths is unknown.

The mean maximum decrease in hemoglobin in patients who were not transfused with PRBCs was 3.7 g/dL (range: 0.1-7 g/dL). Transfusions for treatment-associated anemia were administered within hours to days of the onset of IVH and consisted of between 1-6 units of RBCs. Acute renal insufficiency was noted within 2 to 48 hours of the onset of IVH. The mean maximum increase in serum creatinine was 2.9 mg/dL (range: 0.1-10.3 mg/dL) and occurred within 2-9 days. The renal insufficiency in all surviving patients resolved with medical management, including dialysis, within 4-32 days.

The etiology of IVH following WinRho administration is unknown. No known risk factors associated with this adverse event have yet been identified from among those examined, which included age, gender, pre-treatment renal function, pre-treatment hemoglobin, concomitantly administered PRBCs, or WinRho dose. However, it is noted that about half of the reported cases occurred in children and most of these cases had a diagnosis of acute ITP. The number of reported cases appears to indicate that the IVH event, while still an uncommon occurrence, may not be as rare as initially believed.

In a clinical study of treatment of 48 Rho (D) positive individuals with autoimmune thrombocytopenic purpura of various etiologies with multiple treatments of 50 to 250 IU/kg (10 to 50 µg/kg) body weight of WinRho®(Bussel et al., 1991), five adverse reactions occurred during or immediately after the anti-Rho (D) infusions. Two reactions were severe; one occurred in a patient with known hypersensitivity to plasma products; the other occurred in a patient who had received IV WinRho® before and numerous times since without any reactions. Both reactions resulted in shaking and chills with gradual recovery within one hour.

In clinical trials in subjects (n = 161) with childhood acute ITP, adults and children with chronic ITP, and adults and children with ITP secondary to HIV, 60/848 (7%) of infusions were associated with at least one adverse event that was considered to be related to the study medication. The most common adverse events were headache (19 infusions; 2%), chills (14 infusions; < 2%), and fever (nine infusions; 1%). All are expected adverse events associated with infusions of immunoglobulins.

General Adverse Reactions
In addition to the adverse reactions described above, the following have been reported infrequently in clinical trials and/or postmarketing experience, in patients treated for ITP and/or the prevention of Rh immunization, and are thought to be temporally associated with WinRho® SDF use: asthenia, abdominal or back pain, hypotension, pallor, diarrhea, increased LDH, arthralgia, myalgia, dizziness, hyperkinesia, somnolence, vasodilation, pruritus, rash and sweating.

As is the case with all drugs of this nature, there is a remote chance of an idiosyncratic or anaphylactoid reaction with Win- Rho SDF™ in individuals with hypersensitivity to blood products. In the event of an immediate reaction (anaphylaxis) characterized by collapse, rapid pulse, shallow respiration, pallor, cyanosis, edema or generalized urticaria, subcutaneous injection of epinephrine hydrochloride 0.3 mL 1:1000 aqueous solution should be instituted followed by intravenous administration of hydrocortisone 50 to 100 mg if necessary.

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SYMPTOMS AND TREATMENT OF OVERDOSAGE
If an Rho (D) positive individual is treated with large doses of WinRho® SDF, a mild anaemia may develop. However, this is normally compensated for by elevated red cell production. Normally, medical intervention other than discontinuation of Win- Rho SDF™ treatment would not be required.

There are no reports of known overdoses in patients being treated for Rh isoimmunization or ITP. In clinical studies with non-pregnant Rho (D) positive patients with ITP (n = 141) treated with 600 to 32,500 IU (120 to 6,500 µg) of Rho (D) IGIV there were no signs or symptoms that warranted medical intervention. However, these same doses were associated with a mild, transient haemolytic anaemia.

Dosage
Pregnancy and Other Obstetric Conditions
A 1,500 IU (300 µg) dose of WinRho® SDF, Rho (D) Immune Globulin (Human) should be given by intravenous or intramuscular administration at 28 weeks gestation. A 600 IU (120 µg) dose of WinRho® SDF, Rho (D) Immune Globulin (Human) should be given by intravenous or intramuscular administration as soon after delivery of a confirmed Rho (D) positive baby as possible and no later than 72 hours after delivery. In the event that the Rh status of the baby is not known at 72 hours, WinRho® SDF should be administered to the mother at 72 hours after delivery.

If more than 72 hours have elapsed, WinRho® SDF should not be withheld but administered as soon as possible up to 28 days after delivery.

A 600 IU (120 µg) dose of WinRho® SDF, Rho (D) Immune Globulin (Human) should be given by intravenous or intramuscular administration immediately after therapeutic abortion, amniocentesis (after 34 weeks gestation) or other manipulation late in pregnancy (after 34 weeks gestation) associated with increased risk of Rho (D) immunization and, in any event, no later than 72 hours after the event.

A 1,500 IU (300 µg) dose of WinRho® SDF should be given by intravenous or intramuscular administration immediately after amniocentesis before 34 weeks gestation or after chorion villus sampling, and this dosage should be repeated every 12 weeks while the woman is pregnant. In the case of threatened abortion, WinRho® SDF should be administered as soon as possible.

Obstetric Indications and Recommended Dose

Transfusion
WinRho® SDF, Rho (D) Immune Globulin (Human) should be administered for treatment of incompatible blood transfusions or massive fetal haemorrhage as outlined in the table below:

Transfusion Indication and Recommended Dose

Administer 3,000 IU (600 µg) every 8 hours via the intravenous route, until the total dose, calculated from the above table, is administered.

Administer 6,000 IU (1,200 µg) every 12 hours via the intramuscular route, until the total dose, calculated from the above table, is administered.

Immune Thrombocytopenic Purpura
WinRho® SDF, Rho (D) Immune Globulin (Human), must be given by intravenous administration for the treatment of ITP.

An intravenous dose of 125 to 250 IU/kg (25 to 50 µg/kg) body weight is recommended for individuals with ITP.

WinRho® SDF should be reconstituted only with the accompanying vial of Sterile Diluent. It should not be administered concurrently with other products. After confirming that the patient is Rho (D) positive, an initial dose of 250 IU/kg (50 µg/kg) body weight is recommended for the treatment of ITP. If the patient has a haemoglobin level that is less than 10 g/dL, a reduced dose of 125 to 200 IU/kg (25 to 40 µg/kg) should be given to minimize the risk of increasing the severity of anaemia in the patient(See PRECAUTIONS, Treatment of ITP). The initial dose may be administered in two divided doses given on separate days, if desired.

If subsequent therapy is required to elevate platelet counts, an intravenous dose of 125 to 300 IU/kg (25 to 60 µg/kg) body weight of WinRho® SDF, Rho (D) Immune Globulin (Human), is recommended. The frequency and dose used should be administered by the patient’s clinical response by assessing platelet counts, red cell counts, haemoglobin, and reticulocyte levels.

Administration
Reconstitution:
WinRho® SDF should be reconstituted only with the accompanying vial of Sterile Diluent. Use aseptic technique throughout.

1. Reconstitute shortly before use.
2. Remove caps from the diluent and product vials.
3. Wipe exposed central portion of the rubber stopper with suitable disinfectant.
4. Withdraw diluent using a suitable syringe and needle. Use 1.25 to 2.5 mL of Sodium Chloride Injection for intravenous injection or 1.25 mL for intramuscular injection for 600 IU (120 µg) and 1,500 IU (300 µg). Use 8.5 mL of Diluent for Injection for intravenous and intramuscular injection for 5,000 IU (1,000 µg)(see table below). Discard any unused diluent.
5. Inject diluent slowly at an angle so that the liquid is directed onto the inside glass wall of the vial containing the freeze dried pellet.
6. Wet pellet by gently tilting and inverting the vial. Do not shake. Avoid frothing. Gently swirl upright vial until dissolved (less than ten minutes).

Reconstitution of WinRho® SDF

Injection
Parenteral products such as WinRho® SDF, Rho (D) Immune Globulin (Human) should be inspected for particulate matter and discoloration prior to administration. Use product within four hours of reconstitution. Aseptically administer the product intravenously in a suitable vein with a rate injection of 1,500 IU (300 µg)/5 to 15 seconds. Intramuscular injections are made into the deltoid muscle of the upper arm the anterolateral aspects of the upper thigh. Due to the risk sciatic nerve injury, the gluteal region should not be used as routine injection site. If the gluteal region is used, use only the upper, outer quadrant.

Drug Substance

Description: WinRho® SDF, Rho (D) Immune Globulin (Human), is a sterile freeze-dried gamma globulin (IgG) fraction of human plasma containing antibodies to Rho (D), prepared by Cangene Corporation by an anion-exchange column chromatography method.

The incorporation of the Solvent Detergent step, which includes treatment with Tri-n-butyl phosphate and*Triton® X-100, in the WinRho® SDF process is designed to increase the safety of the product by reducing the risk of transmission of lipid enveloped viruses, such as Hepatitis B, Hepatitis C and HIV. WinRho® SDF is filtered using a *Planova ™ 35 nm Virus Filter which has been validated to be effective in the removal of non-lipid enveloped viruses. Virus models for Hepatitis A and human parvovirus B- 19 were all shown to be removed after Planova™ 35 nm virus filtration. The following table summarizes test viruses and their respective log virus reductions:

Planova™ 35 nm Virus Filter Log Virus Reduction Summary

The WinRho® SDF process is based on the process used to manufacture WinRho®, a product that has been used for over ten years in the prevention of Rh alloimmunization.

The product potency is expressed in international units by comparison to the World Health Organization (WHO) standard. A 1,500 International Unit (IU) (300 µg) vial contains sufficient anti-Rho (D) to effectively suppress the immunizing potential of approximately 17 mL of Rho (D) positive red blood cells. (In the past, a full dose of Rho (D) Immune Globulin (Human) has traditionally been referred to as a “300 µg” dose. Potency and dosing recommendations are now expressed in IU by comparison to the WHO anti-D standard. The conversion of “µg” to “IU” is 1 µg = 5 IU).

Composition
WinRho® SDF, Rho (D) Immune Globulin (Human), is a sterile freeze-dried gamma globulin (IgG) fraction of human plasma containing antibodies to Rho (D). Final product formulation includes the addition of sodium chloride to yield 0.04 M, glycine to yield 0.1 M and polysorbate 80 to yield 0.01%.

Stability and Storage Recommendations
Stability
WinRho® SDF, Rho (D) Immune Globulin (Human) is stable at 2-8°C until the expiry date indicated on the label.

Storage
Store WinRho® SDF, Rho (D) Immune Globulin (Human) at 2- 8° C. Do not freeze. Do not use after expiration date. Discard any unused portion.

Reconstituted Solutions
WinRho® SDF, Rho (D) Immune Globulin (Human) is reconstituted with Sterile Diluent, USP as directed under the Dosage and Administration section of this document. If reconstituted product is not used immediately, then it should be stored at room temperature for no longer than four hours.

Parenteral Products See the Dosage and Administration section of this document pertaining to reconstitution and administration of WinRho® SDF, Rho (D) Immune Globulin (Human).

WinRho® SDF, Rho (D) Immune Globulin (Human) is available in the dosage forms outlined below:

Pharmacokinetics
In a clinical study with four Rho (D) negative volunteers, two subjects received 600 IU (120 µg) WinRho®, Rho (D) Immune Globulin (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 a Curve (AUC) were the same in this study regardless of the route of administration of drug. The t ½ for anti-Rho (D) was about 24 days in this study.

In a clinical study of Rh Prophylaxis in Rho (D) negative pregnant women given 600 IU (120 µg) of WinRho®, Rho (D) Immune Globulin (Human) it became apparent that passive anti-D was not persisting in pregnant women for more than six weeks after administration. The difference from the results of the clinical pharmacology study described above is likely due to several reasons. Pregnant women have a greater blood volume than “normal” subjects. Also, the erythrocytes of an Rho (D) positive fetus will take up some of the anti-Rho (D) of the mother. It is for these reasons that the recommended dose (1,500 IU [300 µg]) for antenatal administration of WinRho® SDF, Rho (D) Immune Globulin (Human) for Rh Prophylaxis is greater than the postnatal dose (600 IU [120 µg]) of WinRho SDF™.

In a clinical study in which seven Rho (D) negative male volunteers, subjects were administered either IV WinRho® or IV Win- Rho SD® at a dose of 250 IU/kg (50 µg/kg) body weight, no difference between these two preparations of Rho (D) Immune Globulin (Human) could be detected in any pharmacokinetic parameter in this study. Peak levels of 1.0 to 1.4 µg of anti-Rho (D) per mL of serum were reached within two hours of administration. The t ½ for anti-Rho (D) in these subjects was about 24 days.

Pharmacodynamics
A clinical study was conducted with ten Rho (D) negative volunteers. All subjects were administered an IV infusion of Rho (D) positive fetal red cells. Two days after injection of the red cells, five subjects were given an IM injection of 600 IU (120 µg) Win- Rho®, Rho (D) Immune Globulin (Human) and five subjects were given an IV injection of 600 IU (120 µg) WinRho®. Fetal 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 alloimmunization either by screening for anti-Rho (D) (two stage papain, indirect Coombs, saline and low ionic Autoanalyzer techniques) or by challenge of the subjects with Rho (D) fetal cells six months after first clearance of the red cells with Win- Rho®.

Another clinical study was conducted with five Rho (D) negative volunteers; the same study design was used for clearance of Rho (D) positive red cells after IV administration of 600 IU (120 µg) WinRho SD®, Rho (D) Immune Globulin (Human). All fetal red cells were cleared from the circulation of the volunteers within eight hours of administration of WinRho SD®. None of the subjects had evidence of Rh alloimmunization by screening for anti- Rho (D) antibodies at three and six months after WinRho SD® administration.

An IV acute toxicity study was conducted in mice using WinRho®, Rho (D) Immune globulin (Human). An LD50 was not determined as the maximal dose used did not kill any experimental animals. A lower limit of 18,750 IU (3,750 µg) anti-Rho (D)/kg body weight was established as the LD50 for this drug. Neither observation nor necropsy of the experimental animals revealed any acute toxicity related to the study drug.

In a clinical study with healthy Rho (D) negative male volunteers, WinRho SD®, Rho (D) Immune Globulin (Human), has been administered IV at a dose of 250 IU/kg (50 µg/kg) of body weight. In that study, there were no signs of toxicity which could be attributed to WinRho SD®. There was a moderate elevation of serum LDH levels (p < 0.03).

WinRho® has undergone clinical testing in Rho (D) positive individuals with Immune Thrombocytopenic Purpura. In these studies, subjects received multiple intravenous injections of from 1,500 IU (300 µg) anti-Rho (D) (total) to 250 IU (50 µg) anti-Rho (D)/kg body weight. In these studies the only associated signs of toxicity which were identified were mild compensated haemolysis.

*Triton® is a trademark of Rohm & Haas Company.
*Planova™ is a trademark of Asahi Kasei Kogyo Kabushiki Kaisha Corporation.

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22. Unpublished data on file, BITP-2 Report, May 1993.

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24. Unpublished data on file, BITP-1 Report, May 1993.

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