WinRho SDF

6 ADVERSE REACTIONS Serious adverse reactions, some of these cases resulted in fatal outcome, have been observed in patients receiving WinRho ® SDF for the treatment of ITP. These include: intravascular hemolysis (IVH), clinically compromising anemia, acute renal insufficiency and DIC [see Adverse Reactions , ( 6.2 )]. The most common adverse reactions observed for all indications are: headache, chills, fever, asthenia, pallor, diarrhea, nausea, vomiting, arthralgia, myalgia, dizziness, hyperkinesia, abdominal or back pain, hypotension, hypertension, increased LDH, somnolence, vasodilation, pruritus, rash and sweating. All adverse reactions listed occurred in ≤ 2% of WinRho ® SDF doses administered in clinical trials. Adverse reactions observed in the use of WinRho ® SDF for Suppression of Rh Isoimmunization are < 0.1% in Rh o (D)-negative individuals. The most common adverse reactions occurring in ≤ 2% of doses are headache, chills, fever, asthenia, pallor, diarrhea, nausea, vomiting, arthralgia, myalgia, dizziness, malaise, hyperkinesia, abdominal or back pain, hypotension, hypertension, increased LDH, somnolence, vasodilation, pruritus, rash and sweating. ( 6.1 ) Serious adverse reactions, such as IVH, clinically compromising anemia, acute renal insufficiency and DIC have been observed in patients receiving WinRho ® SDF for treatment of ITP. Some of these cases resulted in fatal outcome. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Saol Therapeutics Inc. at 1-833-644-4216 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . . 6.1 Clinical Trials Experiences Because clinical studies are conducted under different protocols and widely varying conditions, adverse reaction rates observed in the clinical trials of a specific drug product cannot be directly compared to rates in clinical trials of another drug, and may not reflect rates observed in practice. Treatment of ITP The safety of WinRho ® SDF was evaluated in clinical trials (n=161) in children and adults with acute and chronic ITP and adults and children with ITP secondary to HIV. Overall, 417 adverse events were reported by 91 patients (57%). The most common adverse events were headache (14% of the patients), fever (11% of the patients) and asthenia (11% of the patients). A total of 117 adverse drug reactions were reported by 46 patients (29%). Headache, chills, and fever were the most common related adverse events ( Table 5 ). With respect to safety profile per administration, 60/848 (7%) of WinRho ® SDF infusions had at least one adverse reaction. The most common adverse reactions were headache (19 infusions; 2%), chills (14 infusions; < 2%), and fever (9 infusions; 1%). Table 5: Adverse Drug Reactions with an Incidence ≥ 5% of Patients Body System Adverse Event All Studies Children Adults # of Patients (%) Body as a Whole Headache 18 (11) 8 (11) 10 (12) Chills 13 (8) 4 (5) 9 (10) Fever 9 (6) 5 (7) 4 (5) Asthenia 6 (4) 2 (3) 4 (5) Infection 4 (3) 4 (5) 0 (0) Nervous System Dizziness 6 (4) 2 (3) 4 (5) In four clinical trials of patients treated with the recommended initial intravenous dose of 250 IU/kg (50 mcg/kg), the mean maximum decrease in hemoglobin 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 mcg/kg), the mean maximum decrease in hemoglobin 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 hemoglobin of greater than 4 g/dL (range: -4.2 to -6.1 g/dL). Suppression of Rh Isoimmunization In the clinical trial of 1,186 Rh o (D)-negative pregnant women, no adverse reactions were reported to Rh o (D) IGIV. 6.2 Post-marketing Experience The following adverse reactions listed by body system have been identified during the post-approval use of WinRho ® SDF. Because post-marketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. Intravascular hemolysis (IVH) leading to death has been reported in patients treated with WinRho ® SDF for immune thrombocytopenic purpura (ITP). Serious complications including severe anemia, acute renal insufficiency, renal failure and disseminated intravascular coagulation (DIC) have also been reported. Blood and Lymphatic: Intravascular hemolysis, disseminated Intravascular coagulation, hemoglobinemia Cardiac: Cardiac arrest, cardiac failure, myocardial infarction, tachycardia Gastrointestinal: Nausea General: Chest pain, fatigue, edema, pain Hepatobilliary: Jaundice Immune System: Anaphylactic reaction/shock, hypersensitivity, injection site reaction including induration, pruritus and/or swelling Musculoskeletal: Myalgia, muscle spasm, pain in extremities Renal: Renal failure, anuria, chromaturia, hematuria, hemoglobinuria Respiratory: Acute respiratory distress syndrome, dyspnea, transfusion related acute lung injury Skin: Hyperhidrosis, pruritus, rash Healthcare professionals should report serious adverse reactions following the administration of WinRho ® SDF to Saol Therapeutics Inc. at 1-833-644-4216 or FDA’s MedWatch reporting system by phone (1-800-FDA-1088).

4 CONTRAINDICATIONS WinRho ® SDF is contraindicated in: Patients who have had known anaphylactic or severe systemic reaction to the administration of human immune globulin products. IgA-deficient patients with antibodies to IgA or a history of hypersensitivity reaction to WinRho ® SDF or any of its components. Patients with autoimmune hemolytic anemia, with pre-existing hemolysis or at high risk for hemolysis. Infants for the suppression of Rh o (D) isoimmunization. Patients with known anaphylactic or severe hypersensitivity responses to human immune globulin products. IgA-deficient patients with antibodies to IgA or a history of hypersensitivity reaction to WinRho ® SDF or any of its components. Patients with a history of autoimmune hemolytic anemia, with pre existing hemolysis or at high risk for hemolysis. Infants for the suppression of Rh o (D) isoimmunization.

11 DESCRIPTION WinRho ® SDF is a sterile, liquid gamma globulin (IgG) fraction containing antibodies to the Rh o (D) antigen (D antigen). WinRho ® SDF is to be administered intravenously for the treatment of ITP and either intravenously or intramuscularly for the suppression of Rh isoimmunization. WinRho ® SDF is prepared from human plasma by an anion-exchange column chromatography method. The manufacturing process includes two steps implemented specifically for viral clearance. The solvent detergent treatment step (using tri-n-butyl phosphate and octoxynol) is effective in inactivating lipid enveloped viruses such as hepatitis B, hepatitis C, and HIV. Virus filtration, using a 20N virus filter, is effective in the removal of some non-lipid enveloped viruses. These two processes are designed to increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses, respectively. In addition to the two specific steps, the anion-exchange chromatography step contributes to the removal of small non-lipid enveloped viruses. The inactivation and reduction of known enveloped and non-enveloped model viruses were validated in laboratory studies as summarized in Table 6 . Table 6: Virus Reduction Values Obtained Through Validation Studies * The PRV was retained by the 0.1 µm pre-filter during the virus validation. Since manufacturing employs a 0.1 µm pre-filter before the 20N filter, the claim of ≥5.6 reduction is considered applicable. Abbreviations: HIV-1: human immunodeficiency virus-1; relevant virus for human immunodeficiency virus-1 and model for HIV-2. BVDV: bovine viral diarrhea virus; model virus for hepatitis C virus (HCV) and West Nile virus (WNV) PRV: pseudorabies virus; model for large enveloped DNA viruses, including herpes HAV: human hepatitis A virus; relevant virus for HAV and model for small non-enveloped viruses in general EMC: encephalomyocarditis virus; model for HAV and for small non-enveloped viruses in general MMV: murine minute virus; model for human parvovirus B19 and for small non-enveloped viruses in general PPV: porcine parvovirus; model for human parvovirus B19 and for small non-enveloped viruses in general n.e.: not evaluated Enveloped Non-Enveloped Genome RNA DNA RNA DNA Virus HIV-1 BVDV PRV HAV EMC MMV PPV Family retro flavi herpes picorna parvo Size (nm) 80-100 50-70 120-200 25-30 30 20-25 18-24 Anion Exchange Chromatography (partitioning) n.e. 2.3 n.e. 3.4 n.e. 20N Filtration (size exclusion) ≥ 4.7 ≥ 3.5 ≥ 5.6* n.e. 4.8 n.e. 4.1 Solvent/Detergent (inactivation) ≥ 4.7 ≥ 7.3 ≥ 5.5 n.e. Total Reduction (log 10 ) ≥ 9.4 ≥ 10.8 ≥ 11.1 2.3 4.8 3.4 4.1 The product potency is expressed in international units (IU) by comparison to the World Health Organization (WHO) standard. In the past, a full dose of Rh o (D) Immune Globulin (Human) has traditionally been referred to as a “300 microgram (mcg)” dose. Potency and dosing recommendations are now expressed in IU by comparison to the WHO anti-Rh o (D) standard. The conversion of mcg to IU is: 1 mcg = 5 IU. A 1,500 IU (300 mcg) vial contains sufficient anti-Rh o (D) to effectively suppress the immunizing potential of approximately 17 mL of Rh o (D) (D-positive) RBCs. The liquid formulation is stabilized with 10% maltose and 0.03% polysorbate 80. There are no preservatives in the formulation. WinRho ® SDF does not contain mercury. This product contains ≤ 40 mcg/mL IgA.

2 DOSAGE AND ADMINISTRATION For intravenous or intramuscular use only. IU, International Units; mcg, micrograms ITP ( 2.1 ) (IV administration only) Dose IU Dose mcg Rate of Administration 250 IU kg body weight 50 mcg/kg body weight Single injection over 3 to 5 minutes Suppression of Rh Isoimmunization ( 2.1 ) (IV or IM administration only) Indication Timing Dose (IV or IM) Dose (IV or IM) Pregnancy and other obstetric conditions IU (international units) mcg (micrograms) Routine antepartum prophylaxis 28-weeks gestation 1,500 IU 300 mcg Postpartum prophylaxis Within 72 hours of delivery 600 IU 120 mcg Threatened abortion Immediately 1,500 IU 300 mcg Amniocentesis and chorionic villus sampling before 34-weeks gestation Immediately after procedure 1,500 IU 300 mcg Abortion, amniocentesis, or other manipulation after 34-weeks gestation Within 72 hours 600 IU 120 mcg Incompatible transfusions or massive fetal hemorrhage Within 72 hours of exposure IV administration of 90 IU per 1 mL transfused RBC or per 2 mL transfused whole blood IV administration of 18 mcg per 1 mL transfused RBC or per 2 mL transfused whole blood 2.1 Dose Treatment of ITP ADMINISTER WinRho ® SDF BY THE INTRAVENOUS ROUTE ONLY. Proper care should be taken when calculating the dose of WinRho ® SDF to be administered. A confusion between International Units (IU) and micrograms (mcg) of product (1 mcg = 5 IU), could result in either an overdose that could lead to a severe hemolytic reaction or a dose too low to be effective. Since Win Rho ® SDF is administered on a weight-based regimen per kilogram (kg), patient weight determination must be taken in kilograms (kg) as inappropriate use of pounds (lbs) will result in significant overdosing of WinRho ® SDF. Please note that dose for WinRho ® SDF may be calculated using either international units (IU) or micrograms (mcg) per kilograms. Table 1 provides dosing guidelines for ITP patients. Table 1: ITP Dosing Guidelines (Intravenous use only) All patients should be monitored to determine clinical response by assessing platelet counts, RBCs, hemoglobin (Hgb), and reticulocyte levels [see Warnings and Precautions ( 5.2 ) ] Safety and efficacy of WinRho ® SDF ® in the treatment of ITP at doses exceeding 300 IU/kg (60 mcg/kg) has not been established. Treatment is rarely indicated in patients with platelet count above 50x10 9 /L. To determine the dosage and number of vials needed for the treatment of ITP: weight in lbs/2.21 = weight in kg weight in kg X selected IU (mcg) dosing level = dosage dosage / vial size = number of vials needed Indication Initial Dose (dose in either IU or mcg) Subsequent Doses (dose in either IU or mcg) ITP (intravenous use only) Single intravenous dose or divided doses given on two separate days Determine frequency by clinical response (platelet counts, RBC, Hgb and reticulocyte count) Hemoglobin ≥ 10 g/dl 250 IU/kg 50 mcg/kg 250-300 IU/kg 50-60 mcg/kg Hemoglobin 8 to <10 g/dl (use alternative treatments for Hgb <8 g/dl) 125-200 IU/kg 25-40 mcg/kg 125-200 IU/kg 25-40 mcg/kg Suppression of Rh Isoimmunization Table 2: Rh Isoimmunization Dosing Guidelines If the Rh status of the baby is not known at 72 hours, administer WinRho ® SDF to the mother at 72 hours after delivery. If more than 72 hours have elapsed, administer as soon as possible up to 28 days after delivery. If WinRho ® SDF is administered early in pregnancy for amniocentesis and chorionic villus sampling (before 34 weeks), then administer WinRho ® SDF repeatedly at 12-week interval to maintain adequate levels of passively acquired anti-Rh. Indication Initial Dose (dose in either IU or mcg) Subsequent Doses (dose in either IU or mcg) Suppression of Rh Isoimmunization (intravenous or intramuscular) Single intravenous or intramuscular dose Routine antepartum prophylaxis in Rh- incompatible pregnancy (28 weeks gestation) 1,500 IU 300 mcg Postpartum (within 72 hours of birth of Rh0(D) positive newborn) 600 IU 120 mcg Threatened abortion (immediately) 1,500 IU 300 mcg Amniocentesis and chorionic villus sampling before 34 weeks gestation (immediately following procedure, then every 12 weeks during pregnancy) 1,500 IU 300 mcg 1,500 IU (every 12 weeks) 300 mcg (every 12 weeks) Abortion, amniocentesis, or any other manipulation after 34 weeks gestation (within 72 hours) 600 IU 120 mcg Incompatible Transfusion Table 3: Incompatible Transfusion Dosing Guidelines Indication Dose (dose in either IU or mcg) Frequency Incompatible Transfusion (intravenous or intramuscular) Begin treatment within 72 hours of exposure Intravenous If exposed to Rh 0 (D)-Positive Whole Blood 45 IU per ml blood 9 mcg per ml blood Every 8 hours If exposed to Rh 0 (D)-Positive Red Blood Cells 90 IU per ml cells 18 mcg per ml cells Administer this dose until total dose has been administered 3000 IU 600 mcg Every 8 hours Intramuscular If exposed to Rh 0 (D)-Positive Whole Blood 60 IU per ml blood 12 mcg per ml blood Every 12 hours If exposed to Rh 0 (D)-Positive Red Blood Cells 120 IU per ml cells 24 mcg per ml cells Administer this dose until total dose has been administered 6000 IU 1,200 mcg Every 12 hours For incompatible transfusion or massive fetal hemorrhage, treatment must occur within 72 hours and dose may be intravenous or intramuscular, based on the volume of blood or cells replaced. 2.2 Preparation Bring WinRho ® SDF to room temperature prior to use. Inspect WinRho ® SDF for particulate matter and discoloration prior to administration. Do not use if the solution is cloudy or contains particulates. WinRho ® SDF is for single use only. Discard any unused portion. The solution is ready to use, no reconstitution required. See Table 4 for the target fill volumes for each of the dosage sizes for WinRho ® SDF. Table 4: Liquid WinRho ® SDF Dosage Size and Target Fill Volumes Dose (IU) Dose (mcg) Target Fill Volume 600 IU 120 mcg 0.5 mL 1,500 IU 300 mcg 1.3 mL 2,500 IU 500 mcg 2.2 mL 5,000 IU 1,000 mcg 4.4 mL 15,000 IU 3,000 mcg 13.0 mL Note: Remove the entire contents of the vial to obtain the labelled dosage of WinRho ® SDF. If partial vials are required for dosage calculation, withdraw the entire contents of the vial to ensure accurate calculation of the dosage requirement. For ease in withdrawing the contents of the vial, draw back the plunger of a sterile syringe (with the needle and needle cover in place) to admit air into the syringe. Depress the plunger of the syringe to inject air into the vial. Invert vial and aspirate contents of vial into syringe. 2.3 Administration Route of administration depends on the indication as follows: ITP Intravenous (IV) only Suppression of Rh Intravenous (IV) or intramuscular (IM) Incompatible transfusion Intravenous (IV) or intramuscular (IM) ITP Administer the entire dose of WinRho ® SDF into a suitable vein over three to five minutes. Administer WinRho ® SDF separately from other drugs. If dilution of WinRho ® SDF is preferred prior to intravenous administration, use only normal saline as diluent. Do not use Dextrose (5%) in water (D5W). Suppression of Rh Isoimmunization For intravenous administration, administer WinRho ® SDF separately from other drugs. WinRho ® SDF should be administered at a rate of 2 mL per 5 to 15 seconds. For intramuscular administration, administer into the deltoid muscle of the upper arm or the anterolateral aspects of the upper thigh. Due to the risk of sciatic nerve injury, avoid the gluteal region. If the gluteal region is used, use only the upper, outer quadrant.

1 INDICATIONS AND USAGE WinRho ® SDF is a Rh o (D) Immune Globulin Intravenous (Human) (anti-D) product that is indicated for the treatment of ITP in Rh o (D)-positive patients and for the suppression of Rh isoimmunization in non-sensitized Rh o (D)-negative patients. WinRho ® SDF is a Rh o (D) Immune Globulin Intravenous (Human) indicated for: Immune Thrombocytopenic Purpura (ITP) ( 1.1 ) Raising platelet counts in Rh o (D) positive, non-splenectomized: children with chronic or acute ITP adults with chronic ITP children and adults with ITP secondary to HIV infection Suppression of Rhesus (Rh) Isoimmunization ( 1.2 ) Pregnancy and other obstetric conditions in non-sensitized, Rh o (D)-negative women with a Rh-incompatible pregnancy including: Routine antepartum and postpartum Rh prophylaxis Rh prophylaxis in obstetric complications or invasive procedures Incompatible transfusions in Rh o (D)-negative individuals transfused with blood components containing Rh o (D)-positive red blood cells (RBCs). 1.1 Treatment of ITP WinRho ® SDF is indicated for use in clinical situations requiring an increase in platelet count to prevent excessive hemorrhage in the treatment of non-splenectomized, Rh o (D)-positive children with chronic or acute ITP adults with chronic ITP children and adults with ITP secondary to HIV infection The safety and efficacy of WinRho ® SDF have not been evaluated in clinical trials for patients with non-ITP causes of thrombocytopenia or in previously splenectomized patients or in patients who are Rh o (D)-negative. 1.2 Suppression of Rh Isoimmunization Pregnancy and Other Obstetric Conditions WinRho ® SDF is indicated for the suppression of Rh isoimmunization in non-sensitized, Rh o (D)-negative (D-negative) women with a Rh-incompatible pregnancy, including: Routine antepartum and postpartum Rh prophylaxis Rh prophylaxis in cases of: – Obstetric complication (e.g., miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatidiform mole, transplacental hemorrhage resulting from antepartum hemorrhage) – Invasive procedures during pregnancy (e.g., amniocentesis, chorionic biopsy) or obstetric manipulative procedures (e.g., external version, abdominal trauma) A Rh-incompatible pregnancy is assumed if the fetus/baby is either Rh o (D)-positive or Rh o (D)-unknown or if the father is either Rh o (D)-positive or Rh o (D)-unknown. Incompatible Transfusions WinRho ® SDF is indicated for the suppression of Rh isoimmunization in Rh o (D)-negative individuals transfused with Rh o (D)-positive red blood cells (RBCs) or blood components containing Rh o (D)-positive RBCs. WinRho ® SDF is not indicated for use as immunoglobulin replacement therapy for immune globulin deficiency syndromes.

10 OVERDOSAGE Treatment of ITP and Suppression of Rh Isoimmunization In post-marketing spontaneous reporting, there has been a limited number of medication error reports related to dosage calculations in which higher doses than that recommended for WinRho ® SDF were administered (doses > 60 mcg/kg). Signs and laboratory findings of overdosage in Rh positive (ITP) patients have included hemoglobin decreases in excess of 1.2 g/dL. For the suppression of Rh isoimmunization, hemolytic reactions have been reported in cases of mis-matched blood transfusions where very large doses of WinRho ® SDF were administered. In one ITP case report that involved an overdose due to confusion between mcg and international unit (IU), a patient with significant co-morbidities developed IVH and had a fatal outcome. In the event of overdose, monitor patients closely for signs and symptoms of hemolysis and initiate symptomatic and supportive treatment.

7 DRUG INTERACTIONS Immunoglobulin administration may transiently interfere with the immune response to live virus vaccines, such as measles, mumps and rubella. ( 7.1 ) 7.1 Live Virus Vaccines Administration of WinRho ® SDF concomitantly with other drugs has not been evaluated. Passive transfer of antibodies may transiently impair the immune response to live attenuated virus vaccines such as measles, mumps, rubella, and varicella (see Patient Counseling Information [ 17.1 ]). Do not give immunization with live vaccines within 3 months after WinRho ® SDF administration.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Treatment of ITP WinRho ® SDF has been shown to increase platelet counts in non-splenectomized, Rh o (D)-positive patients with ITP. Platelet counts usually rise within one to two days and peak within seven to 14 days after initiation of therapy. The mechanism of action is not completely understood, but is thought to be due to the formation of anti-Rh o (D)-coated RBC complexes, which are preferentially removed by the reticuloendothelial system, particularly the spleen. This results in Fc receptor blockade, thus sparing antibody-coated platelets. 9,10 Suppression of Rh Isoimmunization The mechanism by which Rh o (D) immune globulin suppresses immunization to Rh o (D)-positive RBCs is not completely understood. WinRho ® SDF when administered within 72 hours of a full-term delivery of a Rh o (D)-positive infant by a Rh o (D) negative mother will reduce the incidence of Rh isoimmunization from 12-13% to 1-2%. The 1-2% is, for the most part, due to isoimmunization 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%. 13,14 When 600 IU (120 mcg) of WinRho ® SDF is administered to pregnant women, passive anti-Rh o (D) antibodies are not detectable in the circulation for more than six weeks and therefore a dose of 1,500 IU (300 mcg) should be used for antenatal administration. 12.2 Pharmacodynamics In a clinical study with Rh o (D)-negative volunteers (nine males and one female), Rh o (D)-positive RBCs were completely cleared from the circulation within 8 hours of intravenous administration of WinRho ® SDF. There was no indication of Rh isoimmunization of these subjects at six months after the clearance of the Rh o (D)-positive RBCs. 12.3 Pharmacokinetics IM versus IV Administration (Lyophilized Powder) In a clinical study involving Rh o (D)-negative volunteers, two subjects received 600 IU (120 mcg) WinRho ® SDF by intravenous (IV) administration and two subjects received this dose by intramuscular (IM) administration. Peak levels (36 to 48 ng/mL) were reached within two hours of IV administration and peak levels (18 to 19 ng/mL) were reached at five to 10 days after IM administration. Although no statistical comparisons were made, the calculated areas under the curve were comparable for both routes of administration. The t ½ for anti-Rh o (D) was about 24 days following IV administration and about 30 days following IM administration. Lyophilized Powder versus Liquid Formulation In two comparative pharmacokinetics studies, 101 volunteers were administered the liquid or lyophilized formulation of WinRho ® SDF intravenously (n=41) or intramuscularly (n=60). The formulations were bioequivalent following IV administration based on area under the curve to 84 days and had comparable pharmacokinetics following IM administration. The average peak concentrations (C max ) of anti-Rh o (D) for both formulations were comparable following IV or IM administration and occurred within 30 minutes or 2-4 days of administration, respectively. Both formulations also had similar elimination half-lives (t ½ ) following IV or IM administration.

12.1 Mechanism of Action Treatment of ITP WinRho ® SDF has been shown to increase platelet counts in non-splenectomized, Rh o (D)-positive patients with ITP. Platelet counts usually rise within one to two days and peak within seven to 14 days after initiation of therapy. The mechanism of action is not completely understood, but is thought to be due to the formation of anti-Rh o (D)-coated RBC complexes, which are preferentially removed by the reticuloendothelial system, particularly the spleen. This results in Fc receptor blockade, thus sparing antibody-coated platelets. 9,10 Suppression of Rh Isoimmunization The mechanism by which Rh o (D) immune globulin suppresses immunization to Rh o (D)-positive RBCs is not completely understood. WinRho ® SDF when administered within 72 hours of a full-term delivery of a Rh o (D)-positive infant by a Rh o (D) negative mother will reduce the incidence of Rh isoimmunization from 12-13% to 1-2%. The 1-2% is, for the most part, due to isoimmunization 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%. 13,14 When 600 IU (120 mcg) of WinRho ® SDF is administered to pregnant women, passive anti-Rh o (D) antibodies are not detectable in the circulation for more than six weeks and therefore a dose of 1,500 IU (300 mcg) should be used for antenatal administration.

12.2 Pharmacodynamics In a clinical study with Rh o (D)-negative volunteers (nine males and one female), Rh o (D)-positive RBCs were completely cleared from the circulation within 8 hours of intravenous administration of WinRho ® SDF. There was no indication of Rh isoimmunization of these subjects at six months after the clearance of the Rh o (D)-positive RBCs.

12.3 Pharmacokinetics IM versus IV Administration (Lyophilized Powder) In a clinical study involving Rh o (D)-negative volunteers, two subjects received 600 IU (120 mcg) WinRho ® SDF by intravenous (IV) administration and two subjects received this dose by intramuscular (IM) administration. Peak levels (36 to 48 ng/mL) were reached within two hours of IV administration and peak levels (18 to 19 ng/mL) were reached at five to 10 days after IM administration. Although no statistical comparisons were made, the calculated areas under the curve were comparable for both routes of administration. The t ½ for anti-Rh o (D) was about 24 days following IV administration and about 30 days following IM administration. Lyophilized Powder versus Liquid Formulation In two comparative pharmacokinetics studies, 101 volunteers were administered the liquid or lyophilized formulation of WinRho ® SDF intravenously (n=41) or intramuscularly (n=60). The formulations were bioequivalent following IV administration based on area under the curve to 84 days and had comparable pharmacokinetics following IM administration. The average peak concentrations (C max ) of anti-Rh o (D) for both formulations were comparable following IV or IM administration and occurred within 30 minutes or 2-4 days of administration, respectively. Both formulations also had similar elimination half-lives (t ½ ) following IV or IM administration.

20201105

5

3 DOSAGE FORMS AND STRENGTHS WinRho ® SDF, Rh o (D) Immune Globulin Intravenous (Human), is available as a ready to use solution for injection available in single dose vials of 600 IU (120 mcg), 1,500 IU (300 mcg), 2,500 IU (500 mcg), 5,000 IU (1,000 mcg) and 15,000 IU (3,000 mcg). WinRho ® SDF is a ready to use solution in single dose vials of 600 IU (120 mcg), 1,500 IU (300 mcg), 2,500 IU (500 mcg), 5,000 IU (1,000 mcg) and 15,000 IU (3,000 mcg).

WinRho SDF rho (d) immune globulin HUMAN RHO(D) IMMUNE GLOBULIN HUMAN RHO(D) IMMUNE GLOBULIN MALTOSE POLYSORBATE 80 WinRho SDF rho (d) immune globulin HUMAN RHO(D) IMMUNE GLOBULIN HUMAN RHO(D) IMMUNE GLOBULIN MALTOSE POLYSORBATE 80 WinRho SDF rho (d) immune globulin HUMAN RHO(D) IMMUNE GLOBULIN HUMAN RHO(D) IMMUNE GLOBULIN MALTOSE POLYSORBATE 80 WinRho SDF rho (d) immune globulin HUMAN RHO(D) IMMUNE GLOBULIN HUMAN RHO(D) IMMUNE GLOBULIN MALTOSE POLYSORBATE 80

BLA103649

WinRho SDF

rho (d) immune globulin

70257-330

HUMAN PRESCRIPTION DRUG

INTRAMUSCULAR,INTRAVENOUS

PRINCIPAL DISPLAY PANEL - NDC: 70257-330-11 - 1500 IU Vial Label 1500 IU Vial Label

Boxed Warning 07/2019 Dosage and Administration, Dose ( 2.1 ) 07/2019 Dosage and Administration, Administration ( 2.3 ) 07/2019 Warnings and Precautions, Hypersensitivity ( 5.1 ) 07/2019

17 PATIENT COUNSELING INFORMATION Information for Patients See FDA-Approved Patient Labeling ITP and Suppression of Rh Isoimmunization Inform patients of the early signs of hypersensitivity reactions to WinRho ® SDF including hives, generalized urticaria, chest tightness, wheezing, hypotension, and anaphylaxis. Advise patients to notify their physicians if they experience any of the above symptoms. Blood Glucose Monitoring Advise patients that the maltose contained in WinRho ® SDF can interfere with some types of blood glucose monitoring systems. Advise patients to use only testing systems that are glucose specific for monitoring blood glucose levels as the interference of maltose could result in falsely elevated glucose readings. This could lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia. Transmittable Infectious Agents Inform patients that WinRho ® SDF is prepared from human plasma and may contain infectious agents (e.g., viruses and, theoretically, the CJD agent) 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 viruses, by testing for the presence of current virus infections, and by inactivating and/or removing certain viruses during manufacturing. Advise patients to report any symptoms that concern them and that may be related to viral infections. Live Virus Vaccines Advise patients that WinRho ® SDF may impair the effectiveness of certain live virus vaccines (e.g., measles, rubella, mumps, and varicella). Instruct patients to notify their treating physician of this potential interaction when they are receiving vaccinations. Immune Thrombocytopenic Purpura (ITP) Instruct patients being treated with WinRho ® SDF for ITP to immediately report symptoms of intravascular hemolysis including back pain, shaking chills, fever, discolored urine, decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath to their physicians. Prior to discharge, instruct patients to continue to self-monitor for the signs and symptoms of IVH over 72 hours, especially for discoloration of urine, and to seek medical attention immediately in the event that signs/symptoms of IVH occur following WinRho ® SDF administration. Laboratory Tests Assess renal function in patients judged to be at an increased risk of developing acute renal failure, including measurement of BUN and serum creatinine, before the initial infusion of WinRho ® SDF. 17.1 FDA Approved Patient Labeling – (Patient Prescribing Information) WinRho ® SDF [pronounced win – row –S-D-F] You should read this leaflet carefully each time before you are scheduled to receive a treatment for your Immune Thrombocytopenic Purpura (ITP) with WinRho ® SDF. This letter is a summary of the important information you need to know about your medicine, and does not take the place of talking with your doctor and does not contain all of the information available about WinRho ® SDF. If you have any questions after reading this leaflet, make sure you ask your doctor or nurse. 1. What is the most important information I should know about WinRho ® SDF? Some patients taking WinRho ® SDF for immune thrombocytopenic purpura (ITP) have had severe, life threatening bleeding and clotting problems. For this reason, you need to remain under observation for at least 8 hours following each treatment with WinRho ® SDF and your doctor will ask you to take blood and urine tests before and after infusion with WinRho ® SDF. Some patients taking WinRho ® SDF have had problems with their kidneys and other organs. Problems usually occur within 4 to 8 hours after getting an infusion. Tell your doctor or healthcare provider right away if you have any of the following signs or symptoms after getting a WinRho ® SDF infusion: back pain shaking chills fever dark or oddly colored urine decreased urination swelling or sudden weight gain shortness of breath rash dizziness Continue monitoring for these signs and symptoms for 72 hours after each treatment with WinRho ® SDF. WinRho ® SDF contains maltose, which can give false readings on some glucose testing meters. If you are diabetic, ask your doctor what types of glucose testing meters can be used safely while you are getting WinRho ® SDF. 2. What is WinRho ® SDF? WinRho ® SDF is a protein product, called an “immune globulin,” which is made from human plasma. It has antibodies to the “D” antigen that people with “Rh-positive” blood have in their blood. WinRho ® SDF is used to increase the number of platelets in the blood of Rh-positive people who have a problem called immune thrombocytopenic purpura (ITP). People with ITP bruise and bleed easily because they have a very low number of platelets in their blood. WinRho ® SDF is also used to treat Rh-negative girls and women who need a blood transfusion using Rh-positive blood and/or are carrying a Rh-positive baby. 3. Who should not use WinRho ® SDF? You should not use WinRho ® SDF for any treatment if you: have ever had a severe allergic reaction (such as trouble breathing, hives, passing out) after getting any blood product or blood product transfusion. have an immune globulin A (IgA) deficiency. You should not use WinRho ® SDF for treatment of ITP if you: have Rh-negative blood. have had your spleen removed. have a problem called “autoimmune hemolytic anemia.” have other pre-existing bleeding problems. 4. How will I get WinRho ® SDF? Your doctor will give you WinRho ® SDF as an injection into your vein. For the treatment of ITP, it will usually take 3 to 5 minutes for an injection. Your doctor will decide if you need one or more injections. For protection against Rh-positive blood, your doctor may decide to give you WinRho ® SDF as a shot in your arm or thigh. 5. What should I avoid while using WinRho ® SDF? WinRho ® SDF may interfere with your immune response to routine immunizations. Tell your doctor if you have recently been vaccinated or are planning to be vaccinated. WinRho ® SDF can interfere with certain blood tests. It is important to tell the person taking your blood and the doctor that you got WinRho ® SDF. 6. What are the possible or reasonably likely side effects of WinRho ® SDF? The most common side effects of WinRho ® SDF are headache chills fever weakness diarrhea nausea and vomiting achy muscles feeling light-headed or dizziness fainting flushing rash sweating Tell your doctor right away if you have: a fever over 100°F shaking or chills that continue or get worse a painful lump or swelling (because this may be a sign of a blood clot) bruising that is increasing in diameter (because this may be a sign of a clotting problem) oddly colored urine trouble urinating severe back pain severe abdominal pain swelling, especially around the ankles hives shortness of breath Talk to your doctor about any side effects that concern you. Additional prescribing information is available to healthcare professionals. 7. What other information do I need to know about WinRho ® SDF? WinRho ® SDF is made from human plasma. Donors are carefully screened and the plasma is carefully cleaned, but it does have a very small risk of giving you viruses from the donor. Talk to your doctor if you have any symptoms that concern you. You may report side effects to Saol Therapeutics Inc. at 1-833-644-4216 or FDA’s MedWatch reporting system by phone (1-800-FDA-1088) WinRho ® SDF [Rh o (D) Immune Globulin Intravenous (Human)] Sterile Solution for Injection and any and all Saol brand, product, service and feature names, logos, slogans are trademarks or registered trademarks of Saol. All rights reserved. Distributed by: Saol Therapeutics Inc. Roswell, GA 30076 US License No. 2098

14 CLINICAL STUDIES 14.1 Treatment of ITP Efficacy was documented in four subgroups of patients with ITP: Childhood Chronic ITP In an open-label, single arm, multicenter study, 24 non-splenectomized, Rh o (D)-positive children with ITP of greater than six-months duration were treated initially with 250 IU/kg (50 mcg/kg) WinRho ® SDF [125 IU/kg (25 mcg/kg) on days 1 and 2, with subsequent doses ranging from 125 to 275 IU/kg (25 to 55 mcg/kg)]. Response was defined as a platelet increase to at least 50,000/mm 3 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/mm 3 (range 43,300 to 456,000), and a mean duration of response of 36.5 days (range 6 to 84). 15 Childhood Acute ITP A multicenter, randomized, controlled trial comparing WinRho ® SDF to high dose and low dose Immune Globulin Intravenous (Human) (IGIV) and prednisone was conducted in 146 non-splenectomized, Rh o (D)-positive children with acute ITP and platelet counts less than 20,000/mm 3 . Of 38 patients receiving WinRho ® SDF [125 IU/kg (25 mcg/kg) on days 1 and 2], 32 patients (84%) responded (platelet count ≥ 50,000/mm 3 ) with a mean peak platelet count of 319,500/mm 3 (range 61,000 to 892,000), with no statistically significant differences compared to other treatment arms. The mean times to achieving ≥ 20,000/mm 3 or ≥ 50,000/mm 3 platelets for patients receiving WinRho ® SDF were 1.9 and 2.8 days respectively. When comparing the different therapies for time to platelet count ≥ 20,000/mm 3 or ≥ 50,000/mm 3 , 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, for IGIV and prednisone respectively. 16,17 Adult Chronic ITP Twenty-four non-splenectomized Rh o (D)-positive adults with ITP of greater than six-months duration and platelet counts < 30,000/mm 3 or requiring therapy were enrolled in a single-arm, open-label trial were treated with 100 to 375 IU/kg (20 to 75 mcg/kg) WinRho ® SDF [mean dose 231 IU/kg (46.2 mcg/kg)]. Twenty-one of 24 patients responded (increase ≥ 20,000/mm 3 ) during the first two courses of therapy for an overall response rate of 88% with a mean peak platelet count of 92,300/mm 3 (range 8,000 to 229,000). 18,19 ITP Secondary to HIV Infection Eleven children and 52 adults, who were non-splenectomized and Rh o (D)-positive, with all Walter Reed classes of HIV infection and ITP, with initial platelet counts of ≤ 30,000/mm 3 or requiring therapy, were treated with 100 to 375 IU/kg (20 to 75 mcg/kg) WinRho ® SDF in an open label trial. WinRho ® SDF 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/mm 3 ) 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/mm 3 (range -2,000 to 565,000), and the mean peak platelet count was 81,700/mm 3 (range 16,000 to 593,000). 18-20 14.2 Suppression of Rh Isoimmunization A study was conducted in 1,186 non-sensitized, Rh o (D)-negative pregnant women in cases in which the blood types of the fathers were Rh o (D)-positive or unknown. WinRho ® SDF was administered according to one of three regimens: 1) 93 women received 600 IU (120 mcg) at 28 weeks; 2) 131 women received 1,200 IU (240 mcg) each at 28 and 34 weeks; 3) 962 women received 1,200 IU (240 mcg) at 28 weeks. All women received a postnatal administration of 600 IU (120 mcg) if the newborn was found to be Rh o (D)-positive. Of 1,186 women who received antenatal WinRho ® SDF, 806 were given WinRho ® SDF postnatal following the delivery of a Rh o (D)-positive infant, of which 325 women underwent testing at six months after delivery for evidence of Rh isoimmunization. Of these 325 women, 23 would have been expected to display signs of Rh isoimmunization, however, none was observed (p <0.001 in a Chi-square test of significance of difference between observed and expected isoimmunization in the absence of WinRho ® SDF).

15 REFERENCES Provan D, et al.: International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168-186. Gupta N, Ahmed I, Nissel-Horowitz S, Patel D, Mehrotra B. Intravenous gammaglobulin-associated acute renal failure. Am J Hematol 2001; 66:151-152 Dalakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events. Neurology 1994; 44:223-226. Woodruff RK, et al.: Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet 1986; 2:217-218. Rushin J, Rumsey, DH, Ewing, CA, Sandler, SG. Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulins. Transfusion Vol. 40, May 2000. Rizk A, et al.: Transfusion-related acute lung injury after the infusion of IVIG. Transfusion 2001; 41:264-8. Gaines AR. Acute onset hemoglobinemia and/or hemoglobinuria and sequalae following Rho(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients. Blood 2000; 95(8): 2523-2529. Gaines AR. Disseminated intravascular coagulation associated with acute hemoglobinemia and/or hemoglobinuria following Rho(D) immune globulin intravenous administration for immune thrombocytopenic purpura. Blood 2005; 106(5); 1532-7. Ballow, M: Mechanisms of action of intravenous immunoglobulin therapy and potential use in autoimmune connective tissue diseases. Cancer. 1991; 68:1430-1436. Kniker, WT: Immunosuppressive agents, γ-globulin, immunomodulation, immunization, and apheresis. J. Aller. Clin. Immunol. 1989; 84:1104-1106. Lazarus AH, Crow AR. Mechanism of action of IVIG and anti-D in ITP. Transfus Apheresis Sci 2003; 28:249-255. Bowman JM. The prevention of Rh immunization. Transfus Med Rev 1988; 2(3):129-150 Bowman, JM, and Pollock, JM: Failures of intravenous Rh immune globulin prophylaxis: An analysis of the reasons for such failures. Trans. Med. Rev. 1987; 1:101-111. Bowman, JM: Antenatal suppression of Rh alloimmunization. Clin Obstet. & Gynec. 1991; 34:296-303. Andrew, M, et al.: A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D. J Pediatrics 1992; 120:522-527. Blanchette, V, et al.: Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet 1994; 344: 703-707. Zunich KM, et al. Intravenous anti-D immunoglobulin for childhood acute immune thrombocytopenic purpura. Lancet 1995; 346:1363-5. Scaradavou A, et al.: Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood 1997; 89:2689-700. Bussel, JB, et al.: Intravenous anti-D treatment of immune thrombocytopenic purpura: Analysis of efficacy, toxicity, and mechanism of effect. Blood 1991; 77: 1884-1893. Zunich KM, et al.: Treatment of human immunodeficiency virus-related thrombocytopenia with intravenous anti-rhesus D immunoglobulin. Clin Infect Dis 1996; 22:1129-30.

8.5 Geriatric Use Clinical studies of WinRho ® SDF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Post marketing clinical experience suggests that patients of advanced age (age over 65) with co-morbid conditions including but not limited to cardio-respiratory decompensation, renal failure or insufficiency or prothrombotic conditions are at increased risk of developing serious complications from acute hemolytic reactions such as IVH. Patients receiving doses in excess of 300 IU/kg of WinRho ® SDF may also be at an increased risk of developing increased hemolysis. Fatal outcomes associated with IVH and its complications have occurred most frequently in patients of advanced age (age over 65) with co-morbid conditions. Given the prevalence of co-morbid conditions and concomitant drug therapy in geriatric patients, consider starting at the low end of the dosing range when using WinRho ® SDF in this population.

8.4 Pediatric Use The safety and effectiveness of WinRho ® SDF has been evaluated for the treatment of chronic or acute ITP in children and in children (<16 years of age) with ITP secondary to HIV infection [see Adverse Reactions ( 6.2 )]. The dosing recommendation in the treatment of children with ITP is the same as in adults [see Dosage and Administration ( 2.1 )].

8.1 Pregnancy Risk Summary For the treatment of ITP, there is no human data or animal data available to establish the presence or absence of drug-associated risk. When administered to pregnant women in a clinical trial to evaluate WinRho ® SDF for suppression of Rh isoimmunization [see Clinical Studies ( 14.2 )] following dosing regimens similar to Table 2 [see Dosing and Administration ( 2.1 )], WinRho ® SDF was not shown to harm the fetus or newborn. 12

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary For the treatment of ITP, there is no human data or animal data available to establish the presence or absence of drug-associated risk. When administered to pregnant women in a clinical trial to evaluate WinRho ® SDF for suppression of Rh isoimmunization [see Clinical Studies ( 14.2 )] following dosing regimens similar to Table 2 [see Dosing and Administration ( 2.1 )], WinRho ® SDF was not shown to harm the fetus or newborn. 12 8.2 Lactation Risk Summary There is no information regarding the presence of WinRho ® SDF in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for WinRho ® SDF and any potential adverse effects on the breastfed infant from WinRho ® SDF or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of WinRho ® SDF has been evaluated for the treatment of chronic or acute ITP in children and in children (<16 years of age) with ITP secondary to HIV infection [see Adverse Reactions ( 6.2 )]. The dosing recommendation in the treatment of children with ITP is the same as in adults [see Dosage and Administration ( 2.1 )]. 8.5 Geriatric Use Clinical studies of WinRho ® SDF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Post marketing clinical experience suggests that patients of advanced age (age over 65) with co-morbid conditions including but not limited to cardio-respiratory decompensation, renal failure or insufficiency or prothrombotic conditions are at increased risk of developing serious complications from acute hemolytic reactions such as IVH. Patients receiving doses in excess of 300 IU/kg of WinRho ® SDF may also be at an increased risk of developing increased hemolysis. Fatal outcomes associated with IVH and its complications have occurred most frequently in patients of advanced age (age over 65) with co-morbid conditions. Given the prevalence of co-morbid conditions and concomitant drug therapy in geriatric patients, consider starting at the low end of the dosing range when using WinRho ® SDF in this population.

16 HOW SUPPLIED/STORAGE AND HANDLING Store at 2 to 8°C (36 to 46°F) Do not freeze Do not use after expiration date Protect from light WinRho ® SDF is available in packages containing: NDC Number Product Description 70257-312-51 A carton containing a single dose vial of 600 IU (120 mcg) anti-Rh o (D) IGIV and a package insert 70257-330-51 A carton containing a single dose vial of 1,500 IU (300 mcg) anti-Rh o (D) IGIV and a package insert 70257-350-51 A carton containing a single dose vial of 2,500 IU (500 mcg) anti-Rh o (D) IGIV and a package insert 70257-310-51 A carton containing a single dose vial of 5,000 IU (1,000 mcg) anti-Rh o (D) IGIV and a package insert 70257-300-51 A carton containing a single dose vial of 15,000 IU (3,000 mcg) anti-Rh o (D) IGIV and a package insert

WARNING: INTRAVASCULAR HEMOLYSIS (IVH) This warning does not apply to Rh o (D)-negative patients treated for the suppression of Rh isoimmunization. Intravascular hemolysis (IVH) leading to death has been reported in patients treated with WinRho ® SDF for immune thrombocytopenic purpura (ITP). IVH can lead to clinically compromising anemia and multi-system organ failure including acute respiratory distress syndrome (ARDS). Serious complications including severe anemia, acute renal insufficiency, renal failure and disseminated intravascular coagulation (DIC) have also been reported. Closely monitor patients treated with WinRho ® SDF for ITP in a healthcare setting for at least 8 hours after administration. A dipstick urinalysis to monitor for hematuria and hemoglobinuria is to be performed at baseline and then after administration at 2 hours, 4 hours and prior to the end of the monitoring period. Alert patients and monitor the signs and symptoms of IVH including back pain, shaking chills, fever, and discolored urine or hemoglobinuria. Absence of these signs and/or symptoms of IVH within 8 hours do not indicate IVH cannot occur subsequently. If signs and/or symptoms of IVH are present or suspected after WinRho ® SDF administration, post-treatment laboratory tests should be performed including plasma hemoglobin, haptoglobin, LDH, and plasma bilirubin (direct and indirect). If ITP patients are to be transfused after receiving WinRho ® SDF, use Rh o (D)-negative red blood cells (PRBCs) so as not to exacerbate ongoing hemolysis. WARNING: INTRAVASCULAR HEMOLYSIS (IVH) IN IMMUNE THROMBOCYTOPENIC PURPURA (ITP) See full prescribing information for complete boxed warning. This warning does not apply to Rh o (D)-negative patients treated for the suppression of Rh isoimmunization. Intravascular hemolysis (IVH) leading to death has been reported in patients treated for ITP with WinRho SDF. IVH can lead to clinically compromising anemia and multi-system organ failure including acute respiratory distress syndrome (ARDS) Serious complications including severe anemia, acute renal insufficiency, renal failure and disseminated intravascular coagulation (DIC) have also been reported. Closely monitor patients treated with WinRho ® SDF for ITP in a healthcare setting for at least 8 hours after administration. Perform dipstick urinalysis to monitor for hematuria and hemoglobinuria at baseline and 2 hours, 4 hours and prior to the end of the monitoring period. Alert patients and monitor the signs and symptoms of IVH including back pain, shaking chills, fever, and discolored urine or hematuria. Absence of these signs and/or symptoms of IVH within 8 hours do not indicate IVH cannot occur subsequently. Perform post-treatment laboratory tests if signs and/or symptoms of IVH are present or suspected after WinRho ® SDF administration ( 5.2 ). If ITP patients are to be transfused after receiving WinRho ® SDF, use Rh o (D)-negative red blood cells (PRBCs) so as not to exacerbate ongoing hemolysis.