WINRHO- human immunoglobulin g liquid
Cangene BioPharma, LLC
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 eight 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 eight 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).
1 INDICATIONS AND USAGE
WinRho � SDF is an 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.
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, or
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 Supression 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 an 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, transplancental hemorrhage resulting from antepartum hemorrhage)
Invasive procedures during pregnancy (e.g., amniocentesis, chorionic biopsy) or obstetric manipulative procedures (e.g., external version, abdominal trauma)
An 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.
2 DOSAGE AND ADMINISTRATION
2.1 Preparation and Handling
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.
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.
2.2 Treatment of ITP
ADMINISTER WinRho � SDF BY THE INTRAVENOUS ROUTE ONLY (see Preparation and Handling [2.1] ). Do not administer intramuscularly.
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 normal saline as diluent. Do not use Dextrose (5%) in water (D5W). No other diluents have been tested.
Initial Dosing: An initial dose of 250 international unit/kg (50 mcg/kg) body weight, given as a single injection is recommended for the treatment of ITP. The initial dose may be administered in two divided doses given on separate days, if desired. If the patient has a hemoglobin level less than 10 g/dL, a reduced dose of 125 to 200 international unit/kg (25 to 40 mcg/kg) should be given to minimize the risk of increasing the severity of anemia in the patient. 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)].
Subsequent Dosing: If subsequent therapy is required to elevate platelet counts, an intravenous dose of 125 to 300 international unit/kg (25 to 60 mcg/kg) body weight of WinRho � SDF is recommended. The frequency of dosing and the dose used in maintenance therapy should be determined by the patient's clinical response by assessing platelet counts, RBCs, Hgb, and reticulocyte levels.
If a patient responded to initial dose with a satisfactory increase in platelets, maintenance dose at 125 to 300 international unit/kg (25 to 60 mcg/kg), individualized based on platelet and Hgb levels. An international consensus report on the investigation and management of primary immune thrombocytopenia states that treatment is rarely indicated in patients with platelet counts above 50 x 10 9 /L and this has been generally accepted as the threshold for satisfactory response. 1 Evaluate whether patient responded with a satisfactory increase in platelets based on the clinical situation and bleeding risks for the individual patient.
If patient did not respond to initial dose, administer a subsequent dose based on Hgb:
If Hgb between 8-10 g/dL, redose between 125 to 200 international unit/kg (25 to 40 mcg/kg).
If Hgb >10 g/dL, redose between 250 to 300 international unit/kg (50 to 60 mcg/kg).
If Hgb < 8 g/dL, alternative treatments should be used.
The following equations are provided 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 international unit (mcg) dosing level = dosage
dosage / vial size = number of vials needed
Safety and efficacy of WinRho � SDF in the treatment of ITP at doses exceeding 300 international unit/kg (60 mcg/kg) has not been established.
2.3 Supression of Rh Isoimmunization
Intravenous or intramuscular use.
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.
Pregnancy and other Obstetric Indications
Table 2 provides dosing guidelines based on the condition being treated.
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 international unit (120 mcg), 1,500 international unit (300 mcg), 2,500 international unit (500 mcg), 5,000 international unit (1000 mcg) and 15,000 international unit (3,000 mcg).
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 and a history of hypersensitivity.
Patients with autoimmune hemolytic anemia, with pre-existing hemolysis or at high risk for hemolysis.
Infants for the suppression of Rh o (D) isoimmunization.
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 Triton � X-100) is effective in inactivating lipid enveloped viruses such as hepatitis B, hepatitis C, and HIV. Virus filtration, using a Planova� 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.
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 international unit (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 international unit (300 mcg) should be used for antenatal administration.
