RhoGAM Ultra-Filtered Plus

Name: RhoGAM Ultra-Filtered Plus

What is the most important information I should know about RHo (D) immune globulin?

You should not receive this medicine if you have immune globulin A (IgA) deficiency with antibody to IgA, or if you have hemolytic anemia (a lack of red blood cells).

RHo(D) immune globulin can cause an abnormal breakdown of red blood cells. This effect can lead to life-threatening blood clots or organ failure.

Call your doctor right away if you have any of the following symptoms: fever, chills, back pain, unusual weakness, red or pink urine, pale skin, feeling short of breath, little or no urinating, rapid weight gain, sudden numbness or weakness, slurred speech, problems with vision or balance, coughing up blood, or swelling or warmth in your leg.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

RhoGAM Ultra-Filtered Plus Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

Rare
  • Bloody urine
  • decreased frequency of urination or amount of urine
  • fever
  • increased blood pressure
  • increased thirst
  • loss of appetite
  • lower back pain
  • nausea or vomiting
  • pale skin
  • swelling of the face, fingers, or lower legs
  • troubled breathing
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common
  • Soreness at the place of injection

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Indications and Usage for RhoGAM Ultra-Filtered PLUS

. Pregnancy and other obstetrical conditions

For administration to Rh-negative women not previously sensitized to the Rho(D) factor, unless the father or baby are conclusively Rh-negative.

  • Delivery of an Rh-positive baby irrespective of the ABO groups of the mother and baby
  • Antepartum prophylaxis at 26 to 28 weeks gestation
  • Antepartum fetal-maternal hemorrhage (suspected or proven) as a result of placenta previa, amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling, other obstetrical manipulative procedure (e.g., version) or abdominal trauma
  • Actual or threatened pregnancy loss at any stage of gestation
  • Ectopic pregnancy

. Transfusion of Rh-incompatible blood or blood products

  • Prevention of Rh immunization in any Rh-negative person after incompatible transfusion of Rh-positive blood or blood products (e.g., red blood cells, platelet concentrates, granulocyte concentrates)

Dosage Forms and Strengths

  • RhoGAM® Ultra-Filtered PLUS - 300 μg (1500 IU)1 – Prefilled Syringes
  • MICRhoGAM® Ultra-Filtered PLUS - 50 μg (250 IU)1 – Prefilled Syringes
1 The anti-D content of RhoGAM / MICRhoGAM is expressed as μg per dose or as International Units (IU) per dose. The conversion factor is 1 μg = 5 IU.8

Warnings and Precautions

Warnings

  • For intramuscular use only, do not inject intravenously.
  • In the case of postpartum use, the product is intended for maternal administration.
  • Do not inject the newborn infant.
  • Patients should be observed for at least 20 minutes after administration.
  • Administer with caution to patients who have had prior severe systemic allergic reactions to human immune globulin.
  • RhoGAM / MICRhoGAM contain a small quantity og IgA. There is a potential risk of hypersensitivity in IgA deficient individuals.
  • Patients treated for Rh-incompatible transfusion should be monitored by clinical and laboratory means for signs and symptoms of a hemolytic reaction.
  • Store at 2 to 8°C. Do not store frozen.
  • Do not use after the expiration date printed on the syringe.

Use of Plasma Derived Products

RhoGAM and MICRhoGAM are made from human plasma and may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically the Creutzfeldt-Jakob disease (CJD) agent. 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 plasma for the presence of certain current virus infections and by using pathogen removal and inactivation techniques during the manufacturing process. All of the above steps are designed to increase product safety by reducing the risk of pathogen transmission. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. All infections thought by a physician possibly to have been transmitted by these products should be reported by the physician or other healthcare provider in the United States to Ortho-Clinical Diagnostics, Inc. at 1-800-421-3311. Outside the United States, the company distributing these products should be contacted. The physician should discuss the risks and benefits of these products with the patient.

Laboratory Tests

Recovery of anti-D in plasma or serum after injection of RhoGAM or other Rho(D) Immune Globulin (Human) products is highly variable among individuals. Anti-D detection in a patient's plasma is dependent on assay sensitivity and time of sample collection post-injection. Currently there are no requirements or practice standards to test for the presence of anti-D in order to determine adequacy or efficacy of dose following an injection of RhoGAM.

The presence of passively acquired anti-D in the maternal serum may cause a positive antibody screening test. This does not preclude further antepartum or postpartum prophylaxis.

Some babies born to women given Rho(D) Immune Globulin (Human) antepartum have weakly positive direct antiglobulin (Coombs) tests at birth.

Fetal-maternal hemorrhage may cause false blood typing results in the mother. Late in pregnancy or following delivery, there may be sufficient fetal Rh-positive red blood cells in the circulation of the Rh-negative mother to cause a positive antiglobulin test for weak D (Du). In this instance if there is any doubt as to the patient's Rh type, RhoGAM or MICRhoGAM should be administered.9

RhoGAM Ultra-Filtered PLUS Description

RhoGAM and MICRhoGAM Rho(D) Immune Globulin (Human) are sterile solutions containing immunoglobulin G (IgG) anti-D (anti-Rh) for use in preventing Rh immunization. They are manufactured from human plasma containing anti-D. A single dose of RhoGAM contains sufficient anti-D (300 μg or 1500 IU) to suppress the immune response to up to 15 mL of Rh-positive red blood cells.4,15 A single dose of MICRhoGAM contains sufficient anti-D (50 μg or 250 IU) to suppress the immune response to up to 2.5 mL of Rh-positive red blood cells. The anti-D dose is measured by comparison to the RhoGAM in-house reference standard, the potency of which is established relative to the U.S./World Health Organization/European Pharmacopoeia Standard Anti-D Immunoglobulin Rho(D) Immune Globulin (Human) CBER Lot 4: NIBSC Lot 01/572 (285 IU/ampoule).16

Plasma for RhoGAM is typically sourced from a donor center owned and operated by Ortho-Clinical Diagnostics. All donors are carefully screened by history and laboratory testing to reduce the risk of transmitting blood-borne pathogens from infected donors. Each plasma donation is tested and found to be non-reactive for the presence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C (HCV) and human immunodeficiency viruses (HIV) 1 and 2. Additionally, plasma is tested by FDA licensed Nucleic Acid Testing (NAT) for HCV and HIV-1 and the results must be negative. Plasma is also tested by investigational NAT for hepatitis B (HBV) and must be non-reactive. However, the significance of a negative result has not been established. Plasma is tested by in-process NAT procedures for hepatitis A virus (HAV) and parvovirus B19 (B19) in a minipool format. Only plasma that has passed virus screening is used for production. The procedure for B19 detects all three genotypes based upon sequence alignment of known virus isolates. The limit of B19 DNA in the manufacturing pool is set not to exceed 104 IU per mL.

Fractionation of the plasma is performed by a modification of the cold alcohol procedure that has been shown to significantly lower viral titers.10 Following plasma fractionation, a viral clearance filtration step and a viral inactivation step are performed. The viral filtration step removes viruses via a size-exclusion mechanism utilizing a patented Viresolve 180 ultrafiltration membrane with defined pore-size distribution of 12-18 nanometers to remove enveloped and non-enveloped viruses. Following viral filtration, quality control tests (CorrTest and diffusion test) are performed on the Viresolve 180 ultrafiltration membrane to insure filter integrity.17 The viral inactivation step utilizes Triton X-100 and tri-n-butyl phosphate (TNBP) to inactivate enveloped viruses such as HCV, HIV and West Nile Virus (WNV)10,18 (Patent Pending).

The donor selection process, the fractionation process, the viral filtration step and the viral inactivation process increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses. Rho(D) Immune Globulin (Human) intended for intramuscular use and prepared by cold alcohol fractionation has not been shown to transmit hepatitis or other infectious diseases.19 There have been no documented cases of infectious disease transmission by RhoGAM or MICRhoGAM.

Laboratory spiking studies10,20 have shown that the cumulative viral removal and inactivation capability of the RhoGAM / MICRhoGAM manufacturing process is as follows:

Virus HIV BVDV PRV PPV EMC WNV HAV
Units = log10 reduction
HIV Human Immunodeficiency Virus, Model for HIV-1 and 2 and Human T-cell Lymphotropic Virus (HTLV) 1 and 2
BVDV Bovine Viral Diarrhea Virus, Model for Hepatitis C Virus
PRV Pseudorabies Virus, Model for Herpes Viruses
PPV Porcine Parvovirus, Model for Parvovirus B19
EMC Encephalomyocarditis Virus, Model for Hepatitis A Virus
WNV West Nile Virus
HAV Hepatitis A Virus
ND Not Determined
N/A Not Applicable
Lipid Enveloped Yes Yes Yes No No Yes No
Size (nm) 80-120 40-70 120-200 18-24 25-30 40-60 27-32
Genome SS-RNA SS-RNA DS-DNA SS-DNA SS-RNA SS-RNA SS-RNA
Fractionation ≥ 7.98 7.29 ≥ 11.74 8.30 ND ND ND
Viral Filtration ≥ 5.60 5.40 ≥ 6.20 3.30 4.16 ND ≥ 5.07
Viral Inactivation ≥ 4.28 ≥ 4.90 ≥ 5.58 N/A N/A ≥ 7.05 N/A
Total Viral Reduction ≥ 17.86 ≥ 17.59 ≥ 23.52 11.60 4.16 ≥ 7.05 ≥ 5.07

The safety of Rho(D) Immune Globulin (Human) has been further shown in an empirical study of viral marker rates in female blood donors in the United States.21 This study revealed that Rh-negative donors, of whom an estimated 55-60% had received Rho(D) Immune Globulin (Human) for pregnancy-related indications, had prevalence and incidence viral marker rates similar to those of Rh-positive female donors who had not received Rho(D) Immune Globulin (Human).

The final product contains 5 ± 1% IgG, 2.9 mg/mL sodium chloride, 0.01% Polysorbate 80 (non-animal derived) and 15 mg/mL glycine. Small amounts of IgA, typically less than 15 μg per dose, are present.10 The pH range is 6.20 - 6.55 and IgG purity is ≥ 98%. The product contains no added human serum albumin (HSA), no thimerosal or other preservatives and utilizes a latex-free delivery system.

RhoGAM Ultra-Filtered PLUS and MICRhoGAM Ultra-Filtered PLUS are manufactured and distributed by Ortho-Clinical Diagnostics, Inc., Raritan, NJ 08869.

Principal Display Panel - 300 ug Carton

Rho(D) Immune Globulin (Human)

RhoGAM®
Ultra-Filtered PLUS – 300 µg Dose (1500 IU*)
Thimerosal-Free
*International Units

Do not store frozen
See Directions for Use

Package Contains:

  • 1 prefilled syringe containing a
    single dose of RhoGAM
  • 1 control form
  • 1 package insert
  • 1 patient identification card

1 single dose

Active Ingredients
Anti-D Rho Immune Globulin (300 µg), the potency of
which is determined relative to the US/WHO/EP Standard
Anti-D Immunoglobulin Rho(D) Immune Globulin (Human)
CBER Lot 4: NIBSC Lot 01/572 (285 IU/ampoule)

Inactive ingredients
2.9 mg/mL sodium chloride
0.01% polysorbate 80
15 mg/mL glycine

ORTHO

Product Code
780501

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