Get your patient on Rhogam Ultra-Filtered Plus (Human Rho(D) Immune Globulin)

RhoGAM is an immune globulin indicated for use in preventing Rh immunization for:

• Pregnancy and other obstetrical conditions in Rh-negative women unless the father or baby are conclusively Rh-negative, e.g. delivery of an Rh-positive baby irrespective of the ABO groups of the mother and baby, any antepartum fetal-maternal hemorrhage (suspected or proven), actual or threatened pregnancy loss at any stage of gestation and ectopic pregnancy. (1.1 )
• Prevention of Rh immunization in any Rh-negative person after incompatible transfusion of Rh-positive blood or blood products. (1.2 )
• Limitation of use
  Pregnancy and other obstetrical conditions:In the case of postpartum use, RhoGAM is intended for maternal administration. Do not inject the newborn infant. (1.3 )

For intramuscular use only.

• RhoGAM ^® Ultra-Filtered PLUS - 300 μg (1500 IU) The anti-D content of RhoGAM is expressed as μg per dose or as International Units (IU) per dose. The conversion factor is 1 μg = 5 IU. ² – Prefilled Syringes

The use of RhoGAM is contraindicated in the following:

• Rh-positive individuals
• Patients with a known history of anaphylactic or severe systemic reactions to the administration of human immune globulin products.

• Severe hypersensitivity reactions may occur with the use of RhoGAM. (5.1 )
• RhoGAM should be administered in a setting where appropriate equipment, medications such as epinephrine, and personnel trained in the management of hypersensitivity, anaphylaxis, and shock are available. (5.1 )
• Products made from human blood may carry a risk of transmitting infectious agents e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. (5.2 )
• After administration of Rho(D) immune globulin, a transitory increase of various passively transferred antibodies in the patient's blood may yield positive serological testing results. (5.3 )

Incompatible blood transfusion

• Patients treated for Rh-incompatible transfusion should be monitored by clinical and laboratory means for signs and symptoms of a hemolytic reaction. (5.4 )

The most frequently reported adverse reactions in patients receiving Rh _o (D) Immune Globulin (Human) products are injection site reactions, such as swelling, induration, redness and mild pain or warmth. Possible systemic reactions are skin rash, body aches or a slight elevation in temperature. Severe systemic reactions include allergic reactions and hemolytic reactions (see Warnings and Precautions [5.2] ).

There have been no reported fatalities due to anaphylaxis or any other cause related to RhoGAM administration.

• May impair the efficacy of live vaccines such as measles, mumps and varicella. Administration of live vaccines should generally be delayed until 12 weeks after the final dose of immune globulin. If administered within 14 days after administration of a live vaccine, the efficacy of the vaccination may be impaired. (7 )
• The postpartum vaccination of rubella-susceptible women with rubella or MMR vaccine should not be delayed because of the receipt of Rho(D) Immune Globulin (Human). (7 )

RhoGAM Rho(D) Immune Globulin (Human) is a sterile solution containing immunoglobulin G (IgG) anti-D (anti-Rh) for use in preventing Rh immunization. It is manufactured from human plasma containing anti-D from Rh-negative donors immunized with Rh-positive red blood cells. 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. ⁷ 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). ⁸

Plasma for RhoGAM is typically sourced from a donor center owned and operated by KEDPlasma LLC., US Lic. No. 1876. 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 hepatitis B virus (HBV), HCV and HIV-1. Each plasma unit must be negative (non-reactive) in all tests. 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 NAT 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 10 ⁴ 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. ³ Following plasma fractionation, a viral clearance filtration step and a viral inactivation step are performed. The viral filtration step removes both enveloped and non‐enveloped viruses as small as approximately 20 nm via a size-exclusion mechanism.

Following viral filtration, quality control tests are performed on the 20 nm filtration membrane to ensure filter integrity. The viral inactivation step (Solvent/Detergent treatment) utilizes Triton X-100 and tri-n-butyl phosphate (TNBP) to inactivate enveloped viruses such as HCV, HIV, HBV and West Nile Virus (WNV). ^{3,9, 10, 11}

The donor selection process, the fractionation process, the viral filtration step, the viral inactivation process and other manufacturing process steps increase product safety by reducing the virus load potentially present in the starting material and thus 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. ¹² There have been no documented cases of infectious disease transmission by RhoGAM.

Laboratory spiking studies, performed in accordance with good laboratory practices ³ have shown that the cumulative viral removal and inactivation capability of the RhoGAM manufacturing process is as follows:

The safety of Rh _o (D) Immune Globulin (Human) has been further shown in an empirical study of viral marker rates in female blood donors in the United States. ¹³ 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. ³ The pH range is 6.20 - 7.00 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 is manufactured by Kedrion Biopharma Inc., 155 Duryea Road, Melville, NY 11747 USA.

Rho(D) Immune Globulin (Human) administered at 28 weeks, as well as within 72 hours of delivery, has been shown to reduce the Rh immunization rate to about 0.1-0.2%. ^15,16 Clinical studies demonstrated that administration of Rh immune globulin within three hours following pregnancy termination was 100% effective in preventing Rh immunization. ¹⁷

Multiple studies have been performed that prove the safety and efficacy of RhoGAM in both the obstetrical and post transfusion settings.

Pollack, Gorman and colleagues ¹⁸ studied the efficacy of RhoGAM in the postpartum setting in a randomized, controlled study completed in 1967. The control group received no immunoglobulin therapy after delivery, while the test group received 300 μg of RhoGAM intramuscularly within 72 hours of delivery of an Rh-positive infant. Six months after delivery, the incidence of Rh immunization in the control group was 6.4% (32/499) versus 0.13% (1/781) in the RhoGAM group (p < 0.001).

Pollack et al. performed two randomized, placebo-controlled studies in the post transfusion setting that were designed to establish the dose response relationship of RhoGAM. In the first study, ⁷ 178 (176 males, 2 females) Rh-negative volunteers received varying volumes of Rh- positive red cells; 92 subjects then received RhoGAM. A single dose of RhoGAM (1.1 mL @ 267 μg/mL) was shown to suppress anti-D formation after injection of up to 15.1 mL of Rh-positive red cells. In a companion study, Pollack administered 500 mL of Rh-positive whole blood to 44 Rh-negative male volunteers. Twenty-two (22) subjects received 20 μg RhoGAM per mL of Rh-positive red cells and 22 received no RhoGAM. None of the RhoGAM-treated subjects developed anti-D; 18/22 control arm subjects developed anti-D (p < 0.0001) ¹⁹ .

A study was conducted in 1985 using the low protein formulation of RhoGAM. None of the 30 Rh negative male volunteers who received RhoGAM after injection of 15 ml of Rh positive red cells developed anti-D.

The following presentations of RhoGAM are available:

RhoGAM acts by suppressing the immune response of Rh-negative individuals to Rh-positive red blood cells. The mechanism of action is unknown. RhoGAM and other Rho(D) Immune Globulin (Human) products are not effective in altering the course or consequences of Rh immunization once it has occurred.