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Data Sheet http://www.medsafe.govt.nz/Profs/DataSheet/r/RhoGaminj.htm

RhoGAM

Rho (D) Immune Globulin (Human)

Ultra-Filtered

Caution: Federal law prohibits dispensing without prescription.

For Intramuscular Injection Only

Description

RhoGAM Rho(D) Immune Globulin (Human) is a sterile solution containing IgG anti-D (RH1) for use in preventing Rh immunization. A single dose of RhoGAM contains sufficient anti-D (RH1) (approximately 300 g) to suppress the immune response to 15 mL (or less) of Rh positive red blood cells. 2,3

All donors are carefully screened to reduce the risk of transmitting disease from individuals in high risk groups. Fractionation of the plasma is performed by a modification of the cold alcohol procedure. Following fractionation, a viral clearance filtration step is incorporated into the manufacturing process. This filtration step removes viruses via a size exclusion mechanism utilizing a patented Viresolve* 180 ultrafiltration membrane with defined pore-size distribution. The filter is inert to the product. This virus removal process has been shown in laboratory spiking studies to reduce the level of some viruses ranging from 18 to 200 nm in size, including enveloped viruses as well as non-enveloped viruses.4 Non-enveloped viruses are known to be resistant to chemical and physical inactivation.

The final product contains 5 1% gamma globulin, 2.9 mg/mL sodium chloride, 0.01% polysorbate 80 and 0.003% thimerosal (mercury derivative), with glycine
(15 mg/mL) as a stabilizer.

This product is for intramuscular injection only.

A full dose of Rh o (D) Immune Globulin (Human) has traditionally been referred to as a "300 g" dose and this usage is employed here for convenience in terminology. It should not be construed as the actual anti-D content. Each full dose of Rh o (D) Immune Globulin (Human) must contain at least as much anti-D as 1 milliliter of the U.S. Reference Rho (D) Immune Globulin (Human). Studies performed at the Food and Drug Administration have shown that the U.S Reference contains 820 international units (IU) of anti-D per milliliter. When the conversion factor determined for the International (WHO) Reference Preparation1 is used, 820 IU per milliliter is equivalent to 164 g per milliliter of anti-D.

Clinical Pharmacology

Intramuscular Rho (D) human immune globulins prepared by cold alcohol fractionation have not been reported to transmit hepatitis or other infectious diseases.

RhoGAM acts by suppressing the immune response of Rh negative individuals to Rh positive red blood cells.

The obstetrical patient may be exposed to red blood cells from her Rh positive fetus during the normal course of pregnancy. Clinical studies have proven that the incidence of Rh immunization as a result of pregnancy was reduced to 1 - 2% from 12 - 13% when RhoGAM was given within 72 hours following delivery.5,6 Further studies in which patients received Rh immune globulin, antepartum at 28 to 32 weeks and postpartum, reduced the risk of immunization to less than 0.1%.7,8

An Rh negative individual transfused with one unit of Rh positive red blood cells has about an 80% likelihood of producing anti-D.3 Protection from Rh immunization is accomplished by administering the appropriate dose of RhoGAM.

Indications and Usage

Pregnancy and Other Obstetric Conditions

RhoGAM is indicated whenever it is known or suspected that fetal red blood cells have entered the circulation of an Rh negative mother unless the fetus or the father can be shown conclusively to be Rh negative.

Transfusion

RhoGAM is indicated for any Rh negative female of childbearing age who receives any Rh positive red blood cells or component such as platelets or granulocytes prepared from Rh positive blood.

Contraindications

Individuals known to have had an anaphylactic or severe systemic reaction to human globulin should not receive RhoGAM or any other Rh o (D) Immune Globulin (Human).

Warnings

Do not inject intravenously.

Do not inject infant.

RhoGAM is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, 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 certain current viral infections and by removing certain viruses during the manufacturing process. Following fractionation, a viral clearance filtration step is incorporated in the manufacturing process. This filtration step removes viruses via a size-exclusion mechanism utilizing a patented Viresolve 180 ultrafiltration membrane with defined pore-size distribution. The filter is inert to the product. This virus removal process has been shown in laboratory spiking studies to reduce the level of some viruses ranging from 18 to 200 nm in size, including enveloped viruses as well as non-enveloped viruses.4 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 possible to have been transmitted by this product should be reported by the physician or other healthcare provider in the U.S. to Ortho Diagnostic Systems Inc. at 1-800-322-6374. Outside of the U.S., the company distributing this product should be contacted. The physician should discuss the risks and benefits of this product with the patient.

Precautions

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 of women given Rh o (D) Immune Globulin (Human) antepartum have weakly positive direct antiglobulin tests at birth.

Late in pregnancy or following delivery there may be sufficient fetal red blood cells in the maternal circulation to cause a positive antiglobulin test for weak D(Du). When there is any doubt as to the patient's Rh type, RhoGAM should be administered.

Pregnancy Category C

Animal reproduction studies have not been conducted with RhoGAM. It is also not known whether Rh o (D) Immune Globulin (Human) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Rh o (D) Immune Globulin (Human) should be given to a pregnant woman only if clearly needed. However, use of Rh antibody during the third trimester in full doses of antibody has been reported to produce no evidence of hemolysis in the infant.9

Adverse Effects

Systemic reactions associated with administration of RhoGAM are extremely rare. Discomfort at the site of injection has been reported and a small number of women have noted a slight elevation in temperature.

About one-quarter of a group of 22 individuals who were given multiple doses of RhoGAM to treat mismatched transfusions noted fever, myalgia and lethargy. Bilirubin levels of 0.4 to 6.8 mg/dL were observed in some of the treated individuals and one had splenomegaly.3

Dosage and Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

A single dose (approximately 300 g) is contained in each prefilled syringe of RhoGAM. This is the usual dose for the indications associated with pregnancy unless there is clinical or laboratory evidence of a fetal-maternal hemorrhage in excess of 15 mL of Rh positive red blood cells. The indications and recommended dosage for RhoGAM are summarized in the following table.

Indications and Recommended Dosage
Indication Dose (approximately)
Threatened abortion at any stage of gestation with continuation of pregnancy 300 g
Abortion or termination of pregnancy at or beyond 13 weeks' gestation** 300 g
Genetic amniocentesis, chorionic villus sampling (CVS) and percutaneous umbilical blood sampling (PUBS) 300 g
Abdominal trauma 300 g
Antepartum prophylaxis at 26 to 28 weeks' gestation 300 g
Postpatum (if newborn Rh positive) 300 g


See footnote under Description
**If abortion or termination of pregnancy occurs up to and including 12 weeks' gestation, a single dose of MICRhoGAM Rh o (D) Immune Globulin (Human) (approximately 50 g) may be used instead of RhoGAM.
If antepartum prophylaxis is indicated, it is essential that the mother receive a postpartum dose if the infant is Rh positive.

If an adverse event requires the administration of RhoGAM early in the pregnancy, there is an obligation to maintain a level of passively acquired anti-D by administration of RhoGAM at 12-week intervals. RhoGAM should be given within 72 hours after delivery if the baby is Rh positive. If delivery occurs within three weeks after the last antepartum dose, the postpartum dose may be withheld, but a test for fetal-maternal hemorrhage (FMH) should still be performed to determine a bleed greater than 15 mL of packed red blood cells.10

Whenever there is a fetal-maternal hemorrhage in excess of 15 mL of Rh positive red blood cells, multiple doses of RhoGAM are required. A fetal-maternal hemorrhage of this magnitude is unlikely prior to the last trimester of pregnancy. Patients who may need multiple doses of RhoGAM can be identified by a fetal-maternal hemorrhage screening test. If the test is positive, the volume of the fetal-maternal bleed should be determined by a quantitative method. A single dose of RhoGAM should be administered for every 15 mL of fetal red blood cells. If the dose calculation results in a fraction, administer the next number of whole syringes of RhoGAM.

Multiple doses of RhoGAM are usual for indications associated with transfusion. For every 15 mL of Rh positive red blood cells transfused, the patient should receive a single dose of RhoGAM. If multiple doses are required, consult your pharmacy for pooling directions.

Administer RhoGAM intramuscularly. Do not inject intravenously. Multiple doses may be administered at the same time or at spaced intervals, as long as the total dose is administered within three days of exposure.

Since there is no lot number and expiration date on the prefilled syringes, they should not be removed from the protective pouch until immediately before use.

How Supplied

RhoGAM is available in packages containing:

5 prefilled single-dose syringes of RhoGAM
(Product Code 780705) NDC 0562-7807-05
5 package inserts
5 control forms
5 patient identification cards

and

25 prefilled single-dose syringes of RhoGAM
(Product Code 780725) NDC 0562-7807-25
25 package inserts
25 control forms
25 patient identification cards

and

100 prefilled single-dose syringes of RhoGAM
(Product Code 780795) NDC 0562-7807-10
100 package inserts
100 control forms
100 patient identification cards

Storage

Store at 2 to 8C. Do not store frozen.

References

  1. Gunson HH, Bowell PJ, Kirkwood TBL. Collaborative study to recalibrate the International Reference Preparation of Anti-D Immunoglobulin. J.Clin Pathol 1980;33:249-53.
  2. Pollack W, Ascari WQ, Kochesky RJ, O'Connor RR, Ho TY, Tripodi D. Studies on Rh prophylaxis. I. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion 1971;11:333.
  3. Pollack W, Ascari WQ, Crispen JF, O'Connor RR, Ho TY. Studies on Rh prophylaxis. II. Rh immune prophylaxis after transfusion with Rh-positive blood. Transfusion 1971;11:340.
  4. Data on file at Ortho Diagnostic Systems Inc.
  5. Pollack W, Gorman JG, Freda VJ, Ascari WQ, Allen AE, Baker WJ. Results of clinical trials of RhoGAM in women. Transfusion 1968;8:151.
  6. Frigoletto FD Jr, Jewett JF, Konugres AA, eds. Rh hemolytic disease: new strategy for eradication. Boston: GK Hall, 1982;34.
  7. Bowman JM, Chown B, Lewis M, Pollock JM. Rh isoimmunization during pregnancy: antenatal prophylaxis. Can Med Assoc J 1978;118:623.
  8. Bowman JM, Pollock JM. Antenatal prophylaxis of Rh isoimmunization: 28-weeks' gestation service program. Can Med Assoc J 1978;118:627.
  9. Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245-56.
  10. Garratty G ed. Hemolytic diseases of the newborn. Arlington,VA: American Association of Blood Banks, 1984;78.

Date of Preparation

December 1998

* Viresolve is a trademark of Millipore Corporation.