A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Rhogam Pharmacology, Pharmacokinetics, Studies, Metabolism - Rho(D) Immune Globulin (Human)
Rhogam Pharmacology, Pharmacokinetics, Studies, Metabolism - Rho(D) Immune Globulin (Human)
CLINICAL PHARMACOLOGY
Mechanism of Action
RhoGAM® and MICRhoGAM® act by suppressing the immune response of Rh-negative individuals to Rh-positive red blood cells. The mechanism of action is unknown. RhoGAM, MICRhoGAM and other Rho(D) Immune Globulin (Human) products are not effective in altering the course or consequences of Rh immunization once it has occurred.
Obstetrical Use
The Rh-negative obstetrical patient may be exposed to red blood cells from her Rh-positive fetus during the normal course of pregnancy or after obstetrical procedures or abdominal trauma. 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.10,11 Antepartum administration of Rh immune globulin 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%.12,13 Clinical studies demonstrated that administration of MICRhoGAM within three hours following abortion was 100% effective in preventing Rh immunization.14
Use after Rh Incompatible Transfusion
An Rh-negative individual transfused with one unit of Rh-positive red blood cells has about an 80% likelihood of producing anti-D.3 However, Rh immunization can occur after exposure to < 1 mL of Rh-positive red blood cells. Protection from Rh immunization is accomplished by administering the appropriate dose of RhoGAM or MICRhoGAM, which is ³20 µg per mL of Rh-positive red blood cells, within 72 hours of transfusion of incompatible red cells.2,15 (See DOSAGE AND ADMINISTRATION section.)
Pharmacokinetic Properties
Pharmacokinetic studies after intramuscular injection were performed on eight Rh-negative subjects.16 Six subjects received a single dose (300 µg) of RhoGAM, while two subjects received four doses (1200 µg). Plasma anti-D levels were monitored for four months using a validated method with sensitivity of approximately 1 ng/mL. The parameters measured and/or calculated included the following:
Cmax = maximum plasma concentration obtained (ng/mL)
Tmax = time to attain Cmax (days)
T1/2 = elimination half-life (days)
Vd = volume of distribution (liters)
|
Mean Pharmacokinetic Parameters for RhoGAM
|
|
Parameter
|
Single Dose
|
Four Doses
|
Dose Ratio
|
| |
(n = 6)
|
(n = 2)
|
(1/4)
|
Cmax |
37.1 |
146.3 |
0.253 |
Tmax |
5 |
5 |
0.999 |
T1/2 |
24.2 |
27.0 |
0.933 |
Vd |
8.59 |
8.16 |
1.053 |
REFERENCE
10. Pollack W, Gorman JG, Freda VJ, Ascari WQ, Allen AE, Baker WJ. Results of clinical trials of RhoGAM in women. Transfusion 1968;8:151-53.
11. Freda VJ, Gorman JG, Pollack W, Bowe E. Prevention of Rh hemolytic disease – ten years’ clinical experience with Rh immune globulin. New Engl J Med 1975; 292:1014-16.
12. Bowman JM, Chown B, Lewis M, Pollock JM. Rh isoimmunization during pregnancy: antenatal prophylaxis. Can Med Assoc J 1978;118:623-27.
13. Bowman JM, Pollock JM. Antenatal prophylaxis of Rh isoimmunization: 28-weeks’ gestation service program. Can Med Assoc J 1978;118:627-30.
14. Stewart FH, Burnhill MS, Bozorgi N. Reduced dose of Rh immunoglobulin following first trimester pregnancy termination. Obstet Gynecol 1978;51:318-22.
15. Crispen J. Immunosuppression of small quantities of Rh-positive blood with MICRhoGAM® in Rh-negative male volunteers. In: Proceedings of a symposium on Rh antibody mediated immunosuppression. Raritan, NJ: Ortho Research Institute of Medical Sciences, 1975:51-54.
16. Data on file at Ortho-Clinical Diagnostics, Inc.
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