mercury in RhoGam
Mercury in Plasma-Derived Products
[<A HREF="http://www.fda.gov/cber/vaccine/thimerosal.htm">Thimerosal in
This is the second update of the original posting. The Ortho-Clinical
Diagnostics product, Rho (D) Immune Globulin (Human), RhoGAM, was
as containing 9 milligrams of mercury in each dose. The first update
that the correct amount is 9 micrograms. In this second update additional
information is included regarding different doses of RhoGAM, and the mercury
content of other Rho (D) Immune Globulin products is described.
The EPA has recently raised concerns regarding mercury exposure. These
concerns have been in the context of chronic exposure to methyl mercury in
amounts. In contrast, plasma-derived products (except anti-venoms) containing
ethyl mercury are usually given as one or two injections. Furthermore, the
ethyl mercury content of these products is in the form of a preservative,
thimerosal, which breaks down to form ethyl mercury in microgram amounts.
In the past, products made in multiple-use vials, e.g. Immune Globulin
(Human), used for Hepatitis A prophylaxis, contained a preservative, such
mercury-containing thimerosal, to avoid contamination. These were older
products and most of them have been discontinued.
Rho (D) Immune Globulin (Human) products are as follows:
RhoGAM, Ortho Clinical Diagnostics
RhoGAM [licensed 1968]
On April 16, 2001, Ortho Diagnostics was approved by FDA to produce RhoGAM
without thimerosal, and at that time, Ortho agreed to distribute only
thimerosal-free product to the US market. The product has a 2-year dating
that material released before April 16, 2001 may still be on the market. The
package insert for RhoGAM containing thimerosal (i.e., for those lots
prior to April 2001) does state that this product contains thimerosal.
However, there is no warning in the package insert related to thimerosal or
Regarding the total thimerosal content of the previously released RhoGAM, the
product was manufactured in two doses only: the standard dose of "300
micrograms" of anti-D, and the micro-dose of "50 micrograms" of anti-D. The
volume for both the standard dose and micro-dose products is typically
and 0.8 mL. Preservative-containing RhoGAM contains thimerosal at 0.003%, or
30 micrograms per milliliter. Thimerosal is about 50% ethyl mercury by
Hence, a patient receiving a dose of RhoGAM (0.7 ml on average) will have
received 10.5 microgram of ethyl mercury.
There are three indications for which an Rh-negative pregnant woman would
receive a significantly larger dose of RhoGAM: a fetal-maternal hemorrhage
in the pregnancy, a fetal-maternal hemorrhage greater than 15 ml of Rh+ red
cells, and an Rh+ transfusion. In the first case, a single 300 microgram
RhoGAM, is recommended at 12-week intervals. For the second two indications,
a procedure exists by which to determine the dose of RhoGAM required, based
the amount of Rho+ red cells in the maternal circulation: the Kleihauer-Betke
elution test (see the AABB Technical Manual, 13th ed., pp. 507-8.) The total
dose of mercury received can be calculated by multiplying the number of
syringes administered by 10.5 micrograms.
BayRho [licensed 1971]
The Bayer Corporation makes a Rho (D) Immune Globulin product (BayRho) which
in the past contained thimerosal; this product has been manufactured without
preservative since 1996, so that no in-date BayRho contains thimerosal.
Regarding the previously distributed product, the volume of a single dose
Bayer product was approximately 0.7 ml. The thimerosal concentration was
the total mercury in a single dose would have been approximately 35
micrograms of ethyl mercury.
WinRho SD [licensed 1996]
The Cangene Corporation makes a freeze-dried Rho (D) Immune Globulin (WinRho
SD); this product has never contained a preservative.
In addition, five other plasma-derived products remain on the market that
contain or contained ethyl mercury preservatives. They are as follows:
Antivenin (Crotalidae) Polyvalent (Equine); Pit viper snake antivenom, Wyeth
Antivenin (Micrurus fulvius); Coral snake antivenom (Equine), Wyeth
Crotalidae Polyvalent Immune Fab (Ovine); Pit viper snake antivenom,
Antivenin (Lacrodectus mactans); Black Widow spider antivenom Equine), Merck
Lymphocyte Immune Globulin: Anti-thymocyte Globulin (Equine), Pharmacia and
Pit Viper [Antivenin (Crotalidae) Polyvalent, licensed 1954] and
Coral Snake [Antivenin (Micrurus fulvius), licensed 1967] antivenoms by Wyeth
These products are equine antisera. They are in lyophilized form and when
reconstituted contain 0.005% thimerosal (50 micrograms per milliliter). The
diluent, WFI, contains the preservative phenylmercuric nitrate at 0.001%
concentration (10 micrograms per milliliter). A patient bitten by a snake
may receive 15
or more vials (doses of 50 vials have been reported) if the envenomization is
severe. A 15 vial dose of this antivenom would contain 4.7 milligrams of
Wyeth plans to discontinue these products; however, the current supply will
last 1-2 years. Rattlesnake bites are dangerous and can cause serious
or mortality. In the interest of the public health these products need to be
available until sufficient Ethyl mercury-free product can be provided to the
Pit Viper antivenom [Crotalidae Polyvalent Immune Fab (Ovine) licensed
October 2000, Protherics]
Mercury is not added to the final product in the form of a preservative, but
thimerosal is used to assure that the affinity columns used in the
manufacturing of this product do not become bacterially contaminated with
The product was approved but the Ethyl mercury content was limited to not
than 104.5 micrograms Ethyl mercury per vial, with a recommended maximum dose
of 18 vials. A patient receiving this product would receive about 1.88
milligrams of mercury.
Black Widow Spider antivenom [Antivenin (Lactrodectus mactans), licensed
This product is an equine antiserum. The reconstituted product contains 0.1
milligrams of mercury per milliliter, so that the maximum 2-vial dose would
contain 0.25 milligrams of mercury. Black Widow Spider bites can be lethal,
the dose is limited to not more than two vials. It has been determined that
removal of the product from the market by the FDA would not be in the best
interests of public health.
Anti-thymocyte Globulin [Lymphocute Immune Globulin, licensed 1981, Pharmacia
This product is an equine immune globulin. In 1995 a thimerosal-free
formulation was approved and in 1998 thimerosal was removed from
Updated October 4, 2002
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