WARNINGS
Thymoglobulin should only be used by physicians experienced in
immunosuppressive therapy for the treatment of renal transplant patients. Medical
surveillance is required during Thymoglobulin infusion.
Immune-mediated reactions
Serious immune-mediated reactions have been reported with the use of
Thymoglobulin and consist of anaphylaxis or severe cytokine release syndrome
(CRS).
Fatal anaphylaxis has been reported. If an anaphylactic reaction occurs,
the infusion should be terminated immediately. Medical personnel should be
available to treat patients who experience anaphylaxis. Emergency treatment such
as 0.3 mL to 0.5 mL aqueous epinephrine (1:1000 dilution) subcutaneously and other
resuscitative measures including oxygen, intravenous fluids, antihistamines,
corticosteroids, pressor amines, and airway management, as clinically indicated,
should be provided. Any further administration of Thymoglobulin to a patient who
has a history of anaphylaxis to Thymoglobulin is not recommended.
Severe, acute infusion-associated reactions (IARs) are consistent with
CRS which is attributed to the release of cytokines by activated monocytes and
lymphocytes. Severe acute CRS can cause serious cardiorespiratory events and/or
death (See
PRECAUTIONS
and
ADVERSE REACTIONS:
Post-Marketing Experience
).
Infection
Thymoglobulin is routinely used in combination with other
immunosuppressive agents. Infections (bacterial, fungal, viral and protozoal),
reactivation of infection (particularly cytomegalovirus [CMV]) and sepsis have
been reported after Thymoglobulin administration in combination with multiple
immunosuppressive agents. Severe acute reactions can be fatal.
PRECAUTIONS
General
Appropriate dosing for Thymoglobulin is different from dosing for other
anti-thymocyte globulin (ATG) products, as protein composition and concentrations
vary depending on the source of ATG used. Physicians should therefore exercise
care to ensure that the dose prescribed is appropriate for the ATG product being
administered.
Thymoglobulin should be used under strict medical supervision in a
hospital setting, and patients should be carefully monitored during the infusion.
The first dose should be infused over a minimum of 6 hours into a high-flow vein.
Close compliance with the recommended dosage and infusion time may reduce the
incidence and severity of infusion associated reactions (IARs). Additionally,
reducing the infusion rate may minimize many of these IARs. Premedication with
corticosteroids, acetaminophen, and/or an antihistamine and/or slowing the
infusion rate may reduce reaction incidence and intensity (See
DOSAGE AND
ADMINISTRATION
).
Rapid infusion rates have been reported with case reports consistent with
cytokine release syndrome (CRS). Severe acute CRS can be fatal.
Hematologic Effects
Thrombocytopenia and/or leukopenia (including lymphopenia and
neutropenia) have been identified and are reversible following dose adjustments
(See
DOSAGE AND
ADMINISTRATION
).
Infection
Infections, reactivation of infection, and sepsis have been reported
after Thymoglobulin administration in combination with multiple immunosuppressive
agents. Careful patient monitoring and appropriate anti-infective prophylaxis are
recommended.
Malignancy
Use of immunosuppressive agents, including Thymoglobulin, may increase
the incidence of malignancies, including lymphoma or post-transplant
lymphoproliferative disease (PTLD) (See
ADVERSE REACTIONS:
Post-Marketing Experience
).
Special Considerations for Thymoglobulin Infusion
Reactions at the infusion site can occur and may include pain, swelling,
and erythema.
The recommended route of administration for Thymoglobulin is intravenous
infusion using a high-flow vein (See
DOSAGE AND
ADMINISTRATION
).
Immunizations
The safety of immunization with attenuated live vaccines following
Thymoglobulin therapy has not been studied; therefore, immunization with
attenuated live vaccines is not recommended for patients who have recently
received Thymoglobulin.
Laboratory Tests
During Thymoglobulin therapy, monitoring the lymphocyte count (i.e.,
total lymphocyte and/or T-cell subset) may help assess the degree of T-cell
depletion (See
Pharmacokinetics and
Immunogenicity
). For safety, WBC and platelet counts should also be monitored (See
DOSAGE AND
ADMINISTRATION
).
Drug Interactions
- No drug interaction studies have been performed.
- Because Thymoglobulin is administered to patients receiving a standard
immunosuppressive regimen, this may predispose patients to
overimmunosuppression. Many transplant centers decrease maintenance
immunosuppression therapy during the period of antibody therapy.
- Thymoglobulin can stimulate the production of antibodies which crossreact
with rabbit immune globulins (See
Pharmacokinetics and
Immunogenicity
).
Drug/Laboratory Test Interactions
Thymoglobulin has not been shown to interfere with any routine clinical
laboratory tests which do not use immunoglobulins. Thymoglobulin may interfere
with rabbit antibody-based immunoassays and with cross-match or panel-reactive
antibody cytotoxicity assays.
Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic and mutagenic potential of Thymoglobulin and its
potential to impair fertility have not been studied.
Pregnancy: Pregnancy Category C
Animal reproduction studies have not been conducted with Thymoglobulin.
It is also not known whether Thymoglobulin can cause fetal harm or can affect
reproduction capacity. Thymoglobulin should be given to a pregnant woman only if
clearly needed.
Nursing Mothers
Thymoglobulin has not been studied in nursing women. It is not known
whether this drug is excreted in human milk. Because other immunoglobulins are
excreted in human milk, breast-feeding should be discontinued during Thymoglobulin
therapy.
Pediatric Use
The safety and effectiveness of Thymoglobulin in pediatric patients has
not been established in controlled trials. However, the dose, efficacy, and
adverse event profile are not thought to be different from adults based on limited
European studies and US compassionate use.
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