ATGAM- equine thymocyte immune globulin injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

EQUINE THYMOCYTE IMMUNE GLOBULIN (UNII: 475247QF1Z) (EQUINE THYMOCYTE IMMUNE GLOBULIN - UNII:475247QF1Z)

Available from:

Pharmacia & Upjohn Company LLC

INN (International Name):

EQUINE THYMOCYTE IMMUNE GLOBULIN

Composition:

EQUINE THYMOCYTE IMMUNE GLOBULIN 50 mg in 1 mL

Administration route:

INTRAVENOUS

Therapeutic indications:

ATGAM is indicated for the management of allograft rejection in renal transplant patients; when administered with conventional therapy at the time of rejection ATGAM increases the frequency of resolution of the acute rejection episode [see Clinical Studies (14.1)] . ATGAM is indicated for the treatment of moderate to severe aplastic anemia in patients unsuitable for bone marrow transplantation [see Clinical Studies (14.2)] . The usefulness of ATGAM has not been demonstrated in patients with aplastic anemia who are suitable candidates for bone marrow transplantation or in patients with aplastic anemia secondary to neoplastic disease, storage disease, myelofibrosis, Fanconi's syndrome, or in patients known to have been exposed to myelotoxic agents or radiation. Do not administer ATGAM to a patient who has had an anaphylactic reaction during prior administration of ATGAM or any other equine gamma globulin preparation [see Warnings and Precautions (5.1)]. Risk Summary There are no adequate and well-controlled studies in pregnant women. There is a limited amount of data from the use of ATGAM in pregnant women. It is also not known whether ATGAM can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. The outcome of pregnancies cannot be determined. Use ATGAM during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcome. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data In embryo-fetal toxicity studies, ATGAM was administered to rats and cynomolgus monkeys for 11 and 16 days, respectively during organogenesis. In rats, hypoplastic cervical vertebrae, a finding consistent with delayed skeletal development, were observed in fetuses whose dams received ATGAM at doses of 100 mg/kg/day during organogenesis. In monkey reproduction studies, maternal toxicity (vaginal bleeding, decreased body weight and loss of appetite) was observed with ATGAM doses ≥20 mg/kg/day after 16 days of dosing. Fetal deaths occurred in dams treated with 20 mg/kg/day ATGAM earlier in organogenesis (days 20‑35), but not when treatment was given at a later part of organogenesis (days 35-50). The maternal and fetal deaths were attributed to maternal anemia due to red blood cell antigen that humans do not share. Therefore, this toxicity is not considered relevant to human fetal development. Risk Summary It is not known if ATGAM is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breast-feeding neonates and infants from ATGAM, a decision should be made whether to discontinue breast-feeding or to discontinue the drug taking into account the importance of the drug to the mother. Data In animal studies, a single dose of ATGAM up to 40 mg/kg was not detected at the limit of quantification in the milk of lactating cynomolgus monkeys. Contraception Females It is not known if ATGAM can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with ATGAM and for at least 10 weeks after cessation of therapy. Males Advise males with a female partner of reproductive potential to use effective contraception during treatment with ATGAM and for at least 10 weeks after cessation of therapy. Infertility In fertility studies, ATGAM at doses 10, 20 and 40 mg/kg/day was administered to cynomolgus monkeys (Macaca fascicularis) for 14 days either before (male monkeys) or before and after (female monkeys) cohabitation with untreated mates. ATGAM treatment was not associated with male or female hormonal or copulation behavior changes. A decrease in fertility index in female monkeys receiving ATGAM was seen. Female toxicity, including death, was observed with ATGAM doses of ≥20 mg/kg/day. While the etiology of this toxicity is uncertain, it may be attributed to hemolytic anemia due to cross-reactivity of ATGAM to a monkey red blood antigen. Experience with children has been limited. ATGAM has been administered safely to a small number of pediatric renal allograft recipients and pediatric aplastic anemia patients at dosage levels comparable to those in adults. Clinical experience in a limited number of elderly patients (≥65 years of age) has not identified differences in responses between the elderly and younger patients. Select the dose for an elderly patient with caution, starting at the low end of the dosage range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of comorbidities or other drug therapy in this age group.

Product summary:

ATGAM Sterile Solution, containing 50 mg/mL lymphocyte immune globulin, anti-thymocyte globulin [equine], is supplied as follows: 5 – 5 mL ampoules: NDC 0009-7224-02 Store in a refrigerator at 2° to 8°C (36° to 46°F). DO NOT FREEZE. Store in the original carton to protect from light. For storage conditions of diluted solution, see Dosage and Administration (2.2) .

Authorization status:

Biologic Licensing Application

Summary of Product characteristics

ATGAM- EQUINE THYMOCYTE IMMUNE GLOBULIN INJECTION, SOLUTION
PHARMACIA & UPJOHN COMPANY LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ATGAM SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ATGAM.
ATGAM (LYMPHOCYTE IMMUNE GLOBULIN, ANTI-THYMOCYTE GLOBULIN [EQUINE]),
STERILE SOLUTION,
FOR INTRAVENOUS USE ONLY
INITIAL U.S. APPROVAL: 1981
WARNING: ANAPHYLAXIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_.
ANAPHYLAXIS HAS BEEN REPORTED WITH THE USE OF ATGAM. ATGAM CAN CAUSE
POTENTIALLY
LIFE‑THREATENING ANAPHYLAXIS WHEN INJECTED INTRAVENOUSLY. MONITOR
PATIENTS FOR SIGNS
AND SYMPTOMS OF ANAPHYLAXIS DURING INFUSION AND FOR AT LEAST 24 HOURS
AFTER INFUSION
_[SEE WARNINGS AND PRECAUTIONS (5.1) AND ADVERSE REACTIONS (6.1)]._
RECENT MAJOR CHANGES
Boxed Warning
5/2023
Dosage and Administration (2)
5/2023
Contraindications (4)
5/2023
Warnings and Precautions (5)
5/2023
INDICATIONS AND USAGE
ATGAM is an immunoglobulin G indicated for:
•
•
•
DOSAGE AND ADMINISTRATION
FOR INTRAVENOUS USE ONLY.
INDICATION
DOSAGE
Renal allograft rejection
10 to 15 mg/kg daily intravenously for 14 days; additional
alternate-day therapy up to a total of 21 doses may be given.
(2.1)
Aplastic anemia
10 to 20 mg/kg daily intravenously for 8 to 14 days; additional
alternate-day therapy up to a total of 21 doses may be given.
(2.1)
DOSAGE FORMS AND STRENGTHS
ATGAM 50 mg/mL concentrate for solution for infusion. (3)
CONTRAINDICATIONS
Anaphylactic reaction during prior administration of ATGAM or any
other equine gamma globulin
preparation. (4)
WARNINGS AND PRECAUTIONS
•
®
Renal allograft rejection. (1.1)
Aplastic anemia (moderate to severe) in patients unsuitable for bone
marrow transplantation. (1.2)
Limitations of Use:
The usefulness of ATGAM has not been demonstrated in patients with
aplastic anemia who are
suitable candidates for bone marrow transplantation or in patients
with aplastic anemia secondary to
neoplastic disease, storage disease, my