antithymocyte globulin equine (Atgam, ATG equine)
Classes: Immunosuppressants; Polyclonal Antibodies
Dosing and uses of Atgam, ATG equine (antithymocyte globulin equine)
Adult dosage forms and strengths
injectable solution
- 50mg/mL
Renal Allograft
Range: 10-30 mg/kg IV qDay
Delaying onset of rejection (start within 24 hours of transplant)
- 15 mg/kg IV qDay x 14 days, THEN qODay x 14 days (total of 21 doses in 28 days)
Treatment of rejection
- 10-15 mg/kg IV qDay x 14 days, THEN qODay PRN (total of 21 doses in 28 days)
Aplastic Anemia
10-20 mg/kg IV qDay x 8-14 days, then qODay PRN up to total of 21 doses
Skin Allograft (Off-label)
Initial: 10 mg/kg IV 24 hours prior to first allograft
Maintenance: usual 10-15 mg/kg IV qODay, but extremely variable (5-40 mg/kg qODay have been used)
Continue till allografts cover >20% of total BSA
Other Indications & Uses
Management of renal allograft rejection, usually with other immunosuppressants
Moderate-severe aplastic anemia (if bone marrow transplant unsuitable)
Off-label: bone marrow allograft
Pediatric dosage forms and strengths
injectable solution
- 50mg/mL
Renal Allograft
Range: 5-25 mg/kg IV qDay
Delaying onset of rejection (start within 24 hours of transplant)
- 15 mg/kg IV qDay x 14 days, THEN qODay x 14 days (total of 21 doses in 28 days)
Treatment of rejection
- 10-15 mg/kg IV qDay x 14 days, THEN qODay PRN (total of 21 doses in 28 days)
Aplastic Anemia
As adult
Atgam, ATG equine (antithymocyte globulin equine) adverse (side) effects
Renal Transplant Patients
>10%
- Fever (33-51%)
- Thrombocytopenia (11-30%)
- Rash (27%)
- Chills (14-16%)
- Leukopenia (14%)
- Systemic infection (13%)
- Dermatologic rxns (12%)
1-10%
- Arthralgia, clotted AV fistula, hypotension, peripheral thrombophlebitis
- Headache
- Diarrhea, nausea or vomiting, stomatitis
- Chest or back pain
- Night sweats
- Pain at the infusion site
- Dyspnea
<1%
- Edema, hypertension, pulmonary edema, tachycardia
- Dizziness, malaise, paresthesia, seizures, weakness or faintness
- Toxic epidermal necrosis, wound dehiscence
- Epigastric pain, hiccoughs, iliac vein obstruction
- Myalgia
- Renal artery thrombosis
- Herpes simplex reactivation, localized infection, systemic infection, serum sickness
- Anaphylaxis, hyperglycemia, laryngospasm
Aplastic Anemia Patients
>10%
- Arthralgia (50%)
- Chills (50%)
- HA (16%)
5-10%
- Myalgia (10%)
- Chest pain (7%)
- Nausea (7%)
- Phlebitis (5%)
(<5%)
- Bilateral pleural effusion, cardiac irregularity, CHF, edema, hypotension
- Agitation, lethargy, seizures
- Diarrhea, vomiting
- Joint stiffness, Lymph node tenderness, muscle ache
- Proteinuria
- Respiratory distress
- Anaphylactic reaction
- Diaphoresis
Post Marketing Experience
Serum sickness
Warnings
Black box warnings
Should only be prescribed by physicians experienced in immunosuppressive therapy for renal transplant recipients
Patients should only receive the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources
Contraindications
Hypersensitivity to antithymocyte globulin, other equine gamma globulins
Cautions
Test for allergic response by intradermal injection before start of treatment
Discontinue if anaphylaxis, unremitting thrombocytopenia, or unremitting leukopenia occur
Aplastic anemia patients may need prophylactic platelet transfusion
Observe patients carefully for previously masked reactions when reducing dose of corticosteroids, other immunosuppressants
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Atgam, ATG equine (antithymocyte globulin equine)
Mechanism of action
IgG against human antigen reactive T lymphocytes (equine-derived); causes either elimination of T lymphocytes in peripheral blood or alteration in T-lymphocyte function; in aplastic anemia may induce complete or partial hematologic response
Pharmacokinetics
Half-Life: 1.5-12 days
Peak Plasma: 727±310 mcg/mL
Excretion: 1% excreted unchanged in urine
Administration
IV Incompatibilities
IV Preparation
Dilute required dose in 1/2NS or NS (usually 250-1000 mL); final concentration preferably <4 mg/mL
Contact with air may result in denaturation of protein
Do not dilute in dextrose injections, may precipitate if low salt concentration
Do not dilute in highly acidic IV solutions because of potential physical instability
Following addition to IV infusion solution, gently rotate or swirl container to thoroughly mix; do not shake
IV Administration
IV infusion over at least 4 hr (usually 4-8 hr)
Administer via high-flow central vein, a vascular shunt, or arteriovenous fistula (eg, Brescia-Cimino fistula); high-flow veins recommended to minimize risk of phlebitis & thrombosis
Use inline filters with all IV infusions to prevent inadvertent administration of any insoluble material that may develop during storage; 0.2-1 micron filters are generally used, but 5 micron filters have also been employed
Storage
Refrigerate
Protect from freezing