antithymocyte globulin equine (Atgam, ATG equine)

Dosing and uses of Atgam, ATG equine (antithymocyte globulin equine)

• Adult
• Pediatric

 

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