Medication Guide App

Anti-thymocyte Globulin (Rabbit Systemic)


VA CLASSIFICATION
Primary: IM402
Secondary: IM403

Commonly used brand name(s): Thymoglobulin.

Another commonly used name is:
Antithymocyte immunoglobulin{02} Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Immunosuppressant—

Indications

Accepted

Transplant rejection, kidney (treatment)—Anti-thymocyte globulin (rabbit) is indicated as an adjunct to existing immunosuppression regimen for the treatment of acute rejection in patients who have undergone renal transplantation.{01}

Note: Anti-thymocyte globulin (rabbit) is not effective for treating antibody (humoral) mediated rejections.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Anti-thymocyte globulin (rabbit) is a purified, pasteurized, gamma immune globulin, obtained from rabbits that are immunized with human thymocytes. Its potency is determined by lymphocytotoxicity and E-rosette inhibition assays. The amount of cross-reactive antibodies are determined by hemagglutination, platelet agglutination, anti-human serum protein antibody, antiglomerular basement membrane antibody, and fibroblast toxicity assays.{01}

Mechanism of action/Effect:

The exact mechanism by which anti-thymocyte globulin (rabbit) suppresses immune response is not fully known. Possible mechanisms of action include T-cell clearance from the circulation and suppression of T-cell activation, homing and cytotoxic activities. Anti-thymocyte globulin (rabbit) contains antibodies against T-cell markers such as CD2, CD3, CD4, CD8, CD11a, CD18, CD25, CD44, CD45, HLA-DR, HLA Class I heavy chains, and beta 2 micro-globulin.{01}

Distribution:

The volume of distribution (Vol D) is 0.12L/kg. {03}

Half-life:

Elimination— 2 to 3 days after the first dose{01}.

Onset of action:

T-cell depletion is usually observed in 1 to 3 days after initiation of anti-thymocyte globulin (rabbit) therapy.{01}{04}

Time to peak concentration:

Times to peak concentration varied from 1 to 12 days in renal allograft recipients receiving 2.5 mg per kg of body weight (mg/kg) per day infused over 12 hour{05}.

Peak plasma concentration:

Mean peak plasma concentration of thymoglobulin was 87 mcg/mL (range, 23 to 170 mcg/mL), 4 to 8 hours post-infusion following administration of an intravenous dose of 1.25 to 1.5 mg/kg a day infused over 4 hours for 7 to 11 days{01}.


Precautions to Consider

Carcinogenicity/Mutagenicity

The carcinogenic and mutagenic potentials of anti-thymocyte globulin (rabbit) have not been studied.{01}

Pregnancy/Reproduction
Fertility—
Studies in humans and animals have not been done.{01}

Pregnancy—
Studies in humans and animals have not been done.{01}

FDA Pregnancy Category C

Breast-feeding

It is not known whether anti-thymocyte globulin (rabbit) distributes into breast milk. Caution should be exercised when it is administered to a nursing woman.{01}

Pediatrics

Appropriate studies on the relationship of age to the effects of anti-thymocyte globulin (rabbit) have not been performed in the pediatric population. Safety and efficacy have not been established.{01}


Geriatrics


No information is available on the relationship of age to the effects of anti-thymocyte globulin (rabbit) in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

» Immunosuppressants    (concurrent use may potentiate the immunosuppressive action of the drugs; dosage may need to be reduced)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Immunoassays, rabbit antibody-based and
Cross-match or panel-reactive antibody cytotoxicity assays    (anti-thymocyte globulin (rabbit) may interfere with the test results)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Previous allergic/anaphylactic reaction to rabbit proteins     (may cause anaphylactic reactions, thrombocytopenia, or neutropenia{01})


Risk-benefit should be considered when the following medical problems exist
» Viral infection, acute    (may severely worsen the infection{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Leukocyte counts, and
» Platelet counts    (recommended during anti-thymocyte globulin (rabbit) treatment)


» Lymphocyte count, total and/or
» T-cell count    (recommended during anti-thymocyte globulin (rabbit) treatment especially upon retreatment)




Side/Adverse Effects

Note: Prolonged use or overdose of thymoglobulin in association with other immunosuppressive agents may cause over-immunosuppression resulting in severe infection, and may increase the incidence of lymphoma or post-transplant lymphoproliferative disease (PTLD) or other malignancies.{01} Thrombocytopenia or neutropenia may result from cross reactive antibodies produced in response to stimulation by anti-thymocyte globulin (rabbit) and is reversible following dosage adjustments.{01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Chills {01}
    
cytomegalovirus infection (chills; cough or hoarseness; fever ; cold; flu-like symptoms){01}
    
fever {01}
    
hyperkalemia (confusion; irregular or slow heartbeat; numbness or tingling around lips hands, or feet; shortness of breath or troubled breathing; tiredness or weakness; unexplained anxiety; weakness or heaviness of legs)
    
hypertension (high blood pressure){01}
    
leukopenia and thrombocytopenia (black, tarry stools; chest pain; chills; cough; fever; painful or difficult urination; shortness of breath; sore throat ; sores, ulcers, or white spots on lips or in mouth; swollen glands; unusual bleeding or bruising; unusual tiredness or weakness)— may be related to overdosage{01}
    
sepsis (chills; fever fast heartbeat){01}
    
urinary tract infection (difficult, burning, or painful urination; frequent urge to urinate; bladder pain; lower back or side pain; cloudy or bloody urine){01}
{01}
Incidents less frequent
    
Gastritis (stomach cramps or pain; nausea; vomiting; bloated feeling or gas; heartburn ; indigestion)
    
herpes simplex infection (burning or stinging of skin ; painful cold sores or blisters on lips, nose, eyes, or genitals){01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal pain {01}
    
asthenia ( loss of strength or energy; muscle pain or weakness; unusual weak feeling){01}
    
diarrhea {01}
    
dizziness {01}
    
dyspnea (shortness of breath; difficult or labored breathing; tightness in chest ; wheezing){01}
    
headache {01}
    
malaise (general feeling of discomfort or illness; unusual tiredness or weakness){01}
    
nausea {01}
    
pain {01}
    
peripheral edema (swelling of ankles, feet, fingers){01}
    
tachycardia (fast or irregular heart beat){01}
{01}
Incidence less frequent
    
Moniliasis, oral (white patches on mouth, tongue, or throat)
{01}




Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and Chronic
    
Leukopenia
    
thrombocytopenia (black, tarry stools; chest pain; chills; cough; fever; painful or difficult urination; shortness of breath; sore throat; sores, ulcers, or white spots on lips or in mouth; swollen glands; unusual bleeding or bruising; unusual tiredness or weakness)


Treatment of overdose


Specific treatment:
The anti-thymocyte globulin (rabbit) dose should be reduced by 50% if the white blood cell (WBC) count is between 2,000 and 3,000 cells/cubic millimeters (mm3) or if the platelet count is between 50,000 and 75,000 cells/mm3. Treatment termination should be considered if the WBC count falls below 2,000 cells/mm 3 or platelet count falls below 50,000 cells/mm 3.{01}

In addition, appropriate prophylactic treatments with antiviral, antibacterial, antiprotozoal, and/or antifungal agents are recommended.{01}



Monitoring:
WBC and platelet counts should be monitored.{01}



Patient Consultation
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:



Carcinogenicity—
Use of anti-thymocyte globulin (rabbit) may be associated with an increased risk of malignancy
Other medications, especially immunosuppressants
Other medical problems, especially previous allergic/anaphylactic reaction to rabbit proteins or acute viral infection.

Precautions while using this medication
Importance of avoiding exposure to colds or infections; checking with physician if feeling onset of cold or other infection

Importance of immediately reporting chest pain, rapid or irregular heartbeat, shortness of breath or wheezing, or swelling of the face or throat, during infusion of medication


Side/adverse effects
Signs of potential side effects, especially chills, cytomegalovirus infection, fever, hyperkalemia, hypertension, leukopenia, thrombocytopenia, sepsis, urinary tract infection, gastritis, and herpes simplex infection


General Dosing Information

For parenteral dosing forms:
Anti-thymocyte globulin (rabbit) should only be used by physicians experienced in immunosuppressive therapy for the treatment of renal transplant patients. Medical monitoring is required during anti-thymocyte globulin (rabbit) infusion.{01}

Anaphylaxis during infusion has been reported in rare instances. {01}

Anti-thymocyte globulin (rabbit) infusion may produce fever and chills, therefore it should be administered intravenously through a high-flow vein. The infusion should be over a minimum of 6 hours for the first dose and over at least 4 hours on subsequent doses through a 0.22 micron in-line filter.{01}

Pretreatment with corticosteroids, acetaminophen, and/or an antihistamine 1 hour before the infusion is recommended to minimize the incidence and intensity of side effects. Slowing the infusion rate also may reduce the incidence and intensity of the reaction.{01}{01}

Antiviral, antibacterial, antiprotozoal, and/or antifungal prophylaxis is recommended.{01}

Anti-thymocyte globulin (rabbit) may stimulate the production of antibodies that crossreact with rabbit immune globulin, lymphocyte count should be monitored to ensure T-cell depletion during retreatment.{01}

For treatment of adverse effects
Recommended treatments for anaphylaxis include termination of infusion, administration of aqueous epinephrine (1:1000) 0.3 to 0.5 mL subcutaneously, and other resuscitative measures including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management as appropriate.{01}


Parenteral Dosage Forms

ANTI-THYMOCYTE GLOBULIN (RABBIT)

Usual Adult Dose
Transplant rejection, kidney
Intravenous, 1.5 milligrams/kilogram (mg/kg) of body weight daily for 7 to 14 days. The first dose should be administered over a minimum of 6 hours and over at least 4 hours on subsequent doses through a high-flow vein.{01} Anti-thymocyte globulin (rabbit) should be administered through an in-line 0.22-micron filter.{01}


Usual Pediatric Dose
Safety and efficacy have not been established.

Usual Geriatric Dose
See Usual adult dose.

Strength(s) usually available
U.S.—


25 mg (Rx) [Thymoglobulin (2 vial set) (diluent contains >5 ml sterile Water for Injection, USP) (glycine 50 mg) ( mannitol 50 mg) (sodium chloride 10 mg)]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). Protect from light. Do not freeze.{01}

Preparation of dosage form:
Anti-thymocyte globulin (rabbit) should be reconstituted by using the diluent provided (sterile Water for Injection, USP) after they reach room temperature. Using aseptic techniques, withdraw and inject 5 ml of the sterile diluent into the lyophilized powder. Rotate vial gently until powder is completely dissolved. Each reconstituted vial contains 25 mg or 5 mg/mL. Transfer the contents of the calculated number of vials into a bag of dextrose or saline infusion solution. Recommended volume is 50 mL per vial used with a total volume usually between 50 and 500 mL. Mix the solution by inverting the bag only once or twice. {01}

Stability:
Reconstituted anti-thymocyte globulin (rabbit) vials of solution should be used within 4 hours if kept at room temperature. Infusion solution of anti-thymocyte globulin (rabbit) should be used immediately. Any unused solution must be discarded.{01}



Developed: 04/20/2000



References
  1. Product Information: Thymoglobulin, anti-thymocyte globulin (rabbit). Sangstat, Menlo Park, CA, (PI revised 1/99) reviewed 3/2000.
  1. Parfitt, K (ed): Martindale, The Complete Drug Reference, 32nd ed. Pharmaceutical Press, London, UK, 1999:p.923.
  1. Bunn D, Lea CK, Bevan DJ et al: The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man. Clin Nephrol 1996; 45:29-32.
  1. Copeland JG, Icenogle TB, Williams RJ et al: Rabbit antithymocyte globulin: a 10-year experience in cardiac transplantation. J Thorac Cardiovasc Surg 1990; 99:852-860.
  1. Martin S, Brenchley PE, O'Donoghue DJ et al: The identification of allo- and auto-lymphocytotoxic antibodies in serum, in the presence of rabbit antithymocyte globulin. Tissue Antigens 1987; 31:26-32.
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