Antithymocyte Globulin (Rabbit)
Class: Immunosuppressive Agents
ATC Class: L04AA04
VA Class: IM600
Should be used only by clinicians experienced in immunosuppressive therapy for the management of renal transplant patients.b
Uses for Antithymocyte Globulin (Rabbit)
Myelodysplastic Syndrome and Aplastic Anemia
Antithymocyte Globulin (Rabbit) Dosage and Administration
To reduce the incidence and intensity of infusion-related adverse effects, the manufacturer and some clinicians recommend premedication with corticosteroids, acetaminophen, and/or an antihistamine (e.g., diphenhydramine) 1 hour prior to each infusion.2 9 a b q u (See Infusion-related Effects under Cautions.)
For drug compatibility information, see Compatibility under Stability.
ATG (rabbit) is administered by IV infusion.1 a b g The manufacturer states that ATG (rabbit) should be infused through an inline 0.22-μm filter into a high-flow vein.a b g Has also been administered via a peripheral vein† in some patients, but safety not fully established and may increase risk of thrombophlebitis and DVT.g h i
Administer in conjunction with other immunosuppressive agents.b
Allow vial to reach room temperature before reconstituting.a b Reconstitute vial containing 25 mg of the drug with 5 mL of sterile water for injection to provide a solution containing 5 mg/mL.a b Gently rotate vial until powder is completely dissolved.a b Use reconstituted solution immediately.b (See Storage under Stability.)
Dilute appropriate dosage of reconstituted ATG (rabbit) in 0.9% sodium chloride or 5% dextrose injection.a b Each reconstituted vial should be diluted in 50 mL of infusion solution; total volume of infusion solution required generally is 50–500 mL.a b Recommended final concentration approximately 0.5 mg/mL.9 a Mix diluted solution by gently inverting infusion bag only once or twice.a b
Rate of Administration
Administer initial dose over ≥6 hours and subsequent doses over ≥4 hours.b g Slowing infusion rate may help prevent or ameliorate acute infusion reactions.9 a b (See Infusion-related Effects under Cautions.)
Appropriate dosage for Thymoglobulin differs from dosages for other antithymocyte globulin (ATG) preparations since protein composition and concentrations vary depending on source of ATG used.b Exercise care to ensure prescribed dose is appropriate for the ATG preparation being administered.b
Reduce ATG (rabbit) dosage by 50% if WBC is ≥2000 but ≤3000/mm3 or platelet count is ≥50,000 but ≤75,000/m3.b Consider drug discontinuance if WBC <2000/mm3 or platelet count <50,000/mm3.b (See Hematologic Effects and Clinical/Laboratory Monitoring under Cautions.)
Prevention of Renal Allograft Rejection (Induction Therapy)†IV Infusion
Treatment of Allograft RejectionIV Infusion
1.5 mg/kg once daily for 7–14 days.2 a b r Usually continue other immunosuppressive agents used for treatment of acute renal transplant rejection (e.g., azathioprine, corticosteroids, cyclosporine) during therapy.2 a b r (See Interactions.)
Prevention of Renal Allograft Rejection (Induction Therapy)†IV Infusion
Optimum dosage not established; 1.5 mg/kg once daily for 5–14 days or 3 mg/kg once daily on day 1 then 1.5 mg/kg once daily on days 2 and 3 has been given.5 9 g r u Intermittent dosage regimens based on CD3+ lymphocyte countsw and regimens in which the first dose is administered intraoperatively also have been given.5 r s u
Myelodysplastic Syndrome†IV Infusion
Optimum dosage not established; 3.75 mg/kg once daily for 5 days has been given.k
Aplastic Anemia†IV Infusion
No special population dosage recommendations at this time.b
Cautions for Antithymocyte Globulin (Rabbit)
Active or acute infections that contraindicate any additional immunosuppression.b
See Boxed Warning.
Cytokine Release Syndrome
Possible increased risk of infections (bacterial, fungal, viral, and protozoal), reactivation of infections (particularly cytomegalovirus [CMV]), and sepsis when ATG (rabbit) is used in combination with multiple immunosuppressive agents.2 5 b m n r u Severe, acute infections may be fatal.b The manufacturer recommends careful patient monitoring and appropriate anti-infective prophylaxis.b
If anaphylaxis or other severe hypersensitivity reaction occurs, discontinue ATG (rabbit) infusion immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, IV fluids, antihistamines, maintenance of BP).a b
Patients with a history of anaphylaxis to ATG (rabbit) should not receive the drug again.b
Hematologic Effects and Clinical/Laboratory Monitoring
Thrombocytopenia and/or leukopenia (including lymphopenia and neutropenia) commonly reported.2 5 a b g r u Monitor WBC and platelet count; reduce dosage and/or consider drug discontinuance in patients who develop leukopenia and/or thrombocytopenia.b (See Dosage under Dosage and Administration.)
Anti-rabbit antibodies developed in 68% of renal transplant patients who received ATG (rabbit) for 7–14 days for treatment of acute rejection; these antibodies were still present in 24% of patients at 90 days.6 a b Presence of anti-rabbit antibodies not correlated with treatment success or failure in these patients;6 a possible effects of these antibodies on drug’s efficacy during subsequent use not evaluated.b
Risk of infusion-related effects (e.g., fever, chills and/or rigors, dyspnea, nausea and/or vomiting, diarrhea, hypotension or hypertension, malaise, rash, and/or headache); may occur as soon as first or second infusion during a single course of treatment.a b
May minimize or prevent infusion-related effects by administering initial ATG (rabbit) infusions over ≥6 hours, administering a pretreatment regimen (corticosteroid, acetaminophen, and/or an antihistamine) 1 hour prior to each ATG (rabbit) infusion, and/or slowing the infusion rate.2 9 a b q u (See General and see Administration under Dosage and Administration.)
Safety of attenuated live vaccine administration following ATG (rabbit) therapy not established.b Manufacturer states that immunization with attenuated live vaccines not recommended in patients who recently received the drug.b
Laboratory Test Interference
The manufacturer states that safety and efficacy not established in children <18 years of age in controlled trials.a 9 b However, ATG (rabbit) has been used as induction therapy in conjunction with maintenance immunosuppressive therapy to prevent renal or hepatic allograft rejection† in pediatric patients 5 months–18 years of age.4 9 10 a m n o p q t (See Hepatic Allotransplantation under Uses.)
Common Adverse Effects
Infectious complications (including sepsis, urinary tract infections, and CMV infections),5 a b n r u fever,b chills,b leukopenia,5 b u lymphopenia,5 d g r thrombocytopenia,b g u cytokine release syndrome,g abdominal pain,b nausea,b diarrhea,b asthenia,b dyspnea,b headache,b pain,b hyperkalemia,b hypertension,b peripheral edema,b tachycardia,b dizziness,b infusion site pain/swelling/erythema.b
Interactions for Antithymocyte Globulin (Rabbit)
No formal drug interaction studies to date.b
No increase in adverse effectsf
Safety data not available on the effects of immunization with live vaccines during ATG (rabbit) therapyb
Avoid use of live vaccines in patients who have recently received ATG (rabbit)b
Antithymocyte Globulin (Rabbit) Pharmacokinetics
Average 21.5 and 87 mcg/mL 4–8 hours post-infusion after first and last IV doses, respectively, when given for 7–11 days.b
Powder for Injection
Although reconstituted solutions are stable at room temperature for up to 24 hours, room temperature storage is not recommended by the manufacturer since the preparation contains no preservatives; use immediately.b
Use diluted solutions immediately.b
Discard any unused drug after infusion.b
For information on systemic interactions resulting from concomitant use, see Interactions.
Heparin sodium with hydrocortisone sodium succinate
Hydrocortisone sodium succinate
Exact mechanism of immunosuppressive action not fully elucidated; appears to involve clearance of peripheral antigen-reactive T lymphocytes (T cells) and modulation of T-cell activation, homing, and cytotoxicity.8 a b g
Not effective for treating antibody-mediated (humoral) transplant rejections.b
Advice to Patients
Importance of informing patients about the potential benefits of ATG (rabbit) and attendant risks of immunosuppressive therapy.b
Potential for reduction of lymphocyte counts, which could increase risk of infection or malignancy.b Importance of informing clinicians promptly if any signs or symptoms of infection or malignancy occur.b
Advise patient of risk of possible fever, chills, itching, and/or rash during ATG (rabbit) infusion and that medication will be given to help control these reactions.b
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal or nutritional supplements, as well as any concomitant illnesses.b
Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.b
Importance of informing patients of other important precautionary information.b (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
For injection, for IV infusion
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions July 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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