Thymoglobulin

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • To treat kidney transplant rejection:
    • Adults—1.5 milligrams for every kilogram (2.2 pounds) of your body weight injected into a vein every day for 7 to 14 days.
    • Children—Use and dose must be determined by your doctor.

• Afinitor
• Atgam
• Cytogam
• Gamunex-C
• Gengraf Capsules

• Gengraf Oral Solution
• Hizentra
• Neoral
• Sandimmune
• Zortress

© Thymoglobulin Patient Information is supplied by Cerner Multum, Inc. and Thymoglobulin Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

General

• 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.)

• The manufacturer recommends prophylactic antiviral therapy (e.g., acyclovir, ganciclovir, valganciclovir) during ATG (rabbit) therapy.9 a b m (See Infectious Complications under Cautions.)

Administration

IV Administration

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

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.)

Dosage

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.)

Pediatric Patients

Optimum dosage not established; 1.5–2.5 mg/kg once daily for 5–10 days has been given.4 9 10 m n p q

Adults

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.)

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

Optimum dosage not established; 3.75 mg/kg once daily for 5 days has been given.k

Optimum dosage not established; 3.5 mg/kg once daily for 5 days has been given.7 a l

Special Populations

No special population dosage recommendations at this time.b

A doctor will give you this medicine in a hospital. This medicine is given through a needle placed in one of your veins. The medicine must be injected slowly, so the needle will need to stay in place for 4 to 6 hours.

This medicine is usually given for 4 to 7 days to prevent rejection of the kidney transplant. It is given for 7 to 14 days to treat rejection of the kidney transplant.

You may be given other medicines (eg, acetaminophen, steroids, allergy medicines) at least 1 hour before you receive anti-thymocyte globulin (rabbit) injection to help prevent infusion reactions.

Missed Dose

This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Management of Immunosuppression

To prevent over-immunosuppression, physicians may wish to decrease the dose of the maintenance immunosuppression regimen during the period of Thymoglobulin use.

Dosing for Thymoglobulin is different from dosing for other ATG products, because protein composition and concentrations vary depending on the source of ATG. The prescribing physician must ensure that the dose prescribed is appropriate for the anti-thymocyte globulin (ATG) product being administered.

Immune-Mediated Reactions

Serious immune-mediated reactions, including anaphylaxis or severe cytokine release syndrome (CRS), have been reported with the use of Thymoglobulin [see Warnings and Precautions (5.3)].

Fatal anaphylaxis has been reported. If an anaphylactic reaction occurs, terminate the infusion immediately. Provide emergency treatment, such as 0.3 mL to 0.5 mL aqueous epinephrine (1:1000 dilution) subcutaneously and other resuscitative measures including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated.

Infusion-Associated Reactions

Cases consistent with cytokine release syndrome (CRS) have been reported with rapid infusion rates. CRS is attributed to the release of cytokines by activated monocytes and lymphocytes. Severe acute CRS can cause serious cardiorespiratory events and/or death [see Adverse Reactions (6.2)]. Close compliance with the recommended dosage and infusion time may reduce the incidence and severity of infusion-associated reactions (IARs). Slowing the infusion rate may minimize many of these IARs.

Reactions at the infusion site may include pain, swelling, and redness of the skin.

Hematologic Effects

Low counts of platelets and white blood cells (including low counts of lymphocytes and neutrophils) have been identified and are reversible following dose adjustments. Total white blood cell and platelet counts should be monitored [see Dosage and Administration (2.3)].

Infection

Thymoglobulin is routinely used in combination with other immunosuppressive agents. Infections (bacterial, fungal, viral and protozoal), reactivation of infection (particularly cytomegalovirus [CMV]) and sepsis have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents. These infections can be fatal.

Monitor patients carefully and administer appropriate anti-infective treatment when indicated [see Dosage and Administration (2.4)].

Malignancy

Use of immunosuppressive agents, including Thymoglobulin, may increase the incidence of malignancies, including lymphoma or lymphoproliferative disorders. These events have been associated with fatal outcome [see Adverse Reactions (6.2)].

Immunizations

The safety of immunization with attenuated live vaccines following Thymoglobulin therapy has not been studied; therefore, immunization with attenuated live vaccines is not recommended for patients who have recently received Thymoglobulin.

Laboratory Tests

Thymoglobulin may interfere with rabbit antibody–based immunoassays and with cross-match or panel-reactive antibody cytotoxicity assays. Thymoglobulin has not been shown to interfere with any routine clinical laboratory tests that do not use immunoglobulins.

Pregnancy

Risk Summary

Animal reproduction studies have not been conducted with Thymoglobulin. It is also not known whether Thymoglobulin can cause fetal harm. Thymoglobulin should be given to a pregnant woman only if the benefit outweighs the risk.

Lactation

Risk Summary

Thymoglobulin has not been studied in nursing women. It is not known whether this drug is excreted in human milk. Because other immunoglobulins are excreted in human milk, breastfeeding should be discontinued during Thymoglobulin therapy.

Females and Males of Reproductive Potential

Contraception

Females

There is a lack of information on the risks associated with the administration of Thymoglobulin during pregnancy. Therefore, effective contraception is recommended during and for a minimum of 3 months after treatment.

Pediatric Use

The safety and effectiveness of Thymoglobulin in pediatric patients have not been established in controlled trials. However, based on limited European studies and U.S. compassionate use, the dose, efficacy, and adverse reaction profile are not thought to be different than for adults.

Thymoglobulin® (anti-thymocyte globulin [rabbit]) is a purified, pasteurized, immunoglobulin G, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains cytotoxic antibodies directed against antigens expressed on human T-lymphocytes.

Thymoglobulin is a sterile, lyophilized powder for intravenous administration after reconstitution with sterile Water for Injection, USP (SWFI). Each single-use 10 mL vial contains 25 mg of anti-thymocyte globulin (rabbit), 50 mg glycine, 10 mg sodium chloride, and 50 mg mannitol.

After reconstitution with 5 mL SWFI, each vial of reconstituted product contains approximately 5 mg/mL of Thymoglobulin, of which >90% is rabbit gamma immune globulin (IgG). The reconstituted solution has a pH of 6.5 to 7.2.

Human red blood cells are used in the manufacturing process to deplete cross-reactive antibodies to non–T-cell antigens. The manufacturing process is validated to remove or inactivate potential exogenous viruses. All human red blood cells are from U.S.-registered or FDA-licensed blood banks. A virus removal step (nanofiltration, using a 20 nm filter) and a viral inactivation step (pasteurization, i.e., heat treatment of active ingredient at 60°C/10 hr) are performed for each lot. Each Thymoglobulin lot is released following potency testing (lymphocytotoxicity and E-rosette inhibition assays), and cross-reactive antibody testing (hemagglutination, platelet agglutination, antiglomerular basement membrane antibody, and fibroblast toxicity assays on every lot).