Atgam

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; chest pain, back pain; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

• fast heartbeat, trouble breathing;
• a light-headed feeling, like you might pass out;
• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin, coughing up blood or vomit that looks like coffee grounds;
• seizure (convulsions); or
• low white blood cell counts--fever, swollen glands, skin sores, rash or itching, muscle or joint pain, feeling very weak or tired.

Common side effects may include:

• fever, chills, night sweats, or other signs of infection;
• blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
• nausea, vomiting, diarrhea;
• pain where the medicine was injected;
• red or itching skin;
• abnormal liver or kidney function tests;
• dizziness, headache, confusion; or
• redness, swelling, warmth, irritation, or tenderness in the veins of your arms or legs.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Do not receive a "live" vaccine for at least 6 months after your last dose of lymphocyte immune globulin. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Other drugs may interact with lymphocyte immune globulin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Before you are treated with lymphocyte immune globulin, your doctor may perform a skin test to make sure you are not allergic to lymphocyte immune globulin.

Lymphocyte immune globulin is injected into a vein through an IV. A healthcare provider will give you this injection.

Lymphocyte immune globulin is sometimes given daily and sometimes given every other day. The medicine is injected slowly, and can take at least 4 hours to complete.

You may be given other medicines to suppress your immune system while you are receiving lymphocyte immune globulin. Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

While using lymphocyte immune globulin, you may need frequent blood tests.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Because you will receive lymphocyte immune globulin in a clinical setting, you are not likely to miss a dose.

Lymphocyte immune globulin, antithymocyte globulin (equine) (ATG [equine]); equine-derived polyclonal antibody preparation; immunosuppressive agent.7 17 18 19 20 21 22 23 24 25 26 27 28 30 31 32 33 34 35 51 52 53 54 55 83 a b c

Absorption

Onset

Immediate reduction in rosette-forming cell (RFC) levels in peripheral blood occurs following IV administration of ATG (equine); time for RFCs to recover to normal levels after drug discontinuance depends on the patient’s catabolic rate and, in some patients, duration of therapy.2 a

Plasma Concentrations

Peak plasma levels of equine IgG vary following IV administration of ATG (equine) depending on the patient’s ability to catabolize foreign IgG.2 a Mean peak plasma concentrations of equine IgG averaged 727 ± 310 mcg/mL after IV infusion of ATG (equine) 10 mg/kg daily for 5 days.2 a

Distribution

Extent

Not fully characterized.2 87 a b

ATG (equine) is likely to be poorly distributed into lymphoid tissues (e.g., spleen, lymph nodes), since antilymphocyte serum poorly distributes into these tissues.3 6 9 a

In vitro, ATG (equine) binds to essentially all circulating lymphocytes, granulocytes, and platelets; bone marrow cells; visceral tissues, including thymus and testis cell membranes, and to nuclear and cytoplasmic components of tonsil, kidney, breast, liver, lung, intestine, and testes (including Leydig cells).87 a

Not known whether ATG (equine) crosses placenta, but placental distribution likely since other immunoglobulins cross placenta;15 a virtually all transplacental passage of immunoglobulins occurs during the last 4 weeks of pregnancy.15 a

Not known whether ATG (equine) distributes into human milk; however, may be distributed into milk since other immunoglobulins (e.g., IgA, IgM, IgG) are present in colostrum.16 a b

Elimination

Elimination Route

Approximately 1% excreted in urine, principally as unchanged equine IgG.2 a

Half-life

Plasma half-life averages about 6 days (1.5–12 days).2 a b

• Equine-derived polyclonal antibody immunosuppressive agent. 7 10 17 18 19 20 21 22 23 24 25 26 27 28 30 31 32 33 34 35 51 52 53 54 55 83 a b c

• Exact mechanism of immunosuppressive action not fully elucidated; appears to involve clearance of peripheral antigen-reactive T lymphocytes (T cells) and/or alteration of T-cell function.2 3 4 5 6 8 9 14 a b

  Exact mechanism of hematologic effects variable, complex, and not fully elucidated.48 49 89 90 a In vitro studies indicate ATG (equine) essentially binds to all circulating lymphocytes (both T and B cells),58 87 a granulocytes,87 a and platelets.87 a May produce leukopenia,2 7 19 32 35 a b thrombocytopenia,2 7 17 19 23 33 35 a b and/or hemolysis.2 a b Also produces a hematopoietic response in some patients with aplastic anemia.36 37 38 39 40 41 42 91 107 108 a

  Appears to have some antineoplastic activity against malignant lymphomas.57 58 59 60 a

• Importance of informing patients about the potential benefits of ATG (equine) and attendant risks of immunosuppressive therapy.b

• Risk of decreased number of WBCs (including lymphocytes), which could increase risk of infection; less commonly, anemia and hemolysis also may occur.a b Necessity of administration under supervision of a clinician with careful monitoring for signs of reduced WBC and platelet counts.a b Importance of informing clinicians promptly if any signs or symptoms of infection occur.a b

• Advise patient of risk of possible fever, chills, allergic reactions, malaise, arthralgia, nausea and vomiting, lymphadenopathy, and/or rash during or following ATG (equine) infusion and that medication will be given to help control these reactions.a 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.)

• It is used to keep the body from turning down the kidney after a kidney transplant.
• It is used to treat aplastic anemia.
• It may be given to you for other reasons. Talk with the doctor.

Hypersensitivity

Serious immune-mediated reactions have been reported with the use of Atgam. Clinical signs associated with anaphylaxis, other infusion associated reactions, and serum sickness have been reported.

Discontinue Atgam if anaphylaxis occurs. A systemic reaction such as a generalized rash, tachycardia, dyspnea, hypotension, or anaphylaxis precludes any additional administration of Atgam.

Skin Testing

To identify those at greatest risk of systemic anaphylaxis, skin testing potential recipients is strongly recommended before commencing treatment. A conservative, conventional approach would first employ epicutaneous (prick) testing with undiluted Atgam. If the subject does not show a wheal ten minutes after pricking, proceed to intradermal testing with 0.02 mL of a 1:1000 v/v (volume/volume) saline dilution of Atgam with a separate saline control injection of similar volume. Read the result at 10 minutes: a wheal at the Atgam site 3 or more mm larger in diameter than that at the saline control site (or a positive prick test) suggests clinical sensitivity and an increased possibility of a systemic allergic reaction should the drug be dosed intravenously.

The predictive value of this test has not been proven clinically. Allergic reactions such as anaphylaxis have occurred in patients whose skin test is negative. Also, skin testing done as described above will not predict for later development of serum sickness. In the presence of a locally positive skin test to Atgam, serious consideration to alternative forms of therapy should be given. The risk to benefit ratio must be weighed. If therapy with Atgam is deemed appropriate following a locally positive skin test, treatment should be administered in a setting where intensive life support facilities are immediately available and a physician familiar with the treatment of potentially life threatening allergic reactions is in attendance.

Transmissible Infectious Agents

Because Atgam is made from equine and human blood components, it may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

No cases of transmission of viral diseases or CJD have been associated with the use of Atgam.

All infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Pfizer, Inc. at 1-800-438-1985.

Monitor patients for concurrent infection. Some studies have suggested an increase in the incidence of cytomegalovirus infection in patients receiving Atgam.

Immunizations

Do not administer live vaccines to patients about to receive, receiving, or after treatment with Atgam. Concomitant administration of Atgam with live virus vaccines carries a potential of uncontrolled viral replication in the immunosuppressed patient. There is insufficient information to fully define the extent of the risk, or the period of time during which the risk exists. If administered, live viruses may interfere with Atgam treatment.

Hepatic and Renal Function Tests

In patients with aplastic anemia and other hematologic abnormalities who have received Atgam, abnormal tests of liver function (SGOT, SGPT, alkaline phosphatase) and renal function (serum creatinine) have been observed.

Pregnancy

Atgam was not teratogenic in rats or monkeys at a dose up to 20 mg/kg. However, 20 mg/kg/day Atgam for 16 days during organogenesis in cynomolgus monkeys was fetotoxic. No fetal or maternal toxicity was seen with 10 mg/kg/day Atgam administered for 16 days during organogenesis [see Nonclinical Toxicology (13.1)].

There are no adequate and well-controlled studies in pregnant women. It is also not known whether Atgam can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Atgam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

In animal studies, a single dose of Atgam up to 40 mg/kg was not detected at the limit of quantification in the milk of lactating cynomolgus monkeys. It is not known whether Atgam is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing neonates and infants from Atgam, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

Experience with children has been limited. Atgam has been administered safely to a small number of pediatric renal allograft recipients and pediatric aplastic anemia patients at dosage levels comparable to those in adults.

Geriatric Use

Clinical experience in a limited number of elderly patients (≥65 years of age) has not identified differences in responses between the elderly and younger patients. The dose for an elderly patient should be selected with caution, starting at the low end of the dosage range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this age group.