Atgam

lymphocyte immune globulin (antithymocyte globulin equine, ATG, ATG equine, LIG)

Atgam

Pharmacologic class: Immunoglobulin

Therapeutic class: Immunosuppressant

Pregnancy risk category C

FDA Box Warning

• Give drug under supervision of physician experienced in immunosuppressive therapy for treatment of renal transplant or asplastic anemia patients, in facility with adequate laboratory and supportive resources

Action

Unknown. Thought to inhibit cell-mediated immune response by altering function of or eliminating T lymphocytes in circulation.

Availability

Injection: 50 mg/ml in 5-ml ampules

Indications and dosages

To prevent acute renal allograft rejection

Adults and children: 15 mg/kg/day I.V. for 14 days, then switch to alternate-day dosing for 14 days (for a total of 21 doses in 28 days). Give first dose within 24 hours of transplantation.

Acute renal allograft rejection

Adults and children: 10 to 15 mg/kg/day I.V. for 14 days, then may switch to alternate-day dosing for 14 days (for a total of 21 doses in 28 days). Start therapy at first sign of rejection.

Aplastic anemia in patients ineligible for bone marrow transplantation

Adults and children: 10 to 20 mg/kg/day I.V. for 8 to 14 days; then may give additional alternate-day doses for a total of up to 21 doses in 28 days

Off-label uses

• Bone marrow, liver, and heart transplantation
• Multiple sclerosis
• Myasthenia gravis
• Scleroderma

Contraindications

• History of severe systemic reaction to lymphocyte immune globulin or other equine preparation

Precautions

Use cautiously in:
• severe renal or hepatic disease
• pregnant or breastfeeding patients
• children.

Administration

Know that drug should be given only by health care professionals experienced in immunosuppressive therapy for treating aplastic anemia or renal transplant patients, in facilities equipped and staffed with adequate laboratory and supportive resources.

Because of high risk of anaphylaxis, perform intradermal skin test before first dose. Inject 0.1-ml dose of 1:1,000 dilution of LIG intradermally; a control test using 0.9% sodium chloride injection is injected contralaterally. Observe site every 15 to 20 minutes during first hour after injection, and monitor patient for systemic manifestations. Local reaction of 10 mm or greater with wheal, erythema, or both (with or without pseudopod formation and itching or marked local swelling) indicates positive test (which warrants consideration of alternate therapy). Systemic reaction (such as tachycardia, dyspnea, hypotension, or anaphylaxis) precludes LIG therapy.
• Premedicate with antipyretic, antihistamine, or corticosteroid, as prescribed, to minimize reactions.
• For I.V. infusion, dilute prescribed dose in 250 to 1,000 ml of 0.45% or 0.9% sodium chloride injection. (Don't dilute in dextrose solutions or highly acidic solutions.) Final concentration shouldn't exceed 4 mg/ml. Infuse total daily dose over at least 4 hours.
• When adding drug to infusion container, invert container so air doesn't enter. Gently swirl or rotate container to mix solution.
• Using in-line filter with pore size of 0.2 to 1 micron, infuse into central vein, shunt, or arteriovenous fistula over at least 4 hours.
• Be aware that drug is usually given concurrently with azathioprine and corticosteroids when used for allograft rejection.

Adverse reactions

CNS: malaise, agitation, headache, dizziness, weakness, syncope, encephalitis, seizures

CV: hypotension, hypertension, chest pain, bradycardia, tachycardia, cardiac irregularities, phlebitis, myocarditis, thrombophlebitis, heart failure

EENT: periorbital edema

GI: nausea, vomiting, diarrhea, stomatitis

Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia

Hepatic: hepatosplenomegaly

Metabolic: hyperglycemia

Musculoskeletal: joint pain or stiffness, myalgia, back pain

Respiratory: dyspnea, pleural effusion

Skin: rash, pruritus, urticaria, diaphoresis, night sweats

Other: burning soles and palms, fever, chills, pain at infusion site, edema, lymphadenopathy, hypersensitivity reactions including serum sickness and anaphylaxis

Interactions

Drug-diagnostic tests.Creatinine, glucose, hepatic enzymes: increased values

Hemoglobin, platelets, white blood cells: decreased values

Kidney and liver function tests: abnormal results

Patient monitoring

During infusion, watch for signs and symptoms of hypersensitivity reaction, such as rash, respiratory distress, or chest, flank, or back pain. Be aware that this reaction may occur even with a negative skin test.

Discontinue drug if renal transplant patient develops signs or symptoms of anaphylaxis or severe thrombocytopenia or leukopenia.
• Be aware that product derives from equine and human blood components and may transmit infections.
• Monitor for signs and symptoms of infection, such as fever, malaise, and sore throat (caused by immunosuppression).

Patient teaching

Tell patient to immediately report adverse reactions during infusion (such as pain at infusion site) as well as systemic complaints (such as easy bruising or bleeding or signs of hypersensitivity reaction).
• Instruct patient to avoid sources of infection, such as people with known infections. Tell him to promptly report signs or symptoms of infection.

Advise patient to immediately report evidence of serum sickness, including fever, joint pain, nausea, vomiting, lymphadenopathy, and rash.

Caution female patient not to take drug if she is pregnant.
• Tell female patient to inform prescriber if she is breastfeeding.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests mentioned above.

lymphocyte immune globulin

(lim-foe-site im-myoon glo-byoo-lin) ,

ATG

(trade name),

antilymphocyte globulin

(trade name),

Atgam

(trade name),

LIG

(trade name)

Classification

Therapeutic: immunosuppressants
Pharmacologic: immune globulins
Pregnancy Category: C

Indications

Management of allograft rejection in renal transplant patients.Treatment of aplastic anemia in patients who are not candidates for bone marrow transplantation.

Action

Decreases the circulating number of T lymphocytes, which are involved in both cell-mediated and humoral immunity.

Therapeutic effects

Resolution of rejection of renal allografts.
Remission of aplastic anemia.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: 5.7 days.

Time/action profile (decreased circulating T lymphocytes)

ROUTEONSETPEAKDURATION
IVrapidunknownunknown

Contraindications/Precautions

Contraindicated in: History of hypersensitivity during previous courses of therapy or systemic reaction to skin testing; Hypersensitivity to thimerosal; Hypersensitivity to equine gamma globulin preparations.
Use Cautiously in: Obstetric / Lactation: Pregnancy or lactation (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • headache

Respiratory

  • dyspnea

Cardiovascular

  • chest pain
  • hypotension

Gastrointestinal

  • diarrhea
  • nausea
  • stomatitis
  • vomiting

Dermatologic

  • dermatologic reactions (most frequent)
  • erythema
  • itching

Hematologic

  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)
  • anemia
  • hemolysis

Local

  • pain/phlebitis at IV site

Musculoskeletal

  • arthralgia

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • chills (most frequent)
  • fever (most frequent)
  • serum sickness–like reactions (most frequent)
  • clotted AV fistula
  • night sweats

Interactions

Drug-Drug interaction

Concurrent use of corticosteroids and immunosuppressants may mask some adverse reactions.

Route/Dosage

Skin Test
Intradermal (Adults) 0.1 mL of 1:1000 dilution (5 mcg of horse serum).
Renal Allograft Recipients
Intravenous (Adults) 10–30 mg/kg/day for 14 days, then every other day for 14 days.
Intravenous (Children) 5–25 mg/kg/day for 14 days, then every other day for 14 days.
Aplastic Anemia
Intravenous (Adults) 10–20 mg/kg/day for 8–14 days, then every other day for 21 doses total.

Availability

Injection: 50 mg/mL

Nursing implications

Nursing assessment

  • Assess patient for hypersensitivity reaction (respiratory distress; hypotension; pain in chest, flank, or back) continuously throughout administration. Keep epinephrine, antihistamines, corticosteroids, syringes, and an airway at bedside at all times. If a reaction occurs, stop infusion immediately; administer 0.3 mL aqueous epinephrine 1:1000 IM. Administer corticosteroids and resuscitative measures as needed. Do not resume therapy.
  • Monitor vital signs frequently throughout administration. Medication frequently causes chills, fever, itching, and erythema. Prophylactic administration of antihistamines and corticosteroids usually controls these symptoms.
  • Lab Test Considerations: Monitor CBC and platelets throughout therapy. May cause leukopenia and thrombocytopenia. Thrombocytopenia is usually transient and does not normally require discontinuation of therapy or transfusion.
    • May also cause hemolysis. Treatment includes transfusion of erythrocytes and administration of mannitol, furosemide, sodium bicarbonate, and fluids, if necessary.

Potential Nursing Diagnoses

Risk for infection (Indications,  Side Effects)

Implementation

  • Medication should be used only by physicians experienced in immunosuppressive therapy and management of renal transplant patients and should be administered only in facilities equipped and staffed with adequate laboratory and medical resources.
    • Patients with aplastic anemia may need a transfusion of platelets before administration to maintain platelets at a clinically acceptable level.
  • Test Dose: Administer an intradermal injection of 0.1 mL of a 1:1000 dilution in 0.9% NaCl and a 0.9% NaCl control. If a wheal or erythema >10 mm forms with or without a pseudopod and itching or a marked local swelling occurs, administer infusion with caution. If a systemic reaction (generalized rash, tachycardia, dyspnea, hypotension, anaphylaxis) occurs, do not administer infusion. Allergic reactions may occur in patients with a negative reaction to test dose.
  • Intravenous Administration
  • Intermittent Infusion: Diluent: Dilute total daily dose in 0.45% NaCl or 0.9% NaCl. Concentration: Not to exceed 1 mg/mL. Invert IV saline bottle so that undiluted drug does not come in contact with the air inside. May be infused through an in-line filter with a pore size of 0.2–1 micron. Refrigerate diluted solution if prepared before administration. Do not freeze; discard if frozen. Stable for 24 hr, including infusion time, if refrigerated.
    • Administer through large veins to minimize phlebitis and thrombosis.
  • Rate: Administer over at least 4 hr.

Patient/Family Teaching

  • Explain the purpose of the medication to the patient.
  • Instruct patient to notify health care professional promptly if fever; chills; cough; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; numbness, tingling, or burning pain in hands, arms, legs, feet, or lips; increased fatigue; confusion; dizziness; weakness; dyspnea; tachycardia; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
  • Instruct patient to notify health care professional immediately if signs of hypersensitivity reaction (itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
  • Advise patient to the importance of follow up lab tests.

Evaluation/Desired Outcomes

  • Prevention or management of allograft rejection in renal transplant patients.
  • Treatment of moderate to severe aplastic anemia.

Atgam®

Antithymocyte globulin, see there.
References in periodicals archive ?
In this trial, conducted at 28 leading transplant centers in the US, Thymoglobulin was compared to Atgam (Pharmacia & Upjohn, Inc.
Tenders are invited for Repairs To Staff Quaters At Dungri, Kalwada, And Atgam Section Irrigation Colony
Immune therapy using biologic antibodies was pioneered in Michigan with the introduction of Atgam, the first antibody drug approved by the FDA.
Tenders are invited for Renovation To Canal Structure On Dharasana Distributory Chainage 0 Mt To 3000 Mt ( Village : Atgam )
A comparison clinical study of two aplastic anemia treatments found that ATGAM, currently the only licensed aplastic anemia drug in the United States, improved blood cell counts and survival significantly more than Thymoglobulin, a similar but reportedly more potent treatment.
The companies said that Phase II/III study results indicate ABX-CBL demonstrated a survival rate of 180 days in patients with acute steroid-resistant GVHD that was similar to Atgam (anti-thymocyte globulin, equine, the study's control arm, which is produced by Pharmacia Corporation, Peapack, NJ.
5% for patients treated with Atgam [Immune globulin, Anti-thymocyte Globulin].
The 1996 Double Blinded Randomized Multicenter Phase III Clinical Trial of Thymoglobulin Vs Atgam in the Treatment of Acute Graft Rejection Following Renal Transplantation; A.
Lowering Laying And Jointing Pvc Pipeline, Readymade One Tap Stand Post, Installation Of Pumping Machienary And Operation & Maintatenaces At Atgam ( Gamtal Dist.
Roy First, MD, Professor of Medicine, University of Cincinnati, a past president of the American Society of Transplant Physicians and a principal investigator in this trial said, "the fact that we could show that THYMOGLOBULIN was significantly more successful in reversing acute rejection than ATGAM, a widely used drug in the U.