Orthoclone OKT3

muromonab-CD3

Orthoclone OKT3

Pharmacologic class: Murine monoclonal antibody

Therapeutic class: Immunosuppressant

Pregnancy risk category C

FDA Box Warning

• Give under supervision of physician experienced in immunosuppressive therapy and management of solid-organ transplant patients, in facility equipped for cardiopulmonary resuscitation where patient can be monitored closely based on health status.

• Drug may cause anaphylactic and anaphylactoid reactions and occasionally life-threatening or lethal systemic, cardiovascular, and CNS reactions. Monitor patient's fluid status closely before and during therapy. Methylprednisolone pretreatment is recommended to minimize symptoms of cytokine release syndrome.

Action

Binds to and blocks function of T lymphocytes responsible for antigen recognition, thereby reversing graft rejection

Availability

Injection: 1 mg/1 ml in 5-ml ampules

Indications and dosages

Acute allograft rejection in kidney transplant patients; steroid-resistant acute allograft rejection in heart and liver transplant patients

Adults and children weighing more than 30 kg (66 lb): 5 mg/day I.V. for 10 to 14 days

Children weighing 30 kg (66 lb) or less: 2.5 mg/day I.V. for 10 to 14 days

Contraindications

• Hypersensitivity to drug or other murine products
• Uncompensated heart failure
• Uncontrolled hypertension
• Predisposition to or history of seizures
• Antimouse antibody titer of 1:1000 or higher
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• fever
• children younger than age 2.

Administration

• In kidney transplant patients, know that therapy should start as soon as acute kidney rejection is diagnosed. In heart and liver transplant patients, therapy should start when physician determines that steroid therapy hasn't reversed allograft rejection.

Know that drug must be given in facility equipped and staffed to treat cardiopulmonary arrest.
• For I.V. bolus injection, draw solution into syringe through low-protein-binding 0.2- or 0.22-micron filter. Discard filter and attach needle-free adapter.
• Administer bolus over less than 1 minute.
• Give antipyretics to decrease fever and corticosteroids to reduce allergic response, as prescribed.

Adverse reactions

CNS: fatigue, headache, weakness, tremors, hallucinations, aseptic meningitis, cerebral edema, seizures, encephalopathy

CV: chest pain, hypertension, hypotension, heart failure, tachycardia, cardiac arrest, shock

EENT: vision loss, blurred vision, conjunctivitis, photophobia, tinnitus, otitis media

GI: nausea, vomiting, diarrhea

GU: oliguria, anuria

Respiratory: dyspnea, wheezing, severe pulmonary edema, adult respiratory distress syndrome (ARDS)

Skin: flushing

Other: fever, chills, flulike symptoms, infection, anaphylaxis, cytokine release syndrome

Interactions

Drug-drug.Indomethacin: increased muromonab blood level, encephalopathy and other adverse CNS effects

Live-virus vaccines: increased viral replication and effects

Other immunosuppressants: increased risk of infection

Drug-diagnostic tests.Blood urea nitrogen, creatinine: increased levels

Drug-herbs.Astragalus, echinacea, melatonin: interference with immunosuppressant effect

Patient monitoring

• Evaluate vital signs and cardiovascular status. Monitor ECG closely.

Stay alert for signs and symptoms of cytokine release syndrome, including fever up to 41.6 °C (107 °F), chills, rigor, nausea, vomiting, abdominal pain, diarrhea, malaise, joint and muscle pain, headache, and tremors.

Be aware that most adverse reactions occur within 30 minutes to 6 hours of first dose.
• Monitor temperature closely. Stay alert for fever and other signs and symptoms of infection.

Assess neurologic status and respiratory status closely. Evaluate for evidence of aseptic meningitis, encephalopathy, cerebral edema, pulmonary edema, and ARDS.

Patient teaching

• Inform patient that drug can cause serious adverse reactions. Reassure him that he will be monitored closely and will receive interventions to relieve these reactions. Teach him which signs and symptoms to report immediately.
• Reassure patient that adverse reactions will subside as treatment progresses.
• Advise female patient to avoid becoming pregnant or breastfeeding during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

muromonab-CD3

(myoo-roe-moe-nab CD3) ,

Orthoclone OKT3

(trade name)

Classification

Therapeutic: immunosuppressants
Pharmacologic: monoclonal antibodies
Pregnancy Category: C

Indications

Acute renal allograft rejection reactions in transplant patients that have occurred despite conventional antirejection therapy.Acute corticosteroid-resistant hepatic or cardiac allograft rejection reactions.

Action

A purified immunoglobulin antibody that acts as an immunosuppressant by interfering with normal T-cell function.

Therapeutic effects

Reversal of graft rejection in transplant patients.

Pharmacokinetics

Absorption: Administered IV only, resulting in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Eliminated by binding to T lymphocytes.
Half-life: 18 hr.

Time/action profile (noted as levels of circulating CD3-positive T cells)

ROUTEONSETPEAKDURATION
IVmins2–7 days1 wk

Contraindications/Precautions

Contraindicated in: Hypersensitivity to muromonab-CD3, murine (mouse) proteins, or polysorbate;Previous muromonab therapy;Fluid overload;Fever >37.8°C or 100°F;Chickenpox or recent exposure to chickenpox;Herpes zoster.
Use Cautiously in: Active infections;Depressed bone marrow reserve;Chronic debilitating illnesses;HF; Obstetric / Lactation / Pediatric: Pregnancy, lactation, or children <2 yr (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • tremor (most frequent)
  • aseptic meningitis
  • dizziness

Respiratory

  • pulmonary edema (life-threatening)
  • dyspnea (most frequent)
  • shortness of breath (most frequent)
  • wheezing (most frequent)

Cardiovascular

  • chest pain (most frequent)

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Miscellaneous

  • cytokine release syndrome (life-threatening)
  • infections (life-threatening)
  • chills (most frequent)
  • fever (most frequent)
  • hypersensitivity reactions (most frequent)
  • ↑ risk of lymphoma

Interactions

Drug-Drug interaction

Additive immunosuppression with other immunosuppressives.Concurrent prednisone and azathioprine dosages should be ↓ during muromonab therapy (↑ risk of infection and lymphoproliferative disorders).Cyclosporine should be ↓ or discontinued during muromonab-CD3 therapy (↑ risk of infection and lymphoproliferative disorders).↑ risk of adverse CNS reactions with indomethacin.May ↓ antibody response to and ↑ risk of adverse reactions from live-virus vaccines.Concomitant use with astragalus, echinacea, and melatonin may interfere with immunosuppression.

Route/Dosage

Intravenous (Adults) 5 mg/day for 10–14 days (pretreatment with corticosteroids, acetaminophen, and/or antihistamines recommended).
Intravenous (Children) 0.1 mg (100 mcg)/kg/day for 10–14 days.

Availability

Solution for injection: 1 mg/mL

Nursing implications

Nursing assessment

  • Assess for fluid overload (monitor weight and intake and output, assess for edema and rales/crackles). Notify health care professional if patient has experienced 3% or more weight gain in the previous week. Chest x-ray examination should be obtained within 24 hr before beginning therapy. Fluid-overloaded patients are at high risk of developing pulmonary edema. Monitor vital signs and breath sounds closely.
  • Assess for cytokine release syndrome (CRS), usually manifested by high fever and chills, headache, tremor, nausea and vomiting, chest pain, muscle and joint pain, generalized weakness, shortness of breath, dizziness, abdominal pain, malaise, diarrhea, and trembling of hands, but may occasionally cause a severe, life-threatening, shock-like reaction. The severity of this reaction is greatest with initial dose. Reaction occurs within 30–48 hr and may persist for up to 6 hr. Acetaminophen and antihistamines may be used to treat early reactions. Patient temperature should be maintained below 37.8°C (100°F) at administration of each dose. Manifestations of CRS may be prevented or minimized by pretreatment with methylprednisolone sodium succinate 8 mg/kg IV given 1–4 hr before 1st dose of muromonab-CD3. Hydrocortisone 100 mg IV may also be given 30 min after the 1st and possibly 2nd dose to control respiratory side effects. Serious symptoms of CRS may require oxygen, IV fluids, corticosteroids, vasopressors, antihistamines, and intubation.
  • Monitor for signs of anaphylactic or hypersensitivity reactions at each dose. Resuscitation equipment should be readily available.
  • Monitor for infection (fever, chills, rash, sore throat, purulent discharge, dysuria). Notify physician immediately if these symptoms occur; may necessitate discontinuation of therapy.
  • Monitor for development of aseptic meningitis. Onset is usually within 3 days of beginning therapy. Assess for fever, headache, nuchal rigidity, and photophobia.
  • Lab Test Considerations: Monitor CBC with differential and platelet count before and periodically throughout therapy.
    • Monitor assays of T cells (CD3, CD4, CD8); target CD3 is <25 cells/mm3 or plasma levels as determined by ELISA daily; target levels should be ≥800 ng/mL.
    • Monitor BUN, serum creatinine, and hepatic enzymes (AST, ALT, alkaline phosphatase, bilirubin), especially during the first 1–3 days of therapy. May cause transient ↑.

Potential Nursing Diagnoses

Risk for infection (Side Effects)
Excess fluid volume (Side Effects)

Implementation

  • Physician will reduce dose of corticosteroids and azathioprine and discontinue cyclosporine during 10–14-day course of muromonab-CD3. Cyclosporine may be resumed 3 days before end of therapy.
    • Initial dose is administered during hospitalization; patient should be monitored closely for 48 hr. Subsequent doses may be administered on outpatient basis.
    • Keep medication refrigerated at 2–8°C. Do not shake vial. Solution may contain a few fine translucent particles that do not affect potency. Discard unused portion.
  • Intravenous Administration
  • pH: 6.5–7.5.
  • Draw solution into syringe via low-protein-binding 0.2- or 0.22-micrometer filter to ensure removal of translucent protein particles that may be present. Discard filter and attach 20-gauge needle for IV administration.
  • Concentration: 1 mg/mL (undiluted).
  • Rate: Administer IV push over <1 min. Do not administer as an infusion.
  • Y-Site Incompatibility: Do not admix; do not administer in IV line containing other medications. If line must be used for other medications, flush with 0.9% NaCl before and after muromonab-CD3.

Patient/Family Teaching

  • Explain purpose of medication to patient. Inform patient of possible initial-dose side effects, which are markedly reduced in subsequent doses. Explain that patient will need to resume lifelong therapy with other immunosuppressive drugs after completion of muromonab-CD3 course.
  • Inform patient of potential for CRS. Describe reportable symptoms.
  • Instruct patient to continue to avoid crowds and persons with known infections, as this drug also suppresses the immune system.
  • Advise patient to notify health care professional at first sign of rash, urticaria, tachycardia, dyspnea, or difficulty swallowing.
  • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response is known.
  • Instruct patient not to receive any vaccinations and to avoid contact with persons receiving oral polio vaccine without advice of health care professional.

Evaluation/Desired Outcomes

  • Reversal of the symptoms of acute organ rejection.

Orthoclone OKT3

a trademark for an immunosuppressant drug (muromonab-Cd3).
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