Muromonab-CD3
Muromonab-CD3 (Orthoclone OKT 3)
Muromonab-cd3
(myour-oh- MON-ab)
Pregnancy Category: C Orthoclone OKT 3 (Rx)

Classification: Immunosuppressive agent

Action/Kinetics: A murine monoclonal antibody that is a purified IgG _2a immunoglobulin. Acts to prevent rejection of transplanted kidney tissue by blocking the action of T cells, which play a significant role in acute rejection. Specifically, the CD3 molecule in the membrane of T cells is blocked; this molecule is necessary for signal transduction. Does not cause myelosuppression. Antibodies to muromonab-CD3 have been observed after approximately 20 days. Average serum levels after 3 days: 0.9 mcg/mL. Time to steady-state trough levels: 3 days. Duration: 1 week for return of circulating CD3 positive T cells to pretreatment levels.

Uses: To reverse acute allograft rejection in kidney transplant clients; used in combination with azathioprine, cyclosporine, corticosteroids. Treatment of steroid-resistant acute allograft rejection in cardiac and hepatic transplant clients.

Contraindications: Hypersensitivity to drug (or any product of murine origin), clients with anti-mouse titers greater than or equal to 1:1,000. Clients with fluid overload or uncompensated CHF as confirmed by CXR or more than a 3% weight gain within the week prior to treatment. History of seizures or predisposition to seizures. Use during pregnancy (IgG antibody potentially hazardous to the fetus) and lactation.

Special Concerns: Although used in children, safety and effectiveness have not been assessed. Following the first two to three doses, a cytokine release syndrome due to the release of cytokines by activated lymphocytes or monocytes may occur. Clients at greatest risk for cytokine release syndrome are those with unstable angina, recent MI, symptomatic ischemic heart disease, heart failure, pulmonary edema, COPD, intravascular volume overload or depletion, cerebrovascular disease, advanced symptomatic vascular disease or neuropathy, history of seizures, or septic shock.

Side Effects: Cytokine release syndrome (CRS): Flu-like symptoms, such as pyrexia, chills, dyspnea, N&V;, chest pain, diarrhea, tremor, wheezing, headache, tachycardia, rigor, and hypertension. Rarely, severe, life-threatening shock-like syndrome including serious CV and CNS effects.
Within the first 45 days of therapy for renal transplants: Infections (which may be life-threatening) due to CMV, HSV, Staphylococcus epidermidis, Pneumocystis carinii, Legionella, Cryptococcus, Serratia and other gram-negative bacteria.
Within the first 45 days of therapy for liver transplants: CMV, fungal infections, HSV, Legionella and other severe, life-threatening gram-positive, gram-negative, and viral infections.
Within the first 45 days of therapy for heart transplants: Most commonly herpes simplex, fungal, and CMV infections. Hypersensitivity reactions: Cardiovascular collapse, cardiorespiratory arrest, shock loss of consciousness, hypotension, tachycardia, tingling, angioedema, airway obstruction, bronchospasm dyspnea, urticaria, pruritus. Neuro-psychiatric: Seizures encephalopathy, cerebral edema, aseptic meningitis headaches. CV: Cardiac arrest, shock, heart failure, CV collapse, MI hypotension, angina, tachycardia, bradycardia, hemodynamic instability, hypertension, LV dysfunction, arrhythmias, chest pain or tightness. Respiratory: Respiratory arrest, ARDS, respiratory failure, cardiogenic or noncardiogenic pulmonary edema, apnea dyspnea, bronchospasm wheezing, SOB, hypoxemia, tachypnea, hyperventilation, abnormal chest sounds, pneumonia, pneumonitis. Dermatologic: Rash, urticaria, pruritus, erythema, flushing, diaphoresis, Stevens-Johnson syndrome. GI: N&V;, diarrhea, abdominal pain, bowel infarction, GI hemorrhage. Hematologic: Pancytopenia, aplastic anemia neutropenia, leukopenia, thrombocytopenia, lymphopenia, leukocytosis, lymphadenopathy, arterial and venous thrombosis of allografts and other vascular beds (heart, lung, brain, bowel), disturbances of coagulation. Musculoskeletal: Arthralgia, arthritis, myalgia, stiffness, aches and pain. Hepatic: Hepatomegaly, splenomegaly, hepatitis (usually secondary to viral infection or lymphoma). GU: Anuria, oliguria, delayed graft function, abnormal urinary cytology (including exfoliation of damaged lymphocytes, collecting ducts, and cellular casts). Ophthalmic: Blindness, blurred vision, diplopia, photophobia, conjunctivitis. Otic: Hearing loss, otitis media, tinnitus, vertigo, nasal and ear stuffiness. Body as a whole: Fever, chills, rigors, flu-like syndrome, fatigue, malaise, generalized weakness, anorexia. Miscellaneous: Palsy of cranial nerve VI, increased risk of developing neoplasms.

Laboratory Test Alterations: AST, ALT. Transient and reversible in BUN and serum creatinine.

Overdose Management: Symptoms: Hyperthermia, myalgia, severe chills, diarrhea, vomiting, edema, oliguria, pulmonary edema, acute renal failure. Treatment: Observe client carefully and provide symptomatic and supportive treatment.

Drug Interactions: Azathioprine, corticosteroids, cyclosporine / Psychosis, infections, malignancies, seizures, encephalopathy, and thrombosis when taken with muromonab-CD3 Echinacea / Do not give with muromonab-CD3 Indomethacin / Encephalopathy and other CNS effects

How Supplied: Injection: 1 mg/mL

Dosage
?IV Bolus Reverse acute allograft rejection in kidney transplants.
Adults: 5 mg/day for 10-14 days, beginning treatment once acute renal rejection is diagnosed.
Cardiac/hepatic allograft rejection, steroid-resistant.
5 mg/day for 10-14 days with treatment beginning after determination that corticosteroids will not reverse the rejection.