- Injection 5 mg per 5 mL
Blocks T-cell function, which plays major role in graft rejection, by reacting with and blocking T3 (CD3) molecule on membrane of human T cells associated with antigen recognition. Serum levels are measured with an enzyme-linked immunosorbent assay (ELISA).
Time to steady-state trough levels is 3 days and C min is 0.9 mcg/mL with 5 mg/day (steady-state).
Onset within minutes.
Duration is approximately 1 wk.
Indications and Usage
Treatment of renal, steroid resistant cardiac, or hepatic allograft rejection.
Hypersensitivity to any product of murine origin; anti-mouse antibody titers at least 1:1,000; fluid overload or uncompensated heart failure; seizures or predisposition to seizures; pregnancy; breastfeeding; uncontrolled hypertension.
Dosage and AdministrationAdults
IV 5 mg/day as bolus given over less than 1 min for 10 to 14 days.Pediatric
IV 2.5 mg/day in patients weighing 30 kg or less, and 5 mg/day in patients over 30 kg. As a single bolus given over less than 1 min for 10 to 14 days. Daily increases in doses (ie, 2.5 mg increments) may be required.
- For IV bolus only. Not for IV infusion, intradermal, subcutaneous, IM, or intra-arterial administration.
- Do not administer if solution is discolored or cloudy. Fine translucent particles may be noted, but this does not affect potency.
- Once ampule has been opened, use immediately and discard any unused solution. Do not save unused solution for later use.
- Prepare injection by drawing solution into syringe though low protein-binding 0.2 or 0.22 micrometer (mcm) filter. Detach filter and attach new needle for the IV bolus injection.
- Do not mix with other IV substances or additives or infuse simultaneously through the same IV line. If the same IV line is used for sequential infusion of different medications, flush line with saline solution before and after injection of muromonab-CD3.
Store unopened vials in refrigerator (36° to 46° F). Do not freeze or shake.
Drug InteractionsImmunosuppressants (eg, azathioprine, corticosteroids, cyclosporine)
Psychosis, infections, malignancies, seizures, encephalopathy, and thrombotic events have occurred with immunosuppressants alone and in conjunction with muromonab-CD3.Indomethacin
May increase risk of encephalopathy and other CNS effects.
Laboratory Test Interactions
None well documented.
CV collapse; angina; MI; chest pain/tightness; bradycardia; tachycardia; hypertension; profound hypotension including shock, heart failure, pulmonary edema, arrhythmias; intravascular thrombosis; cerebrovascular accidents; transient ischemic attacks; hemodynamic instability, left ventricular dysfunction (postmarketing).
Headache; tremor; dizziness; confusion; agitation; auditory and visual hallucinations; obtundation; mood changes; hypotonus; encephalopathy; cerebral edema; aseptic meningitis; encephalitis; aphasia; quadri- or paraparesis; hemiparesis; subarachnoid hemorrhage; vertigo; sixth cranial nerve palsy; hyperreflexia; myoclonus; hypotonus; asterixis; involuntary movements; tremor; cerebritis, cerebral herniation, cerebrovascular accident, CNS infection, CNS malignancy, intracranial hemorrhage, impaired cognition, status epilepticus, stupor, transient ischemic attack (postmarketing).
Rash; urticaria; pruritus; erythema; flushing; diaphoresis; Stevens-Johnson syndrome (postmarketing).
Anorexia; bowel infarction; elevated LFTs; hepatomegaly; splenomegaly or hepatitis.
Anuria; oliguria; delayed renal graft function; transient and reversible increases in blood urea nitrogen and serum creatinine; abnormal urinary cytology (eg, exfoliation of damaged lymphocytes and cellular casts); azotemia (postmarketing).
Pancytopenia; aplastic anemia; neutropenia; leukopenia; thrombocytopenia; lymphopenia; leukocytosis; lymphadenopathy; disturbances of coagulation; arterial venous and capillary thrombosis of allografts and other vascular beds (eg, bowel, brain, heart, lung), disseminated intravascular coagulation, microangiopathic changes (eg, platelet microthrombi), microangiopathic hemolytic anemia (postmarketing).
Anaphylactic reaction, usually occurring with 10 min of administration; angioedema; reduced efficacy of treatment; serum sickness; arthritis; allergic interstitial nephritis; immune complex deposition resulting in glomerulonephritis, vasculitis (including temporal and retinal) and eosinophilia.
Arthralgia; arthritis; myalgia; stiffness.
Dyspnea; shortness of breath; tachypnea; bronchospasm; respiratory arrest; adult respiratory distress syndrome; hypoxemia; apnea can occur during Cytokine Release Syndrome (CRS); nasal stuffiness.
Blindness; blurred vision; diplopia; photophobia; conjunctivitis; hearing loss; otitis media; tinnitus; ear stuffiness.
Lymphoproliferative disorders including lymphomas; patients who receive more than 1 course may have an increased risk of malignancy; infections; immunosuppression; fever, chills, rigors, headache, tremor, nausea, vomiting, diarrhea, abdominal pain, malaise, muscle aches, joint aches, generalized weakness, most frequently develops within 30 to 60 min of administering the first 2 to 3 doses (CRS); flu-like syndrome (postmarketing).
Anaphylactic and anaphylactoid reactions may occur following administration of any dose or course. CRS has been reported.Cardiotoxicity, CNS and systemic reactions
Potentially life-threatening reactions including pulmonary edema, shock, CV collapse, cardiac/respiratory arrest, seizures, coma, cerebral edema, cerebral herniation, blindness, and paralysis have been reported.Monitoring recommendations
Carefully monitor fluid status at baseline and during therapy. Consider pretreatment with methylprednisolone to minimize CRS.
Category C .
Safety and effectiveness have been established in infants (1 mo to 2 yr of age); children (2 yr to 12 yr of age); and adolescents (12 yr to 16 yr of age).
Aseptic meningitis syndrome
The incidence of aseptic meningitis syndrome was 6%. Fever (89%), headache (44%), meningismus (14%), and photophobia (10%) were the most common symptoms. Approximately 1/ 3 with this diagnosis had coexisting signs and symptoms of encephalopathy.
Signs of increased vascular permeability (eg, otitis media, nasal and ear stuffiness).
Temporally associated with administration of first few doses of drug and linked to release of cytokines. Reactions range from mild flu-like illness to more rare and serious shock-like CV and CNS manifestations. Common reactions include high, spiking fever; chills; rigors; headache; tremor; nausea; vomiting; diarrhea; abdominal pain; malaise; muscle and joint aches; weakness. Cardiorespiratory findings include dyspnea; shortness of breath; bronchospasm; tachypnea; respiratory arrest; CV collapse; cardiac arrest; angina; MI; chest pain; tachycardia; hypertension; hemodynamic instability; hypotension; adult respiratory distress syndrome; pulmonary edema; hypoxemia; apnea; arrhythmias. Decreased urine output may occur.
May include impaired cognition, confusion, altered mental status, psychosis, mood changes, hyperreflexia, monoclonus, tremor, asterixis, major motor seizures, lethargy, auditory/visual hallucinations.
Assess patient's fluid status prior to administration. No clinical evidence of volume overload or uncompensated heart failure, including a clear chest x-ray and weight restriction of 3% or less above the patient's minimum weight during the week prior to injection.
Headache is frequently seen after first few doses.
Increases risk, severity, and morbidity from infectious complications.
Arterial or venous thromboses of allografts and other vascular beds have been reported.
Immunosuppression can increase risk of malignancies developing.
Have occurred even after first dose and include seizures, encephalopathy, cerebral edema, aseptic meningitis syndrome, headache.
Seizures, some with loss of consciousness, cardiorespiratory arrest, or death, have occurred.
During the first 1 to 3 days of therapy, some patients have experienced an acute and transient decline in glomerular filtration rate and diminished urine output with an increase in serum creatinine.
Hyperthermia; severe chills; myalgia; vomiting; diarrhea; edema; oliguria; pulmonary edema; acute renal failure; microangiopathic hemolytic anemia syndrome.
- Advise patient, family, or caregiver that it will be necessary to resume lifelong therapy with other immunosuppressive medications after completing therapy with muromonab-CD3.
- Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting with close monitoring.
- Review dosing schedule with patient, family, or caregiver.
- Review signs and symptoms associated with the CRS and the potentially serious nature of this syndrome.
- Instruct patient to seek medical attention if any of the following occur: skin rash, hives, rapid heart beat, difficulty breathing or unexplained shortness of breath, difficult or painful swallowing, any swelling suggesting an allergic reaction.
- Caution patient that medication may impair mental alertness and coordination and to use caution when driving or performing other tasks that require mental alertness or coordination until tolerance is determined.
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