Adult Dosing
Treatment of renal, steroid-resistant cardiac or hepatic allograft rejection
- 5 mg IV bolus injection for <1 minute qd x 10-14 days
Notes:- For acute renal rejection, treatment should commence upon diagnosis
- For steroid-resistant cardiac or hepatic allograft rejection, treatment should be started when the treating physician deems a rejection has not been reversed by an adequate course of corticosteroid therapy
Pediatric Dosing
- Safety and effectiveness in pediatric patients <1 month have not been established
Treatment of acute renal, steroid-resistant cardiac or hepatic allograft rejection
- <30 kg: 2.5 mg IV bolus injection in <1 minute qd x 10-14 days
- >30 kg: 5 mg IV bolus injection for <1 minute qd x 10-14 days
- May increase the dose by 2.5 mg/day to achieve depletion of CD3 positive cells and ensure therapeutic serum concentrations
Notes:- For acute renal rejection, treatment should commence upon diagnosis
- For steroid-resistant cardiac or hepatic allograft rejection, treatment should be started when the treating physician deems a rejection has not been reversed by an adequate course of corticosteroid therapy
[Outline]
See Supplemental Patient Information
- Therapy may cause cytokine release syndrome (CRS) due to the release of cytokines by activated lymphocytes or monocytes; syndrome ranged from mild, self-limited, flu-like illness to occasional, serious, life-threatening shock-like reaction, which may include serious CV and CNS manifestations. The syndrome usually begins within 30-60 minutes after administration of a dose and may persist for several hours. Frequency and severity of this symptom complex is more with the first dose
- Common clinical manifestations of CRS may include high fever (often spiking, up to 107°F), chills/rigors, headache, tremor, nausea/vomiting, diarrhea, abdominal pain, malaise, muscle/joint aches and pains, and generalized weakness
- Cardiorespiratory findings of CRS may include dyspnea, shortness of breath, bronchospasm/wheezing, tachypnea, respiratory arrest/failure/distress, cardiovascular collapse, cardiac arrest, angina/MI, chest pain/tightness, tachycardia (including ventricular), hypertension, hemodynamic instability, hypotension including profound shock, heart failure, pulmonary edema (cardiogenic and noncardiogenic), adult respiratory distress syndrome, hypoxemia, apnea, and arrhythmias
- Therapy may cause potentially fatal, severe pulmonary edema, an acute and transient decline in GFR and diminished urine output, elevations in serum creatinine, and transient elevations in hepatic transaminases
- Patients with unstable angina, recent MI or symptomatic ischemic heart disease, heart failure of any etiology, pulmonary edema of any etiology, any form of COPD, intravascular volume overload or depletion of any etiology (e.g., excessive dialysis, recent intensive diuresis, blood loss), cerebrovascular disease, patients with advanced symptomatic vascular disease or neuropathy, a history of seizures, and septic shock are at high risk for more serious complication of CRS
- Assess the patient's fluid volume status and chest X-ray prior to initiating therapy to rule out volume overload, uncontrolled hypertension, or uncompensated heart failure
- Intensive treatment such as oxygen, IV fluid, pressor amines, corticosteroids, antihistamines, and intubation may be required if any of the more serious presentations of CRS occur
- Instances of seizures, encephalopathy, cerebral edema, aseptic meningitis, headache, and some seizures accompanied by loss of consciousness or cardiorespiratory arrest, or death have been reported during therapy
- Before initiation of therapy, all patients, especially pediatric patients, should be evaluated for fluid retention and hypertension; closely monitor for neurologic symptoms during the first 24 hrs following each of the first few doses
- Closely monitor patients for convulsions and manifestations of encephalopathy, including impaired cognition, confusion, obtundation, altered mental status, disorientation, auditory/visual hallucinations, psychosis (delirium, paranoia), mood changes (mania, agitation, combativeness), diffuse hypotonus, hyperreflexia, myoclonus, tremor, asterixis, involuntary movements, major motor seizures, lethargy/stupor/coma, and diffuse weakness
- Aseptic meningitis syndrome has been associated with the therapy, which is characterized by signs and symptoms of fever, headache, meningismus (stiff neck), and photophobia
- Signs or symptoms of encephalopathy, meningitis, seizures, and cerebral edema, with or without headache, typically have been reversible; however, some events resulted in permanent neurologic impairment
- Patients with known CNS disorder, cerebrovascular disease, conditions having associated neurologic problems, underlying vascular disease, or those receiving a medication concomitantly that may affect the CNS are at greater risk for CNS adverse events
- Cases of serious and occasionally fatal, immediate hypersensitivity reactions have been reported during therapy; acute hypersensitivity reactions may be characterized by cardiovascular collapse, cardiorespiratory arrest, loss of consciousness, hypotension/shock, tachycardia, tingling, angioedema, airway obstruction, bronchospasm, dyspnea, urticaria, and pruritus
- Patients re-exposed to muromonab-CD3 subsequent to their initial course of therapy have reported serious allergic events including anaphylactic or anaphylactoid reactions. Pretreatment with antihistamines and/or steroids may not reliably prevent anaphylaxis in this setting. Weigh the possible allergic hazards of re-treatment against expected therapeutic benefits and alternatives. Epinephrine and other emergency life-support equipment should be immediately available if a patient is retreated with muromonab-CD3
- If hypersensitivity is suspected, promptly discontinue therapy and do not resume or re-expose the patient to muromonab-CD3
- Instances of serious and sometimes fatal infections and neoplasia have been reported in association with all immunosuppressive therapies
- Patients receiving immunosuppressive therapy are at increased risk for developing post-transplant lymphoproliferative disorders and opportunistic infections and should be monitored accordingly
- Due to depressed cell-mediated immunity from immunosuppressive agents, organ transplant patients have an increased risk of developing malignancies
- Continuously monitor patients for evidence of lymphoproliferative disorders through physical examination and histological evaluation of any suspect lymphoid tissue. Close surveillance is advised, since early detection with subsequent reduction of total immunosuppression may result in regression of some of these lymphoproliferative disorders
- It is required to reduce the dose of immunosuppressive drugs used concomitantly, including muromonab-CD3, to the lowest level compatible with an effective therapeutic response in order to reduce the potential for development of lymphoproliferative disorders, severity of infections, and malignant transformations
- Monitor patient's temperature prior to administration of muromonab-CD3; if it exceeds 37.8°C, use antipyretics to lower the temperature. Also, evaluate the possibility of infection
- Concomitant use of immunosuppressive medications with muromonab-CD3 may alter the incidence and magnitude of the host antibody response
- Arterial, venous, and capillary thromboses of allografts and other vascular beds (such as heart, lungs, bowel, brain) have been reported in patients receiving muromonab-CD3. Patients with a history of thrombosis or underlying vascular disease should be given muromonab-CD3 only when the potential benefits outweigh the increased risks of therapy
- Prior to initiation of therapy, monitor renal, hepatic, and hematopoietic tests; perform chest X-ray within 24 hrs before initiating therapy to rule out heart failure or fluid overload. Periodic assessment of organ system functions should be performed
Cautions: Use cautiously in
- Vascular disease
- Head injury
- Electrolyte abnormalities
- Uremia
Supplemental Patient Information
- Advise patients to promptly seek medical attention for skin rash, urticaria, rapid heart beat, respiratory distress, dysphagia, or any swelling suggesting an allergic reaction or angioedema
- Caution patients that muromonab-CD3 may impair mental and/or physical abilities required for performance of hazardous tasks; instruct patients to refrain from driving or operating machinery
Pregnancy Category:C
Breastfeeding: Safety unknown. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, analyzing the importance of the drug to the mother.