Dosing and uses of Orthoclone OKT3 (muromonab CD3)
Adult dosage forms and strengths
injectable solution
- 1mg/mL
Acute Allograft Rejection or Acute Graft-Vs-Host Disease Treatment
5 mg IVP qDay x 10-14 days
Other Indications & Uses
Treatment of acute allograft rejection in renal transplant, with other immunosuppressants
Treatment of steroid-resistant acute allograft rejection in cardiac or hepatic transplant, with other immunosuppressants
Pediatric dosage forms and strengths
injectable solution
- 1mg/mL
Acute Allograft Rejection or Acute Graft-Vs-Host Disease Treatment
<30 kg: 2.5 mg IVP qDay x 10-14 days
>30 kg: 5 mg IVP qDay x 10-14 days; May titrate daily by 2.5 mg to achieve CD3+ cells < 25/cu.mm and serum muromonab-CD3 > 800 ng/mL
Orthoclone OKT3 (muromonab CD3) adverse (side) effects
>10% (Cytokine Release Syndrome 1st 48 Hr)
Pyrexia (90%)
Chills (59%)
Dyspnea (21%)
Nausea/Vomiting (19%)
Chest pain (14%)
Diarrhea (14%)
Tremor (13%)
Wheezing (13%)
Headache (11%)
>10% (Overall Incidence)
Pyrexia (77%)
Chills (43%)
Diarrhea (37%)
Nausea (32%)
Headache (28%)
Tachycardia (26%)
Hypotension (25%)
Vomiting (25%)
Hypertension (19%)
Dyspnea (16%)
Rash (14%)
Edema (12%)
1-10%
Abnl chest sound (10%)
Anorexia (10%)
Tachycardia (10%)
Chest pain (9%)
Fatigue (9%)
HTN (8%)
Arthralgia (7%)
Diaphoresis (7%)
GI pain (7%)
Hyperventilation (7%)
Leukopenia (7%)
Pruritis (7%)
Vasodilation (7%)
Abd pain (6%)
Confusion (6%)
Dizziness (6%)
Lethargy (6%)
Wheezing (6%)
Anemia (2-5%)
Arrhythmia (2-5%)
Bradycardia (2-5%)
Depression (2-5%)
Malaise (2-5%)
Nervousness (2-5%)
Pulmonary edema (2-5%)
Somnolence (2-5%)
Thrombocytopenia, (2-5%)
<1%
Anaphylaxis (rare)
Warnings
Black box warnings
Only physicians experienced in immunosuppressive therapy and management of solid organ transplant patients should prescribe
Anaphylactic or anaphylactoid reactions may occur following administration of any dose or course
Serious and occasionally life-threatening systemic, cardiovascular, and CNS reactions (eg, pulmonary edema, especially in patients with volume overload; shock; cardiovascular collapse; cardiac or respiratory arrest; seizures; coma) have been reported
Must be managed in a facility equipped and staffed for cardiopulmonary resuscitation
Contraindications
Hypersensitivity to any murine-derived products
Anti-mouse Ab titers >= 1:1000
Uncontrolled CHF or fluid overload, uncontrolled HTN, H/O seizures, pregnancy, breastfeeding
Cautions
Pretreatment w/ methylprednisone recommended
Risk of anaphylaxis, cytokine-release syndrome (CRS: flu-like Sx or shock), severe pulmonary edema; stabilize any cardiovascular pathologies before administration
Anaphylaxis usually appears w/in 10 min of administration; CRS appears 30-60 min later
Risk of seizure; monitor neurologic Sx carefully during first 24 hr following the first few doses
Risk of viral infection, lymphoproliferative neoplasia
If temp >100°F, lower by antipyretics before next administration
Monitor renal function, LFTs, WBCs, Plts; during Tx, monitor muromonab-CD3 levels & T cell clearance daily
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Orthoclone OKT3 (muromonab CD3)
Onset: minutes
Duration: 1 wk
Minimum effective serum concentration: 800 ng/mL
CD3+ cells return to normal levels within 1 wk of discontinuation
Mechanism of action
Blocks function of CD3 in T lymphocytes (involved in Ag recognition & signal transduction)
Administration
IV Administration
Give IV push over <1 min undiluted
Do not give Im
Methylprednisolone sodium succinate 1 mg/kg IV given prior to first muromonab-CD3 administration, & IV hydrocortisone sodium succinate 50-100 mg, given 30 min after administration are strongly recommended to decrease the incidence of reaction to the first dose
Filter each dose through a low protein-binding 0.22 micron filter before administration
Pt temperature should not exceed 37.8°C (100°F) at time of administration
Storage
Refrigerate
Do not shake or freeze
