muromonab CD3 (Discontinued)

>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)

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 with methylprednisone recommended

Risk of anaphylaxis, cytokine-release syndrome (CRS: flu-like symptoms or shock), severe pulmonary edema; stabilize any cardiovascular pathologies before administration

Anaphylaxis usually appears within 10 min of administration; CRS appears 30-60 min later

Risk of seizure; monitor neurologic symptoms 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, platelets; during treatment, monitor muromonab-CD3 levels & T cell clearance daily

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.

Mechanism of Action

Blocks function of CD3 in T lymphocytes (involved in Ag recognition & signal transduction)

Pharmacokinetics

Onset: Minutes

Duration: 1 week

Minimum effective serum concentration: 800 ng/mL

CD3+ cells return to normal levels within 1 week of discontinuation

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