al24 hours at room temperature. However, since TRUXIMA solutions do not contain apreservative, diluted solutions should be stored refrigerated (2°C to 8°C). No incompatibilitiesbetween TRUXIMA and polyvinylchloride or polyethylene bags have been observed.
3 DOSAGE FORMS AND STRENGTHS
Injection: TRUXIMA is a clear to opalescent, colorless to pale yellow solution for intravenous
infusion:
• 100 mg/10 mL (10 mg/mL) in a single-dose vial
• 500 mg/50 mL (10 mg/mL) in a single-dose vial
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Infusion Reactions
Rituximab products can cause severe, including fatal, infusion reactions. Severe reactionstypically occurred during the first infusion with time to onset of 30−120 minutes. Rituximabproduct-induced infusion reactions and sequelae include urticaria, hypotension, angioedema,hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardialinfarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death.
Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medicalmanagement (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactionsas needed. Depending on the severity of the infusion reaction and the required interventions,temporarily or permanently discontinue TRUXIMA. Resume infusion at a minimum 50%reduction in rate after symptoms have resolved. Closely monitor the following patients: thosewith pre-existing cardiac or pulmonary conditions, those who experienced priorcardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells(≥25,000/mm3
). [see Warnings and Precautions (5.7), Adverse Reactions (6.1)].
5.2 Severe Mucocutaneous Reactions
Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with rituximabproducts. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome,lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset ofthese reactions has been variable and includes reports with onset on the first day of rituximabexposure. Discontinue TRUXIMA in patients who experience a severe mucocutaneous reaction.The safety of re-administration of TRUXIMA to patients with severe mucocutaneous reactionshas not been determined.
5.3 Hepatitis B Virus (HBV) Reactivation
Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepaticfailure and death, can occur in patients treated with drugs classified as CD20-directed cytolyticantibodies, including rituximab products. Cases have been reported in patients who are hepatitisB surface antigen (HBsAg) positive and also in patients who are HBsAg negative but arehepatitis B core antibody (anti-HBc) positive. Reactivation also has occurred in patients whoappear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive andhepatitis B surface antibody [anti-HBs] positive).
HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapidincrease in serum HBV DNA levels or detection of HBsAg in a person who was previouslyHBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed byhepatitis, i.e., increase in transaminase levels. In severe cases increase in bilirubin levels, liverfailur |
