Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
Severe Neutropenia section added
- Grade 3 or 4 neutropenia occurred in 41-44% of patients with colorectal cancer treated with ELOXATIN in combination with 5-flurouracil (5-FU) and leucovorin compared to 5% with 5-FU plus leucovorin alone. Sepsis, neutropenic sepsis and septic shock have been reported in patients treated with ELOXATIN, including fatal outcomes [see Adverse Reactions (6.1)]. Delay ELOXATIN until neutrophils are = 1.5 x 109/L. Withhold ELOXATIN for sepsis or septic shock. Dose reduce ELOXATIN after recovery from Grade 4 neutropenia or febrile neutropenia.
Cardiovascular Toxicity section added
- QT prolongation and ventricular arrhythmias including fatal Torsade de Pointes have been reported in postmarketing experiences following ELOXATIN administration. ECG monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating ELOXATIN and monitor these electrolytes periodically during therapy. Avoid ELOXATIN in patients with congenital long QT syndrome
Rhabdomyolysis section added
- Rhabdomyolysis, including fatal cases, has been reported in patients treated with ELOXATIN. Discontinue ELOXATIN if any signs or symptoms of rhabdomyolysis occur.
Postmarketing Experience added sections
- septic shock, including fatal outcomes
Musculoskeletal and connective tissue disorders
- rhabdomyolysis, including fatal outcomes
- Infusion reactions/hypersensitivity: laryngospasm
WARNINGS AND PRECAUTIONS
- Rechallenge is contraindicated in these patients
Reversible Posterior Leukoencephalopathy Syndrome
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS, also known as PRES, Posterior Reversible Encephalopathy Syndrome) has been observed in clinical trials (< 0.1%) and postmarketing experience. Signs and symptoms of RPLS could be headache, altered mental functioning, seizures, abnormal vision from blurriness to blindness, associated or not with hypertension. Diagnosis of RPLS is based upon confirmation by brain imaging.
Use in Specific Populations
Patients with Renal Impairment
- The exposure (AUC) of unbound platinum in plasma ultrafiltrate tends to increase in renally impaired patients. Caution and close monitoring should be exercised when Eloxatin is administered to patients with renal impairment. The starting Eloxatin dose does not need to be reduced in patients with mild (creatinine clearance=50-80 mL/min) or moderate (creatinine clearance=30-49 mL/min) renal impairment. However, the starting dose of Eloxatin should be reduced in patients with severe renal impairment (creatinine clearance < 30 mL/min)