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Votrient (Pazopanib) Tablets
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
Increased Toxicity in Developing Organs
- The safety and effectiveness of VOTRIENT in pediatric patients have not been established. VOTRIENT is not indicated for use in pediatric patients. Based on its mechanism of action, pazopanib may have severe effects on organ growth and maturation during early postnatal development.
- Administration of pazopanib to juvenile rats less than 21 days old resulted in toxicity to the lungs, liver, heart, and kidney and in death at doses significantly lower than the clinically recommended dose or doses tolerated in older animals. VOTRIENT may potentially cause serious adverse effects on organ development in pediatric patients, particularly in patients younger than 2 years of age.
WARNINGS AND PRECAUTIONS
Hepatic Toxicity and Hepatic Impairment
- In the randomized RCC trial, ALT >3 X ULN was reported in 18% and 3% of the Votrient and placebo groups, respectively. ALT >10 X ULN was reported in 4% of patients who received Votrient and in <1% of patients who received placebo…
- Concomitant use of Votrient and Simvastatin increases the risk of ALT elevations and should be undertaken with caution and close monitoring [see Drug Interactions (7.3)]. Insufficient data are available to assess the risk of concomitant administration of alternative statins and Votrient.
- In clinical trials with Votrient, events of cardiac dysfunction such as decreased left ventricular ejection fraction (LVEF) and congestive heart failure have occurred. In the overall safety population for RCC (N = 586), cardiac dysfunction was observed in 0.6% (4/586) of patients without routine on-study LVEF monitoring. In the randomized STS trial, myocardial dysfunction was defined as symptoms of cardiac dysfunction or ≥15% absolute decline in LVEF compared to baseline or a decline in LVEF of ≥10% compared to baseline that is also below the lower limit of normal…
- Fatal hemorrhage occurred in 0.9% (5/586) in the RCC trials; there were no reports of fatal hemorrhage in the STS trials.
- In the randomized STS trial, 22% (53/240) of patients treated with Votrient compared to 8% (10/123) treated with placebo experienced at least 1 hemorrhagic event. The most common hemorrhagic events were epistaxis (8%), mouth hemorrhage (3%), and anal hemorrhage (2%). Grade 4 hemorrhagic events in the STS population occurred in 1% (3/240) patients and included intracranial hemorrhage, subarachnoid hemorrhage and peritoneal hemorrhage.
Arterial Thrombotic Events
- Fatal arterial thromboembolic events were observed in 0.3% (2/586) of patients in the RCC trials and in no patients in the STS trials. In the randomized RCC trial, 2% (5/290) of patients receiving Votrient experienced myocardial infarction or ischemia, 0.3% (1/290) had a cerebrovascular accident and 1% (4/290) had an event of transient ischemic attack…
Venous Thromboembolic Event
- In RCC and STS trials of Votrient, venous thromboembolic events including venous thrombosis and fatal pulmonary embolus have occurred. In the randomized STS trial, venous thromboembolic events were reported in 5% of patients treated with Votrient compared to2% with placebo…
Gastrointestinal Perforation and Fistula
- In the RCC and STS trials, gastrointestinal perforation or fistula occurred in 0.9% (5/586) of patients and 1% (4/382) of patients receiving VOTRIENT, respectively…
Reversible Posterior Leukoencephalopathy Syndrome
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been reported in patients receiving Votrient and may be fatal…
- Hypertension (systolic blood pressure ≥150 or diastolic blood pressure ≥100 mm Hg) and hypertensive crisis were observed in patients treated with Votrient.