Label Changes for:
Vaprisol (conivaptan) injection
Changes have been made to the PRECAUTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – May 2010 and February 2012
USE IN SPECIFIC POPULATIONS
Use in Patients with Hepatic Impairment
- No clinically relevant increase in exposure was observed in subjects with mild hepatic impairment; therefore no dose adjustment of Vaprisol is necessary. The exposure to Vaprisol approximately doubles with moderate hepatic impairment. The impact of severe hepatic impairment on the exposure to conivaptan has not been studied.
Use in Patients with Renal Impairment
- No clinically relevant increase in exposure was observed in subjects with mild and moderate renal impairment (CLcr 30 – 80 mL/min). No dose adjustment of Vaprisol is necessary. Because of the high incidence of infusion site phlebitis (which can reduce vascular access sites) and unlikely benefit, use in patients with severe renal impairment(CLcr<30 mL/min) is not recommended.
- In patients unable to make urine, no benefit can be expected
WARNINGS AND PRECAUTIONS
Hyponatremia Associated with Heart Failure
- The amount of safety data on the use of Vaprisol in patients with hypervolemic hyponatremia associated with heart failure is limited. Vaprisol should be used to raise serum sodium in such patients only after consideration of other treatment options
Overly Rapid Correction of Serum Sodium
- Osmotic demyelination syndrome is a risk associated with overly rapid correction of hyponatremia (i.e., > 12 mEq/L/24 hours). Osmotic demyelination results in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma or death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, use slower rates of correction. In controlled clinical trials of Vaprisol, about 9% of patients who received Vaprisol in doses of 20-40 mg/day IV had rises of serum sodium >12 mEq/L/24 hours, but none of these patients had evidence of osmotic demyelination or permanent neurologic sequelae.
Coadministration of Vaprisol and Drugs Eliminated Primarily by CYP3A Mediated Metabolism
- In clinical trials of oral conivaptan, two cases of rhabdomyolysis occurred in patients who were also receiving a CYP3A-metabolized HMG-CoA reductase inhibitor. Avoid concomitant use of VAPRISOL with drugs eliminated primarily by CYP3A-mediated metabolism. Subsequent treatment with CYP3A substrate drugs may be initiated no sooner than 1 week after the infusion of Vaprisol is completed.
Coadministration of Vaprisol and Digoxin
- Coadministration of digoxin with oral conivaptan resulted in a 1.8- and 1.4-fold increase in digoxin Cmax and AUC, respectively. Monitor digoxin levels
- Up to a 2.8-fold increase in exposure after oral administration of conivaptan has been seen in patients with moderate hepatic impairment. Adjust the dose of Vaprisol accordingly
- In patients with renal impairment (CLcr 30 - 60 mL/min or CLcr 10 - 29 mL/min), increases in exposure of 1.7-fold and 1.9-fold, respectively, were observed after oral administration of conivaptan. Adjust the dose of Vaprisol accordingly. Because of the high incidence of infusion site phlebitis (which can reduce vascular access sites) and unlikely benefit, use in patients with severe renal impairment (CLcr<30 mL/min) is not recommended.
Infusion Site Reactions
- Infusion site reactions are common and can include serious reactions, even with proper infusion rates. Administer Vaprisol via large veins, and rotate the infusion site every 24 hours.
- Conivaptan is a potent mechanism-based inhibitor of CYP3A
- Vaprisol (40 mg/day for 4 days) administered with a single 25 mg dose of warfarin, which undergoes major metabolism by CYP2C9 and minor metabolism by CYP3A, increased the mean S-warfarin AUC and S-warfarin Cmax by 14% and 17%, respectively. The corresponding prothrombin time and international normalized ratio values were unchanged.