"ATLANTA, GA â€” The Centers for Disease Control and Prevention (CDC) has issued a warning for healthcare providers and patients to be aware of a potential risk of infection from certain devices used during many open-heart surgeries.
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 [see ADVERSE REACTIONS].
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. Serum sodium concentration and neurologic status should be monitored appropriately during VAPRISOL administration, and VAPRISOL administration should be discontinued if the patient develops an undesirably rapid rate of rise of serum sodium. If the serum sodium concentration continues to rise, VAPRISOL should not be resumed. If hyponatremia persists or recurs (after initial discontinuation of VAPRISOL for an undesirably rapid rate of rise of serum sodium concentration), and the patient has had no evidence of neurologic sequelae of rapid rise in serum sodium, VAPRISOL may be resumed at a reduced dose [see DOSAGE AND ADMINISTRATION].
Hypovolemia Or Hypotension
For patients who develop hypovolemia or hypotension while receiving VAPRISOL, VAPRISOL should be discontinued, and volume status and vital signs should be frequently monitored. Once the patient is again euvolemic and is no longer hypotensive, VAPRISOL may be resumed at a reduced dose if the patient remains hyponatremic.
Infusion Site Reactions
Infusion site reactions are common and can include serious reactions, even with proper infusion rates [see ADVERSE REACTIONS]. Administer VAPRISOL via large veins, and rotate the infusion site every 24 hours [see DOSAGE AND ADMINISTRATION].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Standard lifetime (104 week) carcinogenicity bioassays were conducted in mice and rats. Male and female mice were given oral doses of conivaptan hydrochloride up to 30 mg/kg/day and 10 mg/kg/day, respectively, by gavage. Male and female rats were given oral doses of up to 10 mg/kg/day and 30 mg/kg/day, respectively, by gavage. There was no increased incidence of tumors associated with exposure to conivaptan in either species. The 30 mg/kg/day dosage regimen in male mice and female rats was shown to result in a systemic exposure (AUC) about twice the human systemic exposure from an IV bolus of 20 mg on day 1 followed by IV infusion of 40 mg/day for 3 days. The 10 mg/kg/day dosage regimen in female mice and male rats was shown to result in about one-fourth and one-half the human therapeutic exposure, respectively.
Conivaptan was not genotoxic in the bacterial reverse mutation assay, the in vitro human peripheral blood lymphocyte chromosomal aberration assay, or in vivo rat micronucleus assay.
Fertility of male rats treated with conivaptan hydrochloride by IV bolus doses of up to 2.5 mg/kg/day for the 4 weeks preceding mating and throughout the mating period was unaffected. However, when female rats were given IV bolus conivaptan from 15 days before mating through gestation day 7, there was prolonged diestrus, decreased fertility (decreased numbers of corpora lutea and implantations) and increased post-implantation loss at 2.5 mg/kg/day (systemic exposure less than human exposure at the therapeutic dose).
Use In Specific Populations
There are no available data with VAPRISOL in pregnant women to inform a drug-associated risk for major birth defects and miscarriage.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major malformations and miscarriage in clinically recognized pregnancies is 2-4%, and 15-20%, respectively.
When pregnant rats were given intravenous conivaptan hydrochloride up to 2.5 mg/kg/day on gestation days 7 through 17 (systemic exposures less than human therapeutic exposure based on AUC comparisons), no significant fetal or maternal effects were noted. However, when the same doses were administered to pregnant rats from gestation day 7 through lactation day 20 (weaning), the pups showed decreased neonatal viability and weaning indices, decreased body weight, and delayed reflex and physical development (including sexual maturation). These effects occurred only at the highest dose administered (2.5 mg/kg/day). No maternal adverse effects of conivaptan were seen in this study. When pregnant rabbits were administered intravenous doses of conivaptan hydrochloride up to 12 mg/kg/day on gestation days 6 through 18 (at about twice the human therapeutic exposure), there were no fetal or maternal findings.
Rat fetal tissue levels were < 10% of maternal plasma concentrations while placental levels were 2.2-fold higher than maternal plasma concentrations. Conivaptan that is taken up by fetal tissue is slowly cleared, suggesting that fetal accumulation is possible.
Conivaptan hydrochloride delayed delivery in rats dosed at 10 mg/kg/day by oral gavage (systemic exposure equivalent to the human therapeutic exposure based on AUC comparison).
There is no information regarding conivaptan or its metabolites in human milk, the effects of conivaptan on the breastfed infant, or the effects of conivaptan on milk production. Conivaptan is present in rat milk; however, due to species-specific differences in lactation physiology, the clinical relevance of these data are not clear [see Data]. Because of the potential for serious adverse reactions, including electrolyte abnormalities (e.g., hypernatremia), hypotension, and volume depletion in breastfed infants, advise a woman not to breastfeed during treatment with VAPRISOL.
Milk levels of conivaptan in rats reached maximal levels at 1 hour following intravenous administration and were up to 3 times maternal plasma levels following an intravenous dose of 1 mg/kg (systemic exposure less than human therapeutic exposure based on AUC comparison).
Females And Males Of Reproductive Potential
Based on findings of decreased fertility in female rats, conivaptan may impair fertility in females of reproductive potential. It is not known whether these effects on fertility are reversible [see Nonclinical Toxicology].
Safety and effectiveness in pediatric patients have not been established.
In clinical studies of VAPRISOL administered as a 20 mg IV loading dose followed by 20 mg/day or 40 mg/day IV for 2 to 4 days, 89% (20 mg/day regimen) and 60% (40 mg/day regimen) of participants were greater than or equal to 65 years of age and 60% (20 mg/day regimen) and 40% (40 mg/day regimen) were greater than or equal to 75 years of age. In general, the adverse event profile in elderly patients was similar to that seen in the general study population.
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 systemic exposure to unbound conivaptan doubled in subjects with moderate and severe hepatic impairment [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
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 [see CLINICAL PHARMACOLOGY].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 11/7/2016
Additional Vaprisol Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.