VAPRISOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VAPRISOL (VAPRISOL).
Selective vasopressin V2 receptor antagonist; inhibits water reabsorption in the collecting duct of the kidney, promoting aquaresis without affecting electrolyte excretion.
| Metabolism | Primarily hepatic via CYP3A4 isoenzyme; minor contributions from other CYP450 enzymes. |
| Excretion | Primarily hepatic metabolism, with approximately 99% of the dose recovered in feces via biliary excretion and less than 1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 6.5 to 8 hours in patients with normal renal and hepatic function; may be prolonged in hepatic impairment. |
| Protein binding | Approximately 67% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.8 L/kg, indicating distribution into total body water. |
| Bioavailability | Not applicable; Vaprisol is administered intravenously. Oral bioavailability is not established as it is not used orally. |
| Onset of Action | Intravenous administration: Onset of aquarctic effect (increase in urine output and decrease in urine osmolality) occurs within 30 to 60 minutes. |
| Duration of Action | Duration of aquarctic effect is approximately 4 to 6 hours after a single intravenous dose; clinical effect correlates with plasma concentrations. |
Initial dose: 20 mg IV over 30 minutes, then continuous IV infusion at 20 mg/day for 2-4 days; may increase to 40 mg/day if inadequate response. Maximum duration: 4 days.
| Dosage form | INJECTABLE |
| Renal impairment | Contraindicated in patients with creatinine clearance <30 mL/min. No dose adjustment recommended for mild to moderate renal impairment (CrCl 30-89 mL/min). |
| Liver impairment | Contraindicated in patients with Child-Pugh Class C. For Child-Pugh Class A or B, use with caution; no specific dose adjustment provided. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. Not recommended for use in children. |
| Geriatric use | No specific dose adjustment; select dose cautiously due to greater frequency of decreased hepatic, renal, or cardiac function. Monitor serum sodium closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VAPRISOL (VAPRISOL).
| Breastfeeding | Unknown if excreted in human milk. No M/P ratio available. Discontinue nursing or discontinue drug, taking into account importance of drug to mother. |
| Teratogenic Risk | Pregnancy Category C. No adequate studies in pregnant women. In animal studies, conivaptan (active metabolite) caused fetal harm at doses similar to human exposures. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring |
■ FDA Black Box Warning
Initiation and re-initiation of therapy should be performed in a hospital setting to closely monitor serum sodium and volume status due to risk of overly rapid correction of hyponatremia leading to osmotic demyelination syndrome.
| Serious Effects |
["Hypovolemic hyponatremia","Anuria","Concurrent use with strong CYP3A4 inhibitors","Allergy to conivaptan or any component of the formulation"]
| Precautions | ["Overly rapid correction of hyponatremia may cause osmotic demyelination syndrome; limit serum sodium increase to ≤12 mEq/L in 24 hours.","Monitor for volume status; may cause hypovolemia and hypernatremia.","Use with caution in patients with hepatic impairment; dose adjustment recommended.","Renal impairment: not recommended in patients with end-stage renal disease or anuria.","May cause electrolyte disturbances such as hyperkalemia."] |
Loading safety data…
| Monitor serum sodium, volume status, and blood pressure frequently. Assess for signs of hypovolemia, hypotension, and infusion site reactions. During pregnancy, monitor fetal heart rate and growth if clinically indicated. |
| Fertility Effects | No human data on fertility. In animal studies, no adverse effects on male or female fertility at clinically relevant doses. |