Conivaptan Hydrochloride

(rINNM)
Conivaptan Hydrochloride Chemical formula
Synonyms: CI-1025; Conivaptan, Chlorhydrate de; Conivaptán, hidrocloruro de; Conivaptani Hydrochloridum; YM-087 (conivaptan or conivaptan hydrochloride). 4″-[(4,5-Dihydro-2-methylimidazo[4,5d][1]benzazepin-6(1H)-yl)carbonyl]-2-biphenylcarboxanilide hydrochloride.
Cyrillic synonym: Кониваптана Гидрохлорид.

💊 Chemical information

Chemical formula: C32H26N4O2,HCl = 535.0.

💊 Adverse Effects and Precautions

The most common adverse effects of conivaptan are infusion site reactions such as erythema, pain, phlebitis, and swelling, which are usually mild but can be severe enough in some patients that infusion must be stopped. Other adverse effects include atrial fibrillation, gastrointestinal disturbances, pyrexia, thirst, electrolyte disturbances, headache, and hypertension or hypotension. Conivaptan is contra-indicated in hypovolaemic hyponatraemia, and is not indicated for the treatment of patients with congestive heart failure. Rapid correction of serum-sodium concentrations with conivaptan could increase the risk of osmotic demyelination syndrome. Conivaptan should be used with caution in hepatic or renal impairment because systemic exposure can be increased.

💊 Interactions

As a substrate of the cytochrome P450 isoenzyme CYP3A4, concentrations of conivaptan can be increased by CYP3A4 inhibitors. The use of conivaptan with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir is contra-indicated. Conivaptan itself is also a potent inhibitor of CYP3A4 and may increase the concentrations of other substrates of this isoenzyme, including amlodipine, midazolam, and simvastatin. Conivaptan can reduce the clearance, and subsequently increase concentrations, of digoxin.

💊 Pharmacokinetics

Conivaptan is metabolised by the cytochrome P450 isoenzyme CYP3A4, but inhibits its own metabolism. Using a regimen of intravenous loading dose followed by continuous infusion, concentrations of conivaptan initially decrease from the loading dose peak over about 12 hours, then gradually increase. After stopping the infusion, conivaptan has an elimination half-life of about 5 hours. Conivaptan is highly bound to plasma proteins.

💊 Uses and Administration

Conivaptan hydrochloride is a vasopressin V1a and V2 receptor antagonist. In the management of hyponatraemia it acts mainly at V2 receptors in the renal collecting ducts to increase the excretion of free water. It is used to treat euvolaemic and hypervolaemic hyponatraemia, and is not indicated for congestive heart failure. Conivaptan hydrochloride is given by intravenous infusion. To minimise infusion site irritation, it should be diluted in glucose 5% infusion (loading doses are given in 100 mL of fluid, the subsequent infusions in 250 mL) and given through a large vein; the infusion site should be changed every 24 hours. A loading dose of 20 mg is given over 30 minutes, followed by a continuous infusion of 20 mg over 24 hours. Treatment may be continued at a dose of 20 mg daily titrated to a maximum of 40 mg daily if required. The maximum duration of the infusion is 4 days. If a rapid rise in serum-sodium occurs (more than 12 mmol/litre in 24 hours) conivaptan should be stopped, and serum-sodium and neurological status should be carefully monitored because of the risk of osmotic demyelination syndrome. If hypovolaemia or hypotension develop, conivaptan should be stopped and volume status and vital signs should be monitored. Conivaptan may be resumed at a lower dose, if still indicated, when the rise in serumsodium has stopped, if there is no evidence of adverse neurological effects and the patient is euvolaemic and no longer hypotensive.
1. Walter KA. Conivaptan: new treatment for hyponatremia. Am J Health-Syst Pharm 2007; 64: 1385–95.

💊 Preparations

Proprietary Preparations

USA: Vaprisol.
Published May 08, 2019.