Vaprisol
Vaprisol - General Information
Vaprisol is a non-peptide inhibitor of antidiuretic hormone (vasopressin). It was approved in 2004 for hyponatremia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). Vaprisol inhibits both isotypes of the vasopressin receptor (V1a and V2).
Pharmacology of Vaprisol
Vaprisol is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V1A and V2 receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V2 receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V2 antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance [EWC]) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality.
Vaprisol for patients
This is a summary of the most important information about Vaprisol. For details, talk to your healthcare professional.
What Is Vaprisol?
Vaprisol is a medicine given in a vein (intravenous or I.V.) to raise low blood sodium levels in hospitalized patients with “euvolemic hyponatremia.” Euvolemic hyponatremia is when a patient has too little sodium in the bloodstream but a normal amount of fluid in the body.
Vaprisol should not be used to treat congestive heart failure.
Vaprisol has not been studied in children.
Who Should Not Be Treated With Vaprisol?
You should not be treated with Vaprisol if you:- Have too little sodium in the bloodstream and too little fluid in the body (hypovolemic hyponatremia)
- are allergic to any of its ingredients
- are taking medicines that can interact with Vaprisol, such as:
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- statin medicines, including:
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- simvastatin (Zocor, Vytorin)
- lovastatin (Mevacor, Altocor, Advicor, Altoprev)
- atorvastatin (Lipitor)
- rosuvastatin (Crestor)
- ketoconazole (Nizoral)
- itraconazole (Sporanox)
- clarithromycin (Biaxin)
- ritonavir (Norvir, Kaletra)
- indinavir (Crixivan)
Know the medicines you take. Keep a list of them with you to show your healthcare professional.
What Are The Risks?
The following are the major potential risks and side effects of Vaprisol therapy. This is not a complete list.- There may be serious side effects if your blood sodium levels rise too quickly. Your healthcare professional will monitor your blood sodium levels and check for brain side effects.
- Injection site reactions are the most common side effect of Vaprisol. Serious injection site reactions may require stopping Vaprisol.
- Some other common side effects that may occur with Vaprisol include:
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- headache
- thirst
- low potassium
- vomiting
- increased urination
- diarrhea
- decrease in blood pressure upon standing that may cause faintness
What Should I Tell My Healthcare Professional?
Before you are given Vaprisol, tell your healthcare professional if you:- have congestive heart failure
- have or had liver problems
- have or had kidney problems
- are pregnant or are trying to become pregnant
- are breast-feeding
How Is Vaprisol Given?
Vaprisol is given through a large vein (I.V.) for up to four days.
Vaprisol Interactions
Digoxin
Coadministration of digoxin, a P-glycoprotein substrate, with oral conivaptan resulted in a reduction in clearance and an increase in digoxin Cmax and AUC values. Therefore, if digoxin is administered with VAPRISOL, the clinician should be alert to the possibility of increases in digoxin levels.
Vaprisol Contraindications
VAPRISOL is contraindicated in patients with hypovolemic hyponatremia and in those who have hypersensitivity to any of its components. The coadministration of VAPRISOL with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir, is contraindicated.
Additional information about Vaprisol
Vaprisol Indication: For the treatment of euvolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients.
Mechanism Of Action: Vaprisol is a dual AVP antagonist with nanomolar affinity for human V1A and V2 receptors in vitro. This antagonism occurs in the renal collecting ducts, resulting in aquaresis, or excretion of free water.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Conivaptan
Synonyms: Conivaptan hydrochloride; YM 087
Drug Category: Aquaresis promoters
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Conivaptan: Vaprisol;
Absorption: Not Available
Toxicity (Overdose): Although no data on overdosage in humans are available, conivaptan has been administered as a 20 mg loading dose on Day 1 followed by continuous infusion of 80 mg/day for 4 days in hyponatremia patients and up to 120 mg/day for 2 days in CHF patients. No new toxicities were identified at these higher doses, but adverse events related to the pharmacologic activity of conivaptan, e.g. hypotension and thirst, occurred more frequently at these higher doses.
Protein Binding: 99%
Biotransformation: CYP3A4 is the sole cytochrome P450 isozyme responsible for the metabolism of conivaptan. Four metabolites have been identified. The pharmacological activity of the metabolites at V1a and V2 receptors ranged from approximately 3-50% and 50-100% that of conivaptan, respectively.
Half Life: 5 hours
Dosage Forms of Vaprisol: Not Available
Chemical IUPAC Name: N-[4-(2-methyl4,5-dihydro-3H-imidazo[5,4-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide
Chemical Formula: C32H26N4O2
Conivaptan on Wikipedia: https://en.wikipedia.org/wiki/Conivaptan
Organisms Affected: Humans and other mammals