conivaptan
Brand: Vaprisol
Prototype: tolvaptan
Drug Class: vasopressin receptor antagonist (vaptans)
Drug Family: diuretic
Subclass: non-selective V1a/V2 receptor antagonist
Organ Systems: renalcardiovascular
Mechanism of Action
Competitively antagonizes both V1a (vascular smooth muscle) and V2 (renal collecting duct) vasopressin receptors; blockade of V2 receptors reduces aquaporin-2 channel insertion into collecting duct apical membranes, producing free water excretion (aquaresis) without natriuresis, raising serum sodium in hypervolemic or euvolemic hyponatremia.
vasopressin V1a receptorvasopressin V2 receptor
Indications
- euvolemic hyponatremia (SIADH)
- hypervolemic hyponatremia (heart failure, cirrhosis) — hospitalized patients
Contraindications
- hypovolemic hyponatremia
- anuric patients
- strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) — contraindicated concurrently
- hypersensitivity to corn-derived products (vehicle)
Adverse Effects
Common
- injection site reactions (infusion site phlebitis, pain)
- hypokalemia
- thirst
- headache
- constipation
- fever
Serious
- overly rapid sodium correction causing osmotic demyelination syndrome
- hypotension
- atrial fibrillation
Pharmacokinetics (ADME)
| Absorption | IV administration only (oral formulation not available in US) |
| Distribution | Vd approximately 34 L; 99% protein bound |
| Metabolism | extensive hepatic CYP3A4 metabolism; also a potent CYP3A4 inhibitor |
| Excretion | fecal via biliary excretion; minimal renal |
| Half-life | approximately 5 hours |
| Onset | within hours of initiation |
| Peak | end of loading dose |
| Duration | aquaresis continues while infusion runs |
| Protein Binding | 99% |
| Vd | approximately 34 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CYP3A4 substrates (digoxin, simvastatin, midazolam) | conivaptan is a potent CYP3A4 inhibitor; significantly raises plasma levels of co-administered CYP3A4 substrates | major |
| strong CYP3A4 inhibitors | dramatically increase conivaptan plasma levels; co-administration contraindicated | major |
Nursing Considerations
- Administer only via large peripheral vein or central line; change the infusion site every 24 hours to minimize phlebitis, which occurs in approximately half of patients with peripheral administration.
- Monitor serum sodium every 2-4 hours for the first 24 hours of therapy; the goal is correction at a rate no faster than 12 mEq/L per 24 hours to avoid osmotic demyelination syndrome — if sodium rises too rapidly, reduce or stop infusion and give D5W.
- Conivaptan is a potent CYP3A4 inhibitor; perform comprehensive medication reconciliation before administration and alert the prescriber if the patient is on narrow therapeutic index drugs metabolized by CYP3A4 (cyclosporine, tacrolimus, sirolimus, digoxin).
- Assess volume status frequently; conivaptan is contraindicated in hypovolemic hyponatremia — incorrect patient selection can precipitate dangerous hypotension.
Clinical Pearls
- Conivaptan is the only IV vaptan available in the United States, making it suitable for hospitalized patients who cannot take oral medications; tolvaptan is used for the same indications in patients who can take oral therapy.
- The dual V1a/V2 blockade distinguishes conivaptan from tolvaptan (V2-selective); V1a blockade causes vasodilation and may lower blood pressure, a clinically relevant consideration in hypotensive or borderline-hypotensive patients.
Safety Profile
Pregnancy use-with-caution
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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