CONIVAPTAN HYDROCHLORIDE

CONIVAPTAN HYDROCHLORIDe
(con-i-vap'tin)
Vaprisol
Classifications: electrolytic & water balance agent; diuretic; vasopressin antagonist;
Therapeutic:vasopressin antagonist
; diuretic
Pregnancy Category: C

Availability

5 mg/mL solution for injection

Action

Conivaptan is a vasopressin receptor (V2) antagonist that reduces the effect of vasopressin in the kidney, thus increasing the excretion of free water into the renal collecting ducts.

Therapeutic Effect

Conivaptan increases urine output and decreases urine osmolality in patients with euvolemic hyponatremia, thus restoring serum sodium balance.

Uses

Treatment of euvolemic hyponatremia (e.g., syndrome of inappropriate secretion of antidiuretic hormone, or SIADH) in hospitalized patients.

Contraindications

Hypersensitivity to conivaptan; CHF; hyponatremia associated with hypovolemia; hypotension, syncope; intravenous use only; concurrent administration of potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, etc.; pregnancy (category C), lactation. Safety and efficacy in children not established.

Cautious Use

Renal or hepatic function impairment.

Route & Dosage

Euvolemic Hyponatremia
Adult: IV 20 mg loading dose followed by 20 mg IV over 24 h. May repeat 20 mg/day dose for 1–3 d, or may titrate up to 40 mg/d based on response. Total duration of infusion should not exceed 4 d.

Administration

Intravenous

PREPARE: IV Infusion: Use a filter needle when withdrawing a drug from an ampule. Loading dose infusion: Withdraw 4 mL (20 mg) from one ampule and add to 100 mL of D5W. Gently invert the bag several times to mix. Initial maintenance infusion: Withdraw 4 mL (20 mg) from one ampule and add to 250 mL of D5W. Gently invert the bag several times to mix. Maximum maintenance dose infusion: Withdraw 8 mL (40 mg) from two ampules and add to 250 mL of D5W. Gently invert the bag several times to mix.  

ADMINISTER: IV Infusion: Give via a large vein and change infusion site every 24 h. Loading dose: Give over 30 min. Maintenance dose: Give over 24 h. Frequently monitor the serum sodium level. A reduction in dose or discontinuation of infusion may be required if the serum sodium rises too rapidly. Discontinue infusion immediately and notify physician of a rise in serum sodium >12 mEq/L/24 h. DO NOT resume infusion if serum sodium continues to rise. Infusion may be resumed ONLY if hyponatremia persists or reoccurs and patient demonstrates no indication of neurologic impairment. If the serum sodium rises too slowly, the dose may be titrated up to 40 mg over 24 h.  

INCOMPATIBILITIES Solution/additive: Lactated Ringer's solution, sodium chloride 0.9%. Y-site: None listed.

  • Store vials at 25° C (77° F). Ampules should be stored in the original container and protected from light until ready for use. After diluting with D5W, the solution should be used immediately, with infusion completed within 24 h of mixing.

Adverse Effects (≥2%)

Body as a Whole: Cannula-site reaction, infusion-site reaction, pain, peripheral edema, pyrexia, thirst. CNS: Confusional state, headache, insomnia. CV: Atrial fibrillation, hypertension, hypotension, orthostatic hypotension, phlebitis. GI: Constipation, diarrhea, dry mouth, nausea, vomiting. Hematologic: Anemia. Metabolic: Dehydration, hyperglycemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia. Respiratory: Pneumonia. Skin: Erythema. Special Senses: Oral candidiasis.

Interactions

Drug: Compounds that inhibit CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir) can increase conivaptan levels. Conivaptan can increase the levels of digoxin and drugs that require CYP3A4 for metabolism (e.g., midazolam, hmg coa reductase inhibitors, amlodipine). Food: Grapefruit juice may increase the level of conivaptan. Herbal: St. John's wort may decrease the level of conivaptan.

Pharmacokinetics

Distribution: 99% protein bound. Metabolism: Extensive hepatic metabolism. Elimination: Primarily fecal elimination (83%) with minor renal elimination. Half-Life: 5 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor infusion site for erythema, phlebitis, or other site reaction.
  • Monitor vital signs and neurologic status frequently; report immediately S&S of hypernatremia (see Appendix F).
  • Lab tests: Baseline and frequent serum sodium, serum potassium, and urine osmolality.
  • Monitor digoxin blood levels with concurrent therapy and assess for S&S of digoxin toxicity.
  • Monitor I&O closely. Effective treatment is accompanied by increased urine output, whereas decreasing urine output and oliguria may indicate developing hypernatremia.

Patient & Family Education

  • Report any of the following to a health care provider: pain at the infusion site, dizziness, confusion, palpitations, swelling of hands or feet.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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