Conivaptan and its role in the treatment of hyponatremia

Ghali, Jalal K.; Farah, Jareer; Daifallah, Suleiman; Zabalawi, Hassan A; Zmily, Hammam

doi:10.2147/dddt.s4505

Cited by 18 publications

(12 citation statements)

References 73 publications

(85 reference statements)

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“…Conivaptan is an i.v. administered vasopressin V 1A -and V 2 -receptor antagonist that has been shown to increase serum sodium levels in hospitalized patients with euvolemic or hypervolemic hyponatremia [53], and it is approved for use in this patient population in the U.S. Treatment with this agent is limited to 2-4 days.…”

Section: Treatment Optionsmentioning

confidence: 99%

Diagnosis and Management of Hyponatremia in Cancer Patients

Castillo

Vincent

Justice³

2012

The Oncologist

209

201

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Hyponatremia, a common electrolyte abnormality in oncology practice, may be a negative prognostic factor in cancer patients based on a systematic analysis of published studies. The largest body of evidence comes from small-cell lung cancer (SCLC), for which hyponatremia was identified as an independent risk factor for poor outcome in six of 13 studies. Hyponatremia in the cancer patient is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which develops more frequently with SCLC than with other malignancies. SIADH may be driven by ectopic production of arginine vasopressin (AVP) by tumors or by effects of anticancer and palliative medications on AVP production or action. Other factors may cause hypovolemic hyponatremia, including diarrhea and vomiting caused by cancer therapy. Hyponatremia may be detected on routine laboratory testing before or during cancer treatment or may be suggested by the presence of mostly neurological symptoms. Treatment depends on several factors, including symptom severity, onset timing, and extracellular volume status. Appropriate diagnosis is important because treatment differs by etiology, and choosing the wrong approach can worsen the electrolyte abnormality. When hyponatremia is caused by SIADH, hypertonic saline is indicated for acute, symptomatic cases, whereas fluid restriction is recommended to achieve a slower rate of correction for chronic asymptomatic hyponatremia. Pharmacological therapy may be necessary when fluid restriction is insufficient. The orally active, selective AVP receptor 2 (V 2 )-receptor antagonist tolvaptan provides a mechanism-based option for correcting hyponatremia caused by SIADH or other conditions with inappropriate AVP elevations. By blocking AVP effects in the renal collecting duct, tolvaptan promotes aquaresis, leading to a controlled increase in serum sodium levels. The Oncologist 2012;17:756 -765

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Section: Treatment Optionsmentioning

confidence: 99%

Diagnosis and Management of Hyponatremia in Cancer Patients

Castillo

Vincent

Justice³

2012

The Oncologist

209

201

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“…Conivaptan was approved in 2005 by the FDA (USA) for intravenous treatment of moderate to severe euvolemic hyponatremia and then, in 2007, for hypervolemic hyponatremia in hospitalized patients [66]. The loading dose is 20 mg i.v.…”

Section: Vasopressin Receptor Antagonist Therapy: Mechanisms Indicatmentioning

confidence: 99%

The Syndrome of Inappropriate Antidiuresis: Pathophysiology, Clinical Management and New Therapeutic Options

et al. 2011

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Hyponatremia is a marker of different underlying diseases and it can be a cause of morbidity itself; this implies the importance of a correct approach to the problem. The syndrome of inappropriate antidiuresis (SIAD) is one of the most common causes of hyponatremia: it is a disorder of sodium and water balance characterized by urinary dilution impairment and hypotonic hyponatremia, in the absence of renal disease or any identifiable non-osmotic stimulus able to induce antidiuretic hormone (ADH) release; according to its definition, it is diagnosed through an exclusion algorithm. SIAD is usually observed in hospitalized patients and its prevalence may be as high as 35%. The understanding of the syndrome has notably evolved over the last years, as reflected by the significant change in the name, once the syndrome of inappropriate secretion of ADH (SIADH), today SIAD. This review is up to date and it analyses the newest notions about pathophysiological mechanisms, classification, management and therapy of SIAD, including vaptans.

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“…Conivaptan has been approved by the FDA for the treatment of euvolemic and hypervolemic hyponatremia. In contrast to conivaptan, which exhibits dramatic cytochrome P 450 3A4 (CYP3A4) inhibition and significant drug-drug interactions [19], tolvaptan has no significant drug-drug interactions, particularly with the antiarrythmic agent amiodarone, a common drug administered to patients suffering from CHF. Therefore, a modified dual-specific tolvaptan might have certain therapeutic advantages.…”

Section: Implications For Chemical Modification Of Tolvaptan To Incrementioning

confidence: 99%

Specificity of Three Vasopressin Receptor Antagonists

Saks¹,

Truitt²,

Shoham³

2011

LDDD

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Vasopressin receptor antagonists (vaptans) are a new class of drugs to treat congestive heart failure. Since there are three subtypes of the receptor located in different tissues, it is important to devise tailor-made vaptans to target the appropriate receptor subtype. The binding of three vaptans, OPC21268, mozavaptan and tolvapatan was measured to the human V1-vascular vasopressin receptor (hV1R). Whereas arginine vasopressin (AVP) binds to hV1R and hV2R with equal affinity, vaptans interact differently with the receptor subtypes. The interaction of the three vaptans to the hV1R was probed by binding experiments to point mutants of residues postulated to line the binding pocket. The measurements suggest that the binding pocket on the hV1R is too small for tight binding of tolvaptan. The somewhat smaller mozavaptan is a slightly better binder to the hV1R. The data suggest ways to increase the affinity of tolvaptan to the hV1R by chemical modification.

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Conivaptan and its role in the treatment of hyponatremia

Cited by 18 publications

References 73 publications

Diagnosis and Management of Hyponatremia in Cancer Patients

Diagnosis and Management of Hyponatremia in Cancer Patients

The Syndrome of Inappropriate Antidiuresis: Pathophysiology, Clinical Management and New Therapeutic Options

Specificity of Three Vasopressin Receptor Antagonists

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