2/12/2016
PRO PHARMA TECHNOLOGY TOOLBOX
Generic: Tolvaptan tablets
Brand: SAMSCA
Strengths: 15mg, 30mg, 60mg
1 INDICATION1
SAMSCA is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant
hypervolemic and euvolemic hyponatremia*, including patients with heart failure, cirrhosis, and Syndrome of
Inappropriate Antidiuretic Hormone (SIADH)
*[serum sodium < 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid
restriction]
Important Limitations:
1. Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological
symptoms should not be treated with SAMSCA.
2. It has not been established that SAMSCA provides a symptomatic benefit to patients.

Prevalence: Statistics not available, Incidence: Statistics not available
2 DOSAGE AND ADMINISTRATION1
SAMSCA should be initiated and re-initiated in a hospital. The recommended starting dose is 15 mg once daily. Dosage
may be increased at intervals ≥ 24 hr to 30 mg once daily, and to a maximum of 60 mg once daily as needed to raise
serum sodium. Monitor serum sodium and volume status.
3 MECHANISM OF ACTION1
Tolvaptan is a selective vasopressin V2-receptor antagonist with an affinity for the V2-receptor that is 1.8 times that of
native arginine vasopressin (AVP).
 Drug Structure1,2
4 ADVERSE REACTION/SIDE EFFECTS 3,4
Most common adverse reactions (≥ 5% placebo) are thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and
hyperglycemia.
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5 TREATMENT GUIDELINES2, 3, 4
Regardless of the patient's volume status, another common feature is to restrict free water and hypotonic fluid
intake, since these solutions can only exacerbate hyponatremia. Free water intake from oral intake and
intravenous fluids should generally be less than 1–1.5 L/d.
Hypovolemic patients require adequate fluid resuscitation from isotonic fluids (either normal saline or
lactated Ringer solution) to suppress the hypovolemic stimulus for ADH release. Patients with cerebral
salt wasting may require hypertonic saline or normal saline to prevent circulatory collapse; some may
respond to fludrocortisone.
Hypervolemic patients may require loop diuretics or dialysis, or both, (or other extracorporeal
ultrafiltration) to correct the increased total body water and sodium. Euvolemic patients may respond to
free water restriction alone. Treatment with
Symptomatic and/or severe hyponatremia, in Hypovolemic or Euvolemic state, generally requiring
hospitalization for observation, careful monitoring of fluid balance and weights, and frequent sodium checks.
Any inciting medications should be discontinued if possible.
There is no consensus about the optimal rate of sodium correction in symptomatic hyponatremic
patients. A reasonable rate is 10–12 mEq/L/d in mildly to moderately symptomatic patients. A more
aggressive rate of 1–1.5 mEq/L/h (to a maximum correction of 10–12 mEq/L) has been used in severely
symptomatic patients. Sodium concentration should be monitored as frequently as every 1–2 hours. As
the symptoms improve or resolve, the correction rate should be reduced to roughly 0.5 mEq/L/h. To
avoid overcorrection, the physician should stabilize the sodium in the range of 125 to 130 mEq/L.
In severely symptomatic patients, the physician should calculate the patient's sodium deficit and deliver
hypertonic saline (ie, 3% saline) at the appropriate rate. In general the saline infusion rate should be
approximately 0.5 mL/kg body weight/h; rates of 1 mL/kg/h or greater may represent a miscalculation of the
sodium deficit or mathematical error. Hypertonic saline in hypervolemic patients can be hazardous, resulting in
worsening volume overload, pulmonary edema, and ascites.
1. Demeclocycline (300–600 mg orally twice daily) is used for patients who cannot adequately restrict water
restriction or have an inadequate response to conservative measures. It inhibits the effect of ADH on the distal
tubule. Onset of action may require 1 week, and urinary concentrating ability may be permanently impaired,
resulting in nephrogenic diabetes insipidus and even hypernatremia. Demeclocycline may be more nephrotoxic in
patients with cirrhosis.
2. Vasopressin antagonists may revolutionize the treatment of euvolemic and hypervolemic hyponatremia,
especially in persons with heart failure such as lixivaptan, tolvaptan, and satavaptan, which are selective
vasopressin-2 receptor antagonists. V2 receptors primarily mediate the diuretic effect of ADH. For hospitalized
patients with euvolemic SIADH, conivaptan is given as an intravenous loading dose of 20 mg delivered over 30
minutes, then as 20 mg continuously over 24 hours. Subsequent infusions may be administered every 1–3 days at
20–40 mg/d by continuous infusion.*
* Cho Kerry C, Fukagawa Masafumi, Kurokawa Kiyoshi, "Chapter 21. Fluid & Electrolyte Disorders" (Chapter).
McPhee SJ, Papadakis MA, Tierney LM, Jr.: CURRENT Medical Diagnosis & Treatment 2009:
http://www.accessmedicine.com/content.aspx?aID=10909.
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6 PRICING (relative) 5
7 Drug Comparison1
http://www.accessdata.fda.gov/drugsatfda_docs/l
abel/2009/022275lbl.pdf
http://www.drugbank.ca/drugs/DB00872
http://www.accessdata.fda.gov/drugsatfda_docs/l
abel/2008/021697s001lbl.pdf
Conivaptan is
Tolvaptan is

a nonpeptide, dual vasopressin V1A and V2
receptors antagonist.

a selective vasopressin V2-receptor
antagonist.

Starting dose begin with a loading dose of
20 mg IV administered over 30 minutes,
followed by 20 mg of conivaptan
administered in a continuous intravenous
infusion over 24 hours. Following the initial
day of treatment, conivaptan is to be
administered for an additional 1 to 3 days in
a continuous infusion of 20 mg/day.

Starting dose is 15 mg once daily. Dosage
may be increased at intervals ≥ 24 hr to 30
mg once daily.

Maximum dose is 60 mg once daily as
needed to raise serum sodium.

Tolvaptan affinity for the V2-receptor is 29
times greater than for the V1a-receptor.

Maximum dose (after the loading dose) is 40
mg per day.

The predominant effect of conivaptan is
through its V2 antagonism.
1.
Drugs@FDA : http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/
2.
DrugBank: http://www.drugbank.ca/
3.
Dipiro: USC Pharmacology Website
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2/12/2016
4.
WebMD: http://www.webmd.com/
5.
DrugStore: http://www.drugstore.com/
6.
Rxfiles: http://www.rxfiles.ca/rxfiles/modules/druginfoindex/druginfo.aspx
7.
Rphworld: http://www.rphworld.com/pharmacist/link-347.html
8.
Rphworld: http://www.rphworld.com/pharmacist/viewlink-25534.html
9.
CenterWatch: http://www.centerwatch.com/drug-information/index.htm
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