Tolvaptan
- Atc Codes:C03XA01
- CAS Codes:150683-30-0
- PHARMGKB ID:150683-30-0
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Genes that may be involved
- Substrate of
- Inhibits
- Drug Interactions
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Austria: Samsca; Bulgaria: Samsca; Czech Republic: Samsca; Denmark: Samsca; Estonia: Samsca; Finland: Samsca; Germany: Samska; Ireland: Samsca; Italy: Samsca; Latvia: Samsca; Lithuania: Samsca; Luxembourg: Samsca; Malta: Samsca; Netherlands: Samsca; Poland: Samsca; Portugal: Samsca; Romania: Samsca; Slovakia: Samsca; Slovenia: Samsca; Spain: Samsca; Sweden: Samsca; UK: Samsca.
North America
USA: Samsca.
Drug combinations
Chemistry
Tolvaptan: C~26~H~25~ClN~2~O~3~. Mw: 448.94. (1) N-[4-(7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)-3-methylphenyl]-2-methylbenzamide; (2)(±)-4′-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-o-tolu-m-toluidide. CAS-150683-30-0.
Pharmacologic Category
Diuretics, Miscellaneous; Vasopressin Antagonist. (ATC-Code: C03XA01).
Mechanism of action
Tolvaptan is a selective vasopressin V~2~-receptor antagonist with an affinity for the V~2~-receptor that is 1.8 times that of native arginine vasopressin (AVP). Tolvaptan affinity for the V~2~-receptor is 29 times greater than for the V~1a~-receptor. Antagonism of the V~2~ receptor by tolvaptan promotes the excretion of free water (without loss of serum electrolytes) resulting in net fluid loss, increased urine output, decreased urine osmolality, and subsequent restoration of normal serum sodium levels. Tolvaptan metabolites have no or weak antagonist activity for human V~2~-receptors compared with tolvaptan.
Therapeutic use
Treatment of clinically significant hypervolemic or euvolemic hyponatremia (associated with heart failure, cirrhosis or SIADH) with either a serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and resistant to fluid restriction.
Pregnancy and lactiation implications
Animal studies indicate reduced fetal weight, delayed ossification, increased abortions, fetal death, microphthalmia, open eyelids, cleft palate, brachymelia, and skeletal malformations. There are no adequate and well-controlled studies in pregnant women. Use only if benefit outweighs risk. In nursing mothers, discontinue drug or nursing taking into consideration importance of drug to mother.
Unlabeled use
Contraindications
Hypovolemic hyponatremia; urgent need to raise serum sodium acutely; use in patients unable to sense or appropriately respond to thirst; anuria; concurrent use with strong CYP3A inhibitors (e.g. ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, telithromycin, clarithromycin).
Warnings and precautions
Monitor serum sodium and neurologic status as serious neurologic sequelae can result from over-rapid correction of sodium (should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely). Potential increased risk of gastrointestinal bleeding in patients with cirrhosis. Dehydration and hypovolemia may require intervention. Avoid use with hypertonic saline. Avoid use with CYP3A inducers and moderate CYP3A inhibitors. Consider dose reduction if co-administered with ABCB1 inhibitors. Monitor serum potassium in patients with potassium >5 mEq/L or on drugs known to increase potassium.