Pharmacology · Vasopressin receptor antagonists (vaptans)
Tolvaptan !
An oral V2 receptor blocker that removes free water and raises low sodium in heart failure and SIADH. Started in hospital.
Updated 2026-11-01
The figure shows tolvaptan bound to the human vasopressin V2 receptor (with a helper antibody fragment used to solve the structure).
Mechanism of action
Tolvaptan blocks the V2 receptor for vasopressin (antidiuretic hormone) in the collecting duct. Without that signal, aquaporin-2 water channels are not inserted into the cell membrane, so free water leaves in dilute urine (aquaresis) and serum sodium rises.
- Tolvaptan blocks the V2 receptor in the collecting duct
- Aquaporin-2 channels stay out of the membrane
- Free water is lost in dilute urine (aquaresis)
- Serum sodium rises
Pharmacokinetics
- Absorption
- Absorbed by mouth; grapefruit juice increases levels
- Metabolism
- By CYP3A
- Onset and duration
- The water-losing and sodium-raising effects begin within 2 to 4 hours
Indications
- Clinically significant hypervolaemic or euvolaemic hyponatraemia, including in heart failure and SIADH Heart failure →
- Slowing kidney growth in autosomal dominant polycystic kidney disease (a separate, closely monitored product) Autosomal dominant polycystic kidney disease →
Adverse effects
Common
- Thirst and dry mouth
- Frequent urination
- Weakness
- Constipation
- High blood glucose
Contraindications
- Hypovolaemic hyponatraemia
- Need to raise sodium urgently because of serious neurological symptoms
- Inability to sense or respond to thirst
- Strong CYP3A inhibitors
- Anuria
- Polycystic kidney disease outside the special monitoring programme
Key interactions
- Strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin)
- Much higher tolvaptan levels; contraindicated
- Moderate CYP3A inhibitors and grapefruit juice
- Higher levels; avoided
- Strong CYP3A inducers
- Lower levels and less effect; avoided
- Hypertonic saline
- Risk of overly rapid sodium correction; not recommended together
What is monitored
- Serum sodium often during start and dose changes
- Volume status and fluid balance
- Liver tests
- Neurological status
Administration and safety
- Started and restarted only in hospital, where serum sodium can be checked often.
- Fluid restriction is avoided in the first day; patients drink in response to thirst.
- Use for hyponatraemia is time-limited because of liver risk.
Nursing care
- Check serum sodium as ordered, often in the first day; report a fast rise at once.
- Watch for neurological changes: difficulty speaking or swallowing, weakness, drowsiness.
- Make sure the patient can sense thirst and has water within reach.
- Watch for signs of liver injury: fatigue, dark urine, jaundice, right upper abdominal pain.
- Teach: avoid grapefruit juice, do not stop and restart on their own.
Pregnancy and breastfeeding
Human data are too limited to judge the risk; used only if the benefit justifies it.
Test yourself
Think of the answer, then tap the question to see it.
How does tolvaptan raise serum sodium?
It blocks the V2 receptor, so aquaporin-2 channels are not inserted and free water is lost in the urine (aquaresis).
Why is tolvaptan started in hospital?
Sodium can rise too fast and cause osmotic demyelination; frequent sodium checks are needed.
Which patients cannot receive tolvaptan?
Those with hypovolaemic hyponatraemia, those who cannot sense or respond to thirst, those on strong CYP3A inhibitors and those with anuria.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - TOLVAPTAN tablet (DailyMed (U.S. National Library of Medicine), 2026); Tolvaptan (low blood sodium): MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2018); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); RCSB PDB - 9U81: Cryo-EM structure of tolvaptan-bound human vasopressin V2 receptor complex with Fab (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.