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# 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

- Class: [Vasopressin receptor antagonists (vaptans)](https://durgical.com/en/pharmacology/classes/vasopressin-receptor-antagonists/)
- Receptor: Vasopressin V2 receptor
- ATC code: C03XA01

◎**Vasopressin V2 receptor**Tolvaptan

ⓘ The figure shows tolvaptan bound to the human vasopressin V2 receptor (with a helper antibody fragment used to solve the structure).

**Target in 3D:** Vasopressin V2 receptor. PDB structure 9U81 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/9U81) · Drag to rotate · pinch to zoom

## 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 →](https://durgical.com/en/conditions/heart-failure/)
- Slowing kidney growth in autosomal dominant polycystic kidney disease (a separate, closely monitored product) [Autosomal dominant polycystic kidney disease →](https://durgical.com/en/conditions/autosomal-dominant-polycystic-kidney-disease/)

## Adverse effects

### Common

- Thirst and dry mouth
- Frequent urination
- Weakness
- Constipation
- High blood glucose

### Serious (rare, important)

- Osmotic demyelination from too-rapid rise in sodium: dysarthria, mutism, dysphagia, quadriparesis, seizures, coma
- Liver injury
- Dehydration and low blood pressure

## 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.

## Memory aid

TolVAPtan «vaporises» water: it shuts the aquaporin door and lets water out, not salt; go slowly or the brain pays.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/tolvaptan/)

## Related drugs

- [Furosemide](https://durgical.com/en/pharmacology/furosemide/)

## Related conditions

- [Heart failure](https://durgical.com/en/conditions/heart-failure/)
- [Autosomal dominant polycystic kidney disease](https://durgical.com/en/conditions/autosomal-dominant-polycystic-kidney-disease/)

[← Back to the class: Vasopressin receptor antagonists (vaptans)](https://durgical.com/en/pharmacology/classes/vasopressin-receptor-antagonists/)

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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d9fd11d0-4269-12fb-95cf-b3c11d75e479) (DailyMed (U.S. National Library of Medicine), 2026); [Tolvaptan (low blood sodium): MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a609033.html) (MedlinePlus (U.S. National Library of Medicine), 2018); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=C03XA01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [RCSB PDB - 9U81: Cryo-EM structure of tolvaptan-bound human vasopressin V2 receptor complex with Fab](https://www.rcsb.org/structure/9U81) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/tolvaptan/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/tolvaptan/