Lopinavir
Contraindicated
Textbook
Increased levels and potential adverse effects of tolvaptan.
Tolvaptan should not be given to patients receiving inhibitors of CYP3A4.
Source: KDT 7e · p598
Drug reference
Tolvaptan
Vasopressin Analogue · Agent for Hyponatremia and Polycystic Kidney Disease
Also known as JINARC, SAMSCA
Vasopressin AnalogueAgent for Hyponatremia and Polycystic Kidney DiseaseATC C03XA01
CDSCO approvedSchedule HATC C03XA01
EXCRETION
—
not curated
INTERACTIONS
12 major
incl. contraindicated
PREGNANCY
Avoid—toxicity in animal studies.
FDA category + note
Top interactionssee all 12 →
- LopinavirContraindicatedTextbookKDT 7e · p598
- AmprenavirSevereDatabaseDDInter
- ApalutamideSevereDatabaseDDInter
- AtazanavirSevereDatabaseDDInter
Mechanism
Tolvaptan is a vasopressin V2-receptor antagonist. It selectively blocks the binding of vasopressin to V2 receptors in the renal collecting ducts, thereby increasing free water excretion (aquaresis) without affecting electrolyte excretion. This action leads to an increase in serum sodium concentration and a decrease in urine osmolality.
Indications
Hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretionAutosomal dominant polycystic kidney disease in adults with CKD stage 1 to 4 at initiation of treatment with evidence of rapidly progressing diseaseclinically significant hypervolemic hyponatremiaclinically significant euvolemic hyponatremiaslow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney diseasetherapy-resistant hyponatremiacorrection of water retention and hyponatremia in SIADHcorrection of water retention and hyponatremia in advanced CHFHyponatraemia due to CHFHyponatraemia due to cirrhosis of liverSyndrome of inappropriate ADH secretion (SIADH)Euvolemic hyponatremia due to Tumor-Associated Syndrome of Inappropriate Antidiuretic Hormone (used in combination with fluid restriction)slow the decline of renal function in Autosomal Dominant Polycystic Kidney Disease (ADPKD)reduce renal pain in ADPKDfor ADPKD patients at risk of rapidly progressing diseasereduction in kidney cyst formation, decreased cyst cell growth, and preserved kidney function in preclinical ARPKD models (currently in Phase 3 clinical trials for ARPKD)
Dosing
- Adult
- For Autosomal dominant polycystic kidney disease (JINARC®): Initially 60 mg daily in 2 divided doses for at least a week (45 mg in the morning before breakfast, and 15 mg 8 hours later); increased to 90 mg daily in 2 divided doses for at least a week (60 mg in the morning before breakfast, and 30 mg 8 hours later); then increased if tolerated to 120 mg daily in 2 divided doses (90 mg in the mornin…
- Max dose
- 120 mg daily
Pharmacokinetics
Half-life
2.8 to 12 h
Metabolism
entirely by CYP3A4 metabolism
Excretion
less than 1% excreted in the urine
Contraindications
- Anuria
- Hypernatraemia
- Hypovolaemic hyponatraemia
- Impaired perception of thirst
- Volume depletion
- Abnormal liver function tests and/or signs or symptoms of liver injury (do not initiate if the criteria for permanent discontinuation are met)
- hypovolemic hyponatremia
- liver disease
- strong inhibitors of CYP3A4 (e.g., clarithromycin, ketoconazole)
- use with hypertonic saline
- no long-term benefits in CHF
- Patients receiving inhibitors of CYP3A4
Side effects
Common
Appetite decreasedastheniaconstipationdehydrationdiarrhoeadizzinessdry mouthdyspnoeagastrointestinal discomfortgastrooesophageal reflux diseaseheadachehepatic disordershyperglycaemiahypernatraemiahyperuricaemiainsomniamuscle spasmspalpitationspolydipsiaskin reactionsthirsturinary disordersweight decreasedpolyuriahypotensionpyrexiaincreased thirstxerostomiaGI adverse effectsheadacheshypokalemiahyperglycemiasevere thirstFeverG.I. upsetliver function impairmentdiarrhea
Serious
- Acute hepatic failure (cases requiring liver transplantation reported)
- Osmotic demyelination (leading to serious neurological events)
- osmotic demyelination syndrome (due to too rapid correction of hyponatremia)
- liver damage (administration generally limited to 30 days)
- Thrombotic complications (due to haemoconcentration if hyponatraemia is corrected too rapidly)
Pregnancy & lactation
Pregnancy
Avoid—toxicity in animal studies.
Lactation
Avoid—present in milk in animal studies.
Drug interactions
Amprenavir
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Apalutamide
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Atazanavir
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Berotralstat
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Boceprevir
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Carbamazepine
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Ceritinib
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Clarithromycin
Severe
Database
Increased plasma levels of tolvaptan.
Avoid coadministration.
Source: DDInter
Cobicistat
Severe
Database
Increased levels and potential adverse effects of tolvaptan.
Tolvaptan should not be given to patients receiving inhibitors of CYP3A4.
Source: DDInter
Conivaptan
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Delavirdine
Severe
Database
Clinical effect not specified
Source: DDInter
Related guidelines
Chronic kidney disease — assessment and management
KDIGO · Nephrology · 2024
Coronary angiography with renal dysfunction
CSI · Cardiology · 2020
Fetal growth restriction
FOGSI · Obstetrics & Gynaecology · 2018
Acute coronary syndrome in chronic kidney disease
CSI · Cardiology · 2020
MASLD / non-alcoholic fatty liver disease
AASLD · Gastroenterology · 2023
Ask House about Tolvaptan
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: KD Tripathi 7e, Goodman & Gilman 14e, Harrison 22e, Katzung·Verified: 2026-05-13 · House clinical team