Formulary
Tolvaptan: Indications, Dosing, Side Effects and Interactions
Tolvaptan is a vasopressin V 2 -receptor antagonist.
MedNext Academy | 3 min read
Tolvaptan: Indications, Dosing, Side Effects and Interactions
Tolvaptan is a vasopressin V 2 -receptor antagonist.
Drug action
Tolvaptan is a vasopressin V 2 -receptor antagonist.
Indications and dose
**Autosomal dominant polycystic kidney disease in adults with CKD stage 1 to 4 at initiation of treatment with evidence of rapidly progressing disease (initiated by a specialist)**
- **Adult** (By Mouth): Initially 60 mg daily in 2 divided doses for at least a week, 45 mg in the morning before breakfast, and then 15 mg taken 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 then 30 mg taken 8 hours later, then increased if tolerated to 120 mg daily in 2 divided doses, 90 mg in the morning before breakfast, and then 30 mg taken 8 hours later, dose titration should be performed cautiously; patients may down-titrate to lower doses based on tolerability.
**Hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion (initiated in hospital or under specialist supervision)**
- **Adult** (By Mouth): Initially 15 mg once daily, increased if necessary up to 60 mg once daily, a reduced starting dose of 7.5 mg once daily should be considered for patients at risk of overly rapid correction of serum-sodium concentration.
Cautions
General cautions: Abnormal liver function tests and/or signs or symptoms of liver injury (do not initiate if the criteria for permanent discontinuation are met-consult product literature); diabetes mellitus; patients at risk of dehydration (ensure adequate fluid intake); urinary outflow obstruction (increased risk of acute retention) Specific cautions: When used for Autosomal dominant polycystic kidney disease Serum-sodium abnormalities (correct before treatment initiation) When used for Hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion Patients at risk of demyelination syndromes (e.g hypoxia, alcoholism and malnutrition)
Contraindications
Anuria; hypernatraemia; hypovolaemic hyponatraemia; impaired perception of thirst; volume depletion
Side effects
Common or very common Appetite decreased; asthenia; constipation; dehydration; diarrhoea; dizziness; dry mouth; dyspnoea; gastrointestinal discomfort; gastrooesophageal reflux disease; gout; headache; hepatic disorders; hyperglycaemia; hypernatraemia; hyperuricaemia; insomnia; muscle spasms; palpitations; polydipsia; skin reactions; thirst; urinary disorders; weight decreased Frequency not known Acute hepatic failure (cases requiring liver transplantation reported) Side-effects, further information Interrupt treatment and perform liver-function tests promptly if symptoms of hepatic impairment occur (anorexia, nausea, vomiting, fatigue, abdominal pain, jaundice, dark urine, pruritus)-consult product literature.
Interactions
**Severe interactions:**
- While there does not appear to be a synergistic or additive effect of concomitant use of tolvaptan with loop and thiazide diuretics, each class of agent has the potential to lead to severe...
**Other interactions (30):**
- Effect of other medicinal products on the pharmacokinetics of tolvaptan CYP3A inhibitors Concomitant use of medicinal products that are moderate CYP3A inhibitors (e.g.
- Co-administration of tolvaptan and ketoconazole resulted in a 440 % increase in area under time-concentration curve (AUC) and 248 % increase in maximum observed plasma concentration (C max ) for...
- Co-administration of tolvaptan and fluconazole, a moderate CYP3A inhibitor, produced a 200 % and 80 % increase in tolvaptan AUC and C max , respectively.
- Co-administration of tolvaptan with grapefruit juice, a moderate to strong CYP3A inhibitor, produced a doubling of peak tolvaptan concentrations (C max ).
- Dose reduction of tolvaptan is recommended for patients while taking moderate or strong CYP3A inhibitors (see section 4.2).
- CYP3A inducers Concomitant use of medicinal products that are potent CYP3A inducers (e.g.
Pregnancy
Avoid-toxicity in animal studies.
Breast feeding
Avoid-present in milk in animal studies.
Hepatic impairment
Manufacturer advises caution in severe impairment; avoid if abnormal liver-function tests and/or signs or symptoms of liver injury meet the requirements for permanent discontinuation-consult product literature.
Renal impairment
No information available in severe impairment. For Jinarc , discontinue if progression to CKD stage 5. M
Medicinal forms
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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