Table 2. Prescribing considerations for tolvaptan for autosomal dominant polycystic kidney disease.

Category	Prescribing considerations
Indication	To slow the progression of cyst development and renal insufficiency in adults with ADPKD and CKD Stages 1–3 with rapidly progressing disease
Targets and mechanism of action	Selective vasopressin V2 receptor antagonist, which reduces the reabsorption of water in the collecting duct and promotes free water diuresis. Metabolised by the CYP3A4 system
Contraindications	Elevated liver enzymes, liver injury, volume depletion, anuria, hypernatraemia, poor thirst regulation, hypersensitivity to constituents, pregnancy and breastfeeding
Limiting factors and precautions	Severe liver injury, potent aquaresis, hypernatraemia, hyperkalaemia, dehydration and hyperglycaemia
Drug interactions	CYP3A inhibitors and inducers (e.g. grapefruit juice, clarithromycin, ketoconazole, rifampicin, phenytoin, carbamazepine), P-glycoprotein inhibitors (e.g. ciclosporin and quinidine), digoxin, vasopressin analogues (desmopressin), diuretics
Adverse effects	Aquaretic symptoms (thirst, polyuria, nocturia, polydipsia), drug-induced liver injury, palpitations, constipation, dyspepsia, reduced appetite, gout, hypernatraemia, hyperuricaemia, dry skin, eczema, rash, diarrhoea
Dosage and administration	Oral route. Split-dose regimen. Initiating dose of 60 mg daily (45 mg every morning and 15 mg at night). Uptitrate dose gradually (over weeks to months) to 90 mg daily (60 mg and 30 mg split dose) and then to 120 mg daily (90 mg and 30 mg split dose), based on the patient's tolerance of aquaretic symptoms

ADPKD autosomal dominant polycystic kidney disease

CKD chronic kidney disease

CYP cytochrome P450