Adult: Including cases in patients with heart failure or syndrome of inappropriate antidiuretic hormone secretion (SIADH): Initially, 15 mg once daily; may increase at intervals of at least 24 hours to 30 mg once daily, and subsequently up to 60 mg once daily as needed to achieve the target serum Na concentration. Max treatment duration: 30 days. Patients at risk of overly rapid serum Na correction: 7.5 mg once daily. Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Adult: In patients with CKD stage 1 to 4, to slow the progression of cyst development and renal insufficiency: Jinarc Initially, 60 mg daily in 2 divided doses (45 mg given at least 30 minutes before breakfast; 15 mg given 8 hours later). May increase dose to 90 mg daily in 2 divided doses (60 mg at least 30 minutes before breakfast; 30 mg given 8 hours later); followed by 120 mg daily in 2 divided doses (90 mg given at least 30 minutes before breakfast; 30 mg given 8 hours later). Doses are titrated based on patient's response and tolerability with intervals of at least 1 week between titrations. Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
What are the brands available for Tolvaptan in Hong Kong?
Autosomal dominant polycystic kidney disease (ADPKD): Jinarc:
Patients taking strong CYP3A inhibitors:
Patients on 60 mg daily in 2 divided doses (45 mg + 15 mg): Reduce dose to 15 mg once daily.
Patients on 90 mg daily in 2 divided doses (60 mg + 30 mg) or 120 mg daily in 2 divided doses (90 mg + 30 mg): Reduce dose to 30 mg once daily; if not well tolerated, may further reduce to 15 mg once daily.
Patients taking moderate CYP3A inhibitors:
Patients on 60 mg daily in 2 divided doses (45 mg + 15 mg): Reduce dose to 30 mg daily given in 2 equally divided doses (15 mg + 15 mg).
Patients on 90 mg daily in 2 divided doses (60 mg + 30 mg): Reduce dose to 45 mg daily in 2 divided doses (30 mg + 15 mg).
Patients on 120 mg daily in 2 divided doses (90 mg + 30 mg): Reduce dose to 60 mg daily in 2 divided doses (45 mg + 15 mg).
Further dose reductions may be considered according to patient's tolerability. Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Administration
Tolvaptan May be taken with or without food. Avoid grapefruit juice.
Contraindications
Hypersensitivity to tolvaptan or other benzazepine derivatives. Anuria, volume depletion, hypernatraemia, hypovolaemic hyponatraemia; inability to sense or respond to thirst. Elevated liver enzymes and/or signs and symptoms of liver injury before treatment initiation (when used for ADPKD). Pregnancy and lactation. Concomitant use with strong CYP3A inhibitors (when used for hypervolaemic and euvolaemic hyponatraemia). Contraindications may vary among individual products and between countries (refer to specific product labelling for detailed information).
Special Precautions
Patient with partial urinary outflow obstruction (e.g. prostatic hypertrophy, micturition impairment); at risk of overly rapid correction of Na (e.g. cancer, very low baseline serum Na concentrations, concomitant use of diuretics or Na supplements); diabetes mellitus; hypoxia, alcoholism, malnutrition. Not indicated for use when urgent treatment of hyponatraemia is required to prevent or treat serious neurological symptoms (when used for euvolaemic or hypervolaemic hyponatraemia). Concomitant use with moderate or strong CYP3A inhibitors (when used for ADPKD). Available brands of tolvaptan have different indications; do not switch between brands or products (refer to specific product guidelines). Renal and hepatic impairment.
Adverse Reactions
Significant: Thirst, dry mouth, hypovolaemia or severe dehydration; hyperkalaemia, hyperglycaemia; idiosyncratic elevations of ALT and AST, elevated bilirubin, increased serum uric acid. Very rarely, anaphylaxis (including anaphylactic shock and generalised rash). Gastrointestinal disorders: Nausea, constipation, diarrhoea, dysgeusia. General disorders and administration site conditions: Pyrexia, malaise. Investigations: Blood in urine, increased blood creatinine. Metabolism and nutrition disorders: Decreased appetite, hypoglycaemia, hypernatraemia. Nervous system disorders: Headache, dizziness. Renal and urinary disorders: Pollakiuria, polyuria. Skin and subcutaneous tissue disorders: Ecchymosis, pruritus. Vascular disorders: Orthostatic hypotension. Potentially Fatal: Hepatotoxicity; osmotic demyelination syndrome (when too rapid correction of hyponatremia occurs).
PO: Z (Embryo-foetal death and harm were observed in animal studies. Generally contraindicated.)
Patient Counseling Information
Ensure adequate fluid intake. This drug may cause occasional dizziness, asthenia or syncope; if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor serum Na concentration and rate of Na increase; serum K concentration, volume status. Assess neurologic status; signs and symptoms of hepatotoxicity. When used for ADPKD: Obtain serum transaminases and serum bilirubin prior to therapy initiation, at 2 weeks and 4 weeks after therapy initiation, monthly for 18 months, and every 3 months thereafter.
Overdosage
Symptoms: Polyuria, thirst, dehydration or hypovolaemia. Management: Symptomatic and supportive treatment. Assess vital signs, electrolyte concentrations, fluid status and ECG. Perform continuous replacement of water and electrolytes until aquaresis diminishes.
Drug Interactions
Concurrent use with other agents for hyponatraemia or other agents that increase serum Na concentration may result in an increased risk of developing rapid correction of serum Na. Increased serum concentration with strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, ritonavir, itraconazole) or moderate CYP3A inhibitors (e.g. amprenavir, atazanavir, ciprofloxacin, erythromycin, fluconazole). Decreased serum concentration with strong CYP3A4 inducers (e.g. rifampicin, barbiturates, carbamazepine). May increase the plasma concentration of lovastatin, digoxin and rosuvastatin. Increased risk of severe dehydration with loop and thiazide diuretics. May diminish the therapeutic effect of desmopressin. Increased risk of hyperkalaemia with ARBs, ACE inhibitors and K-sparing diuretics.
Food Interaction
Increased serum concentration with grapefruit juice. Decreased serum concentration with St. John's wort.
Action
Description: Mechanism of Action: Tolvaptan is a selective vasopressin V2-receptor antagonist. It specifically inhibits the binding of arginine vasopressin (AVP) at the V2-receptor of the distal portions of the nephron, therefore promoting the excretion of free water (without the loss of serum electrolytes). This results in net fluid loss, increased urine output, decreased urine osmolality and restoration of normal serum Na levels. Pharmacokinetics: Absorption: Bioavailability: Approx 56%. Time to peak plasma concentration: Approx 2-4 hours. Distribution: Volume of distribution: Approx 3 L/kg. Plasma protein binding: >98%. Metabolism: Metabolised almost exclusively by CYP3A4 isoenzyme into inactive metabolites. Excretion: Via faeces (59%; 19% as unchanged drug); urine (40%; <1% as unchanged drug). Elimination half-life: Approx 8-12 hours.
Chemical Structure
Tolvaptan Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 216237, Tolvaptan. https://pubchem.ncbi.nlm.nih.gov/compound/Tolvaptan. Accessed June 25, 2024.
Sign Out
