Adult: In patient with hypervolaemic or euvolaemic cases associated with Syndrome of Inappropriate Antidiuretic Hormone (SIADH): Initially, 15 mg once daily, increase to 30 mg once daily after 24 hours. Dose may be adjusted up to max 60 mg once daily to achieve desired response. Max treatment duration: 30 days.
Adult: Initially, 60 mg daily in 2 divided doses (45 mg before breakfast and 15 mg after 8 hours). Increase at weekly interval to 90 mg daily in 2 divided doses (60 mg before breakfast and 30 mg after 8 hours up to target dose 120 mg daily in 2 divided doses (90 mg before breakfast and 30 mg after 8 hours). Reduce dose, if needed according to tolerability.
Patient taking strong CYP3A4 inhibitors:
Patient on 60 mg daily dosing: Reduce dose to 15 mg once daily.
Patient on 90-120 mg daily dosing: Reduce dose to 30 mg once daily, may further reduce to 15 mg once daily if needed.
Patient taking moderate CYP3A4 inhibitors: Reduce dose by 50%, given in 2 divided doses. Adjust the first daily dose as needed and maintain 2nd daily dose at 15 mg.
Administration
May be taken with or without food. Avoid grapefruit juice.
Contraindications
Anuria, volume depletion, hypovolaemic hyponatraemia, hypernatraemia, elevated liver enzymes, liver disease (e.g. cirrhosis), inability to perceive or respond to thirst.
Special Precautions
Patient with fluid restriction, urinary outflow obstruction (e.g. prostatic hypertrophy, micturition impairment), risk for demyelination syndromes (e.g. alcoholism or malnutrition), diabetes mellitus. Hepatic and renal impairment (CrCl <10 mL/min). Pregnancy and lactation. Not indicated for urgent treatment of hyponatraemia.
This drug may cause dizziness, asthenia, or syncope, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor serum Na level prior to initiation, within 6 hours and the 1st 2 days of therapy, and every dose adjustments. Monitor neurological status; volume status every 6 hours; fluid and electrolyte balance prior to and during therapy. Maintain adequate hydration and urine osmolality at <300 mOsm/kg during dose adjustments. Monitor vital signs, uric acid, blood pressure, renal function and LFT, signs and symptoms of hepatotoxicity.
Overdosage
Symptoms: Elevated Na concentration, polyuria, thirst, dehydration/hypovolaemia. Management: Symptomatic and supportive treatment. Provide adequate water and electrolyte replacement. Monitor vital signs, respiratory status, ECG, and blood pressure. May administer IV hypotonic fluids in case of dehydration and hypovolaemia.
Drug Interactions
Increased plasma concentration with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin, diltiazem). Decreased plasma concentration with CYP3A4 inducers (e.g. rifampicin, barbiturates). May increase plasma concentration and cardiac effects of digoxin. May diminish therapeutic effect of desmopressin.
Food Interaction
Increased plasma concentration with grapefruit juice. Decreased plasma concentration with St. John’s wort.
Action
Description: Tolvaptan is a selective vasopressin V2-receptor antagonist. It blocks the binding of arginine vasopressin (AVP) at the V2-receptor of the distal portions of the nephrons. This leads to increased urine output resulting to increased water diuresis without electrolyte loss, restoration of normal serum Na concentrations, and decreased urine osmolality. Onset: 2-4 hours. Duration: 24 hours (60% serum Na elevation). Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 40%. Time to peak plasma concentration: 2-4 hours. Distribution: Volume of distribution: 3 L/kg. Plasma protein binding: 99%. Metabolism: Extensively metabolised in the liver by CYP3A4. Excretion: Via faeces (19% as unchanged drug); urine (<1% as unchanged drug). Terminal elimination half-life: Approx 8 hours.
Chemical Structure
Tolvaptan Source: National Center for Biotechnology Information. PubChem Database. Tolvaptan, CID=216237, https://pubchem.ncbi.nlm.nih.gov/compound/Tolvaptan (accessed on Jan. 23, 2020)
Storage
Store below 25°C. Protect from light and moisture.
C03XA01 - tolvaptan ; Belongs to the class of vasopressin antagonists. Used as diuretics.
References
Anon. Tolvaptan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/02/2018.Buckingham R (ed). Tolvaptan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/02/2018.Joint Formulary Committee. Tolvaptan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/02/2018.Samsca (Otsuka America Pharmaceutical, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/02/2018.
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