Tolvaptan


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Hypervolaemic or euvolaemic hyponatraemia associated with SIADH Initial: 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. ADPKD Initial: 60 mg/day in 2 divided doses (45 mg before breakfast and 15 mg after 8 hours). Increase at weekly interval to 90 mg/day in 2 divided doses (60 mg before breakfast and 30 mg after 8 hours) up to target dose 120 mg/day in 2 divided doses (90 mg before breakfast and 30 mg after 8 hours). Reduce dose, if needed according to tolerability.
Dosage Details
Oral
Hyponatraemia
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.

Oral
Autosomal dominant polycystic kidney disease (ADPKD)
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.
Special Patient Group
Autosomal dominant polycystic kidney disease (ADPKD):

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.
Adverse Reactions
Significant: Hyperuricaemia, gout, polydipsia, polyuria, hypovolaemia, dehydration, hyperkalaemia, nocturia, pollakiuria, hyperglycaemia, increased ALT/AST, bilirubin. Rarely, anaphylaxis.
Gastrointestinal disorders: Nausea, dry mouth, constipation, diarrhoea.
General disorders and administration site conditions: Malaise, fever, weakness.
Investigations: Increased creatinine.
Metabolism and nutrition disorders: Hypoglycaemia, decreased appetite, hypernatraemia.
Nervous system disorders: Headache, dizziness.
Skin and subcutaneous tissue disorders: Pruritus, ecchymosis.
Vascular disorders: Syncope, orthostatic hypotension.
Potentially Fatal: Osmotic demyelination, hepatotoxicity.
Patient Counseling Information
This drug may cause dizziness, asthenia, or syncope, if affected, do not drive or operate machinery.
MonitoringParameters
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

Click on icon to see table/diagram/image
Storage
Store below 25°C. Protect from light and moisture.
MIMS Class
ATC Classification
C03XA01 - tolvaptan ; Belongs to the class of vasopressin antagonists. Used as diuretics.
Disclaimer: This information is independently developed by MIMS based on Tolvaptan from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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