Tolvaptan

Class
Diuretics
Subclass
Vasopressin receptor antagonists
Substance name
Tolvaptan
Brand names
Samsca®, Jynarque®
Common formulations
Tablet, Kit
Dosage and administration
Adults patients
Autosomal dominant polycystic kidney disease
•
Start at: 60 mg PO daily, in 2 divided doses (45 mg AM and 15 mg PM)
•
Maintenance: 120 mg PO daily, in 2 divided doses (90 mg AM and 30 mg PM)
Increase to 90 mg daily (60 mg AM and 30 mg PM), then to a maintenance dose of 120 mg daily at ≥ 1-week intervals. Consider decreasing to 45 mg daily (30 mg AM and 15 mg PM) and 30 mg daily (15 mg AM and 15 mg PM) in case of intolerance or side effects.
Hyponatremia • Hypervolemic or euvolemic
•
Start at: 15 mg PO daily
•
Maintenance: 30-60 mg PO daily for up to 30 days
Increase to 30 mg daily after at least 24 hours of the initial dose, and up to a maximum of 60 mg daily as needed to achieve the desired serum sodium level.
Indications for use
Labeled indications
Adults
•
Treatment of autosomal dominant polycystic kidney disease
•
Treatment of hyponatremia (hypervolemic or euvolemic)
Safety risks
Boxed warnings
Osmotic demyelination syndrome
•
Maintain a high level of suspicion, as too rapid correction of hyponatremia (> 12 mEq/L in 24 hours) can cause osmotic demyelination syndrome. Initiate and re-initiate tolvaptan only in a setting where serum sodium can be monitored closely.
Contraindications
Hypersensitivity to tolvaptan or its components
Anuria
Uncorrected urinary outflow obstruction
Concomitant use of CYP3A inhibitors
Concomitant use of hypertonic saline
Warnings and precautions
Dehydration, hypovolemia
•
Maintain a high level of suspicion, as tolvaptan causes copious aquaresis and may lead to dehydration and hypovolemia. Monitor serum electrolytes and volume status. Avoid fluid restriction during the first 24 hours of therapy and advise patients to continue ingestion of fluid in response to thirst.
Hepatotoxicity
•
Maintain a high level of suspicion, as tolvaptan has been associated with an increased risk of serious and potentially fatal liver injury. Limit duration of treatment to 30 days. Avoid use in patients with underlying liver disease, including cirrhosis.
Increased serum potassium
•
Use caution in patients with hyperkalemia or receiving drugs known to increase serum potassium levels.
Increased serum uric acid
•
Use caution in patients with gout.
Specific populations
Renal impairment
CrCl ≥ 10 mL/min
•
Use acceptable. No dose adjustment required.
CrCl < 10 mL/min
•
Do not use.
Renal replacement therapy
Any modality
•
Use acceptable. No dose adjustment required.
Hepatic impairment
Any severity
•
Avoid use.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: D
•
Insufficient evidence. Evidence of fetal harm in animals. In animal studies, cleft palate, brachymelia, microphthalmia, skeletal malformations, decreased fetal weight, delayed fetal ossification, and embryofetal death occurred.
Breastfeeding
Halt breastfeeding temporarily.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
May potentially cause adverse effects in breastfed infants.
Adverse reactions
Very common > 10%
•
Dry mouth, dehydration, ↑ thirst, nausea, polyuria, pollakiuria
Common 1-10%
•
Disseminated intravascular coagulation, ventricular fibrillation, intracardiac thrombus, diabetic ketoacidosis, ischemic colitis, rhabdomyolysis, cerebrovascular accident, pulmonary embolism, deep vein thrombosis, respiratory failure, gastrointestinal bleeding, ↑ blood glucose, ↑PT, vaginal bleeding, asthenia, constipation, fever, loss of appetite
Unknown frequency
•
↑ serum sodium, skin rash, hypovolemia, ↑ serum potassium, osmotic demyelination syndrome, anaphylaxis, drug-induced liver injury
Interactions
Drug(s)
Check Interactions
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