TOLVAPTAN TAB

Clinical Criteria Summary

History, signs or symptoms of significant liver impairment or injury (does not apply to uncomplicated polycystic liver disease)
Use of strong CYP 3A inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, indinavir/ritonavir, ritonavir, conivaptan)
Uncorrected abnormal blood sodium concentrations
Inability to sense or respond to thirst
Hypovolemia
Hypersensitivity (e.g., anaphylaxis, rash) to tolvaptan or any component of the product
Uncorrected urinary outflow obstruction
Anuria
Advanced diabetes (e.g., glycosylated hemoglobin > 7.5%)
Significant kidney disease (currently active glomerulonephritides), renal cancer, single kidney, recent (within past 6 months) renal surgery or acute kidney injury
Chronic kidney disease stage 5 (eGFR < 15 ml/min/1.73m2) or end-stage kidney disease
Inability to adhere to a twice daily treatment regimen

Prescribed by a VA authorized Nephrologist
Enrolled in JYNARQUE REMS Program and VA Specific Ordering Process
Diagnosis of autosomal dominant polycystic kidney disease (ADPKD)
AND one of the following indicating high risk of progression:
Age > 18 to 50 years with eGFR > 60 ml/min/1.73m2 AND total kidney volume (TKV) > 750 ml
Age > 18 to 55 years with eGFR > 25 to < 65 ml/min/1.73m2
Age > 56 to < 66 years with eGFR > 25 to < 44 ml/min AND eGFR decline > 2ml/min/1.73m2 per year

ALT, AST, and bilirubin prior to initiation, at 2 and 4 weeks after initiation, monthly for 18 months, and every 3 months thereafter
Serum sodium monitoring to detect increases above normal range
Assessment of hydration and volume status

Inability to adhere to liver function test monitoring schedule (at 2 and 4 weeks after initiation, monthly for 18 months, then every 3 months)
Inability to adhere to twice daily therapy
Inability to tolerate treatment
Development of chronic kidney disease stage 5 (eGFR < 15 ml/min/1.73m2) or end-stage kidney disease

Initial recommended dosage: 60 mg orally per day divided as 45 mg upon awakening and 15 mg taken 8 hours later
Titrate to 60 mg + 30 mg, then 90 mg + 30 mg per day if tolerated, with at least weekly interval between titrations
Dose may be down-titrated based on tolerability; tablets are not scored
If a dose is missed, take the next dose at the scheduled time
Dose adjustments required for patients taking moderate CYP 3A inhibitors (specific reduced doses provided)

Indicated to slow kidney function decline in adults at risk for rapidly progressing ADPKD
Avoid concomitant use with strong CYP 3A inducers, grapefruit juice, OATP1B1/3 and OAT3 substrates, BCRP substrates, and V2-receptor agonists (e.g., desmopressin)
Patients must be instructed to drink water when thirsty throughout the day and night while awake
Limit dietary salt intake to < 5 grams/day; ingest at least 2 to 3 liters of fluid per day (including 1 to 2 cups of water at bedtime regardless of perceived thirst, and replenish fluids after each episode of nocturia)
Temporarily suspend therapy if serum sodium increases above normal, or if patient becomes hypovolemic/dehydrated and fluid intake cannot be increased
For women of childbearing potential: Insufficient data on fetal risk; breastfeeding is not recommended

Use for autosomal dominant polycystic kidney disease (ADPKD)
Underlying liver disease including cirrhosis
Unable to sense or respond to thirst
Hypovolemic hyponatremia
Urgent need to raise serum sodium acutely
Anuria
Strong CYP 3A inhibitors (e.g., ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, clarithromycin, and telithromycin) or moderate CYP 3A inhibitors (e.g., erythromycin, fluconazole, aprepitant, diltiazem, and verapamil)

Care provided by a VA / VA Community Care endocrinologist, nephrologist, or other locally designated expert
Diagnosis of clinically significant hypervolemic or euvolemic hyponatremia (serum sodium less than 125 mEq/L or less marked hyponatremia that is symptomatic and unresponsive to fluid restriction)
Initiation and re-initiation conducted in a hospital setting for close serum sodium monitoring and avoidance of excessively rapid correction
Duration of treatment limited to 30 days due to the risk of hepatotoxicity
Avoid fluid restriction during the first 24 hours; advise patients to continue to ingest fluids in response to thirst

For women of childbearing potential: Use during pregnancy only if potential benefit justifies potential risk to the fetus based on animal data indicating possible fetal harm
Breastfeeding is not recommended