tolvaptan

REMS

Samsca

Significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked symptomatic hyponatremia that has resisted correction by fluid restriction), including patients with HF and syndrome of inappropriate antidiuretic hormone.

Jynarque

Patients at risk of rapidly progressing autosomal dominant polycystic kidney disease.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hepatic impairment;
Urgent need to acutely raise serum sodium (Samsca);
Patients who cannot appropriately sense/respond to thirst;
Hypovolemia;
Uncorrected abnormal serum sodium concentrations (Jynarque);
Anuria;
Uncorrected urinary outflow obstruction;
Lactation: Lactation.

Use Cautiously in:

Severe malnutrition, alcoholism, or advanced liver disease (↑ risk of osmotic demyelination; correct electrolyte abnormalities at a slower rates);
Cirrhosis (↑ risk of GI bleeding; use only when the need to treat outweighs risk);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may have ↑ sensitivity to effects.

Adv. Reactions/Side Effects ⬆ ⬇

CV: palpitations

Derm: dry skin, rash

Endo: hyperglycemia

F and E: thirst, hypernatremia, hypovolemia

GI: constipation, diarrhea, dry mouth, ↓appetite, dyspepsia, HEPATOTOXICITY

GU: polyuria

Metab: hyperuricemia

Neuro: dizziness, weakness, osmotic demyelination

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inhibitors, including ketoconazole, clarithromycin, itraconazole, nelfinavir, ritonavir, and nefazodone, as well as moderate CYP3A inhibitors, including erythromycin, fluconazole, aprepitant, diltiazem, and verapamil, may ↑ levels and risk of toxicity; avoid concurrent use.
CYP3A inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use with Jynarque; dosage adjustments may be necessary with Samsca.
P-glycoprotein inhibitors, including cyclosporine, may ↑ levels and risk of toxicity; dosage adjustments may be necessary.
May ↑ risk of hyperkalemia with angiotensin II receptor blockers, ACE inhibitors, and potassium-sparing diuretics.
Diuretics may ↑ risk of too rapidly correcting serum sodium concentrations.
May inhibit effects of desmopressin; avoid concurrent use.

Drug-Food:

Grapefruit juice may ↑ levels and the risk of toxicity; avoid concurrent use.

Availability ⬆ ⬇

(Generic available)

Tablets (Jynarque): 15 mg; 30 mg; 45 mg; 60 mg; 90 mg
Tablets (Samsca): 15 mg; 30 mg

Route/Dosage ⬆ ⬇

Samsca and Jynarque should not be used interchangeably.

Hyponatremia (Samsca)

PO (Adults ): 15 mg once daily initially; may ↑ at intervals of ≥1 day to 30 mg once daily, up to a maximum of 60 mg once daily. Do not use for longer than 30 days.

Autosomal Dominant Polycystic Kidney Disease (Jynarque and Jinarc)

PO (Adults ): 60 mg/day initially (taken as 45 mg upon wakening and then 15 mg 8 hr later); may be ↑ after at least 1 wk to 90 mg/day (taken as 60 mg upon wakening and then 30 mg 8 hr later); may then be ↑ after at least 1 wk to 120 mg/day (taken as 90 mg upon wakening and then 30 mg 8 hr later); Concurrent use of moderate CYP3A inhibitors: 30 mg/day initially (taken as 15 mg upon wakening and then 15 mg 8 hr later); may be ↑ after at least 1 wk to 45 mg/day (taken as 30 mg upon wakening and then 15 mg 8 hr later); may then be ↑ after at least 1 wk to 60 mg/day (taken as 45 mg upon wakening and then 15 mg 8 hr later).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as a selective vasopressin V2-receptor antagonist, resulting in increased renal water excretion and increased serum sodium.

Therapeutic effects:

Correction of hyponatremia (Samsca).
Slowed deterioration of renal function (Jynarque).

Classifications ⬆ ⬇

Therapeutic Classification: electrolyte modifiers

Pharmacologic Classification: vasopressin antagonists

Pharmacokinetics ⬆ ⬇

Absorption: 40% absorbed following oral administration.

Distribution: Well distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Extensively metabolized in the liver via the CYP3A4 isoenzyme; 59% excreted in the feces (19% as unchanged drug), with 40% excreted in the urine (<1% as unchanged drug).

Half-Life: 12 hr.

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	within 8 hr	2–4 hr‡	7 days

‡Plasma concentrations.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take tolvaptan as directed. Avoid drinking grapefruit juice during therapy; may cause ↑ levels. Take missed doses as soon as remembered, but not if just before next dose; do not double doses. Do not stop and restart therapy. Restarting therapy may require hospitalization.
REMS: Explain requirements of Tolvaptan for ADPKD Shared System REMS program (providers must be certified and inform patients of risk of hepatotoxicity; patient must enroll, comply with ongoing monitoring requirements, and get Jynarque from pharmacies participating in REMS program).
Inform patients they can continue fluid ingestion in response to thirst during therapy and should have water available to drink at all times during therapy. Following discontinuation of therapy, resume fluid restriction.
Advise patient to notify health care provider immediately if signs and symptoms of hepatotoxicity (feeling tired, fever, loss of appetite, rash, nausea, itching, right upper abdomen pain or tenderness, yellowing of skin and white part of eye, vomiting, dark urine) occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient to notify health care provider if signs of dehydration (vomiting, diarrhea, inability to drink normally, dizziness, feeling faint) or bleeding (vomiting bright red blood, dark blood clots, or coffee-ground-like material; black, tarry stools; bloody stools).
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding.

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Indications ⬇