tol-VAP-tan

Samsca:

• Treatment of 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 heart failure and syndrome of inappropriate antidiuretic hormone (SIADH).

Jynarque:

• Patients at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

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

• Correction of hyponatremia (Samsca).
• Slow deterioration of renal function (Jynarque).

Absorption: 40% absorbed following oral administration.

Distribution: >99%.

Metabolism/Excretion: Extensively metabolized primarily by the CYP3A4 enzyme system; no renal elimination.

Half-life: 12 hr.

Contraindicated in:

• Hypersensitivity
• Liver disease
• Urgent need to acutely raise serum sodium (Samsca)
• Patients who cannot appropriately sense/respond to thirst
• Hypovolemia
• Uncorrected abnormal serum sodium concentrations (Jynarque)
• Concurrent use of strong or moderate CYP3A inhibitors (Samsca)
• Concurrent use of strong CYP3A inhibitors (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)
• Concurrent use of moderate CYP3A inhibitors (↓ dose) (Jynarque)
• 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.

CV: palpitations.

Derm: dry skin, rash.

Endo: hyperglycemia, hyperuricemia.

F and E: thirst, hypernatremia, hypovolemia.

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

GU: polyuria.

Neuro: osmotic demyelination , dizziness, weakness.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS).

Drug-Drug:

• Strong CYP3A inhibitors, including ketoconazole, clarithromycin, itraconazole, saquinavir, 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-gp inhibitors, including cyclosporine may ↑ levels and risk of toxicity; dosage adjustments may be necessary.
• May ↑ risk of hyperkalemia with angiotensin receptor blockers, ACE inhibitors, and potassium-sparing diuretics.
• Diuretics may ↑ risk of too rapid correction of sodium.
• May inhibit effects of desmopressin; avoid concurrent use.

Drug-Food:

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

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).

• Initiate and re-initiate therapy in a hospital.
  • REMS: REMS requirements are for Jynarque product.
  • Avoid fluid restriction during first 24 hr of therapy.
• PO: Administer once daily without regard to meals.

Jynarque, Samsca

Jinarc

Therapeutic Classification: electrolyte modifiers

Pharmacologic Classification: vasopressin antagonists

(Generic available)

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

† Blood level.

• Monitor neurologic status and assess for signs and symptoms of osmotic demyelination syndrome (trouble speaking, dysphagia, drowsiness, confusion, mood changes, involuntary movements, weakness, seizures), especially during initiation and after titration. If a rapid ↑ in sodium or symptoms occur, discontinue tolvaptan and consider administration of hypotonic fluid.
• Monitor fluid balance. If hypovolemia occurs interrupt or discontinue tolvaptan and provide supportive care (monitor vital signs, balance fluid and electrolytes).
• Monitor for signs and symptoms of liver injury (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) periodically during therapy. If symptoms occur, discontinue therapy.

• Monitor serum sodium levels frequently during initiation and dose titration and periodically during therapy. Too rapid correction of hyponatremia (>12 mEq/L/24 hr) can cause osmotic demyelination syndrome.
  • Monitor serum potassium in patients with serum potassium >5 mEq/L or taking medication known to ↑ potassium.
  • Monitor ALT, AST and bilirubin 2 wk and 4 wk after starting therapy, then monthly for first 18 mo and every 3 mo thereafter. If ALT, AST, or bilirubin increase to >2 × ULN, immediately discontinue Jynarque; repeat tests as soon as possible (within 48-72 hrs). If levels stabilize or resolve, Jynarque may be reinitiated with increased frequency of monitoring as long as ALT and AST remain below 3 times ULN. Do not restart in patients with signs or symptoms of hepatic injury or whose ALT or AST ever exceeds 3 times ULN during therapy with tolvaptan, unless another explanation for liver injury exists and the injury has resolved. In patients with a stable, low baseline AST or ALT, an increase >2 times baseline, even if <2 times ULN, may indicate early liver injury. Suspend and promptly (48-72 hrs) reevaluate liver levels before reinitiating therapy with more frequent monitoring.

• 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 Jynarque REMS program (patient must enroll, comply with ongoing monitoring requirements, must 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 professional 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 professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Advise patient to notify health care professional 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).
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding.

• Normalization of serum sodium levels. Therapy should be limited to 30 days.

NDC Code^*

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-020- SAMSCA
    • 59148-020-50- 1 BLISTER PACK in 1 CARTON (59148-020-50) > 10 TABLET in 1 BLISTER PACK

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-021- SAMSCA
    • 59148-021-50- 1 BLISTER PACK in 1 CARTON (59148-021-50) > 10 TABLET in 1 BLISTER PACK

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-082- JYNARQUE
    • 59148-082-13- 1 BOTTLE in 1 CARTON (59148-082-13) > 30 TABLET in 1 BOTTLE

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-083- JYNARQUE
    • 59148-083-13- 1 BOTTLE in 1 CARTON (59148-083-13) > 30 TABLET in 1 BOTTLE

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-087- Jynarque
    • 59148-087-07- 1 BLISTER PACK in 1 CARTON (59148-087-07) > 1 KIT in 1 BLISTER PACK

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-087- Jynarque
    • 59148-087-28- 4 BLISTER PACK in 1 CARTON (59148-087-28) > 1 KIT in 1 BLISTER PACK

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-088- Jynarque
    • 59148-088-07- 1 BLISTER PACK in 1 CARTON (59148-088-07) > 1 KIT in 1 BLISTER PACK

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-088- Jynarque
    • 59148-088-28- 4 BLISTER PACK in 1 CARTON (59148-088-28) > 1 KIT in 1 BLISTER PACK

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-089- Jynarque
    • 59148-089-07- 1 BLISTER PACK in 1 CARTON (59148-089-07) > 1 KIT in 1 BLISTER PACK

• 59148- Otsuka America Pharmaceutical, Inc.
  • 59148-089- Jynarque
    • 59148-089-28- 4 BLISTER PACK in 1 CARTON (59148-089-28) > 1 KIT in 1 BLISTER PACK

• 60505- Apotex Corp.
  • 60505-4704- TOLVAPTAN
    • 60505-4704-0- 1 BLISTER PACK in 1 CARTON (60505-4704-0) > 10 TABLET in 1 BLISTER PACK

• 60505- Apotex Corp.
  • 60505-4705- TOLVAPTAN
    • 60505-4705-0- 1 BLISTER PACK in 1 CARTON (60505-4705-0) > 10 TABLET in 1 BLISTER PACK