jynarque

Recommended dosage ( 2.1 ) Initial Dosage Titration Step Target Dosage 1st Dose 45 mg 1st Dose 60 mg 1st Dose 90 mg 2nd Dose (8 hours later) 15 mg 2nd Dose (8 hours later) 30 mg 2nd Dose (8 hours later) 30 mg Total Daily Dose 60 mg Total Daily Dose 90 mg Total Daily Dose 120 mg Dose adjustment is recommended for patients taking moderate CYP3A inhibitors ( 2.4 , 5.4 , 7.1 ) 2.1 Recommended Dosage The initial dosage for JYNARQUE is 60 mg orally per day as 45 mg taken on waking and 15 mg taken 8 hours later. Titrate to 60 mg plus 30 mg then to 90 mg plus 30 mg per day if tolerated with at least weekly intervals between titrations. Patients may down-titrate based on tolerability. Encourage patients to drink enough water to avoid thirst or dehydration. 2.2 Monitoring To mitigate the risk of significant or irreversible liver injury, perform blood testing for ALT, AST and bilirubin prior to initiation of JYNARQUE, at 2 and 4 weeks after initiation, monthly for 18 months and every 3 months thereafter . Monitor for concurrent symptoms that may indicate liver injury [see Warnings and Precautions (5.1) ] . 2.3 Missed Doses If a dose of JYNARQUE is not taken at the scheduled time, take the next dose at its scheduled time. 2.4 Co-Administration with CYP3A Inhibitors CYP3A Inhibitors Concomitant use of strong CYP3A inhibitors is contraindicated [see Contraindications (4) and Warnings and…

The following adverse reactions are discussed in more detail in other sections of the labeling: Serious Liver Injury [see Boxed Warning and Warnings and Precautions (5.1) ] Hypernatremia, Dehydration and Hypovolemia [see Warnings and Precautions (5.3) ] Drug Interactions with Inhibitors of CYP3A [see Warnings and Precautions (5.4) ] Most common observed adverse reactions with JYNARQUE (incidence >10% and at least twice that for placebo) were thirst, polyuria, nocturia, pollakiuria and polydipsia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. JYNARQUE has been studied in over 3000 patients with ADPKD. Long-term, placebo-controlled safety information of JYNARQUE in ADPKD is principally derived from two trials where 1,413 subjects received tolvaptan and 1,098 received placebo for at least 12 months across both studies. TEMPO 3:4: A Phase 3, Double-Blind, Placebo-Controlled, Randomized Trial in Early, Rapidly-Progressing ADPKD The TEMPO 3:4 (NCT00428948) trial employed a two-arm,…

JYNARQUE is contraindicated in patients: With a history, signs or symptoms of significant liver impairment or injury. This contraindication does not apply to uncomplicated polycystic liver disease [see Warnings and Precautions (5.1) ] Taking strong CYP3A inhibitors With uncorrected abnormal blood sodium concentrations [see Warnings and Precautions (5.3) ] Unable to sense or respond to thirst [see Warnings and Precautions (5.3) ] Hypovolemia [see Warnings and Precautions (5.3) ] Hypersensitivity (e.g., anaphylaxis, rash) to tolvaptan or any component of the product [see Adverse Reactions (6) ] Uncorrected urinary outflow obstruction Anuria History of signs or symptoms of significant liver impairment or injury, does not include uncomplicated polycystic liver disease ( 4 ) Concomitant use of strong CYP3A inhibitors is contraindicated ( 4 ) Uncorrected abnormal blood sodium concentrations ( 4 , 5.3 ) Unable to sense or respond to thirst ( 4 ) Hypovolemia ( 4 ) Hypersensitivity to tolvaptan or any of its components ( 4 ) Uncorrected urinary outflow obstruction ( 4 ) Anuria ( 4 )

Single oral doses up to 480 mg (4 times the maximum recommended daily dose) and multiple doses up to 300 mg once daily for 5 days have been well tolerated in trials in healthy subjects. There is no specific antidote for tolvaptan intoxication. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: a rise in serum sodium concentration, polyuria, thirst, and dehydration/hypovolemia. No mortality was observed in rats or dogs following single oral doses of 2000 mg/kg (maximum feasible dose). A single oral dose of 2000 mg/kg was lethal in mice, and symptoms of toxicity in affected mice included decreased locomotor activity, staggering gait, tremor and hypothermia. In patients with suspected JYNARQUE overdosage, assessment of vital signs, electrolyte concentrations, ECG and fluid status is recommended. Continue replacement of water and electrolytes until aquaresis abates. Dialysis may not be effective in removing JYNARQUE because of its high binding affinity for human plasma protein (>98%).

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Avoid concomitant use with: Strong CYP3A Inducers ( 7.1 ) V 2 -Receptor Agonists ( 7.2 ) 7.1 CYP3A Inhibitors and Inducers CYP3A Inhibitors Tolvaptan's AUC was 5.4 times as large and Cmax was 3.5 times as large after co-administration of tolvaptan and 200 mg ketoconazole [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.3) ] . Larger doses of the strong CYP3A inhibitor would be expected to produce larger increases in tolvaptan exposure. Concomitant use of tolvaptan with strong CYP3A inhibitors is contraindicated [see Contraindications (4) ]. Dose reduction of JYNARQUE is recommended for patients while taking moderate CYP3A inhibitors [see Dosage and Administration (2.4) ]. Patients should avoid grapefruit juice beverages while taking JYNARQUE. Strong CYP3A Inducers Co-administration of JYNARQUE with strong CYP3A inducers reduces exposure to JYNARQUE [see Clinical Pharmacology (12.3) ]. Avoid concomitant use of JYNARQUE with strong CYP3A inducers [see Dosage and Administration (2.4) ]. 7.2 V 2 -Receptor Agonist As a V 2 -receptor antagonist, tolvaptan will interfere with the V 2 -agonist activity of desmopressin (dDAVP). Avoid concomitant use of JYNARQUE with a V 2 -agonist.