Jinarc

Tolvaptan

Slows progression of cyst development & renal insufficiency of autosomal dominant polycystic kidney disease in adults w/ CKD stage 1-4 at treatment initiation w/ evidence of rapidly progressing disease.

Split-dose regimen (bd): Initially 60 mg/day as 45 mg + 15 mg (45 mg taken upon waking & prior the morning meal, & 15 mg taken 8 hr later). Titrate upward to 90 mg/day (60 mg + 30 mg), then to a target dose of 120 mg/day (90 mg + 30 mg), if tolerated, w/ at least wkly intervals between titrations.

Swallow w/o chewing & w/ water. 1st daily dose: Should be taken on an empty stomach.. 2nd daily dose: May be taken with or without food..

Hypersensitivity to tolvaptan or to benzazepine or benzazepine derivatives. Elevated liver enzymes &/or signs or symptoms of liver injury prior to treatment initiation that meet the requirements for permanent discontinuation of tolvaptan. Anuria; vol depletion; hypernatraemia. Patients who cannot perceive or respond to thirst. Pregnancy & lactation.

Immediately discontinue treatment in case of anaphylactic reaction or other serious allergic reactions. Risk of idiosyncratic hepatic toxicity. Perform blood testing for hepatic transaminases & bilirubin prior to treatment initiation, continuing mthly for 18 mth & at regular 3-mthly intervals thereafter. Monitor for symptoms that may indicate liver injury. Interrupt treatment upon confirmation of sustained or increasing transaminase levels & permanently discontinue if significant increases &/or clinical symptoms of hepatic injury persist. Risk of excessive thirst or dehydration. Monitor vol, fluid & electrolyte status. Urinary output must be secured. Correct pre-treatment Na abnormalities (hyponatraemia or hypernatraemia) prior to treatment initiation. Exclude pseudohyponatraemia prior & during treatment in DM patients. May cause hyperglycaemia. Evaluate uric acid conc prior to treatment initiation, & as indicated during treatment based on symptoms. Reversible GFR reduction at treatment initiation. Should not be taken by patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Minor influence on the ability to drive or use machines. Limited safety & efficacy data in patients w/ CKD late stage 4 (eGFR <25 mL/min/1.73 m²). Discontinue treatment if renal insufficiency progresses to CKD stage 5. Carefully evaluate the benefits & risks of treatment in patients w/ severe hepatic impairment. Not recommended in women of childbearing potential not using contraception & in the paed age group.

Polydipsia; headache, dizziness; diarrhoea, dry mouth; nocturia, pollakiuria, polyuria; fatigue, thirst. Dehydration, hypernatraemia, decreased appetite, hyperuricaemia, hyperglycaemia, gout; insomnia; dysgeusia, syncope; palpitations; dyspnoea; abdominal pain/distension, constipation, dyspepsia, GERD; abnormal hepatic function; dry skin, rash, pruritus, urticaria; arthralgia, muscle spasms, myalgia; asthenia; increased ALT & AST, decreased/increased wt.

Increased exposure w/ moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil) or strong CYP3A inhibitors (eg, itraconazole, ketoconazole, ritonavir, clarithromycin). Doubling of peak conc (C_max) w/ grapefruit juice (moderate to strong CYP3A inhibitor). Decreased exposure & efficacy w/ potent CYP3A inducers (eg, rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, St. John's wort). Higher risk for developing hypernatraemia w/ medicinal products that increase serum Na conc. Potential to lead to severe dehydration w/ loop & thiazide diuretics. Can potentially increase exposure to CYP3A4 substrates. Increased C_max & AUC_t of digoxin; rosuvastatin. Caution when co-administering w/ digoxin or other narrow therapeutic P-gp substrates (eg, dabigatran); BCRP substrates (eg, sulfasalazine); OCT1 substrates (eg, metformin). Risk of orthostatic/postural hypotension w/ diuretics or non-diuretic antihypertensive medicinal products. Effect of vasopressin analogues (eg, desmopressin) may be attenuated.

Diuretics

C03XA01 - tolvaptan ; Belongs to the class of vasopressin antagonists. Used as diuretics.

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