Jinarc

Tolvaptan

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

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

May be taken with or without food: Take morning dose at least 30 min before breakfast. Take 2nd dose w/ or w/o food. Swallow whole w/ glass of water, do not chew.

Hypersensitivity to tolvaptan, benzazepine or benzazepine derivatives. Anuria; vol depletion; hypernatraemia; patients who cannot perceive or respond to thirst. Elevated liver enzymes &/or signs or symptoms of liver injury prior to initiation of treatment. Pregnancy & lactation.

Perform blood testing for hepatic transaminases & bilirubin prior to treatment, continuing mthly for 18 mth & at regular 3-mthly intervals thereafter. Discontinue use if anaphylactic reaction or other serious allergic reactions occur; if renal insufficiency progresses to CKD stage 5; if ALT or AST >8 times ULN, ALT or AST >5 times ULN for >2 wk, ALT or AST >3 times ULN & (BT >2 times ULN or INR >1.5), ALT or AST >3 times ULN w/ persistent symptoms of hepatic injury. Idiosyncratic hepatic toxicity. Ensure adequate hydration at 1st sign of thirst to avoid excessive thirst or dehydration. Secure urinary output for patients w/ partial urinary outflow obstruction. Monitor patients w/ DM. Potential reversible reduction in GFR at treatment initiation. Monitor liver enzymes regularly; for liver injury symptoms; body wt; vol, fluid & electrolyte status. Assess serum creatinine, electrolytes & electrolyte imbalances symptoms prior to & after treatment. Evaluate uric acid conc prior to & during treatment. Correct pre-treatment Na abnormalities prior to initiation. Not to be taken by patients w/ galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Not to be taken w/ grapefruit juice. Avoid concomitant use w/ medicinal products increasing serum Na conc; CYP3A inducers eg, rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, St. John's wort). Not recommended to administer w/ vasopressin analogues. Require dose reduction w/ moderate or strong CYP3A inhibitors. Concomitant use w/ BCRP substrates eg, sulfasalazine & OCT1 substrates eg, metformin. May affect ability to drive & use machines. CKD late stage 4 (eGFR <25 mL/min/1.73 m²). Severe hepatic impairment. May affect fertility. Not recommended in women of childbearing potential not using contraception. Not recommended in childn & adolescents. Elderly >55 yr.

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 or strong CYP3A inhibitors. Increased AUC & C_max w/ ketoconazole, fluconazole. Doubling of peak C_max w/ grapefruit juice. Decreased exposure & efficacy w/ potent CYP3A inducers eg, rifampicin. Higher risk for developing hypernatraemia w/ medicinal products increasing serum Na conc. Potential severe dehydration w/ loop & thiazide diuretics. Increased exposure to CYP3A4 substrates. Increased steady state digoxin conc. Inhibited OATP1B1, OAT3, BCRP, OCT1 transporters. Risk of orthostatic/postural hypotension w/ diuretics or non-diuretic antihypertensives. Attenuated effect of vasopressin analogues eg, desmopressin.

Diuretics

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

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