Jinarc

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

Split dose regimen (bid): Initially 60 mg daily 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 daily (60 mg + 30 mg) & then to a target dose of 120 mg daily (90 mg + 30 mg), if tolerated, w/ at least wkly interval between titrations.

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

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

Discontinue immediately if an anaphylactic reaction or other serious allergic reactions occur; if renal insufficiency progresses to CKD stage 5. Immediately interrupt treatment at the onset of symptoms or signs consistent w/ hepatic injury or if clinically significant abnormal ALT or AST increases are detected. Not to be given to patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Idiosyncratic hepatic toxicity. Interrupt or reduce dose if dehydration becomes evident. Perform blood testing for hepatic transaminases & bilirubin prior to initiation of treatment, continuing mthly for 18 mth & at regular 3-mthly intervals thereafter. Monitor for symptoms that may indicate liver injury; vol status; body wt; fluid & electrolyte status; electrolytes every 3 mth during long-term treatment. Correct pre-treatment Na abnormalities (hyponatraemia or hypernatraemia) prior to initiation of therapy. May cause AR related to water loss eg, thirst, polyuria, nocturia & pollakiuria. Ensure adequate hydration. Increased risk of developing acute retention in patients w/ partial urinary outflow obstruction. Exclude pseudohyponatraemia in DM patients prior & during treatment. May cause hyperglycaemia. Evaluate uric acid conc prior to initiation of therapy & as indicated during treatment based on symptoms. Reversible reduction in GFR. Minor influence on the ability to drive or use machines. Not recommended in women of childbearing potential not using contraception. Not recommended 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). Increased AUC & C_max w/ ketoconazole, fluconazole. Doubling of peak tolvaptan C_max w/ grapefruit juice. Decreased exposure & efficacy w/ potent CYP3A inducers (eg, rifampicin). Higher risk for developing hypernatraemia w/ medicinal products that increase serum Na conc. Potential to lead to severe dehydration w/ loop & thiazide diuretics. Increased steady state digoxin conc. May have the potential to inhibit OATP1B1, OAT3, BCRP & OCT1 transporters. Risk of orthostatic/postural hypotension w/ diuretics or non-diuretic antihypertensives. May attenuate effect of vasopressin analogues eg, desmopressin. Smoking & alcohol.

Diuretics

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

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