Jinarc

Tolvaptan

Slows 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: Avoid grapefruit juice.

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 & lactation.

Discontinue use if anaphylactic reaction or other serious allergic reactions occur. Idiosyncratic hepatic toxicity. 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. May cause adverse reactions related to water loss eg, thirst, polyuria, nocturia & pollakiuria. Ensure adequate hydration. Monitor vol, fluid & electrolyte status. Increased risk of developing acute retention in patients w/ partial obstruction of urinary outflow eg, w/ prostatic hypertrophy or micturition impairment. Correct pre-treatment Na abnormalities (hyponatraemia or hypernatraemia) prior to initiation of therapy. Diabetic patients. Evaluate uric acid conc prior to initiation of therapy & as indicated. Reversible reduction in GBR. Measure urine osmolality. Periodically monitor plasma osmolality or serum Na &/or body wt. Not to be taken by patients w/ galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Exclude pseudohyponatraemia in DM patients prior & during treatment. Not to be taken w/ grapefruit juice. Severe hepatic impairment. CKD stage 5. APKD patients >50 yr. May affect ability to drive & use machines. Discontinue treatment if renal insufficiency progresses. Patients w/ severe hepatic impairment. Women of childbearing potential must use adequate contraception during treatment. Not to be used during pregnancy. Not recommended in childn & adolescents.

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

Increased exposure w/ moderate (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil) or strong (eg, itraconazole, ketoconazole, ritonavir, clarithromycin) CYP3A inhibitors. Doubled peak conc (C_max) w/ grapefruit juice. Decreased exposure & efficacy w/ potent CYP3A4 inducers eg, rifampicin. Avoid concomitant administration w/ potent CYP3A inducers eg, rifampicin, rifabutin, rifapentin, phenytoin, carbamazepine & St. John's wort. May increase serum Na conc w/ medicinal products w/ high Na content eg, effervescent analgesic prep & certain Na-containing treatments for dyspepsia. Higher risk for developing hypernatraemia w/ medicinal products increasing serum Na conc. Potential severe dehydration w/ loop & thiazide diuretics. Increased steady state conc of digoxin. Concomitant use w/ substrates of OATP1B1 & OATP1B3 [eg, statins (eg, rosuvastatin & pitavastatin)], OAT3 (eg, MTX, ciprofloxacin), BCRP (eg, sulfasalazine) or OCT1 (eg, metformin). Risk of orthostatic/postural hypotension w/ diuretics or non-diuretic antihypertensive medicinal products. May attenuate effect of vasopressin analogues eg, desmopressin. Smoking & alcohol.

Diuretics

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

Rx