Tolvaptan (ADPKD)

Source: UK SPC (eMC) for Jinarc 15 mg tablets, §4.2 (https://www.medicines.org.uk/emc/product/6849/smpc). Treatment must be INITIATED AND MONITORED under the supervision of physicians with expertise in managing ADPKD and a full understanding of the risks of tolvaptan therapy including hepatic toxicity and monitoring requirements. The three permitted split-dose regimens are 45 mg + 15 mg, 60 mg + 30 mg and 90 mg + 30 mg, giving total daily doses of 60 mg, 90 mg and 120 mg respectively. Titration must be performed cautiously to ensure high doses are not poorly tolerated through overly rapid up-titration; patients may down-titrate to lower doses based on tolerability and must be maintained on the HIGHEST TOLERABLE dose. The aim is to block vasopressin activity at the renal V2 receptor as completely and constantly as possible while maintaining acceptable fluid balance; measurements of urine osmolality are recommended to monitor the adequacy of vasopressin inhibition, and periodic monitoring of plasma osmolality or serum sodium (to calculate plasma osmolarity) and/or body weight should be considered to monitor the risk of dehydration from the aquaretic effect if water intake is insufficient. Patients must be instructed to drink sufficient amounts of water or other aqueous fluids, and THERAPY MUST BE INTERRUPTED if the ability to drink or the accessibility to water is limited. Must not be taken with grapefruit juice. DOSE REDUCTION WITH STRONG CYP3A INHIBITORS (§4.2): 90 mg + 30 mg becomes 30 mg once daily (reduce further to 15 mg if 30 mg is not well tolerated); 60 mg + 30 mg becomes 30 mg once daily (further reduction to 15 mg if not well tolerated); 45 mg + 15 mg becomes 15 mg once daily. DOSE REDUCTION WITH MODERATE CYP3A INHIBITORS: 90 mg + 30 mg becomes 45 mg + 15 mg; 60 mg + 30 mg becomes 30 mg + 15 mg; 45 mg + 15 mg becomes 15 mg + 15 mg. Further reductions have to be considered if patients cannot tolerate the reduced doses. HEPATIC TOXICITY (§4.4): tolvaptan has been associated with idiosyncratic elevations of ALT and AST with infrequent concomitant elevations in total bilirubin, and acute liver failure requiring liver transplantation has been reported post-marketing in ADPKD. Blood testing for hepatic transaminases and bilirubin is REQUIRED prior to initiation, monthly for 18 months, and at regular 3-monthly intervals thereafter, with concurrent monitoring for symptoms of liver injury (fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, dark urine or jaundice). Administration must be interrupted immediately at the onset of symptoms or signs of hepatic injury or if clinically significant ALT/AST increases are detected, with repeat ALT, AST, bilirubin and alkaline phosphatase ideally within 48-72 hours; therapy is to be interrupted on confirmation of sustained or increasing transaminase levels and permanently discontinued if significant increases and/or clinical symptoms persist. HEPATIC IMPAIRMENT: in severe hepatic impairment the benefits and risks must be evaluated carefully with careful management and regular liver enzyme monitoring; no dose adjustment is needed in mild or moderate hepatic impairment (Child-Pugh A and B); contraindicated in patients with elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation that meet the requirements for permanent discontinuation. ELDERLY: increasing age has no effect on tolvaptan plasma concentrations; limited data on safety and effectiveness in ADPKD patients aged over 55. PAEDIATRIC: safety and efficacy in children and adolescents have NOT been established, no data are available, and tolvaptan IS NOT RECOMMENDED in the paediatric age group — hence paedDose is null; verify any paediatric use against a children's formulary. METHOD: oral use; tablets must be swallowed without chewing and with a glass of water. NOTE ON SOURCES: this SPC (Jinarc) is the ADPKD product, matching this page. eMC §4.5 was NOT captured in this bundle — the interaction entries below come from UK §4.2 plus §7 of the US label (JYNARQUE, Otsuka, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3be8a6fe-a8d0-43ca-a84d-183b522a3cf4, label date 2025-11-06), and US labelling may differ from the UK SPC. §4.4 and §4.8 were truncated at the fetch limit.