JINARC TABLET 45MG/15MG

OTSUKA PHARMACEUTICALS (SINGAPORE) PTE. LTD.

OTSUKA PHARMACEUTICALS (SINGAPORE) PTE. LTD.

Therapeutic

Prescription Only

TABLET

**4.2 Posology and method of administration** JINARC treatment must be initiated and monitored under the supervision of physicians with expertise in managing ADPKD and a full understanding of the risks of JINARC therapy including hepatic toxicity and monitoring requirements (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Posology JINARC is to be administered twice daily in split dose regimens of 45 mg + 15 mg, 60 mg + 30 mg or 90 mg + 30 mg. The morning dose is to be taken at least 30 minutes before the morning meal. The second daily dose can be taken with or without food. According to these split dose regimens the total daily doses are 60 mg, 90 mg, or 120 mg. _Dose titration_ The initial dose is 60 mg JINARC per day as a split-dose regimen of 45 mg + 15 mg (45 mg taken upon waking and prior the morning meal and 15 mg taken 8 hours later). The initial dose is to be titrated upward to a split-dose regimen of 90 mg JINARC (60 mg + 30 mg) per day and then to a target split- dose regimen of 120 mg JINARC (90 mg + 30 mg) per day, if tolerated, with at least weekly intervals between titrations. Dose titration has to be performed cautiously to ensure that high doses are not poorly tolerated through overly rapid up-titration. Patients may down-titrate to lower doses based on tolerability. Patients have to be maintained on the highest tolerable JINARC dose. The aim of dose titration is to block activity of vasopressin at the renal V2 receptor as completely and constantly as possible, while maintaining acceptable fluid balance (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Measurements of urine osmolality are recommended to monitor the adequacy of vasopressin inhibition. 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 secondary to the aquaretic effects of JINARC in case of patient’s insufficient water intake. The safety and efficacy of JINARC in CKD stage 5 have not been explored and therefore JINARC treatment should be discontinued if renal insufficiency progresses to CKD stage 5 (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Therapy must be interrupted if the ability to drink or the accessibility to water is limited (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). JINARC must not be taken with grapefruit juice (see section 4.5 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Patients must be instructed to drink sufficient amounts of water or other aqueous fluids (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Dose adjustment for patients taking moderate CYP3A inhibitors_ In patients taking moderate CYP3A inhibitors, JINARC doses have to be reduced as follows:  Further reductions have to be considered if patients cannot tolerate the reduced JINARC doses. Special populations _Elderly population_ Increasing age has no effect on JINARC plasma concentrations. Limited data on the safety and effectiveness of JINARC in ADPKD patients aged over 55 are available (see section 5.1 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Renal impairment_ JINARC is contraindicated in anuric patients (see section 4.3 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Dose adjustment is not required in patients with renal impairment. No clinical trials in subjects with indices of glomerular filtration rate < 10 mL/min or in patients undergoing dialysis have been conducted. The risk of hepatic damage in patients with severely reduced renal function (i.e. estimated glomerular filtration rate \[eGFR\] < 20) may be increased; these patients should be carefully monitored for hepatic toxicity. Data for patients in CKD early stage 4 are more limited than for patients in stage 1, 2 or 3 (see section 5.1 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Limited data are available for patients with eGFR < 25 mL/min/1.73 m2. No data are available for patients with CKD stage 5. JINARC treatment should be discontinued if renal insufficiency progresses to CKD stage 5 (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Hepatic impairment_ In patients with severe hepatic impairment the benefits and risks of treatment with JINARC must be evaluated carefully. Patients must be managed carefully and liver enzymes must be monitored regularly (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). JINARC is contraindicated in patients with elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation of treatment that meet the requirements for permanent discontinuation of JINARC (see sections 4.3 and 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). No dose adjustment is needed in patients with mild or moderate hepatic impairment (Child-Pugh classes A and B). _Paediatric population_ The safety and efficacy of JINARC in children and adolescents has not yet been established. No data are available. JINARC is not recommended in the paediatric age group. Method of administration Oral use. Tablets must be swallowed without chewing and with a glass of water.