JINARC TABLET 45MG/15MG [SIN16609P]

Product Info

JINARC TABLET 45MG/15MG

[SIN16609P]

4.1 Therapeutic indications

JINARC is indicated to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with chronic kidney disease (CKD) at initiation of treatment with evidence of rapidly progressing disease (see section 4.2 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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.

4.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to benzazepine or benzazepine derivatives (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• 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 section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Anuria

• Volume depletion

• Hypernatraemia

• Patients who cannot perceive or respond to thirst

• Pregnancy (see section 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Breastfeeding (see section 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Concomitant use of strong CYP3A inhibitors