Jinarc Special Precautions

Idiosyncratic hepatic toxicity: JINARC has been associated with idiosyncratic elevations of blood alanine and aspartate aminotransferases (ALT and AST) with infrequent cases of concomitant elevations in bilirubin-total (BT).
In post-marketing experience with JINARC in ADPKD, acute liver failure requiring liver transplantation has been reported.
In a double-blind, placebo-controlled trial in patients with ADPKD, the period of onset of hepatocellular injury (by ALT elevations >3× ULN) was within 3 to 14 months after initiating treatment and these increases were reversible, with ALT returning to <3× ULN within 1 to 4 months. While these concomitant elevations were reversible with prompt discontinuation of JINARC, they represent a potential for significant liver injury. Similar changes with other medicinal products have been associated with the potential to cause irreversible and potentially life-threatening liver injury (see Adverse Reactions).
Access to water: JINARC may cause adverse reactions related to water loss such as thirst, polyuria, nocturia, and pollakiuria (see Adverse Reactions). Therefore, patients must have access to water (or other aqueous fluids) and be able to drink sufficient amounts of these fluids (see Dosage & Administration). Patients have to be instructed to drink water or other aqueous fluids at the first sign of thirst in order to avoid excessive thirst or dehydration.
Additionally, patients have to drink 1 to 2 glasses of fluid before bedtime regardless of perceived thirst and replenish fluids overnight with each episode of nocturia.
Dehydration: Volume status must be monitored in patients taking JINARC because treatment with JINARC may result in severe dehydration which constitutes a risk factor for renal dysfunction. Accurate monitoring of body weight is recommended. A progressive reduction in body weight could be an early sign of progressive dehydration. If dehydration becomes evident, take appropriate action, which may include the need to interrupt or reduce the dose of JINARC and increase fluid intake. Special care must be taken in patients having diseases that impair appropriate fluid intake or who are at an increased risk of water loss e.g. in case of vomiting or diarrhoea.
Urinary outflow obstruction: Urinary output must be secured. Patients with partial obstruction of urinary outflow, for example patients with prostatic hypertrophy or impairment of micturition, have an increased risk of developing acute retention.
Fluid and electrolyte balance: Fluid and electrolyte status must be monitored in all patients. Administration of JINARC induces copious aquaresis and may cause dehydration and increases in serum sodium (see Adverse Reactions) and is contraindicated in hypernatraemic patients (see Contraindications). Therefore, serum creatinine, electrolytes and symptoms of electrolyte imbalances (e.g. dizziness, fainting, palpitations, confusion, weakness, gait instability, hyper-reflexia, seizures, coma) have to be assessed prior to and after starting JINARC to monitor for dehydration.
During long-term treatment, electrolytes have to be monitored at least every three months.
Serum sodium abnormalities: Pre-treatment sodium abnormalities (hyponatraemia or hypernatraemia) must be corrected prior to initiation with JINARC therapy.
Anaphylaxis: In post-marketing experience, anaphylaxis (including anaphylactic shock and rash generalised) has been reported very rarely following administration of JINARC. This type of reaction occurred after the first administration of JINARC. Patients have to be carefully monitored during treatment. Patients with known hypersensitivity reactions to benzazepines or benzazepine derivatives (e.g. benazepril, conivaptan, fenoldopam mesylate or mirtazapine) may be at risk for hypersensitivity reaction to JINARC (see Contraindications).
If an anaphylactic reaction or other serious allergic reactions occur, administration of JINARC must be discontinued immediately and appropriate therapy initiated. Since hypersensitivity is a contraindication (see Contraindications) treatment must never be restarted after an anaphylactic reaction or other serious allergic reactions.
Diabetes mellitus: Diabetic patients with an elevated glucose concentration (e.g. in excess of 300 mg/dL) may present with pseudo-hyponatraemia. This condition must be excluded prior and during treatment with JINARC.
JINARC may cause hyperglycaemia (see Adverse Reactions). Therefore, diabetic patients treated with JINARC must be managed cautiously. In particular, this applies to patients with inadequately controlled type II diabetes.
Uric acid increases: Decreased uric acid clearance by the kidney is a known effect of JINARC. In a double-blind, placebo-controlled trial of patients with ADPKD, potentially clinically significant increased uric acid (greater than 10 mg/dL) was reported at a higher rate in JINARC-patients (6.2%) compared to placebo-treated patients (1.7%). Adverse reactions of gout were reported more frequently in JINARC-treated patients (28/961, 2.9%) than in patients receiving placebo (7/483, 1.4%). In addition, increased use of allopurinol and other medicinal products used to manage gout were observed in the double-blind, placebo-controlled trial. Effects on serum uric acid are attributable to the reversible renal hemodynamic changes that occur in response to JINARC effects on urine osmolality and may be clinically relevant. However, events of increased uric acid and/or gout were not serious and did not cause discontinuation of therapy in the double-blind, placebo-controlled trial. Uric acid concentrations are to be evaluated prior to initiation of JINARC therapy, and as indicated during treatment based on symptoms.
Effect of JINARC on glomerular filtration rate (GFR): A reversible reduction in GFR has been observed in ADPKD trials at the initiation of JINARC treatment.
Chronic Kidney Disease: Limited safety and efficacy data are available for JINARC in patients with CKD late stage 4 (eGFR <25 mL/min/1.73 m²). There are no data in patients with CKD stage 5. JINARC treatment should be discontinued if renal insufficiency progresses to CKD stage 5.
Lactose: JINARC contains lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: JINARC has minor influence on the ability to drive or use machines. When driving vehicles or using machines it has to be taken into account that occasionally dizziness, asthenia or fatigue may occur.