Jinarc

The active substance in Jinarc, tolvaptan, is a vasopressin-2-receptor antagonist: it blocks receptors (targets) in the kidneys to which the hormone vasopressin attaches. Vasopressin regulates the level of water and sodium in the body. In autosomal dominant polycystic kidney disease, it is thought that kidney cells do not respond normally to vasopressin, leading to the formation of fluid-filled cysts. By blocking vasopressin receptors in the kidneys, Jinarc can slow down cyst formation.

Jinarc can only be obtained with a prescription and treatment must be started and monitored by a doctor experienced in treating autosomal dominant polycystic kidney disease and with knowledge about the risks of treatment with Jinarc.

Jinarc is available as tablets (15, 30, 45, 60 and 90 mg). It is taken twice a day in two unequal doses. Patients should be started with a dose of 45 mg in the morning and 15 mg in the evening (45+15 mg), and the dose should then be increased to 60+30 mg or 90+30 mg, depending on what the patient can tolerate. The morning dose should be taken at least 30 minutes before the morning meal, whereas the evening dose can be taken with or without food. Doses may need to be reduced in patients taking certain other medicines. Patients should drink plenty of water while on treatment.

For more information about using Jinarc, see the package leaflet or contact your doctor or pharmacist.

Jinarc was shown to be effective at slowing down cyst formation in a main study involving 1,445 adults with autosomal dominant polycystic kidney disease who had rapidly progressing disease but normal or moderately reduced kidney function. In the study, Jinarc was compared with placebo (a dummy treatment) and the main measure of effectiveness was the change in kidney size after 3 years of treatment (a way of measuring the swelling caused by cyst formation). In patients taking placebo, the total size of the kidneys increased by 18.8% whereas in those taking Jinarc the increase was 9.6%. The effects of treatment were greatest in the first year. Subsequent supportive results confirmed that increase in kidney size over 5 years was slower with Jinarc.

The most common side effects with Jinarc (which may affect more than 2 in 10 people) are thirst, polyuria (increase in urine production), nocturia (need to pass urine at night) and pollakiuria (increased need to pass urine during the day). Jinarc may increase blood levels of certain liver enzymes (a sign of possible liver problems). For the full list of all side effects reported with Jinarc, see the package leaflet.

Jinarc must not be started in certain patients with increased blood levels of liver enzymes or with signs or symptoms of liver injury. Blood tests to check the patient’s liver function should be performed before starting treatment with Jinarc, and then repeated every month for 18 months and every three months thereafter. Patients should also be monitored for symptoms of liver injury (such as loss of appetite, nausea and vomiting, itching, tiredness and pain in the upper-right side of the belly) during treatment. Jinarc must not be used in patients who are anuric (cannot pass urine or have difficulty in passing it), volume depleted (have reduced amounts of fluids in the body) and in patients who cannot perceive or respond to thirst. It must not be used in patients with hypernatraemia (increased sodium levels in the blood) and in patients who are allergic to tolvaptan or medicines that are similar to tolvaptan, so-called benzazepines or their derivatives. Jinarc must also not be used in pregnant and breastfeeding women. For the full list of restrictions, see the package leaflet.

The European Medicines Agency decided that Jinarc’s benefits are greater than its risks and that it can be authorised for use in the EU. The Agency noted the unmet need for treatments for autosomal dominant polycystic kidney disease and considered that Jinarc is effective at slowing down cyst formation and possibly the decline in kidney function in patients with the condition. Regarding safety, while the most common side effects are manageable, the Agency identified liver toxicity as the most important risk with Jinarc, which was addressed by putting in place several measures (see below).

Jinarc received a marketing authorisation valid throughout the European Union on 27 May 2015.

The company that markets Jinarc will provide patients and doctors expected to use the medicine with information on the risk of liver toxicity and on the importance of preventing pregnancy during treatment. The company will also carry out a study to further investigate the safety of the medicine, including the risk of liver toxicity, and a study on the effectiveness in patients with severely reduced kidney function.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Jinarc have also been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Jinarc are continuously monitored. Side effects reported with Jinarc are carefully evaluated and any necessary action taken to protect patients.