Jinarc Warnings

Prescribing physicians must comply fully with the safety measures required as follows.
To mitigate the risk of significant and/or irreversible liver injury, blood testing for hepatic transaminases and bilirubin is required prior to initiation of Jinarc, continuing monthly for 18 months and at regular 3-monthly intervals thereafter. Concurrent monitoring for symptoms that may indicate liver injury (such as fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, dark urine or jaundice) is recommended.
If a patient shows abnormal ALT, AST or BT levels prior to initiation of treatment which fulfil the criteria for permanent discontinuation (see as follows) the use of tolvaptan is contraindicated (see Contraindications). In case of abnormal baseline levels below the limits for permanent discontinuation treatment can only be initiated if the potential benefits of treatment outweigh the potential risks and liver function testing must continue at increased time frequency. The advice of a hepatologist is recommended.
During the first 18 months of treatment, Jinarc can only be supplied to patients whose physician has determined that liver function supports continued therapy.
At the onset of symptoms or signs consistent with hepatic injury or if clinically significant abnormal ALT or AST increases are detected during treatment, Jinarc administration must be immediately interrupted and repeat tests including ALT, AST, BT and alkaline phosphatase (AP) must be obtained as soon as possible (ideally within 48-72 hours). Testing must continue at increased time frequency until symptoms/signs/laboratory abnormalities stabilise or resolve, at which point Jinarc may be reinitiated.
Current clinical practice suggests that Jinarc therapy is to be interrupted upon confirmation of sustained or increasing transaminase levels and permanently discontinued if significant increases and/or clinical symptoms of hepatic injury persist.
Recommended guidelines for permanent discontinuation include: ALT or AST >8-times ULN; ALT or AST >5-times ULN for more than 2 weeks; ALT or AST >3-times ULN and (BT >2-times ULN or International Normalized Ratio [INR] >1.5); ALT or AST >3-times ULN with persistent symptoms of hepatic injury noted previously.
If ALT and AST levels remain below 3-times the upper limit of normal (ULN), Jinarc therapy may be cautiously re-started, with frequent monitoring at the same or lower doses, as transaminase levels appear to stabilise during continued therapy in some patients.