Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Type 1 hepatorenal syndrome
Prior to use of terlipressin for hepatorenal syndrome, it must be ascertained that the patient has an acute functional renal failure and this functional renal failure does not respond to a suitable plasma expansion therapy.

Renal impairment
Terlipressin should be avoided in patients with advanced renal dysfunction, i.e., baseline serum creatinine ≥ 442µmol/L (5.0 mg/dL), when treated with terlipressin for type 1 hepatorenal syndrome, unless the benefit is judged to outweigh the risks. Reduced efficacy in reversal of hepatorenal syndrome, increased risk of adverse events, and increased mortality in this patient group have been observed in clinical trials.

Hepatic impairment
Terlipressin should be avoided in patients with severe liver disease defined as Acute-on-Chronic Liver Failure (ACLF) grade 3 and/or a Model for End-stage Liver Disease (MELD) score ≥ 39, when treated with terlipressin for type 1 hepatorenal syndrome, unless the benefit is judged to outweigh the risks.
Reduced efficacy in reversal of hepatorenal syndrome, increased risk of respiratory failure, and increased mortality in this patient group have been observed in clinical trials.

Respiratory events
Fatal cases of respiratory failure, including respiratory failure due to fluid overload, have been reported in patients treated with terlipressin for type 1 hepatorenal syndrome.
Patients with a new onset of breathing difficulties or worsening of respiratory disease should be stabilised prior to receiving their first dose of terlipressin.
Caution should be exercised when terlipressin is administered together with human albumin as part of the standard of care for type 1 hepatorenal syndrome. In case of signs or symptoms of respiratory failure or fluid overload, dose reduction of human albumin should be considered. If respiratory symptoms are severe or do not resolve, treatment with terlipressin should be discontinued.

Sepsis/ septic shock
Cases of sepsis/septic shock, including fatal cases, have been reported in patients treated with terlipressin for type 1 hepatorenal syndrome. Patients should be monitored daily for any signs or symptoms suggestive of infection.

Monitoring during treatment
During treatment regular monitoring and control of blood pressure, ECG or heart rate, oxygen saturation, serum levels of sodium and potassium, as well as fluid balance are required. Particular care is required in management of cardiovascular or pulmonary disease since terlipressin may induce ischemia and pulmonary vascular congestion.
Caution should be exercised in treating patients with hypertension, recognised heart disease, renal dysfunction, cerebral or peripheral vascular disease, asthma or respiratory failure.

Injection site reaction:
To avoid local necrosis at the injection site, the injection must be administered intravenously.

Septic shock
In patients with septic shock with a low cardiac output terlipressin should not be used.
Torsade de pointes
During clinical trials and post-marketing experience, several cases of QT interval prolongation and ventricular arrhythmias including “Torsade de pointes” have been reported (see section 4.8). In most cases, patients had predisposing factors such as basal prolongation of the QT interval, electrolyte abnormalities (hypokalemia, hypomagnesemia) or medications with concomitant effect on QT prolongation. Therefore, extreme caution should be exercised in the use of terlipressin in patients with a history of QT interval prolongation, electrolyte abnormalities, or concomitant medications that can prolong the QT interval (see section 4.5).

Paediatric population and elderly patients
Particular caution should be exercised in the treatment of children and elderly patients, as experience is limited in these groups. There is no data available regarding dosage recommendation in these special patient categories.

Excipients
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.