For use in the short term management of bleeding oesophageal varices. "Emergency treatment of type 1 hepatorenal syndrome, as defined by IAC (International Ascites Club) criteria".

Short term management of bleeding oesophageal varices: Initially an i.v. injection of 2 mg (2x8.5 ml) terlipressin acetate is given every 4 hours. The treatment should be maintained until bleeding has been controlled for 24 hours, but up to a maximum of 48 hours. After the initial dose, the dose can be adjusted to 1 mg (8.5 ml) terlipressin acetate i.v. every 4 hours in patients with body weight <50 kg or if adverse effects

occur.

In type 1 hepatorenal syndrome: An i.v. injection 3 to 4 mg (3x8.5ml to 4x8.5ml) terlipressin acetate every 24 hours as 3 or 4 administrations. In the absence of any reduction of the serum creatinine after 3 days of treatment, cessation of Terlipressin Acetate treatment is advised. In other cases, Terlipressin Acetate treatment is to be pursued until the obtaining either of a serum creatinine less than 130 µmol/litre or of a drop of at least 30% in the serum creatinine with respect to the value measured at the time of diagnosis of hepatorenal syndrome. The standard average duration of treatment is 10 days.

Hypersensitivity to the active substance or to any of the excipients of this preparation. Contraindicated in pregnancy.

The most frequently reported undesired effects in clinical trials are paleness, increased blood pressure, abdominal pain, nausea, diarrhoea, and headache.

Overdose Effects

The recommended dose in the specific patient population should not be exceeded as the risk of severe circulatory adverse effects is dose-dependent. Elevated blood pressure in patients with recognised hypertension can be controlled with 150 mcg clonidine i.v. Bradycardia requiring treatment should be treated with atropine.

Cardiac, pulmonary and vascular disease: During treatment regular monitoring and control of blood pressure, ECG, heart rate, serum levels of sodium and potassium, as well as fluid balance are required. Caution should be exercised in treating patients with hypertension, recognised heart disease, renal dysfunction, cerebral or peripheral vascular disease, asthma or respiratory failure.

Septic shock: In patients with septic shock with a low cardiac output terlipressin should not be used.

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

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. 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.

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.

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 medicinal product contains 1.33 mmol (30.7 mg) of sodium per ampoule, equivalent to 1.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Use in Special Populations

Elderly patients: There is no data available regarding dosage recommendation in the elderly.

Paediatric population: There is no data available regarding dosage recommendation in the paediatric population.

Pregnancy & Lactation

Treatment with Terlipressin Acetate during pregnancy is contraindicated. Terlipressin Acetate has been shown to cause uterine contractions and increased intrauterine pressure in early pregnancy and may decrease the uterine blood flow. Terlipressin Acetate may have harmful effects on pregnancy and foetus. Spontaneous abortion and malformation of the foetus have been shown in rabbits after treatment with Terlipressin Acetate.

It is not known whether Terlipressin Acetate is excreted in human breast milk. The excretion of Terlipressin Acetate in milk has not been studied in animals. A risk to the suckling child cannot be excluded. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Terlipressin Acetate should be made taking into account the benefit of breast-feeding to the child and the benefit of Terlipressin Acetate therapy to the woman.