GLYPRESSIN

What it is

GLYPRESSIN is terlipressin solution for injection. One ampoule contains 0.85 mg terlipressin (equivalent to 1 mg terlipressin acetate) in 8.5 mL of solution, with a concentration of 0.1 mg/mL. It is supplied as a clear, colourless liquid for injection. Terlipressin is a dodecapeptide with three glycyl residues attached to the N-terminal of lysine vasopressin, acting as a pro-drug that is converted via enzymatic cleavage to the biologically active lysine vasopressin.

Approved indications

— Treatment of bleeding oesophageal varices. — Treatment of patients with Type 1 hepatorenal syndrome who are actively being considered for liver transplant.

Dosing overview GLYPRESSIN must only be administered by intravenous injection.

Key safety warnings

Terlipressin should only be used with caution and under strict monitoring in patients with uncontrolled hypertension, cerebral or peripheral vascular diseases, cardiac arrhythmias, coronary artery disease or previous myocardial infarction. Terlipressin should not be used in patients with unstable angina or recent acute myocardial infarction. Particular care is required in management of patients with cardiovascular or pulmonary disease since terlipressin may induce ischaemia and pulmonary vascular congestion. During treatment, regular monitoring of blood pressure, electrocardiogram or heart rate, oxygen saturation, serum levels of sodium and potassium, as well as fluid balance are required. During treatment with terlipressin, serum creatinine should be monitored at least daily as terlipressin should be used with caution in patients with renal insufficiency. Fluid balance and electrolytes should be monitored carefully as hyponatraemia, hypokalaemia, hypomagnesaemia and other electrolyte disturbances have been reported. Cases of sepsis and septic shock, including fatal cases, have been reported in patients treated with terlipressin for type 1 hepatorenal syndrome; causal association has not been established, and patients should be monitored daily for any signs or symptoms suggestive of infection. Several cases of cutaneous ischaemia and necrosis unrelated to the injection site have been reported; patients with peripheral venous hypertension, diabetes mellitus or obesity seem to have a greater tendency to this reaction, and extreme caution should be exercised when administering terlipressin in these patients. Several cases of QT interval prolongation and ventricular arrhythmias including Torsades de Pointes have been reported; most cases occurred in patients with predisposing factors such as basal prolongation of the QT interval, electrolyte abnormalities or medications with concomitant effect on QT prolongation, and extreme caution should be exercised in patients with a history of QT interval prolongation or concomitant medications that can prolong the QT interval. Terlipressin may cause smooth muscle constriction and should be used with caution and under strict monitoring in patients with severe asthma or chronic obstructive pulmonary disease. 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.

Contraindications

Pregnancy. Hypersensitivity to terlipressin or any of the excipients. Current or recent ischaemic cardiovascular disease.

Regulatory history

GLYPRESSIN was first registered on the Australian Register of Therapeutic Goods on 14 May 2012 (ARTG 177708). An Australian Public Assessment Report was issued on 11 May 2012, approving GLYPRESSIN for the treatment of bleeding oesophageal varices, with the conclusion that the benefits outweighed the risks for this short-term, life-threatening indication. The TGA recommended approval based on satisfactory chemistry and manufacturing controls, with nonclinical data supporting registration for short-term use (up to 48 hours) in a life-threatening situation.