Terlipressin Acetate

(BANM, rINNM)
Synonyms: Acetato de terlipresina; Terlipresin Asetat; Terlipressiiniasetaatti; Terlipressin Diacetate; Terlipressinacetat; Terlipressine, Acétate de; Terlipressini Acetas.
Cyrillic synonym: Терлипрессина Ацетат.

💊 Chemical information

Chemical formula: C52H74N16O15S2,2C2H4O2,5H2O = 1437.6.
ATC — H01BA04.
ATC Vet — QH01BA04.

💊 Adverse Effects, Treatment, and Precautions

As for Vasopressin. The pressor and antidiuretic effects of terlipressin are reported to be less marked than those of vasopressin.

Effects on electrolytes.

A report of hypokalaemia in a patient receiving terlipressin.1
1. Stéphan F, Paillard F. Terlipressin-exacerbated hypokalaemia. Lancet 1998; 351: 1249–50.

Effects on the skin.

Ischaemic skin necrosis developed in 3 patients several days after starting terlipressin treatment.1 Skin lesions developed on the abdomen and lower limbs, which are not typical areas for ischaemia related to vasoconstrictors, and the authors concluded that obesity and venous insufficiency in these patients put them at particular risk.
1. Donnellan F, et al. Ischaemic complications of Glypressin in liver disease: a case series. Br J Clin Pharmacol 2007; 64: 550–2.

💊 Uses and Administration

Terlipressin is an inactive prodrug which is slowly converted in the body to lypressin, and has the general physiological actions of vasopressin. Terlipressin acetate is used to control bleeding oesophageal varices and is given by intravenous injection in doses of 2 mg, followed by 1 or 2 mg every 4 to 6 hours if necessary, until bleeding is controlled, for up to 72 hours. Terlipressin is under investigation in the treatment of hepatorenal syndrome and shock.

Hepatorenal syndrome.

Terlipressin has been found to be of benefit in the hepatorenal syndrome, a form of renal impairment associated with cirrhosis of the liver. A retrospective study1found that doses of about 3 mg/day for a mean of 11 days appeared to improve renal function in 58 of 91 patients; it may also have improved survival. Further prospective studies have also reported beneficial effects on renal function; these used doses of terlipressin 1 mg every 4 hours for 7 to 15 days,2 and 1 mg every 12 hours for up to 15 days.3 Meta-analysis4 of 11 studies confirmed the efficacy of terlipressin in hepatorenal syndrome although a significant number of patients who responded to treatment relapsed after it was stopped. A systematic review5 of 3 small randomised controlled studies of terlipressin suggested that it may reduce mortality and improve renal function in patients with hepatorenal syndrome, although the evidence was not sufficiently reliable to make recommendations for clinical practice.
1. Moreau R, et al. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology 2002; 122: 923–30
2. Alessandria C, et al. Renal failure in cirrhotic patients: role of terlipressin in clinical approach to hepatorenal syndrome typ
2. Eur J Gastroenterol Hepatol 2002; 14: 1363–8
3. Solanki P, et al. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol 2003; 18: 152–6
4. Fabrizi F, et al. Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther 2006; 24: 935–44
5. Gluud LL, et al. Terlipressin for hepatorenal syndrome. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2006 (accessed 25/06/08).

Shock.

Terlipressin has vasopressor effects and has been tried1,2in the management of septic shock. In a group of 8 patients who could not be adequately managed with conventional vasopressor therapy, an intravenous bolus of terlipressin 1 to 2 mg produced a progressive increase in mean arterial pressure over 10 to 20 minutes that was sustained for at least 5 hours, allowing reduction or cessation of noradrenaline.3 Similar beneficial results have also been reported by others.4,5 The use of a continuous infusion of terlipressin (500 micrograms/hour for 6 hours followed by half this dose for a further 12 hours) has been described in one case and appeared to be effective.6 There is also a report7 of 4 children treated with bolus doses of 20 micrograms/kg every 4 hours for up to 72 hours.
1. Delmas A, et al. Clinical review: vasopressin and terlipressin in septic shock patients. Crit Care 2005; 9: 212–22
2. Pesaturo AB, et al. Terlipressin: vasopressin analog and novel drug for septic shock. Ann Pharmacother 2006; 40: 2170–7
3. O’Brien A, et al. Terlipressin for norepinephrine-resistant septic shock. Lancet 2002; 359: 1209–10.
4. Morelli A, et al. Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock. Intensive Care Med 2004; 30: 597–604
5. Leone M, et al. Terlipressin in catecholamine-resistant septic shock patients. Shock 2004; 22: 314–19
6. Jolley DH, et al. Terlipressin infusion in catecholamine-resistant shock. Anaesth Intensive Care 2003; 31: 560–4
7. Rodríguez-Núñez A, et al. Terlipressin for catecholamine-resistant septic shock in children. Intensive Care Med 2004; 30: 477–80.

Variceal haemorrhage.

Systematic review has indicated1 that terlipressin is effective in the management of acute oesophageal variceal haemorrhage, and reduces the relative risk of mortality by about one-third. Differences in effectiveness from other therapies could not be conclusively shown. Comparison of a regimen of terlipressin given by intravenous bolus injection, plus glyceryl trinitrate given sublingually, with balloon tamponade in variceal bleeding has suggested similar efficacy.2 However, tamponade was successful in all patients that were previously unresponsive to terlipressin plus glyceryl trinitrate whereas this drug combination failed in all patients previously unresponsive to tamponade. A comparison of terlipressin and endoscopic injection sclerotherapy found them to be equally effective for the control of acute variceal bleeding.3
1. Ioannou G, et al. Terlipressin for acute esophageal variceal hemorrhage. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2003 (accessed 16/09/05)
2. Fort E, et al. A randomized trial of terlipressin plus nitroglycerin vs balloon tamponade in the control of acute variceal hemorrhage. Hepatology 1990; 11: 678–81
3. Escorsell À, et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology 2000; 32: 471–6.

💊 Preparations

Proprietary Preparations

Arg.: Glycylpressin; Austria: Glycylpressin; Haemopressin; Belg.: Glypressin; Braz.: Glypressin†; Cz.: Glypressin; Remestyp; Denm.: Glypressin; Fin.: Glypressin; Fr.: Glypressine; Ger.: Glycylpressin; Haemopressin; Gr.: Glypressin; Hong Kong: Glypressin; Hung.: Glypressin; Irl.: Glypressin; Ital.: Glipressina; Malaysia: Glypressin; Mex.: Glyverase; Neth.: Glypressin; Pol.: Remestyp; Rus.: Remestyp (Реместип)†; Singapore: Glypressin; Spain: Glypressin; Switz.: Glypressine; Thai.: Glypressin; Turk.: Glypressin; UK: Glypressin.
Published May 08, 2019.