Administration Guide : Terlipressin

TERLIPRESSIN  1 MG INJECTION			HIGH ALERT MEDICATION
ROUTE	DILUTION	RUN RATE
INTRAVENOUS Bolus	Undiluted 1	Over 1 min 2,3,6
INTRAVENOUS Infusion   (Typically for Type 1 Hepatorenal Syndrome)	In studies, 1-3 mg was taken and diluted in (qs up to) 50 mL D5	Run over 24 hrs   Run rate = 2.08 mL/hr
	1 mg in 50 mL D5 = 0.02 mg/mL 7
	2 mg in 50 mL D5 = 0.04 mg/mL 8,9
	3 mg in 50 mL D5 = 0.06 mg/mL 10
DILUENT	Usually NOT required If further dilution is required, suggest to use D5 (better stability than NS) 7
STABILITY	Unopened: Store at 2-8°C in original packaging 1,4,5 Stability: Use immediately 2,4 , however, solution of 2mg/50ml has been shown to be stable for up to 24 hrs at room temperature.11
REMARKS	§ Caution: Hypertension, atherosclerosis, cardiac dysrhythmias or coronary insufficiency. 4 § Contraindication: unstable angina, recent MI, septic shock with low cardiac output, pregnancy. 5
DOSE	1 mg terlipressin acetate = 0.85 mg terlipressin free base ; typical dosing is based on terlipressin acetate   Bleeding Oesophageal Varices 1,3-5 * Initial dose: IV 2 mg STAT or 2 mg q4-6h until bleeding has been controlled for at least 24 hours or up to 36-72 hours. Some manufacturers provide dosage adjustments based on body weight: 2,5,6 < 50 kg = 1 mg 50-70 kg = 1.5 mg > 70 kg = 2 mg  * Maintenance dose: 1-2 mg q4-6h for 2-5 days (typically 1 mg/dose).  * Notes from other references: ·         After the initial dose, may consider reduce dose to 1 mg q4h for those with body weight <50 kg or if adverse effects occur. 1 ·         From FUKKM: Maximum daily dosage: 120-150 mcg/kg body weight. 2,3   Type 1 Hepatorenal Syndrome (Off label)1 ü  DO NOT USE SURGICAL STOCK unless authorised by HKGU surgeon. ü  Need to obtain approval for Ubat Kelulusan Khas (UKK) / KPK for both terlipressin and human albumin. *1 mg QID via slow bolus inj, may be increased up to max 2 mg 4-6 hourly if serum creatinine has not been reduced by at least 25% after 3 days. Max duration of treatment: 2 weeks.5 *Increasing evidence has shown that continuous infusion demonstrating a similar rate of response (more stable lowering effect on portal pressure) but lower adverse effects than the administration of the drug by i.v. boluses.8 Shock (Off label) 4 1-2 mg of terlipressin acetate by IV injection produced a progressive increase in mean arterial pressure over 10-20 minutes, that was sustained at least 5 hours, allowing reduction or cessation of noradrenaline therapy. 4
REFERENCES	1.          Product leaflet (GLYPRESSIN - Ferring) 2.          https://www.drugs.com/uk/terlipressin-acetate-1-mg-solution-for-injection-leaflet.html [Accessed 16 Nov 2020] 3.          Formulari Ubat Kementerian Kesihatan Malaysia: Online [Accessed 16 Nov 2020] 4.          Alistair G., Jane W., Vincent G., Lynn B. Injectable Drugs Guide. London:(PhP) Pharmaceutical Press 5.          Mimsgateway: Drug Information: Terlipressin [ Accessed 17 Nov 2020] 6.          UptoDate [Multi Drug National] : Drug Information: Terlipressin [Acessed 17 Nov 2020] 7.          Rodriguez-Nunez et al. Terlipressin Continuous Infusion: Please Mind the Solvent! Current Drug Targets, 2009, Vol. 10, No. 6 577 8.          Cavallin M et al. Terlipressin Given by Continuous Intravenous Infusion Versus Intravenous Boluses in the Treatment of Hepatorenal Syndrome: A Randomized Controlled Study. Hepatology, Vol.63, No.3, 2016. 9.          Angeli P et al. Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Aliment Pharmacol Ther, 23, 75–84 10.      Hospital Selayang Terlipressin Administration Protocol [Accessed on 2 Dec 2020] 11.      An investigation of reconstituted terlipressin infusion stability for use in hepatorenal syndrome. Nature (2020) 10:21037. https://doi.org/10.1038/s41598-020-78044-4 12.      Jha et al. Comparison of continuous versus intermittent infusions of terlipressin for the control of acute variceal bleeding in patients with portal hypertension: An open-label randomized controlled trial. Indian Journal of Gastroenterology Vol. 37, pg 313–320(2018)