Terlipressin

Indications

Terlipressin is used for: Acute oesophageal variceal haemorrhage, Hepatorenal syndrome type 1

Adult Dose

Intravenous Acute oesophageal variceal haemorrhage Adult: As powder and solvent for solution for inj: Initially, 1-2 mg, then 1 mg 4-6 hourly. Max duration of treatment: 72 hours. As solution for inj: Initially, 2 mg 4 hourly, maintain until bleeding is controlled for 24 hours or up to max of 48 hours. Subsequent doses may be reduced to 1 mg 4 hourly in patients weighing <50 kg or if adverse reaction occur. Hepatorenal syndrome type 1 Adult: Initially, 1 mg 6 hourly 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.

Child Dose

Renal Dose

Administration

Powder for solution for inj: Slowly add the contents of the solvent ampoule to the powder vial and roll gently until completely dissolved. Dilute further with 10 mL NaCl 0.9% solution for inj.

Contra Indications

Unstable angina, recent MI, septic shock with low cardiac output. Pregnancy.

Precautions

Patient with uncontrolled hypertension, severe asthma or COPD, cardiac disease, arrhythmias, atherosclerosis, vascular disease (cerebral or peripheral), electrolyte and fluid disturbances. Renal impairment (especially chronic renal failure). Lactation.

Pregnancy-Lactation

Interactions

Increases the hypotensive effect of non-selective β-blockers. Concomitant use of drugs known to induce bradycardia (e.g. propofol, sufentanil) may lower heart rate and cardiac output. May trigger ventricular arrhythmias, including Torsade de pointes, when used with drugs that can prolong QT interval (e.g. class IA and III antiarrhythmics, erythromycin, certain antihistamines and TCAs), or with drugs that may cause hypokalaemia or hypomagnesaemia.

Adverse Effects

Side effects of Terlipressin : Significant: QT interval prolongation, ventricular arrhythmias (including Torsade de pointes), cutaneous ischaemia and necrosis. Cardiac disorders: Tachycardia, bradycardia, pulmonary oedema, dyspnoea. Gastrointestinal disorders: Intestinal ischaemia, abdominal cramps, diarrhea, nausea, vomiting. Metabolism and nutrition disorders: Rarely, hyponatraemia, hyperglycaemia. Nervous system disorders: Convulsion, headache. Reproductive system and breast disorders: Uterine ischaemia. Respiratory, thoracic and mediastinal disorders: Bronchospasm, respiratory failure. Vascular disorders: Hypertension, hypotension, pallor.

Mechanism of Action

Terlipressin, an inactive prodrug, is converted via enzymatic cleavage to lysine-vasopressin. The active vasopressin selectively causes splanchnic and extrarenal vasoconstriction by stimulation of V1 receptors on vascular smooth muscle, thereby reducing splanchnic blood flow and portal pressure. It also increases systemic mean arterial pressure and decrease heart rate. It has minimal action on V2 receptors responsible for its antidiuretic effects.