- terlipressin acetate
POM: Prescription only medicine
This information is intended for use by health professionals
AdultsInitial dose: The recommended initial dose is 1 to 2 mg terlipressin acetate# (equivalent to 5 to 10 ml of solution) administered by intravenous injection over a period of time. Depending on the patient's body weight the dose can be adjusted as follows:
|- weight less than 50 kg:||1 mg terlipressin acetate (5 ml)|
|- weight 50kg to 70 kg:||1.5 mg terlipressin acetate (7.5 ml)|
|- weight exceeding 70 kg:||2 mg terlipressin acetate (10 ml).|
Elderly patientsVariquel should be used with caution in patients over 70 years of age (see section 4.4).
Paediatric populationVariquel is not recommended in children and adolescents due to insufficient experience on safety and efficacy (see section 4.4).
Renal insufficiencyVariquel should only be used with caution in patients with chronic renal failure (see section 4.4).
Hepatic insufficiencyA dose adjustment is not required in patients with liver failure.
Skin Necrosis:During post-marketing experience several cases of cutaneous ischemia and necrosis unrelated to the injection site (see section 4.8) have been reported. Patients with peripheral venous hypertension or morbid obesity seem to have a greater tendency to this reaction. Therefore, extreme caution should be exercised when administering terlipressin in these patients.
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 (see section 4.8). 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, electrolytic anormalities, concomitant medications that can prolong the QT interval, such as class IA and III antiarrhythmics, erythromycin, certain antihistamines and tricyclic antidepressants or medications that can cause hypokalaemia or hypomagnesemia (e.g. some diuretics) (see section 4.5).This medicinal product contains less than 1mmol (23 mg) of sodium per 5 ml, i.e. essentially sodium-free.
Special populationsParticular caution should be exercised in the treatment of children, adolescents and elderly patients, as experience is limited and there are no safety and efficacy data available regarding dosage recommendation in this population.
PregnancyThe use of terlipressin is not recommended during pregnancy as it has been shown to cause uterine contractions and increased intrauterine pressure in early pregnancy and may decrease uterine blood flow. Terlipressin may have harmful effects on pregnancy and foetus. Spontaneous abortion and malformation has been shown in rabbits after treatment with terlipressin (see section 5.3).Variquel should therefore only be used at vital indication on a case by case decision especially in the first trimester, when bleeding cannot be controlled with endoscopic therapy.
BreastfeedingIt is not known whether terlipressin is excreted in human breast milk. The excretion of terlipressin in milk has not been studied in animals. A risk to the suckling child cannot be excluded.A decision on whether to discontinue breast-feeding or to discontinue/abstain from terlipressin therapy taking into account the benefit of breast-feeding to the child and the benefit of therapy for the woman.
|MedDRA System Organ Class||Adverse Reaction (Preferred Term)|
|Metabolism and nutrition disorders|
|uncommon (≥1/1.000 to <1/100)||hyponatraemia if fluid not monitored|
|very rare (<1/10.000)||hyperglycaemia|
|Nervous system disorders|
|common (≥1/100 to <1/10)||headache|
|uncommon (≥1/1.000 to <1/100)||triggering of a convulsive disorder|
|very rare (<1/10.000)||stroke|
|common (≥1/100 to <1/10)||ventricular and supra-ventricular arrhythmia, bradycardia, signs of ischaemia in the ECG|
|uncommon (≥1/1.000 to <1/100)||angina pectoris, acute hypertension rise, in particular in patients already suffering from hypertension (generally, it decreases spontaneously), atrial fibrillation, ventricular extrasystoles, tachycardia, chest pain, myocardial infarction, fluid overload with pulmonary oedema, cardiac failure, Torsade de Pointes|
|very rare (<1/10.000)||myocardial ischemia|
|common (≥1/100 to <1/10)||hypertension, hypotension, peripheral ischaemia, peripheral vasoconstriction, facial pallor|
|uncommon (≥1/1.000 to <1/100)||intestinal ischaemia, peripheral cyanosis, hot flushes|
|Respiratory, thoracic and mediastinal disorders|
|uncommon (≥1/1.000 to <1/100)||pain in the chest, bronchospasm, respiratory distress, respiratory failure|
|Rare (≥1/10.000 to <1/1000)||dyspnoea|
|common (≥1/100 to <1/10)||transient abdominal cramps, transient diarrhoea|
|uncommon (≥1/1.000 to <1/100)||transient nausea, transient vomiting|
|Skin and subcutaneous tissue disorders|
|common (≥1/100 to <1/10)||paleness|
|uncommon (≥1/1.000 to <1/100)||lymphangitis, skin necrosis unrelated to the site of administration|
|Reproductive system and breast disorders|
|common (≥1/100 to <1/10)||abdominal cramps (in women)|
|Pregnancy, puerperium and perinatal conditions|
|uncommon (≥1/1.000 to <1/100)||uterine hypertonus, uterine ischemia|
|not known (cannot be estimated from the available data)||uterine constriction, decreased uterine blood flow|
|General disorders and administration site conditions|
|uncommon (≥1/1.000 to <1/100)||local cutaneous necrosis|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard
Gastrointestinal system:Terlipressin increases the tone of vascular and extravascular smooth muscle cells. The increase in arterial vascular resistance leads to decrease of splanchnic hypervolemia. The decrease of the arterial blood supply leads to reduction of pressure in the portal circulation. Intestinal muscles contract concomitantly which increases intestinal motility. The muscular wall of the esophagus also contracts which leads to closure of experimentally induced varices.
Kidneys:Terlipressin has only 3% antidiuretic effect of the native vasopressin. This residual activity is of no clinical significance. Renal blood circulation is not significantly effected in normovolemic condition. Renal blood circulation is increased, however, under hypovolemic condition.
Blood pressure:Terlipressin induces a slow haemodynamic effect which lasts 2-4 hours. Systolic and diastolic blood pressure increase mildly. More intense blood pressure increase has been observed in patients with renal hypertension and general blood vessel sclerosis.
Heart:All studies reported that no cardio-toxic effects were observed, not even under the highest dose of terlipressin. Influences on the heart, such as bradycardia, arrhythmia, coronary insufficiency, occur possibly because of reflex or direct vascular constrictive effects of terlipressin.
Uterus:Terlipressin causes significant decrease in myometrial and endometric blood flow.
Skin:The vasoconstrictive effect of terlipressin causes significant decrease in blood circulation of the skin. All studies reported obvious paleness on face and body.In conclusion, the main pharmacological properties of terlipressin are its haemodynamic effects and its effects on smooth muscle. The centralization effect under hypovolemic condition is a desired side effect in patients with bleeding oesophageal varices.