Source: Health Products Regulatory Authority (IE) Revision Year: 2022 Publisher: Alliance Pharma (Ireland) Limited, United Drug Distributors, United Drug House, Magna Business Park, Magna Drive, Citywest, Dublin 24, Ireland
Hypersensitivity to the active substance or to any of the excipients lisited in section 6.1.
Haemopressin should only be used with caution and under strict monitoring of the patients in the following cases:
Also hypovolaemic patients often react with an increased vasoconstriction and atypical cardiac reactions.
Due to the weak antidiuretic effect of terlipressin (only 3% of the antidiuretic effect of native vasopressin) especially patients with already disturbed electrolyte metabolism should be monitored for a possible hyponatraemia and hypokalaemia.
In principle the use of the product should be confined to specialist supervision in units with facilities for regular monitoring of the cardiovascular system, haematology and electrolytes.
In emergency situations which require an immediate treatment before sending the patient to a hospital symptoms of hypovolaemia have to be considered.
Terlipressin has no effect on arterial bleeding.
To avoid local necrosis at the injection site, the injection must be administered intravenously.
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.
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).
Particular caution should be exercised in the treatment of children, adolescents and elderly patients, as experience is limited and there is no data available regarding dosage recommendation in these special patient categories.
After reconstitution with the accompanying solvent, this medicinal product contains less than 1 mmol (23 mg) of sodium per 5 ml, i.e. essentially sodium-free.
Terlipressin increases the hypotensive effect of non-selective β-blockers on the portal vein. The reduction in heart rate and cardiac output caused by the treatment can be attributed to the inhibition of the reflexogenic activity of the heart through the vagus nerve as a result of increased blood pressure. Concomitant treatment with drugs known to induce bradycardia (e.g. propofol, sufentanil) can cause severe bradycardia.
Terlipressin can trigger ventricular arrhythmias including Torsade de pointes (see sections 4.4 and 4.8). Therefore, extreme caution should be exercised in the use of terlipressin in patients with concomitant medications that can prolong the QT interval, such as class IA and III antiarrhythmics, erythromycin, certain antihistamines and tricyclic antidepressants or medications that may cause hypokalaemia or hypomagnesemia (e.g. some diuretics).
The 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).
Haemopressin 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.
It 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 continue/discontinue breast‑feeding or to continue/discontinue therapy with terlipressin should be made taking into account the benefit of breast‑feeding to the child and the benefit of terlipressin therapy to the woman.
No studies on the effect on the ability to drive and use machines have been performed.
Treatment of bleeding oesophageal varices with Haemopressin (1 mg intravenously and more) may be accompanied by the adverse reactions in Table 1.
Table 1. Adverse reactions reported with treatment of bleeding oesophageal varices with terlipressin:
| 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 |
| Cardiac disorders | |
| common (>1/100 to <1/10) | ventricular and supra-ventriculararrhythmia, 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 |
| Vascular disorders | |
| 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 |
| Gastrointestinal disorders | |
| 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) | injection site necrosis |
During clinical trials and post-marketing experience, several cases of QT interval prolongation and ventricular arrhythmias including Torsade de pointes have been reported (see sections 4.4 and 4.5).
During post-marketing experience, several cases of cutaneous ischemia and necrosis unrelated to the injection site have been reported (see section 4.4).
Reporting 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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
