Summary of Product Characteristics (SmPC) - Terlipressin Acetate Aft 0.12 mg/ml solution for injection
1 NAME OF THE MEDICINAL PRODUCT
Terlipressin Acetate AFT 0.12 mg/ml solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One vial contains 1 mg terlipressin acetate in 8.5 ml solution for injection, corresponding to 0.85 mg terlipressin. Each ml contains 0.12 mg terlipressin acetate, corresponding to 0.1 mg terlipressin.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for injection.
Clear, colourless solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Terlipressin Acetate AFT is indicated in the treatment of bleeding oesophageal varices.
4.2 Posology and method of administration
Posology
In acute variceal bleeding:
Adults
Initially an i.v. injection of 2 mg Terlipressin Acetate is given every 4 hours. The treatment should be maintained until bleeding has been controlled for 24 hours, but up to a maximum of 48 hours. After the initial dose, the dose can be adjusted to 1 mg i.v. every 4 hours in patients with body weight < 50 kg or if adverse effects occur. Paediatric population
There is no relevant use of Terlipressin Acetate AFT in paediatric population.
Method of administration
Intravenous injection use
4.3 Contraindications
Contraindicated in pregnancy.
Hypersensitivity to terlipressin acetate or any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Blood pressure, heart rate and fluid balance should be monitored during treatment.
To avoid local necrosis at the injection site, the injection must be given i.v.
Caution should be exercised in treating patients with hypertension or recognised heart disease.
In patients with septic shock with a low cardiac output Terlipressin Acetate AFT should not be used.
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, electrolyte abnormalities, or concomitant medications that can prolong the QT interval (see section 4.5).
Children and the elderly: Particular caution should be exercised in the treatment of children and elderly patients, as experience is limited in these groups.
There is no data available regarding dosage recommendation in these special patient categories.
4.5 Interaction with other medicinal products and other forms of interaction
The hypotensive effect of non-selective beta-blockers on the portal vein is increased with terlipressin. Concomitant treatment with medicinal products with a known bradycardic effect (e.g. propofol, sufentanil) may lower the heart rate and cardiac output. These effects are due to reflexogenic inhibition of cardiac activity via the vagus nerve due to the elevated blood pressure.
Terlipressin can trigger “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).
4.6 Fertility, pregnancy and lactation
Pregnancy
Treatment with Terlipressin Acetate AFT during pregnancy is contraindicated (ref. 4.3 and 5.3).
Terlipressin has been shown to cause uterine contractions and increased intrauterine pressure in early pregnancy and may decrease uterine blood flow. Terlipressin Acetate AFT may have harmful effects on pregnancy and foetus.
Spontaneous abortion and malformation have been shown in rabbits after treatment with terlipressin.
Breast-feeding
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.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
4.8 Undesirable effects
Frequency of undesirable effects
| System organ class | Frequency | ||
Common ≥1/100 to <1/10 | Uncommon ≥ 1/1,000 to < 1/100 | Rare ≥1/10,000 to ≤1/1,000 | |
| System organ class | Frequency | ||
Common ≥1/100 to <1/10 | Uncommon ≥ 1/1,000 to < 1/100 | Rare ≥1/10,000 to ≤1/1,000 | |
| Metabolism and nutrition disorders | Hyponatraemia if fluid not monitored | ||
| Nervous system Disorders | Headache | ||
| Cardiac disorders | Bradycardia | Atrial fibrillation Ventrical extrasystoles Tachycardia Chest pain Myocardial infarction Fluid overload with pulmonary oedema Torsade de pointes Cardiac failure | |
| Vascular disorders | Peripheral vasoconstriction Peripheral ischaemia Facial pallor Hypertension | Intestinal ischaemia Peripheral cyanosis Hot flushes | |
| Respiratory thoracic and mediastinal disorders | Respiratory distress Respiratory failure | Dyspnoea | |
| Gastrointestinal disorders | Transient abdominal cramps Transient diarrhoea | Transient nausea Transient vomiting | |
Skin and subcutaneous tissue disorders | Skin necrosis | ||
Pregnancy, puerperium and perinatal conditions | Uterine hypertonus Uterine ischemia | ||
| General disorders and administration site disorders | Injection site necrosis | ||
Reporting of suspected adverse reactions
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 the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
The recommended dose (2 mg/4 hours) should not be exceeded as the risk of severe circulatory adverse effects is dose-dependent.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Posterior pituitary lobe hormones (vasopressin and analogues) (H 01 BA 04)
Terlipressin Acetate AFT may be regarded as a circulating depot of lysine vasopressin. Following intravenous injection, three glycyl moieties are enzymatically cleaved from the N-terminus to release lysine vasopressin.
The slowly released vasopressin reduces blood flow in the splanchnic circulation in a prolonged manner, thereby helping to control bleeding from ruptured oesophageal varices.
5.2 Pharmacokinetic properties
Terlipressin is administered by bolus intravenous injection. It shows a biphasic plasma level curve which indicates that a two-compartment model can be applied.
The half-life of distribution (T1/2α) is about 8 -10 minutes.
The half-life of elimination (T1/2β) is about 50 -70 minutes.
Lysine vasopressin reaches maximum plasma levels about 1-2 hours following intravenous administration and has a duration of activity of 4-6 hours.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium chloride
Sodium acetate
Acetic acid
Water for injection
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
36 months
6.4 Special precautions for storage
Store in a refrigerator (2-8 °C).
6.5 Nature and contents of container
Terlipressin Acetate AFT solution for injection is packed in a 10 mL borosilicate clear glass vial type I with a rubber stopper and aluminium-plastic overseal.
6.6 Special precautions for disposal
Any unused medicine or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
AFT Pharma UK Limited
Olympia House
Unit 13, 2nd Floor, Armitage Road
London, NW11 8RQ
England
8 MARKETING AUTHORISATION NUMBER(S)
PL 57592/0008
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23/09/2024
10 DATE OF REVISION OF THE TEXT
04/02/2026