This information is intended for use by health professionals

1. Name of the medicinal product

Glypressin® Injection

2. Qualitative and quantitative composition

Each vial contains 1mg Terlipressin Acetate

For excipients, see 6.1

3. Pharmaceutical form

Powder and solvent for solution for injection

Vial contains white, freeze-dried powder.

Ampoule contains solvent.

4. Clinical particulars
4.1 Therapeutic indications

Glypressin® 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 Glypressin 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 Glypressin 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 Glypressin should not be used.

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

Treatment with Glypressin during pregnancy is contraindicated (ref. 4.3 and 5.3).

Glypressin has been shown to cause uterine contractions and increased intrauterine pressure in early pregnancy and may decrease uterine blood flow. Glypressin may have harmful effects on pregnancy and foetus.

Spontaneous abortion and malformation have been shown in rabbits after treatment with Glypressin.

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

Table: 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

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.

4.9 Overdose

The recommended dose (2mg/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)

Glypressin® 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

Glypressin® is administered by bolus iv 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 iv 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

Vial:

Mannitol

Hydrochloric Acid 1M

Solvent Ampoule:

Sodium Chloride

Hydrochloric Acid 1M

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

Do not store above 25°C. Keep container in the outer carton.

6.5 Nature and contents of container

Powder: Type I glass vial

Solvent: Type I glass ampoule

Pack size:

Cartons containing 5 packs, each with one vial of powder and one ampoule of 5ml solvent.

6.6 Special precautions for disposal and other handling

Unused drug and waste should be destroyed in accordance with local requirements.

Any unused product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Ferring Pharmaceuticals Ltd.

Drayton Hall

Church Road

West Drayton

UB7 7PS

United Kingdom

8. Marketing authorisation number(s)

PL 03194/0018

9. Date of first authorisation/renewal of the authorisation

18th July 2001

10. Date of revision of the text

September 2017