SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Glypressin 0.12 mg/ml solution for injection

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

One ampoule contains 1mg terlipressin acetate in 8.5ml solution for injection. For excipients, see section 6.1

3    PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless liquid.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Glypressin is indicated in the treatment of bleeding oesophageal varices.

4.2 Posology and method of administration

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.

4.3 Contraindications

Contraindicated in pregnancy.

Hypersensitivity to terlipressin or any other excipients of the product.

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.

Fertility, pregnancy and lactation

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.

Information on transfer of Glypressin to breast milk is insufficient. Glypressin should not be used in breast feeding women.

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

The frequencies used in the table below are: very common (> 1/10), common (> 1/100 to < 1/10), uncommon (> 1/1,000 to < 1/100), rare (> 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).

Table: Frequency of undesirable effects

SYSTEM ORGAN CLASS	Frequency
	COMMON	UNCOMMO N	RARE	VER Y RAR E	NOT KNOWN
Metabolism		Hyponatraemi a if fluid not monitored
Nervous system	Headache
Cardiac	Bradycardia	Atrial fibrillation Ventrical extrasystoles Tachycardia Chest pain Myocardial infarction Fluid overload with pulmonary odemia			Torsade de pointes Cardiac failure
Vascular	Peripheral vasoconstrictio n Peripheral ischaemia Facial pallor Hypertension	Intestinal ischaemia Peripheral cyanosis Hot flushes
Respiratory		Respiratory distress Respiratory failure	Dyspnoe a
Gastrointestin al	Transient abdominal cramps Transient diarrhoea	Transient nausea Transient vomiting
Skin and subcutaneous					Skin necrosis
Pregnancy, puerperium and perinatal conditions					Uterine constrictio n Decreased uterine

					blood flow
General		Injection site necrosis

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 intravenous injection. It shows a biphasic plasma level curve which indicates that a two compartment model can be applied.

The half-life of distribution (Ti_/2a) is about 8 -10 minutes.

The half-life of elimination (T_1/2p) 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.

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 Acetic acid Sodium acetate Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Store in a refrigerator (2-8 °C). Keep the ampoules in the outer carton in order to protect from light.

6.5 Nature and contents of container

Type I clear glass ampoules.

Pack size: 5 x 8.5ml

6.6 Special precautions for disposal

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

7 MARKETING AUTHORISATION HOLDER

Ferring Pharmaceuticals Ltd

Drayton Hall

Church Road

West Drayton

UB7 7PS

UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 03194/0101

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

11/05/2009

10    DATE OF REVISION OF THE TEXT

15/03/2013