GLYPRESSIN INJECTION - summary of medicine characteristics

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.

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 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

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 (T%a) is about 8 –10 minutes.

The half-life of elimination (T%p) 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

Prior to injection, the powder should be reconstituted with the solvent provided. Use immediately after reconstitution.

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 UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 03194/0018

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

October 1983 / 19th July 2001