Glypressin Injection
SUMMARY OF PRODUCT 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
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 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
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 |
UNCOMMON |
RARE |
VERY RARE |
NOT KNOWN | |
|
Metabolism |
Hyponatraemia 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 vasoconstriction Peripheral ischaemia Facial pallor Hypertension |
Intestinal ischaemia Peripheral cyanosis Hot flushes | |||
|
Respiratory |
Respiratory distress Respiratory failure |
Dyspnoea | |||
|
Gastrointestinal |
Transient abdominal cramps Transient diarrhoea |
Transient nausea Transient vomiting | |||
|
Skin and subcutaneous |
Skin necrosis | ||||
|
Pregnancy, puerperium and perinatal conditions |
Uterine constriction 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 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 (Ti/2p) 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.
6.1 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 Instructions for Use/Handling
Prior to injection, the powder should be reconstituted with the solvent provided. Use immediately after reconstitution.
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 THE
AUTHORISATION
October 1983 / 19th July 2001
10 DATE OF REVISION OF THE TEXT
19/10/2012