SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Argipressin 20 IU/ml Solution for Injection

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

20 international units argipressin (vasopressin) USP per ml.

(Equivalent to 0.4mg argipressin, based on 50 international units per mg).

3.    PHARMACEUTICAL FORM

Solution for injection

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

For use in diabetes insipidus, when this is not of nephrogenic origin and control of bleeding from oesophageal varices.

4.2.    Posology and Method of Administration

Subcutaneous, intravenous or intramuscular injection.

Adults

Diabetes Insipidus:

A dose of 0.25ml to 1ml (5 to 20 units) by subcutaneous or intramuscular injection every four hours.

Oesophageal Varices:

For the initial control of variceal bleeding Argipressin should be given intravenously. Argipressin, 20 units diluted in 100ml dextrose 5% w/v may be infused over a 15 minute period.

Elderly (over 65 years)

As for adults, no clinical or pharmacokinetic data specific to this age group are available. However, the drug has been successfully used at normal dosage in the elderly.

Children and infants

No dose recommended.

4.3 Contraindications

Anaphylaxis or hypersensitivity to the drug or its excipients.

Patient with coronary artery disease, or those intended to receive halogenated anaesthetic agents.

Vascular disease (especially disease of coronary arteries), chronic nephritis (until reasonable blood nitrogen concentrations attained)

4.4 Special warnings and precautions for use

This drug should not be used in patients with systemic hypertension or vascular disease, especially disease of the coronary arteries, except with extreme caution. In such patients, even small doses may precipitate pain, and with larger doses, the possibility of myocardial infarction should be considered. If this drug must be used in patients with peripheral vascular disease then the skin should be observed carefully for signs of ischaemia.

Argipressin may produce water intoxication. The early signs of drowsiness, listlessness, and headaches should be recognised to prevent terminal coma and convulsions.

Adjustment of dosage in cases immediately post-hypophysectomy should be controlled on the basis of measurements of urine osmolality.

Argipressin should be used cautiously in the presence of epilepsy, migraine, asthma, heart failure, or any state in which a rapid addition to extracellular water may produce hazard for an already overburdened system.

Chronic nephritis with nitrogen retention contraindicates the use of Argipressin 20IU/ml injection until reasonable nitrogen blood levels have been attained.

4.5 Interaction with other medicinal products and other forms of interaction

The following drugs may potentiate the antidiuretic effect of vasopressin when used concurrently: carbamazepine, chlorpropamine, clofibrate, fludrocortisone, urea or tricyclic antidepressants.

The following drug may decrease the antidiuretic effect of vasopressin of vasopressin when given concurrently: demeclocycline, noradrenaline, lithium, heparin, alcohol.

Ganglion blocking agents may produce a marked increase in sensitivity to the pressor effect of vasopressin.

4.6 Pregnancy and lactation

No animal reproduction studies on Argipressin are available.

Oxytocic effect in third trimester has been reported. However, argipressin has been used successfully during pregnancy for the treatment of diabetes insipidus with no adverse effects on the foetus being reported. Nevertheless, as with all medicines, use during pregnancy should be avoided if possible and the potential benefit to the patient weighed against any possible risk to the foetus.

Argipressin has been administered to breast feeding women without apparent adverse effect on the infant.

4.7. Effects on Ability to Drive and Use Machines

Argipressin may cause vertigo (see side effects).

4.8 Undesirable effects

Local or systemic allergic reactions may occur in hypersensitive individuals.

The following side effects have been reported following the administration of Argipressin: fluid retention, headache, tremor, sweating, vertigo, circumoral pallor, “pounding” in head, abdominal cramps, passage of gas, nausea, vomiting, urticaria, bronchial constriction, desire to defaecate and chest pain. Anaphylaxis (cardiac arrest and/or shock) has been observed shortly after injection of Argipressin. Peripheral ischaemia and rarely gangrene have been reported following use of Argipressin.

4.9. Overdose

If water intoxication occurs, no fluids should be given. In severe cases, small amounts of hypertonic saline may be administered. Urea and mannitol infusions may be helpful in cases of cerebral oedema. If a patient should experience anginal pain after administration of Argipressin, amyl nitrite by inhalation or glyceryl trinitrate sublingually, may be given.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic Properties

The antidiuretic action of Argipressin is ascribed to increase in reabsorption of water by the renal tubules. Argipressin can cause contraction of smooth muscle of the gastrointestinal tract, gall bladder, urinary bladder and all parts of the vascular bed, especially the capillaries, small arterioles and venules with less effect on the smooth musculature of the large veins. The direct effect on the contractile elements is neither antagonised by adrenergic blocking agents nor prevented by vascular denervation.

5.2. Pharmacokinetic Properties

Following subcutaneous or intramuscular administration of Argipressin injection, the duration of antidiuretic activity is variable, but effects are usually maintained for 2-8 hours. The majority of the dose of Argipressin is metabolised and rapidly destroyed in the liver and kidneys. Argipressin has a plasma half-life of about 10 to 20 minutes. Approximately 5% of a subcutaneous dose of Argipressin is excreted unchanged in the urine four hours after dosing.

5.3. Preclinical Safety Data

Preclinical safety data does not add anything of further significance to the prescriber.

6 PHARMACEUTICAL PARTICULARS

6.1.    List of Excipients

Glacial acetic acid, water for injection

6.2.    Incompatibilities

Not known.

6.3. Shelf Life

24 months.

Special Precautions for Storage

Store between 2°C and 8°C. Do not freeze.

6.5.    Nature and Content of Container

Clear OPC/blue glass ampoules. Available in packs of 10 xlml ampoules.

6.6.    Instructions for Use and Handling

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Mercury Pharmaceuticals Ltd Capital House,

85 King William Street,

London EC4N 7BL,

UK

8. MARKETING AUTHORISATION NUMBER

PL 12762/0162

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30^th November 2004

10    DATE OF REVISION OF THE TEXT

08/01/2015