SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Pitressin® 20PU/ml Solution for Injection

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1ml contains 0.4mg of synthetic Pitressin (50 pressure unit per rng) which is equivalent to argipressin 20 pressor units.

3.    PHARMACEUTICAL FORM

A clear, sterile solution.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

For use in diabetes insipidus, when this is not of nephrongenic 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 0.25m1 to 1 ml (5 to 20 units) by subcutaneous or intramuscular injection every four hours.

Oesophageal varices:

For the initial control of variceal bleeding Pitressin should be given intravenously. Pitressin, 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 used successfully at normal dosage in the elderly.

Children and infants

No dose recommended.

4.3 Contraindications

Anaphylaxis or hypersensitivity to the drug or its components.

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 myocardinal 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.

Pitressin 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.

Pitressin 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 contra-indicates the use of Pitressin until reasonable nitrogen blood levels have been attained.

4.5 Interaction with other medicinal products and other forms of interaction

The following drugs may enhance the antidiuretic effect of pitressin when used concurrently: carbamazepine, chlorpropamide, clofibrate, fludrocortisone, urea or tricyclic antidepressants.

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

Ganglion blocking agents may increase sensitivity to the pressor effect of pitressin.

4.6 Pregnancy and lactation

No animal reproduction studies on Pitressin are available.

Oxytocic effects in the third trimester have been reported. However, Pitressin 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.

Pitressin has been administered to breast feeding women without apparent adverse

effect on the

infant.

4.7. Effects on Ability to Drive and Use Machines

Pitressin 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 Pitressin: 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 Pitressin. Peripheral ischaemia and rarely gangrene have been reported following use of Pitressin.

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 cedema. If a patient should experience anginal pain after administration of Pitressin, amyl nitrate by inhalation,, or glyceryl trinitrate sublingually, may be given.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

The antidiuretic action of Pitressin is ascribed to increasing reabsorption of water by the renal tubules. Pitressin 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 antagonized by adrenrgenic blocking agents nor prevented by vascular denervation.

5.2. Pharmacokinetic Properties

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

5.3. Pre-clinical Safety Data

Pre-clinical safety data does not add anything of further significance to the prescriber.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glacial acetic acid and water for injection. 6.2. Incompatibilities

None Known.

6.3. Shelf-Life

24 months.

6.4. Special Precautions for Storage

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

6.5 Nature and contents of container

White neutral glass ampoules with two orange break bands. Available in packs of 10x1ml ampoules.

6.6. Instructions for Use, Handling and Disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Mercury Pharmaceuticals Ltd No. 1 Croydon,

12-16 Addiscombe Road,

Croydon CR0 0XT, UK

8.    MARKETING AUTHORISATION NUMBER(S)

PL 12762/0024

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

11/06/2010

10 DATE OF REVISION OF THE TEXT

30/01/2014