PRESENTATION
Vials of SII SOMASTIN contain synthetic somatostatin (as the acetate) as a white, freeze-dried, sterile and pyrogen-free powder. Two strengths are available: 250 mcg and 3 mg.

Each vial of SII SOMASTIN contains:
Somatostatin 250 mcg or 3.0 mg*
D-Mannitol(excipient) 5.0 mg
*Corresponding to 300 µg and 3.6 mg of somatostatin acetate respectively.

Each vial of the strength 250 mcg and 3.0 mg is accompanied by a diluent ampoule containing 1 ml of isotonic, sterile and pyrogen - free Sodium Chloride Injection solution.

INDICATIONS AND USE
SII SOMASTIN is indicated for:
- Severe acute haemorrhage from oesophageal varices.
- Severe acute haemorrhage from gastric or duodenal ulcers, or accompanying acute erosive or haemorrhagic gastritis.
- Adjuvant treatment in pancreatic, biliary and intestinal fistulae.
- Prophylaxis and treatment of postoperative complications following pancreatic surgery.
- Adjuvant treatment in diabetic ketoacidosis.
- Treatment of acute pancreatitis.

PHARMACODYNAMIC PROPERTIES
SII SOMASTIN is a synthetic cyclic 14 amino-acid peptide, which is identical in structure and action to natural somastin.

By i.v. infusion in humans, somatostatin causes inhibition of Growth Hormone, Thyroid Stimulating Hormone, Insulin and Glucagon secretion as well as inhibition of gastric acid secretion. It also affects the absorption, motility, splanchnic blood flow and trophic functions of the gastro-intestinal tract.

Physiologically, somatostatin is found mainly in the gastrointestinal tract and in the hypothalamus.

Somatostatin inhibits the release of gastrin, gastric acid and pepsin which supports its indication in the treatment of upper G.I. haemorrhage. Furthermore, somatostatin is capable of reducing remarkably splanchnic blood flow without causing significant variations in the systemic arterial pressure, which proves to be valuable for the management of oesophageal variceal haemorrhage.

Somastin reduces both pancreatic endocrine and exocrine secretion which makes it effective in the prophylaxis and treatment of postoperative complications of pancreatic surgery and pancreatic fistulae.

The positive effect of somatostatin in the management of diabetic ketoacidosis can be ascribed to its suppression activity of glucagon secretion.

PHARMACOKINETICS
In healthy persons the plasma level of endogenous somatostatin is low, generally well under 175 ng/L.

Following i.v. Administration, somatostatin shows a very short plasma half-life which, as measured by radioimmunoassay, lies between 1,1 and 3 minutes in normal subjects between 1, 2 and 4,8 minutes in subjects with liver disease, between 2,6 and 4,9 minutes in subjects with chronic renal failure.

Following an i.v. Infusion at a rate 75 µg/h, the plateau level was obtained within 15 minutes and reached 1250 ng/L. The metabolic clearance rate was around 1L/min. and the half-life around 2,7 min.

After i.v. injection of 2µg of 125-I thyrosine somatostatin, urinary excretion contained 40% of the radioactivity after 4 hours and 70% after 24 hours.

Somatostatin is rapidly metabolized in the liver through the action of endopeptidases and aminopeptidases, resulting in cleavage between the N-terminus and the cyclized portion of the molecule.

It has cyctoprotective activity at pancreatic parenchyma, liver and stomach

DOSAGE AND ADMINISTRATION
SII SOMASTIN is given intravenously, by slow bolus injection(3 to 5 minutes) of 250 mcg or by continuous infusion at a rate of 250 mcg/hour(equivalent of approximately 3,5 µg/kg body weight/hour).

The lyophilised powder should be reconstituted with the physiological sodium chloride solution immediately prior to use.
For continuous infusion one 3 mg SII SOMASTIN vial should be used to prepare a 12 hours infusion. The solution may be either saline or 5% dextrose and should be adjusted to guarantee an outflow of 250 mcg somatostatin / hour. The use of a perfusion syringe is recommended.

- Tr e a t m e n t o f s e v e r e a c u t e b l e e d i n g f r o m t h e u p p e r gastrointestinal tract, including from oesophageal varices.
It is recommended to start by a slow intravenous injection of 250 mcg of SII SOMASTIN as loading dose, then immediately followed by an intravenous infusion at a rate of 250 mcg/h. In case of interruption of more than 3 to 5 minutes between two infusions, an additional slow i.v. Injection of 250 mcg is recommended to ensure a continuous treatment. Once the haemorrhage has stopped(usually in less than 12 to 24 hours), treatment should be continued for 48-72 hours in order to avoid rebleeding.
Treatment up to 120 hours has been routinely performed in this indication.

- Adjuvant treatment in pancreatic, biliary and intestinal fistulae:
A continuous infusion of SII SOMASTIN at a rate of 250 mcg/h is recommended until closure of the fistula (2-20 days). This infusion should be performed in addition to total parenteral nutrition. Once the fistula has been closed, treatment should be continued for 1 to 3 days and stopped progressively in order to avoid rebound effect.

- Prophylactic treatment of postoperative complications following pancreatic surgery:
SII SOMASTIN is administered at the beginning of the surgical intervention at a rate of 250 mcg/h and treatment is continued for 5 days.
Adjuvant treatment in diabetic ketoacidosis:
In patients with ketoacidosis, infusion of 100-500 µg/h of somatostatin associated with insulin therapy (bolus of 10 I.U.+
Infusion of 1-4.8 I.U./h) was capable of restoring euglycemia within 4 hours and resolving acidosis within 3 hours.

Precautionary Statements
CONTRA-INDICATIONS
SII SOMASTIN is contra-indicated:
- During pregnancy and the immediate post-partum period (puerperium) as well as during lactation. There is no evidence of the drug's safety in human pregnancy nor is there evidence from animal work that it is free from hazard. Avoid in pregnancy unless there is no safer alternative.
- In states of proven hypersensitivity to somatostatin.

WARNING
Due to its inhibitory effect on the secretion of insulin and glucagon, the administration of SII SOMASTIN can, at the onset of treatment, lead to a transient fall in blood glucose level. Caution is, therefore, called for in insulin- dependent diabetic patients in whom blood glucose should be measured every 3-4 hours. Simultaneous administration of insulin-requiring sugars should, if possible, avoided. If necessary, insulin should be administered.

INTERACTION WITH OTHER DRUGS
Since somatostatin lengthens the time of hexobarbital-induced sleep and potentiates the action of pentetrazol, SII SOMASTIN should not be administered concomitantly with these drugs or with drugs exerting the same effects.

SIDE-EFFECTS
Nausea, vertigo and flushing have been reported rarely. Nausea and vomiting have been reported when the infusion rate is greater than 50 µg/min.

INCOMPATIBILITIES
Physical incompatibilities with other drugs have not been tested, therefore SII SOMASTIN should be administered alone in the syringe and in infusion solutions.

STABILITY AND STORAGE
Vials of SII SOMASTIN should be stored at 2 - 8°C and should not be used after the expiry date stated on the package. Solutions of SII SOMASTIN in physiological sodium chloride are stable for 24 hours.

PRESENTATION
SII SOMASTIN 250 (250 mcg) vial plus 1 ml sodium chloride injection (diluent) ampoule, sterile disposable syringe & needle. Sii SOMASTIN 3000 (3 mg) vial plus 1 ml sodium chloride injection (diluent) ampoule. Drugs should be stored out of reach of children