Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Somatostatin and analogues,             6.4 Special precautions for storage ATC code: H01CB02                                                  Store in the original package in order to protect from light.
Octreotide is a synthetic octapeptide analogue of the              Store in a refrigerator (2 °C – 8 °C).
naturally occurring hormone somatostatin with similar              Octreotide Bendalis 0.05 mg/ml, Octreotide Bendalis 0.1 mg/ml, pharmacological effects, but a considerably longer duration        Octreotide Bendalis 0.5 mg/ml of activity. It inhibits the pathologically increased secretion    For daily use, the ampoules of Octreotide Bendalis 0.05 mg/ml, of growth hormone (GH) and of peptides and serotonin               Octreotide Bendalis 0.1 mg/ml and Octreotide Bendalis produced in the gastroenteropancreatic (GEP) endocrine             0.5 mg/ml may be stored at room temperature for up to system.                                                            2 weeks in the original package.
In animals, Octreotide inhibits the release of growth              The ampoules must be used immediately after opening.
hormone, glucagon and insulin more powerfully than                 Discard any remaining solution after opening.
somatostatin, with greater selectivity for GH and glucagon         Octreotide Bendalis 0.2 mg/ml suppression.                                                       Vials of Octreotide Bendalis 0.2 mg/ml may only be removed In healthy individuals, Octreotide Bendalis has demonstrated       from the refrigerator for preparation of an injection. Between the following effects:                                             injections, they must be kept in the refrigerator at 2 °C – 8 °C - Inhibition of the release of GH stimulated in different ways     in the original package.
(arginine, exertion, and insulin-induced hypoglycaemia)         The product remains stable for two weeks after opening.
- Inhibition of the postprandial release of insulin, glucagon,     Diluted solutions must be used immediately after reconsti- gastrin and other peptides of the GEP system, and of the        tution.
arginine-stimulated secretion of insulin and glucagon
- Inhibition of the release of thyrotropin-releasing hormone       6.5 Nature and contents of container (TRH) (inducing the release of thyroid-stimulating              Ampoules or vials consisting of clear glass (type I).
hormone (TSH))
Octreotide Bendalis 0.05 mg/ml, Octreotide Bendalis 0.1 mg/ml,
Unlike somatostatin, Octreotide primarily inhibits insulin-        Octreotide Bendalis 0.5 mg/ml induced GH secretion and does not result in a rebound              Ampoules containing 1.0 ml solution for injection each.
phenomenon (hypersecretion of GH in patients with acro-            Packs of 5 ampoules or 30 ampoules.
megaly).
Octreotide Bendalis 0.2 mg/ml
In patients with acromegaly, Octreotide Bendalis lowers the        Vials containing 5.0 ml solution for injection each.
plasma levels of GH and IGF-1. A reduction of GH by 50 % or        Packs of 1 or 10 vials.
more occurs in up to 90 % patients, and a reduction of serum
GH to <5 ng/ml can be achieved in about 50 % of cases.             6.6 Special precautions for disposal and other handling In most patients Octreotide Bendalis markedly improves the         Any unused medicinal product or waste material should be clinical symptoms such as headache, skin and soft-tissue           disposed of in accordance with local requirements.
swelling, hyperhidrosis, arthralgia and paraesthesia. In
Instructions for use patients with a large pituitary adenoma, Octreotide Bendalis
Octreotide Bendalis 0.05 mg/ml, Octreotide Bendalis 0.1 mg/ml,
treatment may reduce the volume of the tumour tissue to
Octreotide Bendalis 0.5 mg/ml a certain extent.
The ampoules are intended for single use only. They may
In patients with functional tumours of the gastroenteropan-        only be opened immediately before use. Any unused product creatic endocrine system, Octreotide Bendalis may improve          must be discarded.
the clinical picture due to its diverse endocrinal effects.
Octreotide Bendalis 0.2 mg/ml
Clinical and symptomatic improvements can be achieved in
The vials are intended for multiple use. To prevent contami- patients who continue to experience tumour-induced symp- nation, it is recommended to puncture the cap of the vial toms despite previous treatment (surgery; hepatic artery no more than 10 times.
embolisation; e.g. with streptozocin and 5-fluorouracil).
Subcutaneous administration
Octreotide Bendalis exerts the following effects in different
Octreotide Bendalis should be used undiluted in case of tumour types: subcutaneous administration.
Carcinoid tumours                                                  Patients who are to self-administer the drug by subcutaneous Administration of Octreotide Bendalis will generally improve       injection must receive precise directions from their doctor the symptoms, particularly flushing and diarrhoea. In many         or nurse.
cases, this will be accompanied by a drop in plasma serotonin      To reduce local discomfort, it is recommended that the and reduced urinary excretion of 5-hydroxyindoleacetic acid.       solution should be at room temperature before injection.
VIPomas                                                            Multiple injections at the same site at short intervals should The biochemical feature of these tumours is the over-              be avoided.
production of vasoactive intestinal peptide (VIP). In most         Intravenous use cases, administration of Octreotide Bendalis will alleviate        Parenteral medicinal products should be inspected visually the severe secretory diarrhoea typical of the condition and        for discolouration and particulate matter prior to adminis- consequently improve quality of life. This will be accom-          tration. The product must be diluted prior to intravenous panied by an improvement in the attendant electrolyte              infusion. Octreotide Bendalis (Octreotide acetate) remains disorders, e.g. hypokalaemia, permitting discontinuation of        physically and chemically stable for 24 hours in sterile enteral and parenteral fluid and electrolyte supplementa-          physiological saline solution or sterile solutions of 5 % tion. In some patients, computed tomography imaging may            dextrose (glucose) in water. However, as Octreotide Bendalis suggest that tumour progression has slowed or stopped, or          can affect glucose homeostasis, physiological saline solu- that the size                                                      tions are recommended rather than dextrose. The diluted of the tumour has decreased, particularly in the case of           solutions remain physically and chemically stable for at hepatic metastases. The clinical improvement is usually            least 24 hours below 25 °C. For microbiological reasons, accompanied by a reduction in plasma VIP levels, which may         the diluted solution should be used immediately. If not used return to the normal reference range.                              immediately, in-use storage times and conditions prior to Glucagonomas                                                       use are the responsibility of the user.
Treatment with Octreotide Bendalis in most cases sub-              The content of one 0.5 mg ampoule should normally be stantially improves the necrolytic migratory rash which is         diluted in 60 ml physiological saline, and the resulting characteristic of this condition. The effect of Octreotide         solution administered with the aid of an infusion pump.
Bendalis on mild forms of diabetes mellitus, which frequently      This should be repeated as often as necessary until the occur in patients with glucagonoma, is not pronounced; the         prescribed duration of treatment is achieved.
need for insulin or oral hypoglycaemic agents generally is not reduced. Octreotide Bendalis improves diarrhoea, resulting in weight gain. Although treatment with Octreotide Bendalis        7. MANUFACTURER often leads to an immediate reduction in plasma glucagon levels, this decrease generally is not maintained over a           Bendalis GmbH prolonged treatment period. Symptomatic improvement                Keltenring 17 is sustained, however.                                             82041 Oberhaching Germany
Gastrinomas/Zollinger-Ellison syndrome
Therapy with proton pump inhibitors or H2 receptor blocking agents will generally control gastric acid hypersecretion.         8. REGISTRATION HOLDER However, diarrhoea, which is also a prominent symptom,
may not be adequately alleviated by proton pump inhibitors         David Margalit & Co. Ltd.
or H2 receptor blocking agents. Octreotide Bendalis can help       P.O.Box 16666 Tel Aviv to further reduce gastric acid hypersecretion and improve symptoms, including diarrhoea, as it suppresses elevated gastrin levels in some patients.                                   9. PRODUCT REGISRATION NO.: Insulinomas                                                        Octreotide Bendalis 0.05 mg/ml Administration of Octreotide Bendalis leads to a decrease in       164-14-34086 the level of circulating immunoreactive insulin, but possibly      Octreotide Bendalis 0.1 mg/ml only for a short period (about two hours). In patients with        164-15-34084 operable tumours, Octreotide Bendalis may help to restore and maintain normoglycaemia preoperatively. In patients            Octreotide Bendalis 0.5 mg/ml with inoperable benign or malignant tumours, glycaemic             164-17-34083 control may be improved without a concomitant, sustained           Octreotide Bendalis 0.2 mg/ml reduction in circulating insulin levels.                           164-16-34085 GRFomas
These rare tumors are characterized by production of GH            Revised in August 2021 releasing factor (GRF) alone or in conjunction with other active peptides. Octreotide Bendalis produces improvement in the features and symptoms of the resultant acromegaly.
This is probably due to inhibition of GRF and GH secretion,
and a reduction in pituitary enlargement may follow
Prevention of complications following pancreatic surgery
In patients who must undergo pancreatic surgery, the peri- and postoperative administration of Octreotide Bendalis reduces the incidence of typical postoperative complications
(e.g. pancreatic fistula, abscess followed by sepsis, post- operative acute pancreatitis).
Bleeding from gastro-oesophageal varices
In patients with bleeding from gastro-oesophageal varices due to underlying cirrhosis, Octreotide Bendalis combined with specific treatment (e.g. sclerotherapy) results in better control of bleeding and early re-bleeding, and is associated with lower transfusion requirements and improved 5-day survival. While the precise mode of action of Octreotide
Bendalis has not been fully explained, it is postulated that
Octreotide Bendalis reduces splanchnic blood flow by inhibit- ing vasoactive hormones (e.g. VIP, glucagon).

Pharmacokinetic Properties