Oktreotid-depot

General characteristics. Structure:

Active ingredient: 10 mg, 20 mg or 30 mg of an oktreotid.

Excipients: copolymer of DL milk and glycolic acids, D-mannitol, carboxymethylcelluloses sodium salt, polysorbate-80.

Solvent in an ampoule: A mannitol, solution for injections of 0,8%.

Drug is used at the tumors expressing receptors to somatostatin, endocrine tumors of a GIT and pancreas (carcinoid tumors, insulinoma, Vipoma, a gastrinoma, a glucagonoma, a somatoliberinoma), at an acromegalia, as a part of a combination therapy of a gormonorezistentny prostate cancer.

Pharmacological properties:

Pharmacodynamics. The Oktreotid-depot represents the dosage form of an oktreotid of long action for intramuscular introduction providing maintenance of stable therapeutic concentration of an oktreotid in blood within 4 weeks. Oktreotid is cure of pathogenetic therapy for the tumors which are actively expressing receptors to somatostatin. Oktreotid - the synthetic octapeptide which is to derivatives of natural hormone of somatostatin and having pharmacological effects, similar to it, but considerable the bigger duration of action. Drug suppresses patholologically hypersecretion of the growth hormone (GH), and also the peptides and serotonin produced in gastro-entero-pancreatic endocrine system.

At healthy faces октреотид, like somatostatin, suppresses the secretion of GR caused by arginine, an exercise stress and an insulin hypoglycemia; the secretion of insulin, a glucagon, gastrin and other peptides of gastro-entero-pancreatic endocrine system caused meal and also the secretion of insulin and a glucagon stimulated by arginine; the thyrotropin secretion caused tireoliberiny. Overwhelming action on secretion of GR at an oktreotid, unlike somatostatin, is expressed in much bigger degree, than on insulin secretion. Introduction of an oktreotid is not followed by a phenomenon of hypersecretion of hormones on a negative feedback mechanism.

At patients with an acromegalia introduction of Oktreotida-depot provides in most cases permanent decrease in concentration of GR and normalization of concentration of an insulinopodobny growth factor 1/S (IFR-1) somatomedins.

At most Oktreotid-depots sick with an acromegalia significantly reduces expressiveness of such symptoms as a headache, the increased sweating, paresthesias, fatigue, an ostealgia and joints, peripheral neuropathy. It was reported that treatment oktreotidy led certain patients with the hypophysis adenomas cosecreting GR to reduction of the sizes of a tumor.

At carcinoid tumors use of an oktreotid can lead to reduction of expressiveness of symptoms of a disease, first of all, such as "inflows" and diarrhea. In many cases clinical improvement is followed by decrease in concentration of serotonin in plasma and excretion of 5-hydroxyindolacetic acid with urine.

At the tumors which are characterized by hyperproduction of vasoactive intestinal peptide (Vipoma), use of an oktreatid leads at most of patients to reduction of heavy secretory diarrhea which is characteristic of this state that, in turn, leads to improvement of quality of life of the patient. At the same time there is a reduction of the accompanying disturbances of electrolytic balance, for example, of a hypopotassemia that allows to cancel enteral and parenteral administration of liquid and electrolytes. According to a computer tomography some patients have a delay or a stop of progressing of a tumor, and even reduction of its sizes, especially metastasises in a liver. Clinical improvement usually is followed by reduction (up to normal values) concentration of the vasoactive intestinal peptide (VIP) in plasma.

At glucagonomas use of an oktreotid in most cases leads to noticeable reduction of the necrotizing migrating rash which is characteristic of this state. Oktreotid has no a little significant effect on expressiveness of the diabetes mellitus which is often observed at glucagonomas and usually does not lead to decrease in need for insulin or peroral hypoglycemic drugs. октреотид causes its reduction in the patients having diarrhea that is followed by increase in body weight. At use of an oktreotid bystry decrease in concentration of a glucagon in plasma is often noted, however at prolonged treatment this effect does not remain. At the same time symptomatic improvement remains stable a long time.

At гастриномах / Zollingera-Ellison's syndrome октреотид, applied as monotherapy or in a combination with H2 blockers - histamine receptors and inhibitors of the proton pump, can reduce formation of hydrochloric acid in a stomach and lead to clinical improvement, including and concerning diarrhea. Perhaps also reduction of expressiveness and other symptoms which are possibly connected with synthesis of peptides a tumor including inflows. Decrease in concentration of gastrin in plasma is in certain cases noted.

At patients from insulinoma октреотид reduces concentration of immunoreactive insulin in blood. At patients with resectable tumors октреотид can provide recovery and maintenance of a normoglikemiya in the preoperative period. At patients with nonresectable benign and malignant tumors control of a glycemia can improve also without simultaneous long decrease in concentration of insulin in blood.

At patients with seldom found tumors which are hyper producing a rileasing-factor of a growth hormone (somatoliberinomama) октреотид reduces expressiveness of symptoms of an acromegalia. It, apparently, is connected with suppression of secretion of a rileasing-factor of a growth hormone and GR. Further reduction of the sizes of a hypophysis which prior to treatment were increased is possible.

At patients with a gormonorezistentny prostate cancer (GRRPZh) the pool of the neuroendocrinal cells expressing somatostatinovy receptors, affine to an oktreotid (SS2 and SS5 types) that defines sensitivity of a tumor to an oktreotid increases. Use of oktreotida-depot in a complex with dexamethasone against the background of androgenic blockade (medicamentous or surgical castration) at patients of GRRPZh recovers sensitivity to hormonal therapy and leads to decrease in the prostatic specific antigen (PSA) more than at 50% of patients.

At sick GRPZh with metastasises in a bone this therapy is followed by the expressed and long-term analgesic effect. At the same time at all patients who answered a combination therapy from oktreotidom-depot quality of life and a median of bezretsidivny survival significantly improves.

Indications to use:

In therapy of an acromegalia:
- when adequate control of displays of a disease is exercised due to hypodermic introduction - an oktreotid;
- in the absence of sufficient effect of surgical treatment and radiation therapy;
- for preparation for surgical treatment;
- for treatment between courses of radiation therapy before development of lasting effect;
- at inoperable patients.

In therapy of endocrine tumors of the digestive tract (DT) and pancreas:
- carcinoid tumors with the phenomena of a carcinoid syndrome;
- insulinoma;
- Vipoma;
- gastrinoma (Zollingera-Ellison's syndrome);
- glucagonomas (for control of a hypoglycemia in the preoperative period, and also for a maintenance therapy);
- somatoliberinoma (the tumor which are characterized by hyperproduction of a rileasing-factor of a growth hormone).
- treatment of patients with the cosecreting and not cosecreting widespread (metastatic) neuroendocrinal tumors of the lean, ileal, blind, ascending colonic, cross colon and a worm-shaped shoot, or metastasises of neuroendocrinal tumors without initially revealed center.

In therapy of a gormonorezistentny prostate cancer:
- as a part of a combination therapy against the background of surgical or medicamentous castration.

In prevention of development of acute postoperative pancreatitis:
- at extensive surgeries on an abdominal cavity and thoracoabdominal interventions (including concerning a carcinoma of the stomach, a gullet, a colon, a pancreas, primary and secondary tumoral damage of a liver).

Route of administration and doses:

The Oktreotid-depot should be entered only deeply intramusculary (in oil), into a gluteus. At repeated injections the left and right parties should be alternated. Suspension should be prepared just before an injection. In day of an injection the bottle with drug and an ampoule with solvent can be held at the room temperature.

At treatment of an acromegalia at patients for whom hypodermic (п / to) Oktreotid's introduction provides adequate control of displays of a disease the recommended initial dose of Oktreotida-depot makes on 20 mg each 4 weeks within 3 months. It is possible to begin treatment of Oktreotidom-depot next day after the last p / to Oktreotid's introduction. Further the dose is korrigirut taking into account concentration in GR and IFR-1 serum, and also clinical symptoms. If after 3 months of treatment it was not succeeded to reach adequate clinical and biochemical effect (in particular if concentration of GR remains higher than 2.5 mkg/l), it is possible to increase a dose to 30 mg entered each 4 weeks.

When after 3 months of treatment of Oktreotidom-depot in a dose of 20 mg lower than 1 mkg/l, normalization of concentration of IFR-1 and disappearance of reversible symptoms of an acromegalia is noted permanent reduction of serumal concentration of GR, it is possible to reduce a dose of Oktreotida-depot to 10 mg. However at these patients receiving rather small dose of Oktreotida-depot it is necessary to continue to control carefully serumal concentration of GR and IFR-1, and also disease symptoms.

To the patients receiving a stable dose of Oktreotida-depot, definition of concentration of GR and IFR-1 it is necessary to spend each 6 months.

To patients at whom surgical treatment and radiation therapy are insufficiently effective or in general are inefficient, and also the patients needing short-term treatment in intervals between courses of radiation therapy until development of its full effect are recommended to conduct a trial course of treatment п / to Oktreotid's injections for the purpose of assessment of its efficiency and the general portability, and only after that to pass to use of Oktreotida-depot according to the above-stated scheme.

At treatment of endocrine tumors of a GIT and pancreas at patients to whom п / to Oktreotid's introduction provides adequate control of displays of a disease the recommended initial dose of Oktreotida-depot makes 20 mg each 4 weeks. П / to Oktreotid's introduction it is necessary to continue within 2 weeks after the first introduction of Oktreotida-depot.

At the patients who were not receiving earlier Oktreotid п / to it is recommended to begin treatment with п / to Oktreotid's introduction in a dose of 0.1 mg of 3 times/days during rather short span (about 2 weeks) for the purpose of assessment of its efficiency and the general portability. Only after that appoint Oktreotid-depot according to the above-stated scheme.

In case therapy of Oktreotidom-depot within 3 months provides adequate control of clinical manifestations and biological markers of a disease, it is possible to lower a dose of Oktreotida-depot to 10 mg appointed each 4 weeks. When after 3 months of treatment of Oktreotidom-depot it was succeeded to reach only partial improvement, it is possible to increase a dose of drug to 30 mg each 4 weeks. Against the background of treatment of Oktreotidom-depot in separate days strengthening of the clinical manifestations characteristic of endocrine tumors of a GIT and pancreas is possible. In these cases it is recommended additional п / to Oktreotid's introduction in the dose applied prior to treatment of Oktreotidom-depot. It can occur, mainly, in the first 2 months of treatment, therapeutic concentration of an oktreotid in plasma are not reached yet.

At treatment of a gormonorezistentny prostate cancer the recommended initial dose of Oktreotida-depot makes 20 mg each 4 weeks within 3 months. Further the dose is korrigirut taking into account dynamics of concentration of the DOG in serum, and also clinical symptoms. If after 3 months of treatment it was not succeeded to reach adequate clinical and biochemical effect (decrease in the DOG), it is possible to increase a dose to 30 mg entered each 4 weeks.

Treatment of oktreotidom-depot is combined using dexamethasone which is appointed inside according to the following scheme: 4 mg a day within 1 month, then 2 mg a day within 2 weeks, then 1 mg a day (maintenance dose).

Treatment of oktreotidom-depot and dexamethasone of patients by which carried out medicamentous anti-androgenic therapy earlier combine a gonadotrophin-rileasing of hormone (GNRG) using an analog. At the same time GNRG analog injection (depot of a form) carry out 1 time in 4 weeks.

To the patients receiving Oktreotida-depot, it is necessary to carry out definition of concentration of the DOG every month.

Patients with a renal failure, and at patients of advanced age have a liver no need to korrigirovat the mode of dosing of Oktreotida-depot.

For prevention of acute postoperative pancreatitis drug of Oktreotid-depot in a dose of 10 or 20 mg is entered once not earlier than in 5 days and not later than 10 days before an estimated operative measure

Rules of preparation of suspension and administration of drug. The drug is administered only intramusculary. Suspension for an injection in oil is prepared by means of the enclosed solvent just before introduction.

Drug has to prepare and be entered by only specially trained medical personnel.
Before an injection the ampoule with solvent and a bottle drug needs to be got from the refrigerator and to bring to room temperature (30-50 min. are required).

You discipline a bottle with Oktreotidom-depot vertically. Easily tapping on a bottle, achieve that all lyophilisate was at the bottom of a bottle.

Open packaging with the syringe, attach to the syringe a needle of 1,2 mm x 50 mm in size for a solvent intake.

Open an ampoule with solvent and gather in the syringe all contents of an ampoule with solvent, install the syringe on a dose of 3,5 ml.

Remove a plastic lid from the bottle containing lyophilisate. Disinfect a rubber bung of a bottle a spirit tampon. Enter a needle into a bottle with lyophilisate through the center of a rubber bung and carefully enter solvent on an internal wall of a bottle, without concerning a bottle contents needle. Take out the syringe from a bottle.

The bottle has to remain solvent of lyophilisate and formation of suspension, motionless before full treatment (approximately for 3 – 5 minutes). Then, without overturning a bottle, it is necessary to check availability of dry lyophilisate at walls and a bottom of a bottle. At detection of the dry remains of lyophilisate leave a bottle before full treatment.

After you were convinced of lack of the remains of dry lyophilisate, contents of a bottle should be mixed carefully roundabouts within 30-60 seconds before formation of homogeneous suspension. Do not overturn and do not stir up a bottle, it can lead to flocculation and unfitness of suspension.

Quickly insert a needle through a rubber bung into a bottle. Then the cut of a needle is lowered down and, having inclined a bottle at an angle of 45 degrees, slowly gather in the syringe suspension completely. Do not overturn a bottle at set. A small amount of drug can remain on walls and day of a bottle. The expense on the rest on walls and day of a bottle is considered.

Right after a set of suspension replace a needle with the pink pavilion with a needle with the green pavilion (0,8 mm x 40 mm), accurately turn the syringe and remove air from the syringe. Suspension of Oktreotida-depot should be entered immediately after preparation. Suspension of Oktreotida-depot should not mix up with any other medicine in one syringe.

By means of a spirit tampon disinfect the place of an injection. Enter a needle deeply into a gluteus, then slightly delay the syringe piston back to be convinced that there are no damages of a vessel. Enter suspension intramusculary slowly with constant pressing the syringe piston.

At hit in a blood vessel it is necessary to change the place of an injection and a needle.

At a needle blockage, replace it with other needle of the same diameter.

At repeated injections the left and right parties should be alternated.

Features of use:

At the tumors of a hypophysis cosecreting GR careful observation of patients as increase in the sizes of tumors with development of such serious complications as narrowing of fields of vision is possible is necessary. In these cases it is necessary to consider need of use of other methods of treatment.

At 15-30% of the patients receiving Oktreotid п / to for a long time emergence of stones in a gall bladder is possible. Prevalence in the general population (age of 40-60 years) makes 5-20%. Experience of prolonged treatment by Oktreotid of the prolonged action of patients with an acromegalia and tumors of a GIT and a pancreas demonstrates that Oktreotid, in comparison with Oktreotid of short action, does not lead the prolonged action to increase in frequency of formation of stones of a gall bladder. Nevertheless, performing ultrasonography of a gall bladder before an initiation of treatment by Oktreotid - depot and approximately each 6 months in the course of treatment is recommended. Stones in a gall bladder if after all they are found, as a rule, asymptomatic. In the presence of clinical symptomatology conservative treatment (for example, use of drugs of bile acids) or an operative measure is shown.

At patients with a diabetes mellitus of 1 type of Oktreotid-depot can influence exchange of glucose and, therefore, reduce the need for the entered insulin. For patients with a diabetes mellitus 2 types and patients without the accompanying disturbance of carbohydrate metabolism subcutaneous injections of Oktreotid can lead to a postprandialny glycemia. In this regard it is regularly recommended to control concentration of glucose in blood and in case of need to korrigirovat hypoglycemic therapy.

At patients from insulinoma against the background of treatment oktreotidy increase in expressiveness and duration of a hypoglycemia can be noted (it is connected with more expressed overwhelming influence on secretion of GR and a glucagon, than on insulin secretion, and also with the smaller duration of the inhibiting impact on insulin secretion). Systematic observation of these patients is shown.

Before purpose of an oktreotid patients have to undergo initial ultrasonography of a gall bladder.

During treatment of Oktreotidom-depot it is necessary to carry out repeated ultrasonography of a gall bladder, preferably, bucketed 6-12 months.

If stones of a gall bladder are found even prior to treatment, it is necessary to estimate potential advantages of therapy by Oktreotid - depot in comparison with the possible risk connected with existence of gallstones.

Now there are no certificates that the Oktreotid-depot adversely influences the current or the forecast of already available cholelithiasis.

Maintaining patients at whom stones of a gall bladder are formed in the course of treatment of Oktreotidom-depot.

а). Asymptomatic stones of a gall bladder.

Use of Oktreotida-depot can be stopped or continued - according to ratio assessment advantage/risk. Anyway no other measures, except continuation of carrying out surveys are required, having made them, if necessary, more frequent.
b) Stones of a gall bladder with clinical symptomatology.

Use of Oktreotida-depot can be stopped or continued - according to ratio assessment advantage/risk. Anyway the patient should be treated as well as in other cases of cholelithiasis with clinical manifestations. Drug treatment includes use of combinations of drugs of bile acids (for example, chenodesoxycholic acid in a dose of 7.5 mg/kg/days in combination with ursodezoksikholevy acid in the same dose) under ultrasonic control - before total disappearance of stones.

Use during pregnancy and a lactation. Experience of use of Oktreotida-depot at pregnancy and during breastfeeding is absent. Therefore, during pregnancy drug is appointed only if the potential advantage for mother exceeds potential risk for a fruit. Feeding is not recommended by a breast at use of drug in the period of a lactation.

Influence on ability to drive the car and drugimimekhanizm. Now there are no data on influence of Oktreotida-depot on ability to driving and work with the mechanisms requiring special attention and speed of mental and motor reactions.

Side effects:

Local reactions: at introduction in oil Oktreotida-depots are possible pain, the swelling and rashes in the place of an injection are more rare (as a rule, are poorly expressed, short).

From a GIT: anorexia, nausea, vomiting, spastic abdominal pains, abdominal distention, excess gas generation, liquid chair, diarrhea, steatorrhea. Though release of fat with a stake can increase, there are no proofs that prolonged treatment oktreotidy can lead to development of deficit of some nutritious components owing to disturbance of absorption (malabsorption) today. In rare instances the phenomena reminding acute intestinal impassability can be noted: the progressing abdominal distention, the expressed pain in epigastric area, tension of an abdominal wall. Long use of Oktreotida-depot can lead to formation of stones in a gall bladder.

From a pancreas: it was reported about exceptional cases of the acute pancreatitis which developed during the first hours or days of use of an oktreotid. At prolonged use cases of the pancreatitis connected with a cholelithiasis were noted.

From a liver: there are separate messages on development of abnormal liver functions (an acute hepatitis without cholestasia with normalization of indicators of transaminases after cancellation of an oktreotid); the slow development of a hyperbilirubinemia which is followed by increase in indicators of an alkaline phosphatase gamma глутамилтрансферазы and, to a lesser extent, other transaminases.

From a metabolism: as the Oktreotid-depot exerts overwhelming impact on formation of GR, a glucagon and insulin, it can influence glucose exchange. Decrease in tolerance to glucose after meal is possible. At prolonged use of Oktreotid п / to the resistant hyperglycemia in certain cases can develop. Also conditions of a hypoglycemia were observed.

Others: It was in rare instances reported about a temporary hair loss after introduction of an oktreotid. emergence: bradycardia, tachycardia, otdyshka, skin rash, anaphylaxis. There are separate messages on development of reactions of hypersensitivity.

Interaction with other medicines:

Oktreotid reduces absorption from intestines of cyclosporine and slows down absorption of Cimetidinum.

At simultaneous use of an oktreotid and Bromocriptinum bioavailability of the last increases.

There are literary data that analogs of somatostatin can reduce metabolic clearance of the substances which are metabolized P450 cytochrome enzymes that can be caused by GR suppression. As it is impossible to exclude the similar effects of an oktreotid, drugs which are metabolized enzymes of system of P450 cytochrome and with a narrow therapeutic range (quinidine and терфенадин), it is necessary to appoint with care.

Contraindications:

Hypersensitivity to an oktreotid or other components of drug.

With care: cholelithiasis, diabetes mellitus, pregnancy and lactation.

Overdose:

Now about cases of overdose of Oktreotida-depot it was not reported.

Storage conditions:

In the dry place protected from light at a temperature from 2 °C to 8 °C. To store in the place, unavailable to children.

Special precautionary measures at destruction of unused medicine: a bottle with drug, the syringe and needles destroy separately.

Period of validity: lyophilisate - 3 years, solvent - 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of suspension for intramuscular introduction of the prolonged action. On 0,0100 g, 0,0200 g or 0,0300g an oktreotida in bottles of dark glass with a capacity of 5 ml. On 2 ml of solvent (mannitol solution for injections of 0,8%) in ampoules of neutral glass. 1 bottle with drug, 1 ampoule with solvent (2 ml), 1 syringe of single use with a capacity of 5 ml, 2 sterile needles, a knife for opening of ampoules or the scarificator of ampoule, 2 spirit tampons pack into a blister strip packaging from a film polyvinyl chloride. The set is expected one injection. 1 blister strip packaging together with the application instruction is placed in a cardboard pack or in a pack from a cardboard bandbox.