Octreotide Depot (Octreotide-depo)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceOctreotideOctreotide
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    • Dosage form: & nbsplyophilizate for the preparation of a suspension for intramuscular administration of prolonged action
    Composition:

    1 bottle contains:

    active substance: octreotide 10.0 mg, 20.0 mg or 30.0 mg;

    Excipients: DL-lactic and glycolic acid copolymer 270.0 mg / 560.0 mg / 850.0 mg, D-Mannitol 85.0 mg, carboxymethyl cellulose sodium salt 30 mg, polysorbate-80 2.0 mg.

    Solvent in ampoule: mannitol, solution for injection 0.8%. One ampoule contains: mannite 0.016g, water for injection up to 2.0 ml.

    Description:

    Lyophilized powder or porous, tablet-packed weight of white or white with a weak yellowish hue of color.

    Solvent: colorless transparent liquid

    Reduced suspension: a homogeneous suspension of white or white with a weak yellowish hue of color.

    Pharmacotherapeutic group:Somatostatin analogue synthetic
    ATX: & nbsp

    H.01.C.B.02   Octreotide

    Pharmacodynamics:

    The drug Octreotide Depot is a long-acting octreotide dosage form for intramuscular injection, which ensures the maintenance of stable therapeutic concentrations of octreotide in the blood for 4 weeks. Octreotide is a means of pathogenetic therapy for tumors that actively express somatostatin receptors. Octreotide - synthetic octapeptide, which is a derivative of the natural hormone somatostatin and has similar pharmacological effects, but a significantly longer duration of action. The drug suppresses the pathologically increased secretion of growth hormone (GR), as well as peptides and serotonin produced in the gastroenteropancreatic endocrine system.

    In healthy individuals octreotide, like somatostatin, suppresses the secretion of GH caused by arginine, exercise and insulin hypoglycemia; secretion of insulin, glucagon, gastrin and other peptides of the gastroenteropancreatic endocrine system caused by food intake, as well as the secretion of insulin and glucagon stimulated with arginine; secretion of thyrotropin, caused by thyroidiberin. The suppressive effect on the secretion of GH in octreotide, in contrast to somatostatin, is expressed to a much greater extent than on the secretion of insulin. The introduction of octreotide is not accompanied by the phenomenon of hypersecretion of hormones by the mechanism of negative feedback.

    In patients with acromegaly, the administration of the depot form of octreotide provides, in the vast majority of cases, a persistent decrease in the concentration of GH and the normalization of the concentration of insulin-like growth factor 1 / somatomedin C (IGF-1).

    In most patients with acromegaly, the depot form of octreotide significantly reduces the severity of such symptoms as headache, increased sweating, paresthesia, fatigue, pain in bones and joints, peripheral neuropathy.It was reported that treatment with the depot form of octreotide of individual patients with adenomas of the pituitary gland secreting GH led to a decrease in the size of the tumor.

    When secreting endocrine tumors of the gastrointestinal tract (GIT) and pancreas, the use of the depot form of octreotide provides a constant control of the main symptoms of these diseases.

    Depot form octreotide at a dose of 30 mg every 4 weeks slows tumor growth in patients with secreting and nonsecreting advanced (metastatic) neuroendocrine tumors jejunum, ileum, caecum, the ascending colon, transverse colon, and the appendix, or metastatic neuroendocrine tumors without initially identified hearth . The drug was effective in increasing the time to progression, both for secreting and for non-secreting neuroendocrine tumors.

    In carcinoid tumors, the use of octreotide can lead to a decrease in the severity of the symptoms of the disease, primarily such as "hot flashes" and diarrhea. In many cases, clinical improvement is accompanied by a decrease in plasma serotonin concentration and excretion of 5-hydroxyindoleacetic acid in the urine.

    In tumors characterized by hyperproduction of the vasoactive intestinal peptide (WIPOM), the use of octreotide in most patients reduces the severe secretory diarrhea that is characteristic of this condition, which in turn leads to an improvement in the quality of life of the patient. At the same time, there is a decrease in associated electrolyte imbalance, for example, hypokalemia, which allows to cancel enteral and parenteral administration of fluid and electrolytes. According to computed tomography, in some patients, the progression of the tumor slows or stops, and even the decrease in its size, especially the metastases to the liver. Clinical improvement is usually accompanied by a decrease (up to normal values) of the concentration of vasoactive intestinal peptide (VIP) in plasma.

    With glucagonomes, the use of octreotide in most cases leads to a marked decrease in the necrotizing migrating rash that is characteristic of this condition. Octreotide does not have any significant effect on the severity of diabetes mellitus, often observed with glucagonomes,and usually does not lead to a decrease in the need for insulin or oral hypoglycemic drugs. In patients with diarrhea, octreotide causes it to decrease, which is accompanied by an increase in body weight. When octreotide is used, there is often a rapid decrease in plasma glucagon concentration, but this effect does not persist with long-term treatment. At the same time, symptomatic improvement remains stable for a long time.

    With gastrinomas / Zollinger-Ellison syndrome octreotide, used as a monotherapy or in combination with blockers H2-gistaminovyh receptors and proton pump inhibitors, can reduce the formation of hydrochloric acid in the stomach and lead to clinical improvement, including. and in relation to diarrhea. It is also possible to reduce the severity and other symptoms likely associated with the synthesis of peptides by the tumor, incl. "tides". In some cases, a decrease in the concentration of gastrin in the plasma.

    In patients with insulinomas octreotide reduces the concentration of immunoreactive insulin in the blood. In patients with operable tumors octreotide can provide recovery and maintenance of normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, the control of glycemia can be improved without a simultaneous prolonged decrease in the concentration of insulin in the blood.

    In patients with rare tumors, hyper-producing growth hormone releasing factor (somatoliberinomas), octreotide reduces the severity of symptoms of acromegaly. This, apparently, is due to the suppression of the secretion of the releasing factor of growth hormone and the GH itself. In the future, it is possible to reduce the size of the pituitary gland, which was increased before the start of treatment.

    In patients with hormone-resistant prostate cancer (HRHR), a pool of neuroendocrine cells expressing somatostatin receptors, affinity to octreotide (SS2 and SS5 types) increases, which determines the sensitivity of the tumor to octreotide. The use of Octreotide Depot in combination with dexamethasone against the background of androgen blockade (medication or surgical castration) in patients with PGRM restores sensitivity to hormonal therapy and leads to a decrease in prostate specific antigen (PSA) in more than 50% of patients.

    In patients with PGRD with metastases in the bone, this therapy is accompanied by a pronounced and prolonged analgesic effect. In this case, all patients who responded to combination therapy with Octreotide Depot significantly improve quality of life and median disease-free survival.

    Indications:

    In the therapy of acromegaly:

    - when adequate control of manifestations of the disease is due to subcutaneous administration of octreotide;

    - in the absence of sufficient effect from surgical treatment and radiation therapy;

    - for preparation for surgical treatment;

    - for treatment between radiotherapy courses before the development of a persistent effect;

    - in inoperable patients.

    In therapy of endocrine tumors of the gastrointestinal tract (GIT) and pancreas:

    - carcinoid tumors with the phenomena of carcinoid syndrome;

    - insulinomas;

    - VIPoms;

    - gastrinomas (Zollinger-Ellison syndrome);

    - Glukagonomy (for the control of hypoglycemia in the preoperative period, as well as for maintenance therapy);

    - somatoliberynomas (tumors characterized by hyperproduction of growth hormone releasing factor);

    - treatment of patients with secreting and non-secreting widespread (metastatic) neuroendocrine tumors of lean, iliac, blind, ascending colonic,transverse colon and appendix, or metastases of neuroendocrine tumors without a primary focus.

    In the treatment of hormone-resistant prostate cancer:

    - as part of a combination therapy on the background of surgical or drug castration.

    In the prevention of acute postoperative pancreatitis:

    - with extensive surgical operations on the abdominal cavity and thoracoabdominal interventions (including for stomach cancer, esophagus, colon, pancreas, primary and secondary tumor lesions of the liver).

    Contraindications:

    Hypersensitivity to octreotide or other components of the drug.

    Carefully:Chololithiasis, diabetes, pregnancy and lactation.
    Pregnancy and lactation:

    The experience of using Octreotide Depot during pregnancy and during breastfeeding is absent. Therefore, during pregnancy, the drug is prescribed only if the potential benefit to the mother exceeds the potential risk for the fetus.

    It is not recommended to breast-feed while using the drug during lactation.

    Dosing and Administration:

    The drug Octreotide Depot should be administered only deep intramuscularly (IM), in the gluteal muscle. With repeated injections, the left and right sides should alternate. Suspension should be prepared immediately before injection. On the day of injection, the vial with the preparation and the ampoule with the solvent can be kept at room temperature.

    In the treatment of acromegaly in patients for whom subcutaneous (sc) octreotide administration provides adequate control of the manifestations of the disease, the recommended initial dose of Octreotide Depot is 20 mg every 4 weeks for 3 months. You can start treatment with Octreotide Depot by the next day after the last SC administration of octreotide. In the future, the dose is adjusted taking into account the concentration in the serum of GH and IGF-1, as well as clinical symptoms. If after 3 months of treatment an adequate clinical and biochemical effect could not be achieved (in particular, if the GH concentration remains above 2.5 μg / L), the dose can be increased to 30 mg administered every 4 weeks.

    In those cases when, after 3 months of treatment with Octreotide Depot at a dose of 20 mg, there is a persistent decrease in serum GH concentration below 1 μg / l, normalization of IGF-1 concentration and disappearance of reversible symptoms of acromegaly,You can reduce the dose of Octreotide Depot up to 10 mg. However, in these patients receiving a relatively small dose of Octreotide Depot, serum concentrations of GH and IGF-1, as well as the symptoms of the disease, should be carefully monitored.

    Patients receiving a stable dose of Octreotide Depot, the determination of the concentrations of GH and IGF-1 should be performed every 6 months.

    Patients in whom surgical treatment and radiotherapy are not effective or generally ineffective, as well as patients who need short-term treatment between the radiotherapy courses and the time of its full effect, it is recommended that a trial of treatment with octreotide supplements be made to evaluate it efficiency and general tolerability, and only after this switch to the use of Octreotide Depot according to the above scheme.

    When treating endocrine tumors of the gastrointestinal tract and pancreas in patients to whom SC administration of octreotide provides adequate control of the manifestations of the disease, the recommended initial dose of Octreotide Depot is 20 mg every 4 weeks.S / o administration of octreotide should continue for another 2 weeks after the first administration of Octreotide Depot.

    In patients who have not previously received octreotide sc, it is recommended to start treatment with SC administration of octreotide at a dose of 0.1 mg 3 times a day for a relatively short period of time (about 2 weeks) in order to assess its effectiveness and overall tolerance. Only after this, the Octreotide Depot is prescribed according to the above scheme.

    In the case when therapy with Octreotide Depot for 3 months provides an adequate control of clinical manifestations and biological markers of the disease, it is possible to reduce the dose of Octreotide Depot to 10 mg, administered every 4 weeks. In those cases when, after 3 months of treatment with Octreotide Depot, only partial improvement was achieved, the dose of the drug can be increased to 30 mg every 4 weeks. On the background of treatment with the drug Octreotide Depot on certain days, it is possible to increase the clinical manifestations characteristic of endocrine tumors of the gastrointestinal tract and pancreas. In these cases, an additional SC administration of octreotide is recommended in the dose used before the beginning of treatment with Octreotide Depot.This can occur mainly in the first 2 months of treatment, until the therapeutic concentrations of octreotide in plasma are reached.

    Secreting and non-secretive common (metastatic) neuroendocrine tumors of lean, iliac, blind, ascending colon, transverse colon and appendix, or metastases of neuroendocrine tumors without a primary focus.

    The recommended dose of Octreotide Depot is 30 mg every 4 weeks.

    Therapy with Octreotide Depot should be continued until signs of tumor progression.

    In the treatment of hormone-resistant prostate cancer the recommended initial dose of Octreotide Depot is 20 mg every 4 weeks for 3 months. In the future, the dose is corrected taking into account the dynamics of serum PSA concentration, as well as clinical symptoms. If after 3 months of treatment failed to achieve an adequate clinical and biochemical effect (PSA reduction), the dose can be increased to 30 mg, administered every 4 weeks. Treatment with Octreotide Depot is combined with the use of dexamethasone, which is prescribed by mouth as follows: 4 mg per day for 1 month, then 2 mg per day for 2 weeks, then 1 mg per day (maintenance dose).

    Treatment with Octreotide Depot and dexamethasone in patients who had previously undergone drug-induced antiandrogen therapy is combined with the use of a gonadotropin releasing hormone (GnRH) analogue. In this case, an injection of the GnRH analogue (depot form) is carried out once every 4 weeks.

    Patients receiving the Octreotide Depot drug should be assessed every month.

    In patients with impaired renal function, liver and elderly patients there is no need to correct the dosage regimen of Octreotide Depot.

    For the prevention of acute postoperative pancreatitis the drug Octreotide Depot in a dose of 10 or 20 mg is administered once not earlier than 5 days and no later than 10 days before the proposed surgical intervention.

    Rules for the preparation of suspension and drug administration

    - The drug is administered only intramuscularly.

    - A suspension for intravenous injection is prepared with the help of the applied solvent immediately before administration.

    - The drug should be prepared and administered only by specially trained medical personnel.

    - Before injecting the ampoule with the solvent and the vial with the drug must be obtained from the refrigerator andbring to room temperature (30-50 min is required).

    - Keep the bottle with Octreotide Depot strictly vertically. Tapping lightly on the vial, make sure that all the lyophilizate is on the bottom of the vial.

    - Open the package with a syringe, attach a 1.2 mm x 50 mm needle to the syringe to collect the solvent.

    - Open the ampoule with the solvent and put into the syringe all the contents of the ampoule with the solvent, install the syringe for a dose of 2.0 ml.

    - Remove the plastic cap from the vial containing the lyophilizate. Disinfect the rubber stopper of the vial with an alcohol swab. Insert the needle into the vial with the lyophilizate through the center of the rubber stopper and carefully insert the solvent into the inner wall of the vial without touching the needle with the contents of the vial. Remove the syringe from the vial.

    - The bottle must remain stationary until the solvent is fully saturated with the lyophilizate and the suspension is formed (for about 3-5 minutes). After that, without turning the bottle, you should check the presence of dry lyophilizate at the walls and bottom of the vial. If a dry residue of the lyophilizate is found, leave the vial until it is completely soaked.

    - After you are convinced of the absence of residues of dry lyophilizate,the contents of the vial should be gently stirred in a circular motion for 30-60 seconds until a uniform suspension is formed. Do not overturn or shake the bottle, this can lead to flocculation and the unfitness of the suspension.

    - Quickly insert the needle through the rubber stopper into the vial. Then cut the needle down and, tilting the vial at an angle of 45 degrees, slowly put the suspension in the syringe completely. Do not flip the bottle when typing. A small amount of the drug can remain on the walls and bottom of the vial. The consumption of the residue on the walls and the bottom of the vial is taken into account.

    - Immediately after dialing the suspension, replace the needle with the pink pavilion on the needle with the green pavilion (0.8 x 40 mm), gently turn the syringe and remove air from the syringe.

    - Suspension of Octreotide Depot should be administered immediately after preparation.

    - Suspension of the drug Octreotide Depot should not be mixed with any other drug in one syringe.

    - Use an alcohol swab to disinfect the injection site. Insert the needle deep into the gluteus muscle, then gently pull the plunger of the syringe backward to make sure that there is no damage to the vessel.Insert the suspension intramuscularly slowly with constant pressure on the syringe plunger.

    - If you get into a blood vessel, you need to change the injection site and the needle.

    - When clogging the needle, replace it with another needle of the same diameter.

    - With repeated injections, the left and right sides should alternate.

    Side effects:

    Local reactions: with the / m introduction of Octreotide Depot, pain is possible, less often - swelling and eruptions at the injection site (usually slightly pronounced short-lived).

    From the gastrointestinal tract: anorexia, nausea, vomiting, abdominal cramping, bloating, excessive gas formation, loose stools, diarrhea, steatorrhea. Although the release of fat with feces may increase, to date, there is no evidence that prolonged treatment with octreotide can lead to a deficit in some nutritional components due to impaired absorption (malabsorption). In rare cases, there may be phenomena reminiscent of acute intestinal obstruction, progressive bloating, severe pain in the epigastric region, stress of the abdominal wall. Long-term use of Octreotide Depot can lead to the formation of gallstones.

    From the side of the pancreas: reported rare cases of acute pancreatitis, which developed in the first hours or days of octreotide. With prolonged use, there have been cases of pancreatitis associated with cholelithiasis.

    From the side of the liver: there are some reports of the development of violations of liver function (acute hepatitis without cholestasis with normalization of transaminases after abolition of octreotide); the slow development of hyperbilirubinemia, accompanied by an increase in the parameters of alkaline phosphatase, gamma-glutamyltransferase and, to a lesser extent, other transaminases.

    From the side of metabolism: since Octreotide Depot has an overwhelming effect on the formation of GH, glucagon and insulin, it can affect glucose metabolism. Perhaps a decrease in glucose tolerance after eating. With prolonged use of octreotide s / c in some cases, persistent hyperglycemia may develop. There were also conditions of hypoglycemia.

    Other: In rare cases, reported temporary hair loss after octreotide administration, the occurrence of bradycardia, tachycardia, shortness of breath, skin rash, anaphylaxis.There are separate reports on the development of hypersensitivity reactions.

    Overdose:At present, cases of an overdose of Octreotide-Depot have not been reported.
    Interaction:

    Octreotide reduces intestinal absorption of cyclosporine and slows the absorption of cimetidine.

    With the simultaneous use of octreotide and bromocriptine, the bioavailability of the latter increases.

    There are published data that somatostatin analogues can reduce metabolic clearance of substances metabolized by cytochrome P450 enzymes, which may be caused by GH suppression. Since it is impossible to exclude similar effects of octreotide, drugs metabolized by enzymes of the cytochrome P450 system and with a narrow therapeutic range (quinidine and terfenadine) should be administered with caution.

    Special instructions:

    With tumors of the pituitary gland, secreting GH, careful monitoring of patients is necessary, since it is possible to increase the size of tumors with the development of such serious complications as narrowing of the fields of vision. In these cases, consideration should be given to the need for other treatments.

    In 15-30% of patients receiving Octreotide w / c for a long time, possibly the appearance of stones in the gallbladder. The prevalence in the general population (age 40-60 years) is 5-20%. The experience of prolonged treatment with Octreotide prolonged action of patients with acromegaly and tumors of the gastrointestinal tract and pancreas suggests that Octreotide prolonged action, in comparison with the short-acting Octreotide, does not lead to an increase in the frequency of gallbladder stones formation. Nevertheless, it is recommended to perform an ultrasound of the gallbladder before - beginning treatment with Octreotide Depot and approximately every 6 months during treatment. Stones in the gallbladder, if nevertheless they are found, as a rule, are asymptomatic. In the presence of clinical symptoms, conservative treatment (eg, administration of bile acid preparations) or surgical intervention is indicated.

    In patients with type 1 diabetes mellitus Octreotide depot can influence glucose metabolism and, consequently, reduce the need for injected insulin. For patients with type 2 diabetes mellitus and patients without concomitant disturbance of carbohydrate metabolism, subcutaneous injections of Octreotide may lead to postprandial glycemia.In this regard, it is recommended to regularly monitor the concentration of glucose in the blood and, if necessary, correct hypoglycemic therapy.

    In patients with insulinomas on the background of treatment with octreotide, there may be an increase in the severity and duration of hypoglycemia (this is associated with a more pronounced inhibitory effect on GH and glucagon secretion than on insulin secretion, and also with a shorter duration of inhibitory effect on insulin secretion). A systematic observation of these patients is shown.

    Before the appointment of octreotide, patients must undergo an initial ultrasound of the gallbladder the bubble.

    During treatment with Octreotide Depot, repeated US gallbladder Bubble, preferably at intervals of 6-12 months.

    If gallbladder stones are found even before the start of treatment, it is necessary to evaluate the potential benefits of Octreotide Depot therapy compared to the possible risk associated with the presence of gallstones.

    Currently, there is no evidence that Octreotide Depot adversely affects the course or prognosis of an already existing cholelithiasis.

    Management of patients whose gallstones are formed during treatment with Octreotide Depot

    a) Asymptomatic stones of the gallbladder.

    The use of Octreotide Depot can be stopped or continued - in accordance with the benefit / risk ratio estimate. In any case, no other measures are required, except to continue inspections, making them, if necessary, more frequent.

    b) Stones of the gallbladder with clinical symptoms.

    The use of Octreotide Depot can be stopped or continued in accordance with the benefit / risk ratio estimate. In any case, the patient should be treated in the same way as in other cases of cholelithiasis with clinical manifestations.

    Drug treatment includes the use of a combination of bile acid preparations (for example, chenodeoxycholic acid at a dose of 7.5 mg / kg / day in combination with ursodeoxycholic acid in the same dose) under ultrasound control - until complete disappearance of stones.

    Special precautions for the destruction of unused medicinal product

    A vial with a preparation, a syringe and needles destroy separately.

    Effect on the ability to drive transp. cf. and fur:

    At present, there is no data on the effect of Octreotide Depot on the ability to drive and work with mechanisms that require increased attention and speed of mental and motor reactions.

    Form release / dosage:

    Liofilizate for the preparation of suspension for intramuscular administration of prolonged action.

    Packaging:

    For 0.0100 g, 0.0.200 g or 0.0300 g of octreotide in bottles of dark glass with a capacity of 10 ml. 2 ml of solvent (mannitol solution for injection 0.8%) into neutral glass ampoules with a tension ring or break point for dissection. 1 bottle with the drug; 1 ampoule with solvent; 1 single-use syringe with a capacity of 5 ml, 2 sterile needles, ampoule opener or ampoule scarifier, 2 alcohol tampons are packaged in a polyvinyl chloride film.

    The kit is designed for one injection.

    When you pack the solvent to prepare the suspension into ampoules that have a tension ring or breakpoint for dissection, the ampoule scapper or ampoule opener is not inserted.

    1 circuit cell pack together with the instruction for use is placed in a cardboard box or in a pack of cardboard box.

    Storage conditions:

    In dry, dark place at a temperature of 2 to 8 FROM.

    Keep out of the reach of children.

    Shelf life:

    Lyophilizate: 3 years.

    Solvent: 5 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-001945
    Date of registration:03.08.2011 / 24.11.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:FARM-SYNTHESIS, CJSC FARM-SYNTHESIS, CJSC Russia
    Manufacturer: & nbsp
    Representation: & nbspFARM-SYNTHESIS CJSC FARM-SYNTHESIS CJSC Russia
    Information update date: & nbsp02.06.2017
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