Octreotide-depo Lyophilisate prolonged 20mg vial, 1pc

Composition

Active ingredient:

octreotide;

Auxiliary substances:

copolymer of DL-lactic and glycolic acids;

D-mannitol;

carboxymethylcellulose sodium salt;

polysorbate-80

Pharmacological action

Octreotide depot is a long-acting dosage form of octreotide for intramuscular use, which ensures the maintenance of stable therapeutic concentrations of octreotide in the blood for 4 weeks. Octreotide is a pathogenetic therapy for tumors that actively express somatostatin receptors. Octreotide is a synthetic octapeptide that is a derivative of the natural hormone somatostatin and has similar pharmacological effects, but significantly longer duration of action.

The drug suppresses pathologically increased secretion of growth hormone, as well as peptides and serotonin produced in the gastroenteropancreatic endocrine system.

In healthy individuals, octreotide, like somatostatin, suppresses the secretion of growth hormone caused by arginine, exercise and insulin hypoglycemia; the 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 by arginine; the secretion of thyrotropin caused by thyroliberin. Unlike somatostatin, octreotide has a significantly greater inhibitory effect on growth hormone secretion than on insulin secretion. The introduction of octreotide is not accompanied by the phenomenon of hypersecretion of hormones by the negative feedback mechanism.

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

In most patients with acromegaly, Octreotide depot significantly reduces the severity of symptoms such as headache, increased sweating, paresthesia, fatigue, bone and joint pain, and peripheral neuropathy. Octreotide treatment in some patients with pituitary adenomas that secrete growth hormone has been reported to reduce the size of the tumor.

In carcinoid tumors, the use of octreotide can lead to a reduction in the severity of 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 urinary excretion of 5-hydroxyindoleacetic acid.

In tumors characterized by hyperproduction of vasoactive intestinal peptide (VIPoma), the use of octreotide leads in most patients to a decrease in severe secretory diarrhea, which is characteristic of this condition, which in turn leads to an improvement in the patient’s quality of life. At the same time, concomitant electrolyte balance disorders, such as hypokalemia, are reduced, which makes it possible to cancel enteral and parenteral use of fluids and electrolytes. According to computed tomography, some patients have a slowing or stopping of the tumor progression and even a reduction in its size, especially liver metastases. Clinical improvement is usually accompanied by a decrease (up to normal values) in the concentration of vasoactive intestinal peptide (VIP) in plasma.

In glucagonomics, the use of octreotide in most cases leads to a noticeable 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, which is often observed with glucagonomics, and usually does not lead to a decrease in the need for insulin or oral hypoglycemic drugs. In patients suffering from diarrhea, octreotide causes its decrease, which is accompanied by an increase in body weight. When using octreotide, a rapid decrease in the concentration of glucagon in plasma is often noted, but this effect does not persist with long-term treatment. At the same time, the symptomatic improvement remains stable for a long time.

In gastrinomas/Zollinger-Ellison syndrome, octreotide used as monotherapy or in combination with_H2-histamine receptor blockers and proton pump inhibitors can reduce the formation of hydrochloric acid in the stomach and lead to clinical improvement, including with respect to diarrhea. It is also possible to reduce the severity of other symptoms, probably associated with the synthesis of peptides by the tumor, including hot flashes. In some cases, there is a decrease in the concentration of gastrin in plasma.

In patients with insulinomas, octreotide reduces the concentration of immunoreactive insulin in the blood. In patients with operable tumors, octreotide can restore and maintain normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, glycemic control may improve even without a simultaneous prolonged decrease in the concentration of insulin in the blood.

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

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

In patients with PGRC with bone metastases, this therapy is accompanied by a pronounced and long-lasting analgesic effect. At the same time, all patients who responded to combination therapy with Octreotide-depo significantly improved their quality of life and increased the median disease-free survival.

Indications

In the treatment of acromegaly:

• when adequate control of the manifestations of the disease is carried out by subcutaneous use of octreotide;
• in the absence of sufficient effect from surgical treatment and radiation therapy;
• for preparation for surgical treatment;
• for treatment between courses of radiation therapy until a persistent effect develops;
• in inoperable patients.

In the treatment of endocrine tumors of the gastrointestinal tract and pancreas:

• carcinoid tumors with signs of carcinoid syndrome;
• insulinomas;
• VIPomas;
• gastrinomas (Zollinger-Ellison syndrome);
• glucagonomas (for controlling hypoglycemia in the preoperative period, as well as for maintenance therapy);
• somatoliberinomas (tumors characterized by hyperproduction of the releasing factor of growth hormone).

In the treatment of hormone-resistant prostate cancer:  in combination therapy with surgical or medical castration.

In the prevention of acute postoperative pancreatitis:  for extensive surgical operations on the abdominal cavity and thoracoabdominal interventions (including for cancer of the stomach, esophagus, colon, pancreas, primary and secondary liver cancer).

Contraindications

Hypersensitivity to octreotide or other components of the drug.

With caution:  cholelithiasis; diabetes mellitus; pregnancy and lactation.

Side effects

Local reactions:  with intravenous use of Octreotide depot, pain is possible, less often-swelling and rashes at the injection site (usually weakly expressed, short-lived).

From the gastrointestinal tract:  anorexia, nausea, vomiting, spastic abdominal pain, bloating, excessive gas formation, loose stools, diarrhea, steatorrhea. Although the excretion of fat in the faeces may increase, to date there is no evidence that long-term treatment with octreotide can lead to the development of a deficiency of certain nutritional components due to malabsorption. In rare cases, there may be phenomena that resemble acute intestinal obstruction: progressive bloating, severe pain in the epigastric region, tension of the abdominal wall. Prolonged use of Octreotide depot can lead to the formation of gallstones.

From the pancreas:  rare cases of acute pancreatitis that developed during the first hours or days of octreotide use have been reported. Cases of pancreatitis associated with cholelithiasis have been reported with prolonged use.

From the liver:  there are separate reports of the development of liver function disorders (acute hepatitis without cholestasis with normalization of transaminase parameters after octreotide withdrawal); slow development of hyperbilirubinemia, accompanied by an increase in ALP, GGT, and to a lesser extent other transaminases.

From the side of metabolism:  since Octreotide depot has a suppressive effect on the formation of growth hormone, glucagon and insulin, it can affect glucose metabolism. It is possible to reduce glucose tolerance after a meal. With prolonged use of Octreotidap/k, persistent hyperglycemia may develop in some cases. Hypoglycemic states were also observed.

Other services:  in rare cases, temporary hair loss after octreotide use, bradycardia, tachycardia, shortness of breath, skin rash, and anaphylaxis have been reported.There are isolated reports of hypersensitivity reactions.

Interaction

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

Concomitant use of octreotide and bromocriptine increases the bioavailability of the latter.

There is literature evidence that somatostatin analogues can reduce the metabolic clearance of substances metabolized by cytochrome P450 enzymes, which may be caused by growth hormone suppression. Since it is impossible to exclude such effects of octreotide, drugs that are metabolized by cytochrome P450 enzymes and with a narrow therapeutic range (quinidine and terfenadine) should be prescribed with caution.

How to take, course of use and dosage

In / m, deep into the gluteal muscle. For repeated injections, the left and right sides should be alternated. The suspension should be prepared immediately before injection. On the day of injection, the vial with the drug and the ampoule with the solvent can be kept at room temperature.

In the treatment of acromegaly in patients for whom subcutaneous use of Octreotide 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 the day after the last subcutaneous injection of Octreotide. In the future, the dose is adjusted taking into account the concentration of growth hormone and IGF-1 in the serum, as well as clinical symptoms. If after 3 months of treatment it was not possible to achieve an adequate clinical and biochemical effect (in particular, if the concentration of growth hormone remains above 2.5 mcg/l), the dose can be increased to 30 mg, administered every 4 weeks.

In cases where, after 3 months of treatment with Octreotide-depot at a dose of 20 mg, there is a persistent decrease in the serum concentration of growth hormone below 1 mcg/l, the concentration normalizes IGF-1 and the disappearance of reversible symptoms of acromegaly, you can reduce the dose of Octreotide depot to 10 mg. However, these patients receiving a relatively low dose of Octreotide depot should continue to have their serum growth hormone and IGF-1 concentrations carefully monitored, as well as their symptoms.

Patients receiving a stable dose of Octreotide depot should have their growth hormone and IGF-1 concentrations measured every 6 months.

It is recommended to conduct a trial course of treatment with subcutaneous injections of Octreotide in order to assess its effectiveness and overall tolerability, and only then switch to the use of Octreotide depot according to the above scheme.

In the treatment of endocrine tumors of the gastrointestinal tract and pancreas in patients for whom subcutaneous use of Octreotide provides adequate control of the manifestations of the disease, the recommended initial dose of Octreotide depot is 20 mg every 4 weeks. Subcutaneous use of Octreotide should be continued for another 2 weeks after the first use of Octreotide depot.

In patients who have not previously received Octreotide subcutaneously, it is recommended to start treatment with subcutaneous use of Octreotide at a dose of 0.1 mg 3 times a day for a relatively short period of time (approximately 2 weeks) in order to assess its effectiveness and overall tolerability. Only after that, Octreotide depot is prescribed according to the above scheme.

If Octreotide-depo therapy for 3 months provides adequate control of clinical manifestations and biological markers of the disease, it is possible to reduce the dose of Octreotide-depo to 10 mg, prescribed every 4 weeks.

In cases where only partial improvement was achieved after 3 months of treatment with Octreotide depot, the dose of the drug can be increased to 30 mg every 4 weeks. Against the background of treatment with Octreotide-depot on some days, it is possible to increase the clinical manifestations characteristic of endocrine tumors of the gastrointestinal tract and pancreas. In these cases, additional subcutaneous use of Octreotide at the dose used before starting treatment with Octreotide-depot is recommended. This may occur mainly in the first 2 months of treatment, until therapeutic plasma concentrations of octreotide are reached.

In the treatment of PGRC, the recommended starting 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 concentration Serum PSA, as well as clinical symptoms. If after 3 months of treatment it was not possible to achieve an adequate clinical and biochemical effect (decrease in the number of patients treated). PSA), 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 orally according to the following scheme: 4 mg/day for 1 month, then-2 mg/day for 2 weeks, then-1 mg/day (maintenance dose).

Treatment with Octreotide-depo and dexamethasone in patients who have previously received medical antiandrogenic therapy is combined with the use of an analog of GnRH. In this case, the injection of an analog GnRH (depot forms) is performed once every 4 weeks.

Patients receiving Octreotide depot, determination of concentrations PSA should be performed every month.

In patients with impaired renal, hepatic and elderly function, there is no need to adjust the dosage regimen of Octreotide depot.

For the prevention of acute postoperative pancreatitis, Octreotide depot in a dose of 10 or 20 mg is administered once not earlier than 5 days and not later than 10 days before the intended surgical intervention.

Rules for the preparation of the slurry and drug use

• the drug to only enter V/m;
• suspension for a/m injection to cook with the supplied solvent immediately before use;
• prepare and inject the drug should only specially trained medical staff;
• prior to injection, an ampoule of solvent and the vial must be removed from the refrigerator and bring to room temperature (requires 30-50 min);
• a bottle of Octreotide-depo keep strictly vertically. Easy tapping the vial to ensure that all the lyophilisate was at the bottom of the vial;
• to open the package with a syringe, attach the needle to the syringe size of 1.2 ×50 mm for the intake of the solvent;
• to open a vial of solvent and type in the syringe all the contents of the vial with the solvent, set the syringe at a dose of 3.5 ml;
• remove the plastic cap from the vial containing the lyophilized. Disinfect the rubber stopper of the bottle with an alcohol swab. Insert the needle into the lyophilizate bottle through the center of the rubber stopper and carefully insert the solvent along the inner wall of the bottle, without touching the contents of the bottle with the needle. Remove the syringe from the vial;
• the vial should remain stationary until the lyophilizate is completely soaked in the solvent and a suspension is formed (approximately 3-5 minutes). After that, without turning the bottle over, you should check for the presence of dry lyophilizate on the walls and bottom of the bottle. If dry lyophilizate residues are detected, leave the bottle until they are completely soaked;
• after the health worker is satisfied that there are no dry lyophilizate residues, the contents of the bottle should be carefully mixed in circular movements for 30-60 seconds until a homogeneous suspension is formed. Do not turn or shake the bottle, as this may cause flakes to fall out and make the suspension unusable;
• quickly insert the needle through the rubber stopper into the bottle. Then lower the needle section down and, tilting the bottle at an angle of 45°, slowly fill the suspension completely into the syringe. Do not turn the bottle over when typing. A small amount of the drug may remain on the walls and bottom of the bottle. The cost residue on the walls and bottom of the vial is taken into account;
• immediately after dialing the suspension to replace the needle with the pink pavilion at the needle with green pavilion (0,8 x 40 mm), gently turn the syringe and remove the air from the syringe;
• a suspension of Octreotide-depo enter immediately after preparation;
• the suspension of Octreotide-depo should not be mixed with any other drugs in the same syringe;
• with an alcohol swab to disinfect the injection site. Insert the needle deep into the gluteal muscle, then pull the plunger of the syringe back slightly to make sure that there is no damage to the vessel. Enter the suspension in / m slowly, with constant pressure on the plunger of the syringe;
• if it gets into a blood vessel, the injection site and needle should be changed;
• if the needle is clogged, replace it with another needle of the same diameter;
• for repeated injections, the left and right sides should alternate.

Precautions for use

With pituitary tumors that secrete growth hormone, careful monitoring of patients is necessary, since it is possible to increase the size of tumors with the development of such a serious complication as narrowing of the visual fields. In these cases, other treatment options should be considered.

In 15-30% of patients receiving Octreotide subcutaneous injection for a long time, gallstones may appear. Prevalence in the general population (age 40-60 years) it is 5-20%. The experience of long-term treatment with prolonged-acting octreotide in patients with acromegaly and gastrointestinal and pancreatic tumors indicates that prolonged-acting octreotide, in comparison with short-acting octreotide, does not lead to an increase in the frequency of gallbladder stones.However, it is recommended to conduct Ultrasound of the gallbladder before starting treatment with Octreotide depot and approximately every 6 months during treatment. Gallstones, if they do show up, are usually asymptomatic. In the presence of clinical symptoms, conservative treatment (for example, the use of bile acid preparations) or surgical intervention is indicated.

In patients with type 1 diabetes, Octreotide depot may affect glucose metabolism and therefore reduce the need for injectable insulin. For patients with type 2 diabetes mellitus and patients without concomitant carbohydrate metabolism disorders, subcutaneous injections of Octreotide can 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.

Patients with insulinomas treated with octreotide may experience an increase in the severity and duration of hypoglycemia (this is due to a more pronounced suppressive effect on the secretion of growth hormone and glucagon than on insulin secretion, as well as a shorter duration of inhibitory effects on insulin secretion). Systematic monitoring of these patients is indicated.

Before octreotide is prescribed, patients should undergo an initial ultrasound of the gallbladder.

During treatment with Octreotide-depot, repeated ultrasound of the gallbladder should be performed, preferably at intervals of 6-12 months.

If gallstones are detected before starting treatment, the potential benefits of Octreotide depot therapy should be evaluated over the possible risk associated with the presence of gallstones.

Currently, there is no evidence that Octreotide depot adversely affects the course or prognosis of pre – existing gallstone disease.

Management of patients who develop gallbladder stones during treatment with Octreotide-depot

Asymptomatic gallstones. The use of Octreotide-depo can be discontinued or continued – in accordance with the assessment of the benefit/risk ratio. In any case, no other measures are required other than continuing to carry out inspections, making them, if necessary, more frequent.

Gallbladder stones with clinical symptoms. The use of Octreotide-depo can be discontinued or continued – in accordance with the assessment of the benefit/risk ratio. In any case, the patient should be treated in the same way as in other cases of gallstone disease with clinical manifestations. Drug treatment includes the use of combinations of bile acid preparations (for example, henodeoxycholic acid at a dose of 7.5 mg / kg / day in combination with ursodeoxycholic acid at the same dose) under ultrasound control — until the stones completely disappear.

Special instructions

When pituitary tumors that secrete GH, patients should be carefully monitored, since it is possible to increase the size of the tumors with the development of such serious complications as narrowing of the visual fields. In these cases, other treatment options should be considered. Gallstones may occur in 15-30% of patients receiving Octreotide subcutaneously for a long time.

Prevalence in the general population (age 40-60 years) it is 5-20%. The experience of long-term treatment with Octreotide prolonged action in patients with acromegaly and tumors of the gastrointestinal tract and pancreas indicates that the drug Octreotide prolonged action, in comparison with the drug Octreotide short action, does not lead to an increase in the frequency of gallbladder stones. However, it is recommended to perform an ultrasound of the gallbladder before starting treatment with Octreotide depot and approximately every 6 months during treatment.

Gallstones, if they do show up, are usually asymptomatic. In the presence of clinical symptoms, conservative treatment (for example, the use of bile acid preparations) or surgical intervention is indicated. In patients with type 1 diabetes, Octreotide depot may affect glucose metabolism and, consequently, reduce the need for injectable insulin. For patients with type 2 diabetes mellitus and patients without concomitant carbohydrate metabolism disorders, subcutaneous injections of Octreotide may lead to postprandial glycemia.

In this regard, it is recommended to regularly monitor the level of glycemia and, if necessary, correct hypoglycemic therapy. Patients with insulinomas treated with octreotide may experience an increase in the severity and duration of hypoglycemia (this is due to a more pronounced suppressive effect on GH and glucagon secretion than on insulin secretion, as well as a shorter duration of inhibitory effect on insulin secretion).

Systematic monitoring of these patients is indicated. Before octreotide is prescribed, patients should undergo an initial ultrasound of the gallbladder. During treatment with Octreotide depot, repeated ultrasound examinations of the gallbladder should be performed, preferably at intervals of 6-12 months.

If gallstones are detected before starting 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 pre-existing gallstone disease.

Form of production

Lyophilizate for the preparation of a suspension for intramuscular use

Storage conditions

Store in a dry place, protected from light, at a temperature of 2 to 8 °C.

Shelf life

2 years

Active ingredient

Octreotide

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection