Octreotide: indications and contraindications, method of application, side effects. Octreotide: instructions for use of injection solution Octreotide 100mcg ml solution

Octreotide: instructions for use and reviews

Latin name: Octreotide

ATX code: H01CB02

Active substance: octreotide (octreotide)

Manufacturer: F-Synthesis, CJSC (Russia), Pharmstandard-UfaVITA (Russia), Nativa, LLC (Russia), Deko company (Russia), ALTAIR (Russia)

Description and photo update: 02.09.2019

Octreotide is a somatostatin-like drug.

Release form and composition

Dosage form - solution for intravenous and subcutaneous administration: transparent, colorless, odorless [1 ml in ampoules: at a dose of 50 and 100 mcg / ml - 5 ampoules in blister packs, in a carton pack 1 or 2 packs; at a dose of 300 and 600 mcg / ml - 1, 2 or 5 ampoules in blisters, in a cardboard pack 1 (1, 2 or 5 ampoules) or 2 (5 ampoules) packages; each pack also contains instructions for the use of Octreotide].

The active substance is octreotide (in the form of acetate), its content in 1 ml of solution is 50, 100, 300 or 600 mcg.

Inactive ingredients: sodium chloride and injection water.

Pharmacological properties

Pharmacodynamics

Octreotide is a synthetic analogue of somatostatin, has pharmacological effects similar to it, but with a longer duration of action.

Octreotide helps to suppress the secretion of the following substances:

• Growth hormone: pathologically elevated or induced by exercise, arginine and insulin hypoglycemia;
• Insulin, glucagon, gastrin, serotonin: pathologically elevated or food-induced;
• Insulin, glucagon: stimulated by arginine;
• Thyrotropin: caused by thyroliberin.

The use of octreotide before, during and after pancreatic surgery can reduce the incidence of typical postoperative complications, in particular abscesses, sepsis, pancreatic fistulas, and acute postoperative pancreatitis.

With bleeding from varicose veins of the stomach and esophagus and with cirrhosis of the liver, due to the use of octreotide in combination with specific therapy (in particular with hemostatic and sclerosing treatment), a more effective stop of bleeding is observed. Octreotide is also used to prevent rebleeding.

Pharmacokinetics

Octreotide after subcutaneous administration is rapidly and completely absorbed. C max (maximum concentration of the substance) of octreotide in blood plasma is reached in 30 minutes.

The level of binding to plasma proteins is 65%. The substance binds to the formed elements of the blood to an extremely small extent. V d (volume of distribution) - 0.27 l / kg.

T 1/2 (half-life) after subcutaneous administration is 100 minutes. Removal of octreotide after intravenous use is carried out in two phases with a T 1/2 of 10 minutes (first phase) and 90 minutes (second phase). Most of the substance is excreted through the intestines, approximately 32% of the dose is excreted by the kidneys unchanged. The total clearance is 160 ml / min.

In elderly patients, clearance decreases, and T 1/2 increases.

In patients with severe renal insufficiency, clearance is reduced by 2 times.

Indications for use

• Stopping bleeding from varicose veins of the esophagus and stomach in patients with liver cirrhosis and prevention of relapses (in combination with endoscopic sclerosing therapy or other specific therapeutic measures);
• Acromegaly - to control the symptoms of the disease and reduce insulin-like growth factor-1 (IGF-1) and growth hormone in blood plasma in cases where the effect of radiation or surgical treatment is not enough; for the treatment of the disease in cases where the patient refused the operation or has contraindications to its implementation; for short-term treatment in the intervals between courses of radiation therapy until the effect is obtained from its implementation;
• Secreting endocrine tumors of the pancreas and gastrointestinal tract (to control symptoms): glucagonomas, somatoliberinomas, VIPomas, carcinoid tumors with the presence of carcinoid syndrome, insulinomas (for maintenance therapy, as well as to control hypoglycemia in the preoperative period), gastrinomas and Zollinger's syndrome - Ellison (usually in combination with histamine H 2 receptor blockers and proton pump inhibitors);
• Treatment of acute pancreatitis;
• Treatment and prevention of complications after surgical interventions on the abdominal organs;
• Stop bleeding in gastric ulcer and duodenal ulcer.

Contraindications

The use of Octreotide is strictly contraindicated in children and adolescents under 18 years of age, as well as in all patients with hypersensitivity to any component of the drug.

With caution, the drug should be used in the treatment of patients with diabetes mellitus and cholelithiasis (cholelithiasis).

The effect of the drug on the course of pregnancy has not been studied, so its use is possible only in extreme cases, if the intended benefit outweighs the possible risks.

It is not known whether octreotide passes into breast milk, so it is recommended that breastfeeding be discontinued during treatment.

Octreotide, instructions for use: method and dosage

Octreotide is intended for subcutaneous (s / c) and intravenous (in / in) administration.

Assigned dosing regimens depending on the indications and purpose of use:

• Treatment of acute pancreatitis: 100 mcg s / c 3 times a day for 5 days. In some cases, the doctor may advise on / in the introduction of the drug in a daily dose of up to 1200 mcg;
• Prevention of complications after pancreatic surgery: 100-200 mcg s / c. The first dose is administered 1-2 hours before laparotomy, after surgery - 3 times a day for 5-7 days;
• Stop ulcer bleeding: 25-50 mcg / hour as an IV infusion, course - 5 days;
• Stopping bleeding from varicose veins of the esophagus and stomach: 25-50 mcg / hour as a continuous IV infusion, the course of treatment is 5 days;
• Acromegaly: starting dose - 50-100 mcg s / c every 8 or 12 hours. In case of inefficiency (the target concentration of growth hormone is less than 2.5 ng / ml, and the IGF-1 index is within the normal range), the single dose is increased to 300 mcg. The maximum allowable daily dose is 1500 mcg. In patients receiving octreotide at a stable dose, it is necessary to determine the level of growth hormone every 6 months. If after 3 months of treatment there is no sufficient decrease in this indicator and improvement in the clinical course of the disease, Octreotide should be discontinued;
• Tumors of the gastroenteropancreatic endocrine system: the initial dose is 50 mcg 1-2 times a day, if necessary, it is gradually increased to 100-200 mcg 3 times a day s / c. In case of inefficiency (estimated based on the data on the achieved clinical effect, the concentration of hormones that produce the tumor, and the tolerability of the drug), the dose is increased to 300 mcg s / c 1-2 times a day. In exceptional cases, an even greater increase in dose is possible - up to 300-600 mcg 3 times a day. The doctor selects maintenance doses for each patient individually. If therapy at the maximum tolerated dose was ineffective for carcinoid tumors within 1 week, Octreotide is canceled.

Patients with impaired liver function require a maintenance dose adjustment.

Rules for subcutaneous administration of Octreotide:

• Carefully inspect the ampoule for the presence of impurities in the solution and discoloration;
• Warm the ampoule to room temperature;
• Open the ampoule immediately before the introduction;
• Throw away the unused amount of solution;
• Do not inject into the same place at short intervals.

Rules for intravenous drip:

• Carefully inspect the ampoule for the presence of impurities and discoloration;
• Warm the solution to room temperature;
• For dilution, use 0.9% sodium chloride (for example, 1 ampoule of 600 mcg is diluted with 60 ml of saline);
• Prepare an injection solution immediately before administration;
• If necessary, store no more than 24 hours after dilution in the refrigerator (at a temperature of 2 to 8 ºС).

Side effects

Criteria for assessing the incidence of side effects: very often - not more often than in 1 case out of 10, often - ≥1 / 100, but<1/10, иногда – ≥1/1000, но <1/100.

Adverse reactions identified in the course of clinical studies of Octreotide:

• From the digestive system: very often - diarrhea or constipation, bloating, nausea, abdominal pain; often - steatorrhea, discoloration of the stool, feeling of fullness or heaviness of the abdomen, soft stool consistency, dyspeptic disorders, anorexia, vomiting;
• From the hepatobiliary system: gallstones (cholelithiasis); often - increased activity of hepatic transaminases, cholecystitis, hyperbilirubinemia, the formation of cholesterol microcrystals due to a violation of the colloidal stability of bile;
• From the side of the cardiovascular system: often - bradycardia; sometimes - tachycardia;
• From the endocrine system: very often - hyperglycemia; often - hypoglycemia, impaired glucose tolerance, hypothyroidism, impaired thyroid function (manifested by a decrease in the levels of thyroid-stimulating hormone, total and free thyroxine);
• From the respiratory system: often - shortness of breath;
• From the nervous system: very often - headache; often - dizziness;
• Dermatological reactions: often - rash, itching, hair loss;
• Local reactions: very often - pain at the injection site;
• Other: sometimes - dehydration.

The causal relationship of the following side effects with the use of Octreotide has not been established:

• From the hepatobiliary system: cholestasis, jaundice, cholestatic hepatitis, acute hepatitis without cholestasis, cholestatic jaundice, acute pancreatitis, increased levels of gamma-glutamyl transferase and alkaline phosphatase;
• From the immune system: hypersensitivity reactions, anaphylactic reactions;
• From the side of the cardiovascular system: arrhythmias;
• Dermatological reactions: urticaria.

Overdose

The main symptoms: a feeling of flushing to the face, a short-term decrease in heart rate, spastic pain in the abdomen, a feeling of emptiness in the stomach, nausea, diarrhea.

Therapy: symptomatic.

special instructions

Women of childbearing age with acromegaly should use reliable methods of contraception during therapy. with a decrease in the level of growth hormone and normalization of the level of IGF-1 under the influence of octreotide, it is possible to restore childbearing function.

With long-term treatment, it is necessary to monitor the function of the thyroid gland.

In patients with a history of vitamin B 12 deficiency, it is necessary to monitor the content of cobalamin in the body.

Before the appointment of Octreotide, patients should be referred for an ultrasound examination of the gallbladder. If stones are found, the drug may be prescribed after a thorough assessment of the expected benefits of therapy and possible risks. Repeated examinations should be carried out every 6-12 months during treatment.

If stones are detected during treatment:

• Asymptomatic: You can stop the drug or continue therapy after assessing the benefit/risk ratio. There is no need to take any measures, more frequent monitoring is required;
• With clinical symptoms: you can stop the drug or continue treatment after assessing the benefit/risk ratio. Patients need standard therapy for gallstone disease (including bile acid preparations) and regular ultrasound monitoring.

Patients with pituitary tumors that secrete growth hormone require close medical supervision during treatment, since the drug can increase the tumor in size and develop serious complications, such as narrowing of the visual fields. If this occurs, consideration should be given to the use of other methods of treatment.

Octreotide may interfere with intestinal fat absorption.

With the development of bradycardia, it is necessary to consider the possibility of reducing the dose of calcium channel blockers, beta-blockers or drugs that affect the water and electrolyte balance.

It should be remembered that Octreotide is not an antitumor agent, therefore, it does not help to cure secreting endocrine tumors of the pancreas and gastrointestinal tract.

In the treatment of endocrine tumors of the gastrointestinal tract and pancreas, in some cases, a sudden relapse is possible. With the development of insulinoma during the use of octreotide, an increase in the duration and severity of hypoglycemia is possible. Such patients should be closely monitored, especially with each dose change.

Octreotide affects the concentration of glucose in the blood. It is possible to reduce fluctuations due to the more frequent administration of the drug in smaller doses. In type 1 diabetes mellitus, the drug can reduce the need for insulin, in type 2 diabetes (with partially preserved insulin secretion) and in patients without diabetes, it can lead to the development of postprandial hyperglycemia. For this reason, patients with diabetes need to control blood glucose levels and conduct antidiabetic therapy.

It is also necessary for patients to control the concentration of glucose in the blood after bleeding from varicose veins of the stomach or esophagus, since in this case the risk of developing type 1 diabetes increases.

Influence on the ability to drive vehicles and complex mechanisms

Due to the risk of side effects from the central nervous system, it is recommended to be careful when driving a car and performing any work that requires increased attention and speed of reactions.

Use during pregnancy and lactation

• Pregnancy: the use of Octreotide is possible only under strict indications after assessing the ratio of the expected benefit to the possible risk;
• Lactation period: therapy is contraindicated.

Application in childhood

For impaired renal function

Patients with impaired renal function do not need to adjust the dose of Octreotide.

For impaired liver function

Patients with impaired hepatic function are advised to adjust the maintenance dose of Octreotide.

Use in the elderly

Elderly patients do not require correction of the dosing regimen.

drug interaction

Caution should be used simultaneously with drugs that are metabolized by the cytochrome P 450 system and have a narrow range of therapeutic concentrations (for example, quinidine or terfenadine), because. increases the likelihood of side effects.

Octreotide reduces the absorption of cyclosporine, increases the bioavailability of bromocriptine, slows down the absorption of cimetidine, reduces the metabolism of drugs that are metabolized with the participation of enzymes of the cytochrome P 450 system.

In the case of simultaneous use of the following drugs, dose adjustment is required: insulin, oral hypoglycemic drugs, glucagon, calcium channel blockers, beta-blockers and diuretics.

Analogues

Analogues of Octreotide are: Octreotide Fsintez, Octrid, Octretex, Sandostatin, Somatostatin, Diferelin, Sermorelin.

Terms and conditions of storage

Keep out of the reach of children and protected from light, in a temperature range of 8-25 ºС.

Shelf life - 5 years.

Octreotide is a synthetic derivative of the natural hormone somatostatin, characterized by similar pharmacological effects, but a much longer duration of action; inhibits the secretion of thyrotropin, serotonin, gastrin, insulin, glucagon, growth hormone, both pathologically elevated and caused by external factors (arginine, food intake, insulin hypoglycemia, etc.).

Release form and composition

Dosage forms of Octreotide:

• Solution for intravenous and subcutaneous administration at a dose of 50 and 100 mcg: colorless, transparent liquid, odorless (1 ml per ampoule, 5 ampoules (50 mcg) in a blister pack; 5 ampoules (100 mcg) in a blister pack, in a carton a pack of 1 or 2 packs);
• Solution for intravenous and subcutaneous administration at a dose of 300 and 600 mcg: colorless, transparent liquid, odorless (1 ml in a dark glass ampoule with a tension ring for opening or with a break point, or in a colorless glass ampoule marked as two green strips; in a blister pack 1 or 2 ampoules, in a carton pack 1 pack; in a blister pack 5 ampoules, in a carton pack 1 or 2 packs).

Composition of 1 ml solution for intravenous and subcutaneous administration at a dose of 50 and 100 mcg:

• Active substance: octreotide - 50 and 100 mcg;

Composition of 1 ml solution for intravenous and subcutaneous administration at a dose of 300 and 600 mcg:

• Active substance: octreotide acetate, in terms of octreotide - 300 and 600 mcg;
• Additional components: water for injections, sodium chloride.

Indications for use

• Acute pancreatitis (at a dose of 50 and 100 mcg);
• Peptic ulcer of the stomach and duodenum, in order to stop bleeding (at a dose of 50 and 100 mcg);
• Acromegaly (to control the main manifestations of the lesion and a decrease in the level of growth hormone and insulin-like growth factor-1 (IGF-1); with insufficient effectiveness or impossibility of surgical treatment or radiation therapy; with the patient refusing surgery or with short-term treatment in the periods between radiation courses therapy, until the full development of its effect);
• Secreting endocrine tumors of the pancreas and gastrointestinal tract, in order to control symptoms (carcinoid tumors (with the presence of carcinoid syndrome), glucagonomas, VIPomas, gastrinomas / Zollinger-Ellison syndrome (in combination with histamine H2 receptor blockers and proton pump inhibitors), insulinoma (including for maintenance therapy and control of hypoglycemia before surgery), somatoliberinoma).

The solution is used to treat and prevent complications in the period after surgery on the abdominal organs, as well as in patients with cirrhosis of the liver to stop bleeding and prevent re-bleeding from varicose veins of the stomach and esophagus. The use of the agent is possible in combination with specific therapeutic measures (for example, with endoscopic sclerotherapy).

Contraindications

• Children and adolescents up to 18 years of age;
• Hypersensitivity to the components of the drug.

With extreme caution, the drug should be used for cholelithiasis (cholelithiasis) and diabetes mellitus. Experience with the use of the drug during pregnancy is not available. As a result, Octreotide is recommended for pregnant women only when the expected benefit of therapy outweighs the potential risk of adverse reactions.

If it is necessary to administer the drug during lactation, it is required to refuse breastfeeding (because it is not known whether the drug passes into breast milk).

Method of application and dosage

Octreotide is used subcutaneously and intravenously.

In the treatment of acute pancreatitis, 100 mcg of the solution is administered subcutaneously 3 times a day for 5 days; intravenous infusion at a dose not exceeding 1200 mcg per day is also acceptable.

To stop bleeding from varicose veins of the esophagus or peptic ulcer, long-term intravenous infusions are prescribed at a dose of 25-50 mcg / hour for 5 days.

In order to prevent complications after undergoing surgical interventions on the pancreas, the agent is administered subcutaneously. The first injection at a dose of 100-200 mcg is carried out 1-2 hours before laparotomy, and the next - at a dose of 100-200 mcg after surgery, 3 times a day, daily for 5-7 days.

In acromegaly, it is recommended to administer 300 micrograms of Octreotide subcutaneously at intervals of 8 or 12 hours, this dose is prescribed if there is no effect during initial therapy (50-100 micrograms of solution at intervals of 8 or 12 hours). The effectiveness of treatment is determined by taking into account monthly indicators of the concentration of somatotropic hormone in the blood, tolerability of the agent and clinical symptoms. To achieve the desired effect, if necessary, it is possible to use the drug in a dose exceeding 300 mcg, but not more than 1500 mcg per day.

If within 3 months of therapy there is no improvement in the clinical picture and a sufficient decrease in the level of growth hormone, the use of the drug is inappropriate.

For tumors of the gastroenteropancreatic endocrine system, the drug is administered subcutaneously. The initial dose of Octreotide is 50 mcg, applied 1-2 times a day, in the future it is possible to increase the dose to 100-200 mcg with a frequency of administration 3 times a day. With the ineffectiveness of the initial therapy, assessed by the concentration of hormones produced by the tumor, the tolerability of the drug and the achieved clinical effect, subcutaneous injections are prescribed 1-2 times a day at a dose of 300 mcg. In exceptional cases, a gradual increase in dose to 300-600 mcg, administered 3 times a day, is acceptable. If there is no therapeutic effect during the treatment of carcinoid tumors with Octreotide at the maximum tolerated dose for 7 days, treatment should be discontinued.

The elderly, as well as patients with functional impairment of the kidneys, do not require correction of the dosing regimen.

When prescribing an intravenous drip infusion of the drug, the contents of the ampoule at a dose of 600 μg must be dissolved in 60 ml of physiological sodium chloride solution (0.9%). Diluted solutions must be administered immediately after preparation (to avoid microbial contamination). If it is impossible to use the drug immediately after dilution, it can be stored at a temperature of 2-8 ° C for no longer than 24 hours (the total time from the moment of dilution until the end of its administration).

Side effects

• Digestive system: very often - bloating, constipation, nausea, abdominal pain, diarrhea; often - anorexia, discoloration / soft stool consistency, steatorrhea, feeling of heaviness / fullness of the abdomen, vomiting, dyspeptic disorders;
• Endocrine system: very often - hyperglycemia; often - hypothyroidism, disorders of the thyroid gland (decrease in the levels of free and total thyroxine, and thyroid-stimulating hormone); impaired glucose tolerance, hypoglycemia;
• Hepatobiliary system: very often - the formation of stones in the gallbladder (cholelithiasis); often - increased activity of hepatic transaminases, hyperbilirubinemia, impaired colloidal stability of bile, cholecystitis;
• Nervous system: very often - headache; often - dizziness;
• Cardiovascular system: often - bradycardia; sometimes - tachycardia;
• Respiratory system: often - shortness of breath;
• Skin: often - itching, rash, hair loss;
• General disorders and local reactions: very often - pain at the injection site; sometimes dehydration.

Also, when using the drug in clinical practice, the following undesirable effects were observed (regardless of the presence of a causal relationship with the use of the drug): cholestatic jaundice, cholestasis, jaundice, cholestatic hepatitis, acute hepatitis without cholestasis, acute pancreatitis, increased levels of gamma-glutamyl transferase ( GGT) and alkaline phosphatase (AP), arrhythmia, allergic reactions, urticaria, anaphylactic reactions.

With subcutaneous injections of octreotide at a daily dose of 3000-30000 mcg, divided into several injections, no new side effects were detected in patients with tumors (other than those indicated above).

With accidental intravenous administration of the drug at a dose of 2400-6000 mcg per day (at a rate of 100-250 mcg / h) or subcutaneous administration of 1500 mcg 3 times a day, the following reactions were observed: weight loss, lactic acidosis, hepatomegaly, lethargy, weakness, diarrhea, fatty degeneration of the liver, pancreatitis, cerebral hypoxia, sudden cardiac arrest, lowering blood pressure, development of arrhythmias. Treatment is symptomatic.

special instructions

Patients with diabetes who take insulin may experience a decrease in insulin requirements during therapy.

Before starting treatment, as well as during a long course, it is recommended to conduct an ultrasound examination of the gallbladder at intervals of 6-12 months.

In case of detection of stones in the gallbladder before the start of therapy, the issue of using the drug is decided individually, after the ratio of the potential benefits of therapy and the risk of developing possible complications associated with the presence of stones.

Manifestations of adverse reactions from the digestive system can be reduced by the introduction of octreotide at bedtime or in between meals.

With a long course, thyroid function should be monitored.

In rare cases, during the treatment of endocrine tumors of the gastrointestinal tract and pancreas, there may be a sudden relapse of the symptoms of the disease.

When using octreotide in patients with a history of vitamin B12 (cobalamin) deficiency, it is recommended to control its content in the body (cobalamin absorption worsens).

To reduce discomfort and pain at the injection site, it is recommended to warm the solution to room temperature before use and inject it in a smaller volume. Injections of the drug at short intervals at the same injection site should be avoided.

drug interaction

The effect of octreotide on concomitantly taken substances / drugs:

• Cyclosporine - reduces its absorption;
• Bromocriptine - increases its bioavailability;
• Cimetidine - slows down its absorption;
• Drugs metabolized by the cytochrome P450 system (terfenadine, quinidine) - reduces their metabolism.

When octreotide is combined with diuretics, oral hypoglycemic drugs, insulin, blockers of "slow" calcium channels, beta-blockers, a correction of the dosing regimen is required.

Terms and conditions of storage

Store in a place protected from moisture and light, out of the reach of children, at a temperature of 8 to 25 °C.

Shelf life - 5 years.

Latin name: Octreotide
ATX code: H01CB02
Active substance: Octreotide
Manufacturer: F-Sintez, Russia
Pharmacy leave condition: On prescription

Octreotide is a drug that has a somatostatin-like effect.

Indications for use

The use of Octreotide is provided for:

• Acute course of pancreatitis (enzymatic phase)
• Neoplasms in the organs of the endocrine system (gastrinoma, insulinoma, glucagonoma, and vipoma)
• Opening of bleeding in the gastrointestinal tract in the presence of ulcerative lesions, as well as preventive measures for varicose veins of the esophagus, complicated by liver cirrhosis
• Acromegaly
• Prevention of possible complications in the abdominal organs after surgery
• Prevention of gastric bleeding (especially from the cardiac section).

Compound

1 ml of the drug contains 100 mcg of the main active ingredient, which is represented by octreotide. As auxiliary substances are:

• Sodium chloride
• Purified water.

Medicinal properties

The drug Octreotide is an artificial analogue of such a substance as somatostatin, it has the same pharmacological properties, but it is characterized by a prolonged therapeutic effect. It is worth noting that the trade and international name (name) of the drug is the same.

This drug termozit process of production of growth hormone, including pathological and that provoked by insulin-dependent hypoglycemia, excessive physical activity or arginine. Along with this, it inhibits the production of not only insulin, glucagon, but also gastrin, serotinin (impaired, due to pathological changes, and provoked by food).

The use of Okreotide helps to suppress the production of:

• Glucagon with insulin, which is caused by arginine
• Thyrotropin, provoked by a high level of thyreoliberin.

In persons who are preparing for surgical intervention on the pancreas, there is a low risk of serious complications (fistulas, sepsis, abscesses, development of acute pancreatitis) after surgery if the drug was taken before and immediately after.

To stop bleeding and prevent its occurrence in persons with cirrhosis of the liver and varicose veins, it is recommended to carry out combined treatment with Octreotide and other drugs included in the number of sclerosing, hemostatic therapy.

The drug is quickly absorbed after its introduction under the skin. Its highest concentration in the blood is observed within half an hour after the injection.

Communication with plasma proteins is equal to 65%. The duration of the half-life of metabolic products after the introduction of the drug under the skin is about 100 minutes; when injected into a vein, the active component of the solution is excreted in two phases, the duration of which is 10 and 90 minutes. Metabolites are excreted from the body by the intestines and kidneys. The total clearance is approximately equal to 160 ml / min.

In elderly patients, there is a decrease in the total clearance, while the half-life of metabolites is slightly increased. It should be noted that an increase in clearance is recorded in persons suffering from severe renal failure.

Release form

Octreotide is a clear and almost colorless solution that has no pronounced odor. One ampoule contains 1 ml of drug solution. Inside the carton box there is 1 or 2 blister. packages that contain 5 amps.

Octreotide: detailed instructions for use

Price: from 600 to 3616 rubles.

Injections are made both under the skin and directly into a vein.

Usually prescribed the following doses of the drug:

• Scheme for the use of Octreotide in pancreatitis: 100 mcg subcutaneously three times a day, the duration of therapeutic therapy is 5 days, during the first two days the highest therapeutic effect is recorded; it is also possible to inject the drug into a vein (daily dose - up to 1200 mcg)
• Prevention of postoperative complications: 100 mcg before surgery, subsequently - 100 mcg three times a day, the total duration of therapy is 7 days.
• Stopping gastric bleeding in esophageal varicose veins: a solution is injected into a vein by infusion at a rate of 25-50 mcg / hour, therapy lasts 5 days.
• Ulcerative lesions of the gastrointestinal tract: in a vein (infusion) at a rate of 25 mcg / hour, a five-day treatment is indicated.

Use during pregnancy and breastfeeding

At the moment, there is no reliable data on how the drug affects the body of a woman and a child.

Treatment of this group of patients should be carried out under close medical supervision in order to prevent the development of complications.

Contraindications

Do not start treatment with the drug in case of hypersensitivity to the active substance.

With extreme caution, drugs are prescribed to people with diabetes mellitus, as well as cholelithiasis.

Precautionary measures

Elderly patients will need to adjust the dose of drugs (reduce it).

At the injection site, there may be a burning sensation, slight itching, hyperemia and swelling.

To reduce discomfort during the injection of the drug, it is recommended to warm the solution to room temperature and inject it as slowly as possible.

You can make injections using other drugs, but each subsequent procedure must be carried out after several hours.

Individuals with diabetes who are taking insulin will need to adjust the prescribed dosage. To normalize the level of insulin in the blood, it is recommended to resort to frequent administration of the drug, but in minimal doses. In the case of type 1 diabetes during treatment with octreotide, the need for insulin may decrease sharply, in patients with type 2 diabetes, postprandial hyperglycemia may develop. That is why it will be necessary to control blood sugar levels and carry out the necessary antidiabetic treatment.

If a patient is diagnosed with gallstone disease before starting therapy, the decision to administer octreotide is made individually (taking into account the likely benefits and perceived risks).

To reduce the severity of adverse reactions from the gastrointestinal tract, injections will be required between main meals or before bed at night.

Cross-drug interactions

The drug significantly reduces the absorption of drugs such as Cyclosporine and Cimetidine.

If it is necessary to take diuretic drugs, insulin, hypoglycemic drugs, calcium antagonists, beta-blockers, their dosage should be adjusted.

With the simultaneous administration of bromocriptine, an increase in its bioavailability is observed.

Drugs that undergo the process of metabolism due to the participation of specific cytochrome P450 isoenzymes and are characterized by a narrow dosage range are prescribed with extreme caution.

Alcohol compatibility

Alcohol can inhibit the production of certain hormones, so drinking alcohol during treatment is contraindicated.

Side effects

There may be reactions from the gastrointestinal tract: severe nausea, turning into vomiting, the development of anorexia, spastic pain in the abdomen, increased gas formation in the intestines, steatorrhea, and loose stools. During treatment, the excretion of lipids with feces may increase, but the risk of developing malabsorption syndrome does not increase. Very rarely, there are manifestations that are characteristic of intestinal obstruction. It is not excluded the development of hepatitis without cholestasis or hyperbilirubinemia. With prolonged use, gallstone disease may develop. In some cases, an exacerbation of pancreatitis is recorded (during the first hours after the completion of the drug intake).

CCC may also respond to treatment with octreotide - bradycardia or arrhythmia occurs.

Lipid metabolism: glucose tolerance may develop (especially after meals), such a reaction of the body is associated with inhibition of insulin production, hyper- or hypoglycemia.

Local reactions: soreness at the injection site, hyperemia, swelling, itching and severe burning. Such symptoms disappear on their own after 15 minutes.

Other side effects: allergies, alopecia.

Overdose

There may be a short-term decrease in heart rate, spastic pains, flushing of the skin of the face, diarrhea, stool changes are recorded. Symptomatic therapy is recommended. After stopping acute symptoms, you should consult a doctor for advice.

Storage conditions and shelf life

The shelf life of the ampoules is 5 years. During use, ampoules can be stored for up to 2 weeks. at room temperature.

Analogues

Novartis Pharma, Switzerland

Price from 1129 to 2237 rubles.

Sandostatin is an imported analogue of Octreotide, but is produced in the form of a solution, as well as microspheres for suspension preparation. The medicine is used for the complex treatment of gastroenterological ailments.

Pros:

• Decreases secretion of gastrin and insulin
• Available in two dosage forms
• Supports normoglycemia.

Minuses:

• May cause hyperbilirubinemia
• Released by prescription
• It is not excluded the development of liver pathologies and the occurrence of diarrhea.

Ipsen Pharma, France

Price from 2441 to 21010 rubles.

Diphereline is a hormonal drug, the active substance of which is triptorelin. It is prescribed for female infertility, early puberty, endometriosis, oncopathologies of the reproductive system, reduced potency. Diferelin is produced in the form of a lyophilizate for the manufacture of a solution or suspension.

Pros:

• High efficacy in the treatment of female infertility
• Convenient to use
• May be used with other drugs.

Minuses:

• Expensive
• Available by prescription only
• Contraindicated in pregnancy, HB.

analogue of somatostatin. Drug for intensive care in gastroenterology

Active substance

Octreotide (as acetate) (octreotide)

Release form, composition and packaging

Excipients: - 9 mg, water for injection - up to 1 ml.

Solution for intravenous and s / c administration transparent, colorless, odorless.

Excipients: sodium chloride - 9 mg, water for injections - up to 1 ml.

1 ml - ampoules (1) - blister packs (1) - cardboard packs.
1 ml - ampoules (2) - blister packs (1) - cardboard packs.
1 ml - ampoules (5) - blister packs (1) - cardboard packs.
1 ml - ampoules (5) - blister packs (2) - cardboard packs.

pharmachologic effect

Octreotide is a synthetic analogue of somatostatin, which is a derivative of the natural hormone somatostatin and has pharmacological effects similar to it, but with a much longer duration of action. Octreotide suppresses the secretion of growth hormone (GH), both pathologically increased and caused by arginine, exercise and insulin hypoglycemia. The drug also suppresses the secretion of insulin, glucagon, gastrin, both pathologically increased and caused by food intake; also suppresses the secretion of insulin and glucagon, stimulated by arginine. Octreotide inhibits thyrotropin secretion caused by thyreoliberin.

Unlike somatostatin, octreotide suppresses GH secretion to a greater extent than insulin secretion, and its administration is not accompanied by subsequent hypersecretion of hormones (for example, GH in patients with acromegaly).

In patients with acromegaly, octreotide reduces the concentration of GH and insulin-like growth factor (IGF-1) in the blood. A decrease in the concentration of GH by 50% or more is observed in 90% of patients, while the value of the GH concentration of at least 5 ng/ml is achieved in about half of the patients. In most patients with acromegaly, octreotide reduces the severity of headache, soft tissue swelling, hyperhidrosis, joint pain and paresthesia. In patients with large pituitary adenomas, treatment with octreotide may result in some reduction in tumor size.

In case of secreting tumors of the gastroenteropancreatic endocrine system, in cases of insufficient effectiveness of the therapy performed (surgical intervention, hepatic artery embolization, chemotherapy, including streptozotocin and), the appointment of octreotide can lead to an improvement in the course of the disease. So, in carcinoid tumors, the use of octreotide can lead to a decrease in the severity of the sensation of flushing to the face, diarrhea, which in many cases is accompanied by a decrease in plasma serotonin concentration and excretion of 5-hydroxyindoleacetic acid by the kidneys. In tumors characterized by hyperproduction of vasoactive intestinal peptide (VIPoma), the use of octreotide in most patients leads to a decrease in severe secretory diarrhea, and, accordingly, to an improvement in the quality of life of the patient. At the same time, there is a decrease in concomitant electrolyte imbalances, for example, hypokalemia, which makes it possible to cancel enteral and parenteral administration of fluids and electrolytes. In some patients, the progression of the tumor slows down or stops, its size decreases, as well as the size of liver metastases. Clinical improvement is usually accompanied by a decrease in the concentration of vasoactive intestinal peptide (VIP) in plasma or its normalization. In glucagonomas, the use of octreotide leads to a decrease in erythema migrans. Octreotide does not have any significant effect on the severity of hyperglycemia in diabetes mellitus, while the need for insulin or oral hypoglycemic drugs usually remains unchanged. The drug causes a decrease in diarrhea, which is accompanied by an increase in body weight. Although the decrease in plasma glucagon concentration under the influence of octreotide is transient, clinical improvement remains stable throughout the entire period of drug use. In patients with gastrinomas / Zollinger-Ellison syndrome, when using octreotide alone or in combination with proton pump inhibitors or H2-histamine receptor blockers, it is possible to reduce the hypersecretion of hydrochloric acid in the stomach, reduce the concentration of gastrin in the blood plasma, as well as reduce the severity of diarrhea and tides. In patients with insulinomas, octreotide reduces the level of immunoreactive insulin in the blood (this effect may be short-lived - about 2 hours). In patients with resectable tumors, octreotide may provide restoration and maintenance of normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, glycemic control may improve without a simultaneous prolonged decrease in blood insulin levels.

In patients with rare tumors that overproduce growth hormone releasing factor (somatoliberinoma), octreotide reduces the severity of symptoms of acromegaly. This is due to the suppression of the secretion of growth hormone releasing factor and growth hormone itself. In the future, hypertrophy of the pituitary gland may decrease.

When bleeding from varicose veins of the esophagus and stomach in patients with cirrhosis of the liver, the use of octreotide in combination with specific treatment (for example, sclerotherapy) leads to more effective control of bleeding and early rebleeding, a decrease in the volume of transfusions and an improvement in 5-day survival. It is believed that the mechanism of action of octreotide is associated with a decrease in organ blood flow through the suppression of vasoactive hormones such as VIP and glucagon.

Pharmacokinetics

Suction

After subcutaneous administration, octreotide is rapidly and completely absorbed. C max octreotide in plasma is achieved within 30 minutes.

Distribution

Communication with blood plasma proteins is 65%. The binding of octreotide with blood cells is extremely insignificant. V d is 0.27 l / kg.

breeding

T 1/2 after s / c administration of octreotide is 100 minutes. After intravenous administration, the excretion of octreotide is carried out in 2 phases, with T 1/2 - 10 and 90 minutes, respectively. Most of octreotide is excreted through the intestines, about 32% - unchanged by the kidneys. The total clearance is 160 ml / min.

Indications

Acromegaly: to control the main manifestations of the disease and reduce plasma levels of GH and IGF-1 in cases where there is no sufficient effect of surgical treatment or radiation therapy. Octreotide is also indicated for the treatment of patients with acromegaly who have refused surgery or who have contraindications to it, as well as for short-term treatment in between courses of radiation therapy until its effect is fully developed.

Secreting endocrine tumors of the gastrointestinal tract and pancreas - to control symptoms:

- carcinoid tumors with the presence of carcinoid syndrome;

- VIPomas;

- glucagonomas;

- gastrinomas / Zollinger-Ellison syndrome - usually in combination with proton pump inhibitors and histamine H 2 receptor blockers;

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

- somatoliberinomas (tumors characterized by hyperproduction of growth hormone releasing factor).

The drug is not and its use cannot lead to a cure in this category of patients.

Stop bleeding and prevention of recurrence of bleeding from varicose veins of the esophagus and stomach in patients with cirrhosis of the liver. Octreotide is used in combination with specific therapeutic measures, such as endoscopic sclerosing therapy.

Contraindications

- hypersensitivity to octreotide or other components of the drug;

- children's age up to 18 years.

Carefully: cholelithiasis (cholelithiasis); diabetes

Dosage

Subcutaneously, intravenously drip.

With acromegaly- s / c, at a dose of 300 mcg at intervals of 8 or 12 hours. This dose is used in case of failure of initial therapy (Octreotide drug, solution for i / v and s / c, 50-100 mcg at intervals of 8 or 12 hours). Initial therapy failure is assessed based on monthly determinations of blood GH concentration (target concentration: GH< 2.5 нг/мл; ИФР – 1 в пределах нормальных значений), анализе клинических симптомов и переносимости препарата. В случае неэффективности дозы 300 мкг, рекомендуется проводить подбор дозы, основываясь на вышеуказанных критериях. Не следует превышать максимальную дозу, составляющую 1500 мкг/сут.

In patients receiving octreotide at a stable dose, the determination of the concentration of GH should be carried out every 6 months. If after three months of treatment with octreotide there is no sufficient decrease in the concentration of GH and improvement in the clinical picture of the disease, therapy should be discontinued.

For tumors of the gastroenteropancreatic endocrine system: s / c, at a dose of 300 mcg 1-2 times / day. This dose is used in case of failure of initial therapy (Octreotide preparation, solution for intravenous and s / c administration, 50 mcg 1-2 times / day with a gradual increase to 100-200 mcg 3 times / day). The ineffectiveness of initial therapy is evaluated based on the clinical effect achieved, the effect on the concentration of hormones produced by the tumor (in the case of carcinoid tumors, the effect on the excretion of 5-hydroxyindoleacetic acid by the kidneys) and tolerability. In exceptional cases, it is allowed to prescribe to the patient a dose exceeding 600 mcg / day, the dose of the drug can be gradually increased to 300-600 mcg 3 times / day. Maintenance doses of the drug should be selected individually. In carcinoid tumors, if therapy with octreotide at the maximum tolerated dose for 1 week has not been effective, treatment should not be continued.

With bleeding from varicose veins of the esophagus and stomach: IV drip at a rate of 25 mcg/h for 5 days.

Application in certain groups of patients

At present, there is no data to indicate that the elderly reduced tolerability of octreotide and require a change in dosing regimen.

At patients with impaired renal function correction of the dosing regimen of octreotide is not required.

Experience with octreotide in children limited.

Rules for the use of the drug

Subcutaneous administration

Patients self-administering subcutaneous octreotide should receive detailed instructions from their doctor or nurse.

Before administration, the solution should be warmed to room temperature - this helps to reduce discomfort at the injection site. Do not inject the drug in the same place with short intervals. Ampoules should be opened immediately before the administration of the drug; discard any unused solution.

Intravenous drip

If necessary, intravenous drip of octreotide, the contents of one ampoule containing 600 μg of the active substance should be diluted in 60 ml of 0.9% sodium chloride solution. Octreotide at temperatures below 25 ° C for 24 hours retains physical and chemical stability in a sterile 0.9% sodium chloride solution or 5% dextrose solution in water. However, since octreotide may interfere with glucose metabolism, it is preferable to use a 0.9% sodium chloride solution. Before the / in the introduction of the ampoule should be carefully examined for changes in the color of the solution and the presence of foreign particles.

To avoid microbial contamination, diluted solutions should be used immediately after preparation. If the solution is not to be used immediately, it should be stored at 2-8°C. Before administration, the solution should be warmed to room temperature. The total time between dilution, storage in the refrigerator and the end of the introduction of the solution should not exceed 24 hours.

Side effects

The main adverse events observed with the use of octreotide were side effects on the part of the digestive, nervous, hepatobiliary systems, as well as metabolic disorders and the development of nutritional deficiencies.

In clinical studies, diarrhea, abdominal pain, nausea, bloating, headache, formation of gallstones, hyperglycemia and constipation were most often observed during the administration of the drug. Dizziness, pain of various localization, impaired colloidal stability of bile (formation of cholesterol microcrystals), thyroid dysfunction (decreased levels of thyroid-stimulating hormone, total and free thyroxine), soft stool consistency, decreased glucose tolerance, vomiting, asthenia and hypoglycemia were also often noted.

When using the drug in rare cases, there may be phenomena resembling acute intestinal obstruction: progressive bloating, severe pain in the epigastric region, tension in the abdominal wall, muscle protection.

Although the excretion of fat in the feces may increase, there is no evidence to date that long-term treatment with octreotide can lead to the development of malnutrition due to malabsorption.

Very rare cases of acute pancreatitis have been reported, developing in the first hours or days of s / c use of octreotide and disappearing after discontinuation of the drug. In addition, cases of pancreatitis associated with cholelithiasis have been reported with prolonged use of octreotide s.c.

According to the ECG study on the background of the use of the drug in patients with acromegaly and carcinoid syndrome: there were observed prolongation of the QT interval, deviation of the electrical axis of the heart, early repolarization, low-voltage type of ECG, displacement of the transition zone, early P wave and non-specific changes in the ST segment and T wave. In this category of patients there are heart diseases, a causal relationship between the use of octreotide and the development of these adverse events has not been established.

To determine the frequency of adverse reactions identified during clinical trials of the drug, the following criteria were used: very often (≥ 1/10); often (≥ 1/100,< 1/10); иногда (≥ 1/1000, < 1/100); редко (≥1/10000, < 1/1000); очень редко (< 1/10000), включая отдельные сообщения.

From the digestive system: very often - diarrhea, abdominal pain, nausea, constipation, bloating; often - dyspeptic disorders, vomiting, feeling of fullness / heaviness of the abdomen, steatorrhea, soft stool consistency, discoloration of the stool, anorexia.

From the nervous system: very often - headache; often - dizziness.

From the endocrine system: very often - hyperglycemia; often - hypothyroidism / thyroid dysfunction (decreased levels of thyroid-stimulating hormone, total and free thyroxine); hypoglycemia, impaired glucose tolerance.

very often - cholelithiasis, i.e. the formation of stones in the gallbladder; often - cholecystitis, impaired colloidal stability of bile (formation of cholesterol microcrystals), hyperbilirubinemia, increased activity of hepatic transaminases.

Dermatological reactions: often - itching, rash, hair loss.

From the respiratory system: often - shortness of breath.

often - bradycardia; sometimes - tachycardia.

General disorders and reactions at the injection site: very often - pain at the injection site; sometimes dehydration.

During octreotide therapy in clinical practice, the following adverse events were noted, regardless of the presence of a causal relationship with the use of the drug:

From the immune system: anaphylactic reactions, allergic reactions/hypersensitivity.

Dermatological reactions: hives.

From the hepatobiliary system: acute pancreatitis, acute hepatitis without cholestasis, cholestatic hepatitis, cholestasis, jaundice, cholestatic jaundice, increased levels of alkaline phosphatase, gamma-glutamyl transferase.

From the side of the cardiovascular system: arrhythmias.

Overdose

Isolated cases of octreotide overdose have been reported in children and adults in clinical practice. In case of accidental use of octreotide in adults at a dose of 2400-6000 mcg / day, administered intravenously (infusion rate
100-250 mcg / hour) or s / c (1500 mcg 3 times / day), it was observed: the development of arrhythmias, a decrease in blood pressure, sudden cardiac arrest, cerebral hypoxia, pancreatitis, fatty degeneration of the liver, diarrhea, weakness, lethargy, weight loss bodies, hepatomegaly and lactic acidosis.

In case of accidental use of octreotide in children at a dose of 50-3000 mcg / day, administered intravenously (infusion rate 2.1-500 mcg / h) or s / c (50-100 mcg), only moderate hyperglycemia was noted.

With s / c administration of octreotide at a dose of 3000-30000 mcg / day (divided into several injections) in patients with tumors, no new adverse events (with the exception of those indicated in the "Side Effects" section) were identified.

drug interaction

Pharmacokinetic interaction

Reduces the absorption of cyclosporine, slows down the absorption of cimetidine. It is necessary to correct the dosing regimen of concomitantly used diuretics, beta-blockers, blockers of "slow" calcium channels, oral hypoglycemic drugs, glucagon.

The combined use of octreotide and bromocriptine increases the bioavailability of bromocriptine.

Reduces the metabolism of substances metabolized with the participation of enzymes of the cytochrome P450 system (may be due to the suppression of GR). Since similar effects of octreotide cannot be excluded, caution should be exercised when prescribing drugs metabolized by the cytochrome P450 system and having a narrow range of therapeutic concentrations (eg, quinidine, terfenadine).

special instructions

In case of pituitary tumors secreting GH, careful monitoring of patients receiving octreotide is necessary, since an increase in the size of tumors with the development of such a serious complication as narrowing of the visual fields is possible. In these cases, the need for other treatments should be considered.

Since a decrease in the level of growth hormone and normalization of the level of insulin-like factor-1 during octreotide therapy can lead to the restoration of fertility in women with acromegaly, patients of childbearing age should use reliable methods of contraception when using the drug.

When prescribing octreotide for a long period of time, it is necessary to monitor thyroid function.

In the case of the development of bradycardia against the background of the use of octreotide, if necessary, it is possible to reduce the dose of beta-blockers, or drugs that affect the water and electrolyte balance.

In some patients, octreotide may alter intestinal fat absorption.

Against the background of the use of octreotide, there was a decrease in the content of cobalamin (vitamin B 12) and deviations from the norm of the cobalamin absorption test (Schilling test).

When using octreotide in patients with a history of vitamin B12 deficiency, it is recommended to control the content of cobalamin in the body.

Patients should undergo baseline gallbladder ultrasound prior to administering octreotide.

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

If gallstones are detected prior to treatment, the potential benefits of octreotide therapy should be weighed against the possible risks associated with their presence. There are no data on any negative effect of octreotide on the course or prognosis of already existing cholelithiasis.

Asymptomatic gallbladder stones. The use of octreotide can be discontinued or continued - in accordance with the assessment of the benefit / risk ratio. In any case, there is no need to do anything other than continue the observation, making it more frequent if necessary.

Gallbladder stones with clinical symptoms. The use of octreotide 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 acids (for example, chenodeoxycholic acid at a dose of 7.5 mg/kg per day in combination with ursodeoxycholic acid at the same dose) under ultrasound guidance until the stones disappear completely.

In the treatment of endocrine tumors of the gastrointestinal tract and pancreas with octreotide, in rare cases, a sudden relapse of the symptoms of the disease may occur.

In patients with insulinomas during treatment with octreotide, there may be an increase in the severity and duration of hypoglycemia (this is due to 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). Careful regular monitoring of these patients should be ensured both at the beginning of treatment with Octreotide and at each change in the dose of the drug. Significant fluctuations in blood glucose concentrations can be attempted to be reduced by more frequent administration of octreotide at lower doses. In patients with type 1 diabetes mellitus, octreotide may reduce the need for insulin. In patients without diabetes and with type 2 diabetes with partially preserved insulin secretion, the administration of octreotide can lead to postprandial hyperglycemia. When using octreotide in patients with diabetes mellitus, it is recommended to monitor the concentration of glucose in the blood and antidiabetic therapy.

Since after bleeding from varicose veins of the esophagus and stomach, the risk of developing type 1 diabetes is increased, and in patients with diabetes, changes in insulin requirements are also possible, in these cases systematic monitoring of blood glucose concentration is necessary.

It is necessary to correct the dosing regimen of simultaneously used diuretics, beta-blockers, blockers of "slow" calcium channels, insulin, oral hypoglycemic agents, glucagon.

Influence on the ability to drive vehicles and control mechanisms

Some side effects of octreotide may adversely affect the ability to drive vehicles and other mechanisms that require increased concentration and speed of psychomotor reactions. In this regard, it is recommended that when these symptoms appear, be careful when driving vehicles or mechanisms that require increased concentration.

Correction of the dosing regimen of octreotide is not required. The drug should be stored in a dry, dark place, out of the reach of children, at a temperature of 8 to 25°C.

Best before date - 5 years. Do not use after the expiration date.

Composition and form of release

Solution - 1 ml:

• Active substance: octreotide 100 mcg.
• Excipients: sodium chloride - 9 mg, water for injections - up to 1 ml.

1 ml - ampoules (5) - contour packaging (2) - cardboard packs.

Description of the dosage form

Solution for intravenous and s / c administration, clear, colorless liquid, odorless.

pharmachologic effect

Synthetic analogue of somatostatin, which has similar pharmacological effects, but a much longer duration of action.

The drug suppresses the secretion of growth hormone, both pathologically increased and caused by arginine, exercise and insulin hypoglycemia. The drug also suppresses the secretion of insulin, glucagon, gastrin, serotonin, both pathologically increased and caused by food intake; also suppresses the secretion of insulin and glucagon, stimulated by arginine. Octreotide inhibits thyrotropin secretion caused by thyreoliberin.

In patients scheduled for pancreatic surgery, the use of octreotide before, during, and after surgery reduces the incidence of typical postoperative complications (eg, pancreatic fistulas, abscesses, sepsis, acute postoperative pancreatitis).

When bleeding from varicose veins of the esophagus and stomach in patients with cirrhosis of the liver, the use of octreotide in combination with specific treatment (for example, sclerosing and hemostatic therapy) leads to more effective control of bleeding and prevention of rebleeding.

Pharmacokinetics

Suction

After subcutaneous administration, Octreotide is rapidly and completely absorbed. C max octreotide in plasma is achieved within 30 minutes.

Distribution

Plasma protein binding is 65%. Binding of Octreotide with blood cells is extremely insignificant. Vd is 0.27 l/kg.

breeding

After s / c injection of the drug T1 / 2 octreotide is 100 minutes. After intravenous administration, the excretion of octreotide is carried out in 2 phases with a T1 / 2 of 10 minutes and 90 minutes, respectively. Most of octreotide is excreted through the intestines, about 32% is excreted unchanged by the kidneys. The total clearance is 160 ml / min.

Pharmacokinetics in special clinical situations

In elderly patients, clearance decreases, and T1 / 2 increases.

In severe renal failure, clearance is reduced by 2 times.

Pharmacodynamics

Octreotide is a synthetic analog of somatostatin with similar pharmacological effects, but a much longer duration of action. Octreotide suppresses the secretion of growth hormone (GH), both pathologically increased and caused by arginine, exercise and insulin hypoglycemia. The drug also suppresses the secretion of insulin, glucagon, gastrin, serotonin, both pathologically increased and caused by food intake; also suppresses the secretion of insulin and glucagon, stimulated by arginine. Octreotide inhibits thyrotropin secretion caused by thyreoliberin.

In patients undergoing pancreatic surgery, the use of octreotide before, during and after surgery reduces the incidence of typical postoperative complications (eg, pancreatic fistulas, abscesses, sepsis, acute postoperative pancreatitis). When bleeding from varicose veins of the esophagus and stomach in patients with liver cirrhosis, the use of octreotide in combination with specific treatment (for example, sclerosing and hemostatic therapy) leads to more effective control of bleeding and prevention of rebleeding.

Clinical pharmacology

analogue of somatostatin. The drug for intensive care in gastroenterology.

Indications for use

• Treatment of acute pancreatitis;
• stop bleeding in peptic ulcer of the stomach and duodenum;
• stop bleeding and prevention of rebleeding from esophageal varices in patients with cirrhosis of the liver;
• prevention and treatment of complications after operations on the abdominal organs.

Contraindications for use

• Children's age up to 18 years;
• hypersensitivity to octreotide or other components of the drug.

With caution: cholelithiasis (cholelithiasis), diabetes mellitus, pregnancy, lactation.

Use in pregnancy and children

The use of octreotide during pregnancy has not been studied. Octreotide should only be used during pregnancy if the potential benefit to the mother outweighs the potential risk to the fetus.

It is not known whether the drug passes into breast milk, therefore, when using the drug during lactation, breastfeeding should be abandoned.

Use in children

Contraindicated in children under the age of 18

Side effects

On the part of the gastrointestinal tract and pancreas: possible - anorexia, nausea, vomiting, abdominal cramps, a feeling of bloating, excessive gas formation, loose stools, diarrhea, steatorrhea. Although the excretion of fat in the feces may increase, there is no indication that long-term treatment with octreotide can lead to the development of malabsorption. In rare cases, there may be phenomena resembling acute intestinal obstruction. There are isolated cases of acute hepatitis without cholestasis, hyperbilirubinemia in combination with an increase in the activity of alkaline phosphatase, GGT and, to a lesser extent, other transaminases.

Prolonged use of Octreotide may lead to the formation of gallstones.

Since the cardiovascular system: in some cases - arrhythmia, bradycardia.

On the part of carbohydrate metabolism: a violation of glucose tolerance after a meal is possible (due to the suppression of insulin secretion by the drug), hypoglycemia; in rare cases, with prolonged treatment, persistent hyperglycemia may develop.

Local reactions: at the injection site, pain, itching or burning sensation, redness, swelling are possible (usually disappear within 15 minutes).

Other: allergic reactions, alopecia.

drug interaction

Octreotide reduces the absorption of cyclosporine, slows down the absorption of cimetidine.

It is necessary to correct the dosing regimen of simultaneously used diuretics, beta-blockers, blockers of "slow" calcium channels, insulin, oral hypoglycemic drugs.

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

Drugs metabolized by enzymes of the cytochrome P450 system and having a narrow therapeutic dose range should be administered with caution.

Dosage

For the treatment of acute pancreatitis, the drug is administered s / c at a dose of 100 mcg 3 times / day for 5 days. Perhaps the appointment of up to 1200 mcg / day using the / in the route of administration.

To stop ulcerative bleeding, it is administered intravenously at a dose of 25-50 mcg / h as an intravenous infusion for 5 days.

To stop bleeding from varicose veins of the esophagus, it is administered intravenously at a dose of 25-50 mcg / h in the form of continuous intravenous infusions for 5 days.

In elderly patients, there is no need to reduce the dose of Octreotide.

To prevent complications after operations on the pancreas, the first dose of 100-200 mcg is administered s / c 1-2 hours before laparotomy; then after the operation, s / c is injected at 100-200 mcg 3 times / day for 5-7 consecutive days.

Overdose

Symptoms: a short-term decrease in heart rate, a feeling of "rush" of blood to the face, spastic pain in the abdomen, diarrhea, nausea, a feeling of emptiness in the stomach.

Treatment: symptomatic.

Precautionary measures

In diabetic patients receiving insulin, octreotide may reduce the need for insulin.

If gallstones are identified prior to treatment, the use of octreotide is decided on an individual basis, depending on the relationship between the potential therapeutic effect of the drug and possible risk factors associated with the presence of gallstones.

Gastrointestinal side effects may be reduced if octreotide injections are given between meals or at bedtime.

To reduce the symptoms of discomfort at the injection site, it is recommended to bring the drug solution to room temperature before administration and inject a smaller volume of the drug. Multiple injections at the same site at short intervals should be avoided.

Influence on the ability to drive vehicles and control mechanisms

Some side effects of octreotide may adversely affect the ability to drive vehicles and other mechanisms that require increased concentration and speed of psychomotor reactions.