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

Octreotide: instructions for use and reviews

Latin name: Octreotide

ATX code: H01CB02

Active substance: octreotide

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

Updating the description and photo: 02.09.2019

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

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, 1 or 2 packs in a cardboard pack; at a dose of 300 and 600 mcg/ml - 1, 2 or 5 ampoules in blister packs, in a cardboard pack 1 (1, 2 or 5 ampoules) or 2 (5 ampoules) packs; Each pack also contains instructions for using 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 components: sodium chloride and injection water.

Pharmacological properties

Pharmacodynamics

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

Octreotide helps suppress the secretion of the following substances:

• Growth hormone: pathologically increased or caused by exercise, arginine and insulin hypoglycemia;
• Insulin, glucagon, gastrin, serotonin: pathologically increased or caused by food intake;
• Insulin, glucagon: stimulated by arginine;
• Thyrotropin: called thyrotropin-releasing hormone.

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.

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

Pharmacokinetics

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

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

T1/2 (half-life) after subcutaneous administration is 100 minutes. The elimination of octreotide after intravenous use is carried out in two phases with T1/2 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 unchanged by the kidneys. Total clearance – 160 ml/min.

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

In patients with severe renal failure, 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 preventing relapses (in combination with endoscopic sclerotherapy 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 the blood plasma in cases where the effect of radiation or surgical treatment is not enough; for the treatment of a disease in cases where the patient refuses surgery or has contraindications to it; for short-term treatment in the intervals between courses of radiation therapy until the effect is obtained;
• Secreting endocrine tumors of the pancreas and gastrointestinal tract (for symptom control): glucagonomas, somatoliberinomas, VIPomas, carcinoid tumors with the presence of carcinoid syndrome, insulinomas (for maintenance therapy, as well as for the control of hypoglycemia in the preoperative period), gastrinomas and Zollinger syndrome - Ellison (usually in combination with histamine H2 receptor blockers and proton pump inhibitors);
• Treatment of acute pancreatitis;
• Treatment and prevention of complications after surgical interventions on the abdominal organs;
• Stopping bleeding in gastric and duodenal ulcers.

Contraindications

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

The drug should be used with caution when treating 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 expected benefits outweigh the possible risks.

It is unknown whether octreotide passes into breast milk, so it is recommended that you avoid breastfeeding during treatment.

Octreotide, instructions for use: method and dosage

Octreotide is intended for subcutaneous (SC) and intravenous (IV) administration.

Prescribed dosage regimens depending on the indications and purpose of use:

• Treatment of acute pancreatitis: 100 mcg subcutaneously 3 times a day for 5 days. In some cases, the doctor may recommend intravenous administration 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;
• Stopping ulcer bleeding: 25-50 mcg/hour as an intravenous infusion, course – 5 days;
• Stopping bleeding from varicose veins of the esophagus and stomach: 25-50 mcg/hour as a continuous IV infusion, course of treatment – ​​5 days;
• Acromegaly: initial dose – 50-100 mcg subcutaneously every 8 or 12 hours. In case of ineffectiveness (the target concentration of growth hormone is less than 2.5 ng/ml, and the IGF-1 value is within normal values), the single dose is increased to 300 mcg. The maximum permissible daily dose is 1500 mcg. In patients receiving octreotide at a stable dose, growth hormone levels should be determined every 6 months. If after 3 months of treatment there is no sufficient reduction in this indicator and improvement in the clinical course of the disease, Octreotide should be discontinued;
• Tumors of the gastroenteropancreatic endocrine system: initial dose - 50 mcg 1-2 times a day, if necessary, it is gradually increased to 100-200 mcg 3 times a day subcutaneously. In case of ineffectiveness (assessed based on data on the achieved clinical effect, the concentration of hormones that produce the tumor, and tolerability of the drug), the dose is increased to 300 mcg subcutaneously 1-2 times a day. In exceptional cases, it is possible to increase the dose even further - up to 300-600 mcg 3 times a day. The doctor selects maintenance doses for each patient individually. If, for carcinoid tumors, therapy at the maximum tolerated dose is ineffective within 1 week, Octreotide is discontinued.

Patients with impaired liver function require adjustment of the maintenance dose.

Rules for subcutaneous administration of Octreotide:

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

Rules for intravenous drip administration:

• Carefully inspect the ampoule for foreign impurities and color changes;
• 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 the injection solution immediately before administration;
• If necessary, store for no more than 24 hours after dilution in the refrigerator (at a temperature of 2 to 8 ºС).

Side effects

Criteria for assessing the frequency of side effects: very often - no more than 1 case out of 10, often - ≥1/100, but<1/10, иногда – ≥1/1000, но <1/100.

Adverse reactions identified during clinical trials of Octreotide:

• From the digestive system: very often - diarrhea or constipation, bloating, nausea, abdominal pain; often - steatorrhea, change in stool color, feeling of fullness or heaviness in the abdomen, soft stool consistency, dyspeptic disorders, anorexia, vomiting;
• From the hepatobiliary system: gallstones (cholelithiasis); often - increased activity of liver transaminases, cholecystitis, hyperbilirubinemia, formation of cholesterol microcrystals due to a violation of the colloidal stability of bile;
• From the cardiovascular system: often – bradycardia; sometimes - tachycardia;
• From the endocrine system: very often – hyperglycemia; often - hypoglycemia, impaired glucose tolerance, hypothyroidism, dysfunction of the thyroid gland (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 cause-and-effect 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-glutamyltransferase and alkaline phosphatase;
• From the immune system: hypersensitivity reactions, anaphylactic reactions;
• From the cardiovascular system: arrhythmias;
• Dermatological reactions: urticaria.

Overdose

Main symptoms: a feeling of flushing of blood to the face, a short-term decrease in heart rate, cramping abdominal pain, 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, because with a decrease in the level of growth hormone and normalization of the level of IGF-1 under the influence of octreotide, restoration of reproductive function is possible.

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

In patients with a history of vitamin B12 deficiency, it is necessary to monitor the level of cobalamin in the body.

Before prescribing Octreotide, patients should be referred for an ultrasound examination of the gallbladder. If stones are detected, the drug can be prescribed after a careful assessment of the expected benefits of therapy and possible risks. Repeat examinations should be performed every 6-12 months during treatment.

If stones are detected during treatment:

• Asymptomatic: you can discontinue 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 discontinue the drug or continue treatment after assessing the benefit/risk ratio. Patients require standard therapy for gallstone disease (including bile acid preparations) and regular ultrasound monitoring.

Patients with growth hormone-secreting pituitary tumors require close medical monitoring during treatment, as the drug may cause the tumor to increase in size and develop serious complications such as narrowing of visual fields. If this occurs, it is necessary to consider the use of other treatment methods.

Octreotide may interfere with the absorption of fats in the intestines.

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

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

When treating endocrine tumors of the gastrointestinal tract and pancreas, sudden relapse is possible in some cases. If insulinoma develops during use of octreotide, the duration and severity of hypoglycemia may increase. Such patients should be closely monitored, especially whenever the dose of the drug is changed.

Octreotide affects blood glucose concentrations. Fluctuations can be reduced by administering the drug more frequently 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 monitoring of blood glucose levels and antidiabetic therapy.

Patients also need to monitor 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 mellitus increases.

Impact on the ability to drive vehicles and complex mechanisms

Due to the risk of developing side effects from the central nervous system, it is recommended to exercise caution 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 expected benefits to possible risks;
• Lactation period: therapy is contraindicated.

Use in childhood

For impaired renal function

In patients with impaired renal function, there is no need to adjust the dose of Octreotide.

For liver dysfunction

In patients with impaired hepatic function, adjustment of the maintenance dose of Octreotide is recommended.

Use in old age

Elderly patients do not require dosage adjustment.

Drug interactions

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

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

Analogues

Analogs of Octreotide are: Octreotide Fsynthesis, Octride, Octretex, Sandostatin, Somatostatin, Diferelin, Sermorelin.

Terms and conditions of storage

Store out of 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 pharmacological effects similar to it, but a significantly longer duration of action; suppresses 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 strip pack; 5 ampoules (100 mcg) in a strip pack; in a cardboard box pack 1 or 2 packages);
• 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 breaking point, or in a colorless glass ampoule marked as two green stripes; in a blister pack 1 or 2 ampoules, in a cardboard box 1 package; in a blister pack 5 ampoules, in a cardboard box 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 injection, sodium chloride.

Indications for use

• Acute pancreatitis (at a dose of 50 and 100 mcg);
• Peptic ulcer of the stomach and duodenum, to stop bleeding (at a dose of 50 and 100 mcg);
• Acromegaly (to control the main manifestations of the lesion and decrease the level of growth hormone and insulin-like growth factor-1 (IGF-1); in case of insufficient effectiveness or impossibility of surgical treatment or radiation therapy; if the patient refuses surgery or for short-term treatment in the periods between courses of radiation therapy until its effect is fully developed);
• Secreting endocrine tumors of the pancreas and gastrointestinal tract, for the purpose of controlling 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), insulinomas (including for maintenance therapy and control of hypoglycemia before surgery), somatoliberins).

The solution is used for the treatment and prevention of 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 recurrent bleeding from varicose veins of the stomach and esophagus. The use of the drug is possible in combination with specific therapeutic measures (for example, endoscopic sclerotherapy).

Contraindications

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

The drug should be used with extreme caution in case of cholelithiasis (cholelithiasis) and diabetes mellitus. There is no experience of using the product during pregnancy. As a result, Octreotide is recommended for pregnant women to use only if the expected benefit of therapy outweighs the potential risk of adverse reactions.

If it is necessary to administer the drug during lactation, it is necessary to avoid breastfeeding (since it is unknown whether the drug passes into breast milk).

Directions for use and dosage

Octreotide is used subcutaneously and intravenously.

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

To stop bleeding from esophageal varices or peptic ulcers, long-term intravenous infusions are prescribed at a dose of 25-50 mcg/hour for 5 days.

In order to prevent complications after surgery on the pancreas, the drug is administered subcutaneously. The first injection in a dose of 100-200 mcg is carried out 1-2 hours before laparotomy, and subsequent injections in a dose of 100-200 mcg after surgery, 3 times a day every day for 5-7 days.

For acromegaly, it is recommended to administer 300 mcg of Octreotide subcutaneously at intervals of 8 or 12 hours; this dose is prescribed if there is no effect during initial therapy (50-100 mcg solution at intervals of 8 or 12 hours). The effectiveness of treatment is determined taking into account the monthly concentrations of growth hormone in the blood, tolerability of the drug 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. If initial therapy is ineffective, assessed by the concentration of hormones produced by the tumor, drug tolerability and the achieved clinical effect, subcutaneous injections at a dose of 300 mcg are prescribed 1-2 times a day. In exceptional cases, a gradual increase in dose to 300–600 mcg administered 3 times a day is permissible. If, when treating carcinoid tumors with Octreotide at the maximum tolerated dose, no therapeutic effect is observed within 7 days, treatment should be discontinued.

Elderly people, as well as patients with functional renal impairment, do not require dosage adjustment.

When prescribing an intravenous drip infusion of the drug, the contents of the ampoule in a dose of 600 mcg 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 completion of its administration).

Side effects

• Digestive system: very often - bloating, constipation, nausea, abdominal pain, diarrhea; often - anorexia, change in color/soft consistency of stool, steatorrhea, feeling of heaviness/fullness in 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 - formation of gallstones (cholelithiasis); often - increased activity of liver 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 cause-and-effect 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 (ALP), arrhythmia, allergic reactions, urticaria, anaphylactic reactions.

With subcutaneous injections of octreotide at a daily dose of 3000–30,000 mcg, divided into several injections, no new side effects (except those mentioned above) were identified in patients with tumors.

With random 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 liver, pancreatitis, cerebral hypoxia, sudden cardiac arrest, decreased blood pressure, development of arrhythmias. Treatment is symptomatic.

special instructions

In patients with diabetes mellitus taking insulin, a decrease in insulin requirements may be observed 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.

If gallstones are detected before starting therapy, the question of using the drug is decided individually, after balancing the potential benefits of therapy and the risk of developing possible complications associated with the presence of stones.

The occurrence of adverse reactions from the digestive system can be reduced by administering octreotide before bedtime or between meals.

With a long course, thyroid function should be monitored.

In rare cases, during therapy for endocrine tumors of the gastrointestinal tract and pancreas, a sudden relapse of symptoms of the disease may occur.

When using octreotide in patients with a history of vitamin B12 (cobalamin) deficiency, it is recommended to monitor its content in the body (the absorption of cobalamin 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. Injecting the drug at short intervals at the same injection site should be avoided.

Drug interactions

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) reduce their metabolism.

When combining octreotide with diuretics, oral hypoglycemic drugs, insulin, blockers of “slow” calcium channels, and beta-blockers, adjustment of the dosage regimen is required.

Terms and conditions of storage

Store in a place protected from moisture and light, out of 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
Conditions for dispensing from a pharmacy: On prescription

Octreotide is a drug characterized by somatostatin-like effects.

Indications for use

The use of Octreotide is intended 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 cirrhosis of the liver
• Acromegaly
• Prevention of possible complications in the abdominal organs after operations
• Prevention of gastric bleeding (especially from the cardiac region).

Compound

1 ml of the drug contains 100 mcg of the main active ingredient, which is octreotide. The excipients are:

• Sodium chloride
• Purified water.

Medicinal properties

The drug Octreotide is an artificial analogue of a substance such as somatostatin; it has the same pharmacological properties, but 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 inhibits the process of growth hormone production, including pathological and those provoked by insulin-dependent hypoglycemia, excessive physical activity or arginine. Along with this, the production of not only insulin and glucagon, but also gastrin and serotinin (disturbed due to pathological changes or provoked by food) is inhibited.

The use of Octreotide helps suppress the production of:

• Glucagon with insulin, which is caused by arginine
• Thyrotropin, provoked by high levels of thyroid hormone.

In persons who are preparing to undergo surgery 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 people with cirrhotic liver disease and varicose veins, it is recommended to carry out combined treatment with Octreotide and other drugs included in sclerosing, hemostatic therapy.

The medicine is absorbed quite quickly after it is introduced under the skin. Its highest concentration in the blood is observed within half an hour after the injection.

The connection with plasma proteins is 65%. The half-life of metabolic products after administration of the drug under the skin is about 100 minutes; when administered 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 160 ml/min.

In elderly patients, a decrease in total clearance is observed, while the half-life of metabolites increases slightly. It is worth noting that increased clearance is recorded in individuals suffering from severe renal failure.

Release form

Octreotide is presented as a transparent and almost colorless solution that has no pronounced aroma. One ampoule contains 1 ml of medicinal solution. There are 1 or 2 blisters inside the cardboard box. packages that hold 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.

The following doses of medication are usually prescribed:

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

Use during pregnancy and pregnancy

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

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

Contraindications

You should not start treatment with the drug if you are hypersensitive to the active substance.

Drugs are prescribed with extreme caution to persons with diabetes mellitus, as well as cholelithiasis.

Precautionary measures

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

A burning sensation, slight itching, hyperemia and swelling may be felt at the injection site.

To reduce discomfort during 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.

People with diabetes who take insulin will need to adjust their prescribed dosage. To normalize insulin levels 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 mellitus, during treatment with octreotide, the need for insulin may sharply decrease; in patients with type 2 diabetes, postprandial hyperglycemia may develop. That is why you will need to monitor your blood sugar levels and carry out the necessary antidiabetic treatment.

If gallstone disease is detected in a patient before starting therapy, the decision to administer octreotide is made individually (the likely benefits and expected risks are taken into account).

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

Cross-drug interactions

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

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

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

Drugs that undergo a metabolization process through 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

Reactions from the gastrointestinal tract may be observed: severe nausea leading to vomiting, the development of anorexia, cramping pain in the abdomen, increased gas formation in the intestines, steatorrhea, and loose stools. During treatment, the excretion of lipids in feces may increase, but the risk of developing malabsorption syndrome does not increase. Very rarely, manifestations that are characteristic of intestinal obstruction are observed. It is possible that hepatitis may develop without cholestasis or hyperbilirubinemia. With prolonged use, cholelithiasis may develop. In some cases, exacerbation of pancreatitis is recorded (during the first hours after stopping taking the drug).

The cardiovascular system may also respond to treatment with octreotide - bradycardia or arrhythmia occurs.

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

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

Other side effects: allergies, alopecia.

Overdose

A short-term decrease in heart rate may occur, spastic pain, flushing of the facial skin, diarrhea, and changes in stool are recorded. Symptomatic therapy is recommended. After relief of acute symptoms, you should consult a doctor for advice.

Storage conditions and shelf life

The shelf life of 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 rub.

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

Pros:

• Reduces the secretion of gastrin and insulin
• Available in two dosage forms
• Maintains normoglycemia.

Minuses:

• May cause the development of hyperbilirubinemia
• Available with prescription
• The development of liver pathologies and the occurrence of diarrhea cannot be ruled out.

Ipsen Pharma, France

Price from 2441 to 21010 rub.

Diferelin is a hormonal drug whose active ingredient is triptorelin. Prescribed for female infertility, early puberty, endometriosis, oncopathologies of the reproductive system, and reduced potency. Diferelin is produced in the form of a lyophilisate for the preparation of a solution or suspension.

Pros:

• Highly effective in the treatment of female infertility
• Easy to use
• Can be used with other drugs.

Minuses:

• Expensive
• Available only by prescription
• Contraindicated during pregnancy, breastfeeding.

Somatostatin analogue. Drug for intensive therapy in gastroenterology

Active substance

Octreotide (as acetate)

Release form, composition and packaging

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

Solution for intravenous and subcutaneous administration transparent, colorless, odorless.

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

1 ml - ampoules (1) - contour cell packaging (1) - cardboard packs.
1 ml - ampoules (2) - contour cell packaging (1) - cardboard packs.
1 ml - ampoules (5) - contour cell packaging (1) - cardboard packs.
1 ml - ampoules (5) - contour cell packaging (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 a significantly longer duration of action. Octreotide suppresses growth hormone (GH) secretion, both pathologically elevated and induced 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 suppresses the secretion of thyrotropin caused by thyrotropin-releasing hormone.

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 GH concentration by 50% or more is observed in 90% of patients, while a GH concentration of at least 5 ng/ml is achieved in approximately 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 lead to some reduction in tumor size.

For secreting tumors of the gastroenteropancreatic endocrine system, in cases of insufficient effectiveness of the therapy (surgery, embolization of the hepatic artery, chemotherapy, including streptozotocin, etc.), the administration of octreotide can lead to an improvement in the course of the disease. Thus, in carcinoid tumors, the use of octreotide can lead to a decrease in the severity of the sensation of flushing and diarrhea, which in many cases is accompanied by a decrease in the concentration of serotonin in plasma and the excretion of 5-hydroxyindoleacetic acid by the kidneys. For tumors characterized by overproduction of vasoactive intestinal peptide (VIP), the use of octreotide in most patients leads to a reduction in severe secretory diarrhea, and, accordingly, to an improvement in the patient’s quality of life. 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, tumor progression slows down or stops, its size decreases, as does the size of liver metastases. Clinical improvement is usually accompanied by a decrease in the plasma concentration of vasoactive intestinal peptide (VIP) or its normalization. For 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 concentrations under the influence of octreotide is transient, clinical improvement remains stable throughout the period of drug use. In patients with gastrinomas/Zollinger-Ellison syndrome, when using octreotide as monotherapy 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 can be short-term - about 2 hours). In patients with operable tumors, octreotide can ensure the 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 (somatoliberinomas), 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, pituitary hypertrophy may decrease.

For bleeding from varices of the esophagus and stomach in patients with liver cirrhosis, the use of octreotide in combination with specific treatment (for example, sclerosing therapy) leads to more effective control of bleeding and early rebleeding, a reduction 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. Cmax of octreotide in plasma is achieved within 30 minutes.

Distribution

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

Removal

T1/2 after subcutaneous administration of octreotide is 100 minutes. After IV administration, octreotide is eliminated in 2 phases, with T1/2 - 10 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.

Indications

Acromegaly: to control the main manifestations of the disease and reduce the level of GH and IGF-1 in plasma in cases where there is no sufficient effect from surgical treatment or radiation therapy. Octreotide is also indicated for the treatment of patients with acromegaly who refuse surgery or have contraindications to it, as well as for short-term treatment in the intervals 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;

— VIPs;

- glucagonomas;

- gastrinomas/Zollinger-Ellison syndrome - usually in combination with proton pump inhibitors and histamine H2 receptor blockers;

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

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

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

Stopping bleeding and preventing recurrent bleeding from varicose veins of the esophagus and stomach in patients with liver cirrhosis. Octreotide is used in combination with specific therapeutic measures, for example, endoscopic sclerotherapy.

Contraindications

- hypersensitivity to octreotide or other components of the drug;

- children under 18 years of age.

Carefully: cholelithiasis (cholelithiasis); diabetes

Dosage

Subcutaneously, intravenously.

For acromegaly– subcutaneously, at a dose of 300 mcg at intervals of 8 or 12 hours. This dose is used in case of ineffectiveness of initial therapy (drug Octreotide, solution for intravenous and subcutaneous injection, 50-100 mcg at intervals of 8 or 12 hours). Failure of initial therapy is assessed based on monthly determinations of GH concentrations in the blood (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, GH concentrations should be measured every 6 months. If after three months of treatment with octreotide there is no sufficient reduction in GH concentrations and improvement in the clinical picture of the disease, therapy should be discontinued.

For tumors of the gastroenteropancreatic endocrine system: subcutaneously, at a dose of 300 mcg 1-2 times a day. This dose is used in case of ineffectiveness of initial therapy (Octreotide, solution for intravenous and subcutaneous administration, 50 mcg 1-2 times a day with a gradual increase to 100-200 mcg 3 times a day). Failure of initial therapy is assessed based on the clinical response achieved, the effect on the concentration of hormones produced by the tumor (in the case of carcinoid tumors, the effect on the renal excretion of 5-hydroxyindoleacetic acid) and tolerability. In exceptional cases, the patient may be prescribed 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. For carcinoid tumors, if therapy with octreotide at the maximum tolerated dose for 1 week has not been effective, treatment should not be continued.

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

Use in certain groups of patients

There is currently no data to suggest that elderly people the tolerability of octreotide is reduced and a change in dosage regimen is required.

U patients with impaired renal function No adjustment of the octreotide dosage regimen is required.

Experience with octreotide in children limited.

Rules for using the drug

Subcutaneous administration

Patients who self-administer subcutaneous octreotide should receive detailed instructions from a doctor or nurse.

Before administration, the solution should be warmed to room temperature - this helps reduce discomfort at the injection site. The drug should not be administered to the same place at short intervals. Ampoules should be opened immediately before administering the drug; any unused amount of solution is discarded.

Intravenous drip

If intravenous drip administration of octreotide is necessary, the contents of one ampoule containing 600 mcg of 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 affect glucose metabolism, it is preferable to use 0.9% sodium chloride solution. Before intravenous administration, the ampoule should be carefully inspected 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 a temperature of 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 solution administration should not exceed 24 hours.

Side effects

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

In clinical studies, the most common symptoms observed with the drug were diarrhea, abdominal pain, nausea, bloating, headache, gallstones, hyperglycemia and constipation. Dizziness, pain of various localizations, impaired colloidal stability of bile (formation of cholesterol microcrystals), dysfunction of the thyroid gland (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, phenomena resembling acute intestinal obstruction may be observed: progressive bloating, severe pain in the epigastric region, abdominal wall tension, muscle protection.

Although the excretion of fat in the feces may be increased, there is no evidence to date that long-term treatment with octreotide can lead to the development of nutritional deficiencies due to malabsorption (malabsorption).

Very rare cases of acute pancreatitis have been reported that developed in the first hours or days of subcutaneous use of octreotide and disappeared after discontinuation of the drug. In addition, with long-term use of octreotide subcutaneously, cases of pancreatitis associated with cholelithiasis have been reported.

According to an ECG study during the use of the drug in patients with acromegaly and carcinoid syndrome: prolongation of the QT interval, deviation of the electrical axis of the heart, early repolarization, low-voltage ECG type, displacement of the transition zone, early P wave and nonspecific changes in the ST segment and T wave were observed. This category of patients has heart disease; a cause-and-effect 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 in the abdomen, steatorrhea, soft stool consistency, change in stool color, 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. formation of gallstones; often - cholecystitis, impaired colloidal stability of bile (formation of cholesterol microcrystals), hyperbilirubinemia, increased activity of liver 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 therapy with octreotide, the following adverse events were observed in clinical practice, regardless of the presence of a cause-and-effect 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-glutamyltransferase.

From the cardiovascular system: arrhythmias.

Overdose

Isolated cases of octreotide overdose in children and adults have been reported 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 subcutaneously (1500 mcg 3 times/day), the following were observed: the development of arrhythmias, decreased blood pressure, sudden cardiac arrest, cerebral hypoxia, pancreatitis, fatty liver degeneration, diarrhea, weakness, lethargy, weight loss body, hepatomegaly and lactic acidosis.

With the occasional use of octreotide in children at a dose of 50-3000 mcg/day, administered intravenously (infusion rate 2.1-500 mcg/hour) or subcutaneously (50-100 mcg), only moderate hyperglycemia was observed.

With subcutaneous administration of octreotide at a dose of 3000-30000 mcg/day (divided into several injections) in patients with tumors, no new adverse events (except for those listed in the “Side Effects” section) were identified.

Drug interactions

Pharmacokinetic interaction

Reduces the absorption of cyclosporine, slows down the absorption of cimetidine. It is necessary to adjust the dosage regimen of simultaneously used diuretics, beta-blockers, slow calcium channel blockers, oral hypoglycemic drugs, and 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 suppression of GR). Since similar effects of octreotide cannot be excluded, caution should be exercised when prescribing drugs that are metabolized by the cytochrome P450 system and have a narrow range of therapeutic concentrations (for example, quinidine, terfenadine).

special instructions

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

Since a decrease in the level of growth hormone and normalization of the level of insulin-like factor-1 during therapy with octreotide 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.

If bradycardia develops during the use of octreotide, if necessary, it is possible to reduce the dose of beta-blockers or drugs that affect water and electrolyte balance.

In some patients, octreotide may alter the absorption of fats in the intestine.

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

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

Before prescribing octreotide, patients should undergo an initial ultrasound examination of the gallbladder.

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

If gallstones are detected before treatment begins, the potential benefits of octreotide therapy must be weighed against the possible risks associated with their presence. There is no data on any negative effect of octreotide on the course or prognosis of existing gallstone disease.

Asymptomatic gallbladder stones. The use of octreotide can be stopped 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 monitoring, making it more frequent if necessary.

Gallstones with clinical symptoms. The use of octreotide can be stopped 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 cholelithiasis with clinical manifestations. Drug treatment includes the use of combinations of bile acid preparations (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 control until the stones completely disappear.

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

In patients with insulinomas, during treatment with octreotide, an increase in the severity and duration of hypoglycemia may be observed (this is due to a more pronounced suppressive effect on the secretion of GH and glucagon than on insulin secretion, as well as a shorter duration of the inhibitory effect on insulin secretion). Careful regular monitoring of these patients should be ensured both at the beginning of treatment with Octreotide and whenever the dose of the drug is changed. Significant fluctuations in blood glucose concentrations can be reduced by administering octreotide more frequently and in smaller 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, administration of octreotide may lead to postprandial hyperglycemia. When using octreotide in patients with diabetes mellitus, monitoring of blood glucose concentrations and antidiabetic therapy is recommended.

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

It is necessary to adjust the dosage regimen of simultaneously used diuretics, beta-blockers, slow calcium channel blockers, insulin, oral hypoglycemic agents, and glucagon.

Impact on the ability to drive vehicles and operate machinery

Some side effects of octreotide may negatively 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, caution is exercised when driving vehicles or machinery that require increased concentration.

No adjustment of the octreotide dosage regimen is required. The drug should be stored in a dry place, protected from light, out of reach of children at a temperature of 8 to 25°C.

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

Composition and release form

Solution - 1 ml:

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

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

Description of the dosage form

Solution for intravenous and subcutaneous administration, clear, colorless liquid, odorless.

pharmachologic effect

A synthetic analogue of somatostatin, which has similar pharmacological effects, but a significantly longer duration of action.

The drug suppresses the secretion of growth hormone, both pathologically increased and caused by arginine, physical 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 arginine-stimulated insulin and glucagon secretion. Octreotide suppresses the secretion of thyrotropin caused by thyrotropin-releasing hormone.

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 stoppage of bleeding and prevention of rebleeding.

Pharmacokinetics

Suction

After subcutaneous administration, Octreotide is quickly and completely absorbed. Cmax of octreotide in blood plasma is achieved within 30 minutes.

Distribution

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

Removal

After subcutaneous injection of the drug, T1/2 of octreotide is 100 minutes. After intravenous administration, octreotide is eliminated in 2 phases with 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 analogue of somatostatin, which has similar pharmacological effects, but a significantly longer duration of action. Octreotide suppresses growth hormone (GH) secretion, both pathologically elevated and induced 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 arginine-stimulated insulin and glucagon secretion. Octreotide suppresses the secretion of thyrotropin caused by thyrotropin-releasing hormone.

In patients planning to undergo pancreatic surgery, the use of octreotide before, during and after surgery reduces the incidence of typical postoperative complications (for example, 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 stoppage of bleeding and prevention of rebleeding.

Clinical pharmacology

Somatostatin analogue. A drug for intensive therapy in gastroenterology.

Indications for use

• Treatment of acute pancreatitis;
• stopping bleeding from gastric and duodenal ulcers;
• stopping bleeding and preventing re-bleeding from esophageal varices in patients with cirrhosis of the liver;
• prevention and treatment of complications after abdominal surgery.

Contraindications for use

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

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

Use during pregnancy and children

The use of octreotide during pregnancy has not been studied. Octreotide should be used during pregnancy only if the expected 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 avoided.

Use in children

Contraindicated in children under 18 years of age

Side effects

From the gastrointestinal tract and pancreas: possible - anorexia, nausea, vomiting, cramping abdominal pain, feeling of bloating, excessive gas formation, loose stools, diarrhea, steatorrhea. Although the excretion of fat in the feces may be increased, there is no indication that long-term treatment with octreotide may lead to the development of malabsorption problems (malabsorption). In rare cases, phenomena resembling acute intestinal obstruction may occur. 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.

Long-term use of Octreotide may lead to the formation of gallstones.

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

From the side of carbohydrate metabolism: possible impairment of glucose tolerance after meals (due to suppression of insulin secretion by the drug), hypoglycemia; in rare cases, with long-term treatment, persistent hyperglycemia may develop.

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

Other: allergic reactions, alopecia.

Drug interactions

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

It is necessary to adjust the dosage regimen of simultaneously used diuretics, beta-blockers, blockers of “slow” calcium channels, insulin, and oral hypoglycemic drugs.

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

Drugs that are metabolized by enzymes of the cytochrome P450 system and have a narrow therapeutic dose range should be prescribed with caution.

Dosage

For the treatment of acute pancreatitis, the drug is administered subcutaneously at a dose of 100 mcg 3 times a day for 5 days. It is possible to prescribe up to 1200 mcg/day using the intravenous route of administration.

To stop ulcer bleeding, it is administered intravenously at a dose of 25-50 mcg/hour 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/hour 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 pancreatic surgery, the first dose of 100-200 mcg is administered subcutaneously 1-2 hours before laparotomy; then after surgery, 100-200 mcg is administered subcutaneously 3 times a day for 5-7 consecutive days.

Overdose

Symptoms: short-term decrease in heart rate, a feeling of a “rush” of blood to the face, cramping abdominal pain, diarrhea, nausea, a feeling of emptiness in the stomach.

Treatment: symptomatic.

Precautionary measures

In diabetic patients receiving insulin, octreotide may reduce insulin requirements.

If gallstones are identified before starting treatment, the use of octreotide is decided individually, 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 discomfort at the injection site, it is recommended to bring the drug solution to room temperature before administration and administer a smaller volume of the drug. Multiple injections into the same site at short intervals should be avoided.

Impact on the ability to drive vehicles and operate machinery

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