Octreotide, 0.005% ampoules, 1ml, 5pcs

Composition

Active ingredient:  

octreotide acetate;

Excipients

sodium chloride;

water for injection

Pharmacological action

Octreotide is a synthetic analog of somatostatin, which is a derivative of the natural hormone somatostatin and has similar pharmacological effects, but significantly longer duration of action. Octreotide suppresses growth hormone secretion, both pathologically elevated and caused by arginine, exercise, and insulin hypoglycemia. The drug also suppresses the secretion of insulin, glucagon, gastrin, serotonin, both pathologically elevated and caused by food intake; it also suppresses the secretion of insulin and glucagon stimulated by arginine. Octreotide suppresses the secretion of thyrotropin caused by thyroliberin. Unlike somatostatin, octreotide suppresses growth hormone secretion to a greater extent than insulin secretion, and its use is not accompanied by subsequent hypersecretion of hormones (for example, growth hormone in patients with acromegaly).

In patients with acromegaly, octreotide reduces the concentration of growth hormone and insulin-like growth factor (IGF-1) in the blood plasma. A decrease in the concentration of growth hormone by 50% or more is noted in 90% of patients, while the value of the growth hormone concentration of at least 5 ng / ml is achieved in about half of 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, octreotide treatment may lead to some reduction in the size of the tumor.

For secreting tumors of the gastroenteropancreatic endocrine system, in cases of insufficient effectiveness of the therapy performed (surgery, embolization of the hepatic artery, chemotherapy, including streptozotocin and fluorouracil), 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 hot flashes to the face, diarrhea, which in many cases is accompanied by a decrease in the concentration of serotonin in plasma and excretion of 5-hydroxyindoleacetic acid by the kidneys.

In tumors characterized by hyperproduction of vasoactive intestinal peptide (VIPoma), the use of octreotide leads in most patients to a reduction in severe secretory diarrhea and, accordingly, to an improvement in the patient’s quality of life. At the same time, concomitant electrolyte balance disorders, such as hypokalemia, are reduced, which makes it possible to cancel enteral and parenteral use of fluids and electrolytes.

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 the concentration of glucagon in blood plasma under the influence of octreotide is transient, the clinical improvement remains stable throughout the entire period of use of the drug. In patients with gastrinomas/Zollinger-Ellison syndrome, the use of octreotide as monotherapy or in combination with proton pump inhibitors or_H2-histamine receptor blockers may reduce hypersecretion of hydrochloric acid in the stomach, reduce the concentration of gastrin in blood plasma, and reduce the severity of diarrhea and hot flashes. In patients with insulinomas, octreotide reduces the level of immunoreactive insulin in the blood (this effect can be short-lived — about 2 hours).

In patients with operable tumors, octreotide can restore and maintain normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, glycemic control may improve even without a simultaneous long-term decrease in blood insulin levels.

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

When bleeding from esophageal and gastric varicose veins in patients with cirrhosis of the liver, the use of octreotide in combination with specific treatment (for example, sclerosing therapy) leads to more effective stopping of bleeding and early re-bleeding, reducing the volume of transfusions and improving 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 use, octreotide is rapidly and completely absorbed. T_max octreotide in plasma — within 30 minutes.

Distribution

The binding to plasma proteins is 65%. The binding of octreotide to the formed blood elements is extremely insignificant. Vd is 0.27 l/kg.

Elimination

of T 1/2 after subcutaneous use of octreotide is 100 minutes. After intravenous use, octreotide is eliminated 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

• prevention and treatment of complications after operations on the pancreas and in the gastroduodenal zone;
• stopping bleeding and preventing repeated bleeding from esophageal varicose veins in patients with cirrhosis of the liver (as part of complex therapy);
• treatment of acute pancreatitis;
• stopping bleeding in peptic ulcer of the stomach and duodenum.

Contraindications

Hypersensitivity to octreotide or other components of the drug; children under 18 years of age.

With caution:  cholelithiasis( cholelithiasis); diabetes mellitus.

Side effects

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

Nervous system disorders:  very often — headache; often-dizziness.

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

From the side of the hepatobiliary system:  very often – cholelithiasis, i. e. the formation of gallstones; often-cholecystitis, violation of the colloidal stability of bile (formation of cholesterol microcrystals), hyperbilirubinemia, increased activity of hepatic transaminases.

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

Respiratory system disorders:  often-shortness of breath.

From the CCC side:  often — bradycardia; infrequently-tachycardia.

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

Against the background of octreotide therapy, the following adverse events were observed in clinical practice, regardless of the causal relationship with the use of the drug.

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

Dermatological reactions:  urticaria.

From the side of the hepatobiliary system:  acute pancreatitis, acute hepatitis without cholestasis, cholestatic hepatitis, cholestasis, jaundice, cholestatic jaundice, elevated alkaline phosphatase, GGT.

From the CCC side:  arrhythmias.

Interaction

Reduces the absorption of cyclosporine, slows down the absorption of cimetidine. It is necessary to adjust the dosage regimen of concomitantly used diuretics, beta-blockers, BCC, oral hypoglycemic drugs, and glucagon.

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

Reduces the metabolism of substances that are metabolized with the participation of cytochrome P enzymes%^%450 (may be due to the suppression of growth hormone).

Since such 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).

How to take it, course of use and dosage

Subcutaneous, intravenous drip.

With acromegaly-subcutaneous injection, at a dose of 300 mcg at intervals of 8 or 12 hours. This dose is used if the initial therapy is ineffective (Octreotide, solution for intravenous and subcutaneous use,50-100 mcg at intervals of 8 or 12 hours). The ineffectiveness of initial therapy is assessed based on monthly determinations of the blood growth hormone concentration (target concentration: growth hormone

In patients receiving a stable dose of octreotide, the concentration of growth hormone should be determined every 6 months.If after 3 months of treatment with octreotide there is not a sufficient decrease in the concentration of growth hormone and an improvement in the clinical picture of the disease, therapy should be discontinued.

For tumors of the gastroenteropancreatic endocrine system-subcutaneous injection, at a dose of 300 mcg 1-2 times a day. This dose is used if the initial therapy is ineffective (Octreotide, solution for intravenous and subcutaneous use,50 mcg 1-2 times a day with a gradual increase to 100-200 mcg 3 times a day). The ineffectiveness of initial therapy is assessed based on the achieved clinical effect, 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 a dose exceeding 600 mcg/day to the patient, the dose of the drug can be gradually increased to 300-600 mcg 3 times a day. Maintenance doses of the drug should be selected individually. In carcinoid tumors, if octreotide therapy at the maximum tolerated dose for 1 week was not effective, treatment should not be continued.

When bleeding from varicose veins of the esophagus and stomach — iv drip, at a rate of 25 mcg / h for 5 days.

Special patient groups

Currently, there are no data that would indicate that the elderly have reduced octreotide tolerance and require a change in the dosage regimen.

It is recommended to adjust the maintenance dose in patients with impaired liver function.

In patients with impaired renal function, correction of the dosage regimen of octreotide is not required.

Experience with octreotide in children is limited.

Rules for using the drug

N / a introduction. Patients who self-administer octreotide subcutaneously should receive detailed instructions from a doctor or nurse. Before use, the solution should be heated to room temperature — this helps to reduce unpleasant sensations at the injection site. Do not administer the drug in the same place for short periods of time. Ampoules should be opened immediately before use of the drug; the unused amount of solution should be discarded.

Intravenous drip use. If intravenous drip use of octreotide is necessary, the contents of one ampoule containing 600 micrograms of the Active ingredient 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 can affect glucose metabolism, it is preferable to use 0.9% sodium chloride solution. Before intravenous use, the ampoule should be carefully examined for discoloration of the solution and the presence of foreign particles.

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

Special instructions

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

Since a decrease in growth hormone levels and normalization of IGF-1 levels during octreotide therapy can lead to restoration of the ability to procreate 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 the function of the thyroid gland.

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

In some patients, octreotide may alter intestinal fat absorption.

Against the background of octreotide use, there was a decrease in the content of cobalamin (vitamin_B12) 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 monitor the content of cobalamin in the body.

Recommendations for the management of patients during treatment with Octreotide in relation to the formation of gallstones:

– prior to the appointment of octreotide, patients should undergo an initial ultrasound of the gallbladder;

– during treatment with Octreotide, repeated ultrasound of the gallbladder should be performed, preferably at intervals of 6-12 months;

– if gallstones are detected before the start of treatment, it is necessary to evaluate the potential benefits of octreotide therapy compared to the possible risk associated with their presence. There are no data on any negative effect of octreotide on the course or prognosis of pre-existing cholelithiasis.

Management of patients who develop gallbladder stones during treatment with Octreotide:

– asymptomatic gallstones. The use of octreotide can be discontinued or continued, depending on the benefit / risk ratio assessment. In any case, there is no need to do anything other than continue monitoring, if necessary making it more frequent;

– gallbladder stones with clinical symptoms. The use of octreotide can be discontinued or continued, depending on the benefit / risk ratio assessment. 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, henodeoxycholic acid at a dose of 7.5 mg / kg / day in combination with ursodeoxycholic acid at the same dose) under ultrasound control — until the stones completely disappear.

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. Patients with insulinomas treated with octreotide may experience an increase in the severity and duration of hypoglycemia (this is due to a more pronounced suppressive effect on the secretion of growth hormone and glucagon than on insulin secretion, as well as a shorter duration of inhibitory effects on insulin secretion). These patients should be carefully monitored regularly both at the beginning of treatment with Octreotide and at each dose change.

Significant fluctuations in blood glucose concentrations can be tried to reduce by more frequent use of octreotide in smaller doses. In patients with type 1 diabetes, octreotide may reduce the need for insulin. In patients without diabetes and with type 2 diabetes with partially preserved insulin secretion, octreotide use 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 bleeding from varicose veins of the esophagus and stomach increases the risk of developing type 1 diabetes, and in patients with diabetes, changes in the need for insulin are also possible, in these cases, systematic monitoring of blood glucose concentration is necessary.

It is necessary to adjust the dosage regimen of concomitantly used diuretics, beta-blockers, BCC, insulin, oral hypoglycemic agents, and glucagon.

Influence on the ability to drive vehicles and work with mechanisms. Some side effects of octreotide may negatively affect the ability to drive vehicles and other mechanisms that require increased concentration, accuracy, and speed of psychomotor reactions. In this regard, it is recommended that when appropriate symptoms appear, caution should be exercised when driving vehicles or mechanisms that require increased concentration of attention.

Form of production

Solution for intravenous and subcutaneous use

Storage conditions

In a dark place, at a temperature of 8 to 25 °C

Shelf life

5 years

Active ingredient

Octreotide

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

Adult Doctor’s prescription