Octreotide solution 50 µg/ml 1ml ampoules, 10pcs

Composition

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1 ml of the solution contains:

Active ingredient:

Octreotide acetate (based on octreotide) 0.050 mg,0.100 mg and 0.300 mg

Auxiliary substances:

• Sodium Chloride 9.0 mg
• Water for injection up to 1.0 ml

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

• Acromegaly — to control the main manifestations of the disease and reduce the level of growth hormone and IGF-1 in plasma in cases where there is no sufficient effect from surgical treatment or radiation therapy. Octreotide indicated for the treatment of patients with acromegaly who refused surgery or contraindications to it, as well as for short-term treatment in the intervals between courses of radiation therapy until fully developing its effect;
• – secreting endocrine tumors of the gastrointestinal tract and the pancreas — to control symptoms: carcinoid tumors with the presence of carcinoid syndrome; Vipoma; glucagonoma; gastrinoma syndrome of zollingerellison — usually in combination with proton pump inhibitors and histamine H₂-receptors; the insulinoma (to control hypoglycemia in the preoperative period, as well as for maintenance therapy); somatoliberin (tumor, characterized by the overproduction releasing factor growth hormone).
• stopping bleeding and preventing recurrent 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.

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

Use during pregnancy and lactation

Pregnancy

There is a limited amount of data (less than 300 pregnancy outcomes) on the use of octreotide in pregnant women, and in about one-third of cases, pregnancy outcomes are unknown.

More than 50% of cases when a woman received octreotide during pregnancy were reported in patients with acromegaly. Most women received octreotide in the first trimester of pregnancy by subcutaneous use of octreotide at a dose of 100-1200 mcg / day or by intravenous use of an octreotide suspension at a dose of 10-40 mg / month. Congenital malformations were reported in approximately 4% of pregnancies with a known outcome.

In these cases, there is no causal relationship between these phenomena and octreotide. In animal studies, no toxic effect of octreotide on reproduction was detected, with the exception of temporary fetal growth retardation.

Use the drug Octreotide during pregnancy should only be absolute indications. Women with preserved reproductive potential should use reliable contraceptives.

Breast-feeding period

It is not known whether octreotide is excreted in human breast milk.

Animal studies have shown that octreotide penetrates the milk of lactating rats.

You should stop breastfeeding during therapy with Octreotide.

Contraindications

• Hypersensitivity to octreotide and / or any excipient in the preparation;
• age up to 18 years;
• breast-feeding period.

Caution

• cholelithiasis (gallstone disease);
• diabetes mellitus;
• pregnancy (see “Use during pregnancy and breastfeeding”);
• while the use of drugs with a narrow therapeutic index, the metabolism of which is carried out with the participation of isoenzyme CYP3A4 (e. g., quinidine, terfenadine);
• in patients with pituitary tumors secreting GR.

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 P450 enzymes (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, course of use and dosage

Octreotide is recommended to be administered subcutaneously or intravenously.

Injections of the drug are recommended between meals or before bedtime.

For acromegaly-subcutaneous injection, at an initial dose of 0.05-0.1 mg at intervals of 8 or 12 hours. Further dose adjustment should be carried out on monthly determinations of the concentration of GY in the blood (target concentration: GY In most patients, the optimal daily dose is 0.2-0.3 mg subcutaneously. Do not exceed the maximum dose of 1.5 mg/lpg.

In patients receiving a stable dose of octreotide, the concentration of GH and IGF-1 should be determined every 6 months. If after 1 month of treatment with octreotide, there is no sufficient decrease in the concentration of GH and/or IGF-1 and improvement in clinical symptoms of the disease, therapy should be discontinued.

For endocrine tumors of the gastrointestinal tract and pancreas – subcutaneous injection, at an initial dose of 0.05 mg 1-2 times a day.

In the future, depending on the achieved therapeutic effect, the effect on the concentration of hormones produced by the tumor (in the case of carcinoid tumors – the effect on the release of 5-hydroxy-indoleacetic acid by the kidneys) and the tolerability of the drug, the dose can be gradually increased to 0.2 mg subcutaneously 3 times / day. In exceptional cases, higher doses may be required.

The maintenance dose 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.

For refractory diarrhea in AIDS patients-subcutaneous injection, at an initial dose of 0.1 mg 3 times a day. If there is no clinical improvement after 1 week of therapy, the dose is increased individually (subject to normal tolerance) to 0.25 mg 3 times / day.

Dose adjustment is carried out taking into account the dynamics of stool and tolerability of the drug. If no improvement occurs during 1 week of octreotide therapy (at a dose of 0.25 mg 3 times/day), therapy should be discontinued.

To prevent complications after pancreatic surgery, the drug is administered subcutaneously at a dose of 0.1 mg 3 times a day for 7 days, starting from the day of surgery (the first dose of octreotide is administered no later than 1 hour before surgery).

For bleeding from varicose veins of the esophagus and stomach – by continuous intravenous infusion at a rate of 0.025 mg / h for 5 days.

Octreotide should be diluted in 0.9% sodium chloride solution.

Patients with cirrhosis of the liver with bleeding from esophageal varicose veins are well tolerated by continuous intravenous infusion at a dose of 0.05 mg / h for 5 days.

Use of octreotide in special clinical groups of patients

For children and adolescents under 18 years of age

Experience with octreotide in children and adolescents under 18 years of age is limited.

In elderly patients (≥ 65 years)

No dose adjustment of octreotide is required in elderly patients. In patients with impaired liver function

In patients with cirrhosis of the liver, the half-life of octreotide may be prolonged, and therefore it is recommended to adjust the maintenance dose in patients with impaired liver function.

In patients with impaired renal function

No dose adjustment of octreotide is required in patients with impaired hepatic function.

Recommendations for use

Subcutaneous use

Before self-use of subcutaneous injections of Octreotide, the doctor or nurse should teach the patient the correct manipulation technique. In order to reduce pain at the injection site, a solution of room temperature should be administered.

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 the solution is disposed of.

Intravenous use

If necessary, intravenous use of the drug Octreotide, the contents of 1 ampoule containing 0.5 mg of octreotide should be diluted in 60 ml of 0.9% sodium chloride solution, the resulting solution is administered using an infusomat. The infusion is repeated with the necessary frequency in accordance with the recommended duration of therapy. Possible intravenous use of the drug and in a lower concentration.

It is possible to dilute the drug in a 5% dextrose (glucose) solution in water. However, it is preferable to use 0.9% sodium chloride solution, since octreotide can affect glucose metabolism.

Before intravenous use, the ampoule should be carefully examined for damage, discoloration of the solution, the presence of foreign particles and kept at room temperature.

To avoid microbial contamination, the diluted solution should be used immediately after preparation. Unused solution residues should be destroyed.

Overdose

It is known that the introduction of octreotide in a dose of up to 2000 mcg as a subcutaneous injection 3 times for several months was well tolerated. The maximum single dose for intravenous bolus use to an adult patient was 1000 mcg.

At the same time, symptoms such as a decrease in heart rate, “flushes” of blood to the face, abdominal pain of a spastic nature, diarrhea, nausea, and a feeling of emptiness in the stomach were noted.

All of these symptoms resolved within 24 hours of drug use. One patient was mistakenly given an excessive dose of octreotide 250 mcg/h (instead of 25 mcg/h) by prolonged infusion, which was not accompanied by side effects. No life-threatening reactions were observed in acute overdose.

Treatment: symptomatic therapy.

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;

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Side effects of Octreotide solution for intravenous and subcutaneous use 50 µg/ml 1ml ampoules, 10pcs.[/col][/row]