Octretex - instructions for use, dose, side effects, contraindications

Octreotide is a synthetic analogue of somatostatin. It is a derivative of the natural hormone somatostatin and has similar pharmacological effects, but a much longer duration of action.

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

In contrast to somatostatin, octreotide suppresses the secretion of GH more than insulin secretion, and its administration is not accompanied by subsequent hypersecretion of hormones (eg, GH in patients with acromegaly). In patients with acromegaly octreotide reduces the concentration of GH and insulin-like growth factor (IGF-1) in blood plasma.Reducing the concentration of GH by 50% or more is observed in 90% of patients, with a GH concentration of less than 5 ng / ml achieved in about half of the patients. In most patients with acromegaly octreotide reduces the severity of headache, soft tissue swelling, hyperhidrosis, joint pain and paresthesia. In patients with large adenomas of the pituitary gland, treatment with octreotide can lead to some reduction in tumor size.

When secreting tumors of the gastroentero-pancreatic endocrine system in cases of insufficient effectiveness of the therapy (surgical intervention, embolization of the hepatic artery, chemotherapy, including streptozotocin and fluorouracil), the administration of octreotide may lead to an improvement in the course of the disease. Thus, with carcinoid tumors, the use of octreotide can lead to a decrease in the intensity of the sensation of "tides" of blood to the face, diarrhea, which in many cases is accompanied by a decrease in serotonin concentration in the plasma and excretion of 5-hydroxyindoleacetic acid by the kidneys. In tumors characterized by hyperproduction of the vasoactive intestinal peptide (VIPoma),the use of octreotide leads in most patients to reduce severe secretory diarrhea and, accordingly, to improve the quality of life of the patient. At the same time, there is a decrease in associated electrolyte imbalance, for example, hypokalemia, which allows to cancel enteral and parenteral administration of fluid and electrolytes. Some patients slow or stop the progression of the tumor, there is a decrease in its size, as well as the size of metastases in the liver. Clinical improvement is usually accompanied by a decrease in the concentration of vasoactive intestinal peptide (VIP) in the plasma or its normalization. With glucagonomes, the use of octreotide leads to a decrease in migrating erythema. 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 glucagon concentration in blood plasma under the influence of octreotide is transient, the clinical improvement remains stable throughout the period of application of the drug.In patients with gastrinomas / Zollinger-Ellison syndrome with octreotide in the form of monotherapy or in combination with proton pump inhibitors or H blockers₂-gistaminovyh receptors may reduce hypersecretion of hydrochloric acid in the stomach, a decrease in the concentration of gastrin in the blood plasma, as well as a decrease in 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-term - about 2 hours). In patients with operable tumors octreotide can provide recovery and maintenance of normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, the control of glycemia can be improved without a simultaneous prolonged decrease in the concentration of insulin in the blood.

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

With refractory diarrhea in patients with acquired immunodeficiency syndrome (AIDS), the use of octreotide results in complete or partial normalization of the stool in about 1/3 of patients with diarrhea not controlled by adequate antimicrobial and / or anti-diarrhea drugs.

In patients with pancreas surgery, the use of octreotide during and after surgery reduces the incidence of typical postoperative complications (eg pancreatic fistula, abscesses, sepsis, postoperative acute pancreatitis).

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

Pharmacokinetics:

Suction

After subcutaneous administration octreotide quickly and completely absorbed. The maximum concentration of octreotide in the blood plasma is reached within 30 minutes.

Distribution

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

Excretion

The half-life after subcutaneous administration of octreotide is 100 minutes. After intravenous administration octreotide excretion is carried out in 2 phases, with half-lives of 10 and 90 minutes, respectively. Most of the octreotide is excreted through the intestine, about 32% - in unchanged form by the kidneys. The total clearance is 160 ml / min.

In elderly patients, clearance of octreotide decreases, and the half-life increases. In severe chronic renal failure (CRF), the clearance decreases by a factor of 2.

Indications:

- Acromegaly (in the absence of sufficient effect from surgical treatment, radiotherapy (in between the radiotherapy courses until the full effect of its effect)), treatment with dopamine receptor agonists; in inoperable patients, as well as in patients who refused surgical treatment;

- relief of symptoms of secretive tumors of the gastroenteropancreatic endocrine system (carcinoid tumors with carcinoid syndrome, Vipoma, glucagonoma, gastrinoma / Zollinger-Ellison syndrome), insulinoma, somatoliberalinoma;

- refractory diarrhea in AIDS patients;

- prevention of complications after operations on the pancreas;

- stop bleeding and prevent the recurrence of bleeding from varicose veins of the esophagus and stomach with cirrhosis of the liver (in combination with endoscopic sclerosing therapy).

Contraindications:

- Hypersensitivity to octreotide or other components of the drug;

- children's age till 18 years.

Carefully:

- Chololithiasis (cholelithiasis);

- diabetes;

- pregnancy and lactation period (see section "Application during pregnancy and during breast-feeding").

Pregnancy and lactation:

The experience with octreotide in pregnant women is limited. Octretex® should be used during pregnancy only if the intended benefit to the mother exceeds the potential risk to the fetus.

It is not known whether the drug enters the breast milk,so when using the drug during lactation, breastfeeding should be abandoned.

Dosing and Administration:

Subcutaneously, intravenously drip.

With acromegaly - subcutaneously, in an initial dose of 0.05-0.1 mg at intervals of 8 or 12 hours. Subsequently, the dose selection is based on monthly determinations of the concentration of GH in the blood (target concentration: GH <2.5 ng / ml, IGF-1 within the limits of normal values), analysis of clinical symptoms and drug tolerability. In most patients, the optimal daily dose is 0.2-0.3 mg. Do not exceed the maximum dose of 1.5 mg / day.

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

With tumors of the gastroenteropancreatic endocrine system - subcutaneously, in the initial dose of 0.05 mg 1-2 times / day. In the future, depending on the clinical effect achieved, the effect on the concentration of hormones produced by the tumor (in the case of carcinoid tumors - the effects on the release of 5-hydroxyindoleacetic acid by the kidneys) and tolerability,the dose of the drug can be gradually increased to 0.1-0.2 mg 3 times / day. In exceptional cases, higher doses may be required.

Supportive doses of the drug should be selected individually. In carcinoid tumors, if treatment with octreotide at the maximum tolerated dose for 1 week is not effective, treatment should not continue.

With refractory diarrhea in AIDS patients - subcutaneously, in the initial dose of 0.1 mg 3 times / day. If after 1 week of treatment the diarrhea does not subside, the dose is increased individually (subject to normal tolerability) to 0.25 mg 3 times / day. If during the week of treatment with octreotide (at a dose of 0.25 mg 3 times a day) there is no improvement, therapy should be discontinued.

To prevent complications after operations on the pancreas - subcutaneously, the first dose of 0.1 mg for 1 hour before laparotomy, after surgery - 0.1 mg 3 times / day for 7 consecutive days.

When bleeding from varicose veins of the esophagus and stomach - drip intravenously at a rate of 0.025 mg / h for 5 days.

Use in selected patient groups

At present, there is no evidence to suggest that the tolerability of octreotide has been reduced in elderly people and that a change in the dosing regimen is required.

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

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

The experience with octreotide in children is limited.

Terms of use

Subcutaneous administration

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

Before the introduction of warm the solution to room temperature - this helps to reduce the unpleasant sensations at the injection site. Do not administer the drug in the same place with short periods of time. Ampoules should be opened immediately before the administration of the drug; an unused amount of solution is discarded.

Intravenous drip introduction

If you need intravenous drip octreotide, the contents of one ampoule containing 0.1 mg of the active substance should be diluted in 60 ml of 0.9% sodium chloride solution. Octreotide at a temperature 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.Nevertheless, since octreotide can influence glucose metabolism, preferably use 0.9% solution of sodium chloride.

Before intravenous administration, the ampoule should be carefully examined for changes in the color of the solution and the presence of foreign particles.

To avoid microbial contamination diluted solutions should be used immediately after preparation. If the solution is not used immediately, it should be stored at a temperature of 2-8 ° C. Before the introduction, heat the solution to room temperature.

The total time between dilution, storage in the refrigerator and the end of the administration of the solution should not exceed 24 hours.

Side effects:

The frequency of side effects noted with octreotide is given in accordance with the classification of the World Health Organization (WHO): very often -1/10 appointments (> 10%), often - 1/100 appointments (> 1% and <10%), infrequently -1/1 000 appointments (> 0.1% and <1%), rarely 1/10 000 prescriptions (> 0.01% and <0.1%), very rarely 1/10 000 prescriptions (< 0.01%), including individual reports.

From the gastrointestinal tract: very often - diarrhea, pain in the abdomen, nausea, constipation, bloating, cholelithiasis; often - dyspepsia, vomiting, a feeling of heaviness in the abdomen, a mild consistency of the stool, a discoloration of the stool, anorexia,cholecystitis, violation of colloidal bile stability (formation of microcrystals of cholesterol), hyperbilirubinemia, increased activity of hepatic transaminases, steatorrhea (without malabsorption phenomena). Although the release of fat with feces may increase, to date, there is no evidence that prolonged treatment with octreotide can lead to malnutrition due to malabsorption.

Rarely are symptoms reminiscent of acute intestinal obstruction: progressive bloating, severe pain in the epigastric region, abdominal wall tension, decreased glucose tolerance (due to suppression of insulin secretion), persistent hyperglycemia, hypoglycemia, acute pancreatitis (during the first hours or days of drug treatment) .

From the liver and bile ducts: in some cases - acute hepatitis without cholestasis, hyperbilirubinemia, increased activity of "liver" transaminases (after the abolition of octreotide, the activity of hepatic transaminases in the blood serum is normalized), alkaline phosphatase, gamma-glutamyltransferase. With prolonged use, it is possible to form stones in the gallbladder, the development of reactive pancreatitis.

The frequency of side effects from the gastrointestinal tract can be reduced by increasing the time intervals between meals and the administration of octreotide (see section "Special instructions").

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

From the endocrine system: very often hyperglycemia; often - hypothyroidism of thyroid dysfunction (decrease in TSH concentration, total and free T4); hypoglycemia, impaired glucose tolerance.

From the side of the cardiovascular system: in some cases - bradycardia.

Local Reactions: very often - pain, itching or burning sensation, redness and swelling at the site of subcutaneous injection (usually within 15 minutes). The severity of local reactions can be reduced by using a room temperature solution, or by introducing a smaller volume of a more concentrated solution. Other: rarely - cutaneous allergic reactions, in some cases - anaphylactic reactions, transient alopecia.

Overdose:

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

Treatment: symptomatic.

Interaction:

Pharmacokinetic

Reduces the absorption of cyclosporine, slows the absorption of cimetidine.

It is necessary to correct the dosage regimen of concomitantly used diuretics, beta-blockers, blockers of "slow" calcium channels, oral hypoglycemic drugs, glucagon.

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

Reduces the metabolism of substances metabolized with the participation of enzymes of the cytochrome P450 system (may be due to the suppression of GH). Since such effects of octreotide can not be ruled out, caution should be exercised in prescribing drugs metabolized by the cytochrome P450 system and having a narrow range of therapeutic concentrations (for example, quinidine, terfenadine).

Special instructions:

For pituitary tumors, careful monitoring of patients receiving octreotide, since it is possible to increase the size of tumors with the development of narrowing of the fields of vision. In these cases, consideration should be given to the need for other treatments.

In the treatment of gastroenteropancreatic endocrine tumors, a sudden relapse of symptoms may occur in rare cases.

The incidence of side effects from the gastrointestinal tract can be reduced by increasing the time intervals between meals or at bedtime.

In patients with insulinomas against the background of treatment, there may be an increase in the severity and duration of hypoglycemia.

Fluctuations in blood glucose concentration can be reduced by more frequent administration of smaller doses.

During the period of treatment, a systematic control of the concentration of glucose in the blood, especially in patients with bleeding from varicose-esophageal veins in the case of cirrhosis, is necessary.

In patients with type 1 diabetes mellitus octreotide can reduce the need for insulin.

In patients without diabetes mellitus and type 2 diabetes mellitus with partially preserved insulin secretion, the administration of octreotide may lead to postprandial hyperglycemia.

Since after the bleeding from the varicose veins of the esophagus and stomach, the risk of developing type 1 diabetes is increased, and in patients with diabetes it is also possible changes in the need for insulin, in these cases, a systematic control of the concentration of glucose in the blood.

Application during pregnancy and lactation only on absolute indications (see.section "With caution", "Application during pregnancy and during breast-feeding").

Recommendations for management of patients during treatment with Octremex® in relation to the formation of gallstones

1. Before the appointment of octreotide, patients should undergo a preliminary ultrasound examination of the gallbladder.

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

3. If gallbladder stones are found even 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 is no data on any negative effect of octreotide on the course or prognosis of an already existing cholelithiasis.

Management of patients in whom gallstones are formed during the treatment with Octretex®

a) Asymptomatic stones of the gallbladder.

The use of octreotide can be discontinued or continued - according to the benefit / risk ratio estimate. In any case, there is no need to do anything other than to continue monitoring, if necessary, making it more frequent.

b) Stones of the gallbladder with clinical symptoms.

The use of octreotide can be discontinued or continued - according to the benefit / risk ratio estimate. 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 in the same dose) under ultrasound control - until the stones disappear completely.

Effect on the ability to drive transp. cf. and fur:

Some of the side effects of octreotide can adversely affect the ability to drive vehicles and other mechanisms that require increased concentration and speed of the speed of psychomotor reactions. In this regard, it is recommended that when these symptoms occur, use caution when operating vehicles or mechanisms that require increased concentration.

Form release / dosage:

Solution for infusion and subcutaneous administration, 0.1 mg / ml.

Packaging:

1 ml per ampoule of light-protective or colorless glass with a color fracture ring or with a colored dot and a notch.

One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding are additionally applied to the ampoules.

By 5 ampoules in a contour cell box made of a polyvinylchloride film and aluminum foil or a polymer film, or without a foil and film.

1 or 2 contour mesh packages together with instructions for use in a pack of cardboard.

For 1 ml in sterile syringe syringes graduated with or without graduation with a needle, protective cap, with an additional automatic or non-automatic device to protect the needle after using the syringe or without it.

1 or 2 syringes in a contoured cell pack of a polyvinylchloride or polyethylene terephthalate film and a polymer or polypropylene or polyethylene film or a polymer-wrapped packaging paper or paper for packaging medical products or aluminum foil.

5 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of 2 to 8 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001885

Date of registration:24.10.2012 / 21.01.2016

Expiration Date:24.10.2017

The owner of the registration certificate:FarmSirma Soteks, ZAO FarmSirma Soteks, ZAO Russia

Manufacturer: & nbsp

FarmSirma Soteks, ZAO Russia

ELLARA, LTD. Russia

Representation: & nbspPharm Company Sotex CJSC Pharm Company Sotex CJSC Russia

Information update date: & nbsp02.06.2017

Illustrated instructions

Instructions

Octretex® (Octretex® )