Composition, form of production and packaging
Solution for infusion and s / c of administration is transparent, colorless, odorless.
1 ml
octreotide (in the form of acetate) 0.1 mg
Excipients: mannitol - 45 mg, lactic acid - 3.4 mg, sodium hydrogen carbonate - up to pH 3.9-4.5, water d / u - up to 1 ml.
1 ml - ampoules of dark glass (5) - packings of cellular contour (1) - packs cardboard.
1 ml - ampoules of dark glass (5) - packings of cellular contour (2) - packs cardboard.
1 ml - ampoules of colorless glass (5) - packings of cellular contour (1) - packs cardboard.
1 ml - ampoules of colorless glass (5) - packings of cellular contour (2) - packs cardboard.
1 ml - glass syringes (1) - packings of cellular contour (5) - packs cardboard.
1 ml - glass syringes (2) - packings, cellular planimetric (5) - packs cardboard.
1 ml - glass syringes (1) with device for protection of needles - packages, cellular outline (5) - packs of cardboard.
1 ml - glass syringes (2) with device for protection of needles - packages, cellular contour (5) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Synthetic analogue of somatostatin. Octreotide is a derivative of the natural hormone somatostatin and has similar pharmacological effects, but a much longer duration of action. Octreotide inhibits the secretion of growth hormone, 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 inhibits the secretion of growth hormone more than insulin secretion, and its administration is not accompanied by subsequent hypersecretion of hormones (eg, 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. Reducing the concentration of growth hormone by 50% or more is observed in 90% of patients, while the value of the concentration of growth hormone less than 5 ng / ml is achieved in about half of the patients. In most patients with acromegaly, octreotide reduces the severity of headache, soft tissue swelling, hyperhidrosis, joint pain and paresthesia. In patients with large adenomas of the pituitary gland, treatment with octreotide can lead to some reduction in tumor size.
When secreting tumors of the gastroenteropancreatic endocrine system in cases of insufficient effectiveness of the therapy (surgical intervention, 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. Thus, with carcinoid tumors, the use of octreotide can lead to a decrease in the intensity of the sensation of blood flushes to the face, diarrhea, which in many cases is accompanied by a decrease in serotonin concentration in plasma and excretion of 5-hydroxyindoleacetic acid by the kidneys. In tumors characterized by hyperproduction of the vasoactive intestinal peptide (WIPOMA), the use of octreotide in most patients leads to a reduction in severe secretory diarrhea and, accordingly, to an improvement in the quality of life of the patient. At the same time, there is a decrease in 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 H2-histamine receptor blockers, hypersecretion of hydrochloric acid in the stomach, a decrease in the concentration of gastrin in the blood plasma, and a decrease in the severity of diarrhea and tides.In patients with insulinomas, octreotide reduces the level of immunoreactive insulin in the blood (this effect may be short-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, glycemic control can be improved without a simultaneous prolonged decrease in insulin concentration in the blood.
In patients with rare tumors, hyper-growth hormone releasing factor (somatoliberinomas), octreotide reduces the severity of the symptoms of acromegaly. This is due to the suppression of the secretion of the releasing factor of growth hormone and the growth hormone itself. In the future, the pituitary gland hypertrophy may decrease. With refractory diarrhea in patients with Acquired Immunodeficiency Syndrome (AIDS), the use of octreotide leads to complete or partial stool normalization in approximately 1/3 of patients with diarrhea not controlled by adequate antimicrobial and / or antidiarrhoea therapy.
In patients who are scheduled to undergo pancreatic 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-dilated esophagus and stomach veins in patients with cirrhosis of the liver, the use of octreotide in combination with specific treatment (eg, sclerosing therapy) leads to more effective stopping of bleeding and early rebleeding, a decrease in transfusion volume, 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 by suppressing such vasoactive hormones as VIP and glucagon.
PHARMACOKINETICS
Suction
After sc administration octreotide is quickly and completely absorbed. C max octreotide in blood plasma is achieved within 30 min.
Distribution
Binding to plasma proteins is 65%. The binding of octreotide to the formed elements of the blood is extremely insignificant. V d is 0.27 l / kg.
Excretion
T 1/2 after SC administration of octreotide is 100 minutes. After intravenous administration octreotide removal is carried out in 2 phases, with T 1/2 10 and 90 min, 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.
Pharmacokinetics in special clinical cases
In elderly patients, clearance of octreotide decreases, and T 1/2 increases.
In chronic renal failure of severe severity, the clearance decreases by a factor of 2.
INDICATIONS
- Acromegaly (in the absence of a sufficient effect from surgical treatment, radiotherapy (in between the radiotherapy courses until the full effect of its effect), treatment with dopamine receptor agonists, inoperable patients, as well as patients who refused surgical treatment);
- relief of symptoms of secretive tumors of the gastroentero-pancreatic endocrine system (carcinoid tumors with carcinoid syndrome, Vipoma, glucagonoma, gastrinoma / Zollinger-Ellison syndrome), insulinoma, somatoliberinoma;
- 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).
DOSING MODE
P / to, in / in a drip.
In acromegaly , sc, at the initial dose of 0.05-0.1 mg at intervals of 8 or 12 hours. Further dose selection is based on monthly determinations of the concentration of growth hormone in the blood (target concentration: growth hormone <2.5 ng / ml, IGF-1 in 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, the determination of the concentration of growth hormone should be performed every 6 months. If, after 3 months of treatment with octreotide, there is no sufficient reduction in the concentration of growth hormone and an improvement in the clinical picture of the disease, therapy should be discontinued.
With tumors of the gastroenteropancreatic endocrine system - SC, in the initial dose of 0.05 mg 1-2 times / day. Further, depending on the clinical effect achieved, the effect on the concentration of hormones produced by the tumor (in the case of carcinoid tumors - the effect on the 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 patients with AIDS - SC, 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 (with the condition of 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 / day) there is no improvement, therapy should be discontinued.
To prevent complications after operations on the pancreas - sc, the first dose of 0.1 mg is administered 1 h before laparotomy, after surgery - 0.1 mg 3 times / day for 7 consecutive days.
In case of bleeding from the varicose-dilated veins of the esophagus and stomach - intravenous drip at a rate of 0.025 mg / h for 5 days.
There is currently no evidence to suggest that the tolerability of octreotide is lower in elderly patients 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
F / c introduction
Patients who are self-administered with octreotide are required to receive detailed instructions from a doctor or nurse.
Before the introduction, the solution should be warmed 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; The unused amount of the solution should be discarded.
IV injection
If necessary in / in the 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 В° C for 24 hours retains physical and chemical stability in a sterile 0.9% solution of sodium chloride or 5% dextrose in water. However, since octreotide can affect glucose metabolism, it is preferable to use 0.9% sodium chloride solution. Before / in the introduction of the ampoule should be carefully examined for changes in the color of the solution and the presence of foreign particles.
To avoid microbial contamination, 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 В° 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 EFFECT
The frequency of side effects noted with the use of 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%), (> 0.1% and <1%), rarely - 1/10 000 appointments (> 0.01% and <0.1%), very rarely - 1/10 000 prescriptions (<0.01%), including individual messages .
From the digestive system: very often - diarrhea, abdominal pain, 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 hepatic transaminases (after the abolition of octreotide, the activity of hepatic transaminases in the blood serum is normalized), APF, GGT. 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.
From the nervous system: very often - headache; often - dizziness.
From the endocrine system: very often - hyperglycemia; often - hypothyroidism / 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 the injection (usually for 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.
CONTRAINDICATIONS
- children and adolescence under 18;
- Hypersensitivity to octreotide or other components of the drug.
With caution should apply the drug for cholelithiasis, diabetes, pregnancy and lactation.
PREGNANCY AND LACTATION
The use of the drug during pregnancy and during lactation is possible only on absolute indications.
The experience with octreotide in pregnant women is limited. Octretex В® 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 is excreted in breast milk, so if it is necessary to use the drug during lactation, breastfeeding should be abandoned.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function, correction of the octreotide dosage regimen is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
It is recommended to correct the maintenance dose in patients with impaired liver function .
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years of age (experience with octreotide in children is limited).
APPLICATION IN ELDERLY PATIENTS
There is currently no evidence to suggest that the tolerability of octreotide is lower in elderly patients and that a change in the dosing regimen is required.
SPECIAL INSTRUCTIONS
For tumors of the pituitary gland, careful monitoring of patients receiving octreotide is necessary, because it is possible to increase the size of tumors with the development of narrowing of the fields of vision. In these cases, the advisability of using other treatments should be considered.
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 and the administration of octreotide or by injecting before bed.
In patients with insulinomas, the treatment may show an increase in the severity and duration of hypoglycemia.
Fluctuations in blood glucose concentration can be reduced by more frequent administration of the drug in 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, octreotide may reduce the need for insulin. In patients without diabetes and type 2 diabetes with partly intact insulin secretion administering octreotide may result in postprandial hyperglycemia.
Because after bleeding from varicose veins of the esophagus and the stomach increased risk of developing type 1 diabetes and in patients with diabetes also may be changes in insulin requirements, in these cases, the regular control of blood glucose concentration.
Recommendations for the management of patients during treatment with Oktreteks В® against cholelithiasis
Prior to the appointment of octreotide patients should conduct a preliminary ultrasound examination of the gallbladder. During treatment with Oktreteks В®It should be repeated ultrasound gallbladder, preferably at intervals of 6-12 months. If gallstones are found before the start of the treatment, it is necessary to evaluate the potential benefits of therapy with octreotide compared with the potential risks associated with their presence. Information about any negative effect of octreotide on the course or prognosis existing cholelithiasis not.
Management of patients with cholelithiasis arising during treatment with Oktreteks В®
In asymptomatic cholelithiasis use of octreotide can terminate or continue - in accordance with the evaluation benefit / risk ratio. In any case, there is no need to do anything except to continue monitoring, making it more frequently if necessary.
When symptomatic cholelithiasis with use of octreotide can stop or continue - in line with the assessment of benefit / risk ratio. In any case, the patient should be treated in the same way as in other cases of gallstone disease with clinical manifestations. Drug treatment includes the use of combinations of bile acids preparations (e.g., chenodeoxycholic acid at a dose of 7.5 mg / kg / day in combination with ursodeoxycholic acid at the same dose) under ultrasound guidance - until complete disappearance of stones.
Impact on the ability to drive vehicles and manage mechanisms
Some side effects of octreotide may adversely affect the ability to drive vehicles and other machines that require high concentration and speed of psychomotor reactions, and therefore it is recommended to be careful with the appearance of these symptoms.
OVERDOSE
Symptoms: a transient reduction in heart rate, flushing, abdominal cramps, diarrhea, nausea, a feeling of emptiness in the stomach.
Treatment: symptomatic therapy.
DRUG INTERACTION
Reduces the absorption of cyclosporine, slows the absorption of cimetidine.
Requires correction dosing regimen simultaneously used diuretics, beta-blockers, calcium channel blockers slow, oral hypoglycemic drugs, glucagon.
Combined application of octreotide and bromocriptine increases the bioavailability of bromocriptine.
Decreases substances metabolism extending involving cytochrome P450 enzymes (may be due to the suppression of growth hormone). Since such effects can not be excluded octreotide, caution should be exercised when administering the drug metabolized by cytochrome P450 system and having a narrow range of therapeutic concentrations (e.g., quinidine, terfenadine).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of the reach of children, protected from light at a temperature of from 2 В° to 8 В° C. Do not freeze. Shelf life - 2 years.
