Composition, form of production and packaging
The solution for the / in and / or the introduction of a transparent, colorless.
1 ml
octreotide (in the form of free peptide) 50 Ојg
- "100 Ојg
- "500 Ојg
[PRING] lactic acid, mannitol, sodium hydrogen carbonate, carbon dioxide, water d / and.
1 ml - ampoules (5) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Sandostatin is a synthetic octapeptide, which is a derivative of the natural somatostatin hormone and possesses similar pharmacological effects, but a much longer duration of action. Sandostatin inhibits 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. Sandostatin suppresses the secretion of thyrotropin, caused by thyroidiberin.
Unlike somatostatin, octreotide suppresses GH secretion 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, Sandostatin 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 the majority of patients with acromegaly, Sandostatin reduces the severity of headache, soft tissue swelling, hyperhidrosis, joint pain and paresthesia. In patients with large adenomas of the pituitary gland, treatment with Sandostatin can lead to some reduction in tumor size.
With the secreting endocrine tumors of the gastrointestinal tract and pancreas in cases of insufficient effectiveness of the therapy (surgical intervention, embolism of the hepatic artery, chemotherapy, including streptozotocin and 5-fluorouracil), the appointment of Sandostatin can improve the course of the disease. Thus, in carcinoid tumors, the use of Sandostatin helps to reduce the intensity of flushing of the face, diarrhea, which in many cases is accompanied by a decrease in the serotonin concentration in the plasma and the excretion of 5-hydroxyindoleacetic acid in the urine. In tumors characterized by hyperproduction of the vasoactive intestinal peptide (VIPoma), the use of Sandostatin 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 Sandostatin leads to a decrease in migrating erythema. Sandostatin does not have a 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 a decrease in the concentration of glucagon in the blood plasma under the influence of Sandostatin is transient, the clinical improvement remains stable throughout the period of application of the drug.
In patients with gastrinomas / Zollinger-Ellison syndrome, when Sandostatin is used alone or in combination with proton pump inhibitors or histamine H2 receptor blockers, hypersecretion of hydrochloric acid in the stomach, a reduction in the concentration of gastrin in the blood plasma, and a decrease in the severity of diarrhea and tides.
In patients with insulinomas Sandostatin reduces the level of immunoreactive insulin in the blood (this effect can be short-term - about 2 hours). In patients with operable tumors, Sandostatin can restore and maintain normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, glycemic control may improve without a simultaneous prolonged decrease in insulin levels in the blood.
In patients with rare tumors, hyper-releasing hormone releasing factor (somatoliberinomas), Sandostatin 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 AIDS, the use of Sandostatin leads to a complete or partial normalization of the stool in about 1/3 of patients suffering from diarrhea not controlled by adequate antimicrobial and / or antidiarrhoeal therapy.
In patients with pancreas surgery, the use of Sandostatin 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 liver cirrhosis, the use of Sandostatin in combination with specific treatment (eg, sclerosing therapy) leads to more effective stopping of bleeding and early rebleeding, a reduction in transfusion volume, and an improvement in 5-day survival. It is believed that the mechanism of action of Sandostatin is associated with a decrease in organ blood flow by suppressing such vasoactive hormones as VIP and glucagon.
PHARMACOKINETICS
Suction
After the administration s / s Sandostatin is quickly and completely absorbed. C max octreotide in plasma is achieved within 30 min.
Distribution
Binding to plasma proteins is 65%. The binding of Sandostatin to the shaped elements of blood is extremely insignificant. V d is 0.27 l / kg.
Excretion
T 1/2 after injection of the drug is 100 minutes. After IV introduction, excretion of the drug is carried out in 2 phases, with T 1/2 10 and 90 minutes, respectively. Most of the drug is excreted with feces, about 32% - unchanged in urine. The total clearance is 160 ml / min.
INDICATIONS
Acromegaly:
- to control the main manifestations of the disease and reduce the levels of GH and IGF-1 in plasma in those cases when there is insufficient effect from surgical treatment or radiation therapy;
- treatment of patients with acromegaly who refused surgery or who have contraindications to it, as well as for short-term treatment between the courses of radiotherapy,
While its effect does not fully develop.
Secreting endocrine tumors of the gastrointestinal tract and pancreas - to control the symptoms:
- carcinoid tumors with carcinoid syndrome;
- VIPoms;
- Glucagon;
- gastrinomas / Zollinger-Ellison syndrome - usually in combination with proton pump inhibitors and histamine H2-blockers;
- insulinoma (for the control of hypoglycemia in the preoperative period, as well as for maintenance therapy);
- somatoliberynomas (tumors characterized by hyperproduction of growth hormone releasing factor).
Sandostatin is not an antitumor drug and its use can not lead to the cure of this category of patients.
Control of symptoms of refractory diarrhea in AIDS patients.
Preventive maintenance of complications after operations on a pancreas.
Stopping bleeding and preventing recurrence of bleeding from varicose veins of the esophagus and stomach in patients with cirrhosis of the liver. Sandostatin is used in combination with specific therapeutic measures, for example,
endoscopic sclerotherapy.
DOSING MODE
In acromegaly, initially the drug is administered at 50-100 Ојg p / c at intervals of 8 or 12 hours. Further dose adjustment should be based on monthly determinations of the concentration of GH and IGF-1 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 300 Ојg. Do not exceed the maximum dose of 1.5 mg / day. In patients receiving stable dosage of Sandostatin, the determination of the GH concentration should be performed every 6 months. If, after 3 months of treatment with Sandostatin, there is no sufficient reduction in the level of growth hormone and an improvement in the clinical picture of the disease, therapy should be discontinued.
With endocrine tumors of the gastrointestinal tract and pancreas, the drug is administered SC in the initial dose of 50 Ојg 1-2 times / day. In the future, depending on the clinical effect achieved, the effect on the levels of hormones produced by the tumor (in the case of carcinoid tumors - the effect on the release of 5-hydroxyindoleacetic acid in the urine) and tolerability, the dose of the drug can be gradually increased to 100-200 Ојg 3 times / day. In exceptional cases, higher doses may be required. Supportive doses of the drug should be selected individually.
In case of carcinoid tumors , if therapy with Sandostatin is not effective at the maximum tolerated dose for 1 week, treatment should not be continued.
With refractory diarrhea in patients with AIDS, the drug is given SC in the initial dose of 100 Ојg 3 times / day. If after 1 week of treatment the diarrhea does not subside, the dose of the drug should be increased individually, up to 250 mcg 3 times / day. Correction of the dose is carried out taking into account the dynamics of stool and the tolerance of the drug. If during the week of treatment with Sandostatin 250 Ојg dose 3 times / day no improvement occurs, therapy should be discontinued.
For the prevention of complications after operations on the pancreas, enter SC 100 Ојg 3 times / day for 7 consecutive days, starting from the day of surgery (at least 1 hour before laparotomy).
When bleeding from the varicose veins of the esophagus and stomach, administer the drug at a dose of 25 mcg / h by continuous intravenous infusion for 5 days.Sandostatin can be diluted with an isotonic solution of sodium chloride. In patients with cirrhosis with bleeding from varicose veins of the esophagus , Sandostatin was well tolerated, applied for 5 days to 50 mcg / h as a continuous intravenous infusion.
At present, there is no evidence to suggest that the tolerance of Sandostatin has been reduced in elderly patients and that a change in the dosage regimen is required for them.
The experience with Sandostatin in children is very limited.
In patients with impaired liver function, a maintenance dose adjustment is recommended, since there are data on an increase in T 1/2 octreotide in patients with cirrhosis of the liver.
In patients with impaired renal function, correction of the dosage regimen of Sandostatin is not required.
Terms of use
The drug in its original packaging, intended for use in the near future, can be stored at a temperature of no higher than 30 В° C for not more than 2 weeks.
F / c introduction
Patients who self-administer subcutaneous administration of Sandostatin should receive detailed instructions from a doctor or nurse.
Before administration, the solution should have room temperature, which 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.
IV introduction
Before use, the solution for intravenous administration should be carefully examined for changes in the color of the solution and the presence of foreign particles.Sandostatin (octreotide acetate) for 24 hours retains physical and chemical stability in a sterile physiological solution or 5% glucose solution in water. However, since Sandostatin can affect glucose metabolism, it is preferable to use physiological saline. The prepared solution retains its physical and chemical stability at a temperature below 25 В° C for at least 24 hours. 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 В° to 8 В° C until its use. Before use, the solution should be held at 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.
If necessary, in / in the administration of Sandostatin, the contents of one ampoule containing 500 Ојg of active substance should be diluted in 60 ml of saline and the solution prepared should be injected / dripped. Infusions are repeated at the required frequency in accordance with the recommended duration of treatment. Sandostatin can also be administered at lower concentrations.
SIDE EFFECT
The main undesirable phenomena observed with the application of Sandostatin were reactions at the injection site of the drug and the reaction from the gastrointestinal tract.
Most often with the application of Sandostatin, diarrhea, abdominal pain, flatulence, pain or irritation at the injection site were observed.
Transient abnormalities from the gastrointestinal tract were noted in 10% of patients and usually passed while continuing therapy with the drug.
Determination of the frequency of development of adverse reactions: very often (? 1/10), often (? 1/100,? 1/10), sometimes (? 1/1000,? 1/100), rarely (? 1/10 000,? 1/1000), very rarely (? 1/10 000), including individual messages.
From the digestive system: often - diarrhea, spastic abdominal pain, constipation, flatulence; sometimes - cholecystitis; rarely - steatorrhea, nausea, vomiting, bloating, the formation of stones in the gallbladder; very rarely - acute pancreatitis, anorexia, loose stools, acute hepatitis without the phenomena of cholestasis, hyperbilirubinemia, increased levels of alkaline phosphatase, GGT, and hepatic transaminase activity.
Dermatological reactions: sometimes - temporary hair loss.
From the cardiovascular system: sometimes - bradycardia, tachycardia.
Allergic reactions : rarely - hypersensitivity, rash; very rarely anaphylaxis.
On the part of the endocrine system: very rarely - hypoglycemia, hyperglycemia.
From the respiratory system: very rarely - shortness of breath.
Local reactions: pain, itching or burning sensation, redness and swelling at the site of the injection (usually within 15 minutes). The severity of local reactions can be reduced by using a room temperature solution, or by introducing a smaller one; volume of a more concentrated solution.
Other
Although the release of fat with feces may increase, there is no evidence to date that prolonged treatment with octreotide can lead to malnutrition due to malabsorption.
The incidence of side effects from the gastrointestinal tract can be reduced by increasing the time intervals between meals and the introduction of Sandostatin.
It was reported that very rare cases of acute pancreatitis, which developed in the first hours or days of the application of Sandostatin and disappeared after the drug was discontinued. In addition, with prolonged use of Sandostatin n / k cases of pancreatitis associated with cholelithiasis have been reported.
When Sandostatin was used, thyroid dysfunctions (both decrease and increase of activity) and dyspeptic symptoms were rarely noted.
There have been reports of arrhythmia in patients treated with octreotide acetate.
According to the ECG-study data, prolongation of the RT interval, deviation of the electric axis of the heart, early repolarization, low-voltage ECG type, displacement of the transition zone, early tooth P and nonspecific changes in the ST segment and the T wave were observed on the background of the application of the drug. Since many patients with acromegaly and carcinoid tumors have cardiac diseases, a causal relationship between the use of Sandostatin and the development of these undesirable phenomena has not been established.
CONTRAINDICATIONS
- Hypersensitivity to the components of the drug.
With caution should apply the drug for cholelithiasis, diabetes.
PREGNANCY AND LACTATION
The experience with Sandostatin in pregnant women and nursing mothers is limited, so this category of patients is prescribed only if the intended benefit to the mother exceeds the potential risk to the fetus or infant.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function, correction of the dosage regimen of Sandostatin is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired liver function, a maintenance dose adjustment is recommended, since there are data on an increase in T 1/2 octreotide in patients with cirrhosis of the liver.
APPLICATION FOR CHILDREN
The experience with Sandostatin in children is very limited.
APPLICATION IN ELDERLY PATIENTS
At present, there is no evidence to show that elderly patients are less tolerant of Sandostatin and require a change in dosing regimen.
SPECIAL INSTRUCTIONS
With tumors of the pituitary gland secreting GH, careful monitoring of the patients receiving Sandostatin is necessary. it is possible to increase the size of tumors with the development of such a serious complication, as narrowing the fields of vision. In these cases, consideration should be given to the need for other treatments.
In the case of bradycardia with the use of Sandostatin, it is necessary to reduce the dose of beta-blockers, calcium channel blockers or drugs that affect the water-electrolyte balance.
In some patients, octreotide can alter the absorption of fats in the intestine. Against the background of octreotide, there was a decrease in cyanocobalamin (vitamin B12 ) and a deviation from the norm of the cyanocobalamin absorption test (Shilling test).
In applying Sandostatin in patients with deficiency of vitamin B 12 in anamnesis it is recommended to control the content of cyanocobalamin in the body.
Recommendations for the management of patients during treatment with Sandostatin for education gallstones
1. Prior to the appointment of Sandostatin patients should undergo initial ultrasound examination of the gallbladder.
2. During treatment with Sandostatin should be repeated ultrasound examination of the gallbladder, preferably at intervals of 6-12 months.
3. If gallstones are found before the start of the treatment, it is necessary to evaluate the potential benefits of therapy Sandostatin compared with the potential risks associated with their presence. Information about any negative effect of Sandostatin on the course or prognosis existing cholelithiasis not.
4. Maintain patients with gall bladder stones are formed during treatment Sandostatin.
a) Asymptomatic gallstones.
The use of Sandostatin can stop or continue - in line with the assessment of benefit / risk ratio. In any case, there is no need to do anything except to continue monitoring, making it more frequently if necessary.
b) Gallstones symptomatic.
The use of Sandostatin 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 per day in combination with ursodeoxycholic acid at the same dose) under ultrasound guidance - until complete disappearance of stones.
In the treatment of gastrointestinal and pancreatic endocrine tumors Sandostatin in rare cases may occur sudden recurrence of disease symptoms. Patients with insulinomas during treatment with octreotide can be marked increase in the severity and duration of hypoglycemia (this is due to more pronounced overwhelming effect on GH secretion and glucagon than insulin secretion, as well as the shorter duration of inhibition of insulin secretion). It should ensure thorough regular monitoring of these patients in the early treatment of Sandostatin, and at each change of dosage. Substantial fluctuations in blood glucose concentration can try to reduce by more frequent administration of Sandostatin in smaller doses. In patients with diabetes mellitus type 1 Sandostatin may reduce insulin requirement.In patients without diabetes, and can lead to postprandial hyperglycemia with type 2 diabetes when insulin secretion partially intact administration of Sandostatin. In applying Sandostatin in patients with diabetes is recommended to control blood glucose concentration and antidiabetic therapy.
Because after bleeding from varicose veins of the esophagus and stomach increased risk of developing type 1 diabetes mellitus, and in patients suffering from diabetes are also possible changes in insulin requirements; In these cases, the regular control of blood glucose concentration.
Requires correction dosing regimen used simultaneously diuretics, beta-blockers, calcium channel blockers slow, insulin, oral hypoglycemic agents, glucagon.
Impact on the ability to drive vehicles and manage mechanisms
Data on the effect of Sandostatin on the ability to drive and work with no mechanisms.
OVERDOSE
Doses up to 2000 mg of octreotide in the form n / k injection 3 times / day for several months were well tolerated.
Symptoms: maximum single dose at / in an adult patient bolus of 1 mg, the observed decrease in heart rate, flushing, abdominal cramps, diarrhea, sensation of emptiness in stomach, and nausea; all of these symptoms resolved within 24 hours from the time of drug administration.
One patient by continuous infusion dose excess Sandostatin was introduced in error (250 ug / hour for 48 hours instead of 25 g / h), which is not accompanied by side effects.
In cases of acute overdose has not been observed any life-threatening reactions.
Treatment: symptomatic therapy.
DRUG INTERACTION
Sandostatin reduces the absorption of cyclosporin and slows the absorption of cimetidine.
Combined application of octreotide and bromocriptine increases the bioavailability of bromocriptine.
There is evidence that somatostatin analogs can reduce the metabolic clearance of substances metabolized by the cytochrome P450 isoenzyme system that may be due to the suppression of GH. Since it is possible that octreotide can also have this effect, caution should be exercised when administering the drug metabolized isoenzyme CYP3A4 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 stored in reach of children, in the original package, in the refrigerator at 2 В° to 8 В° C; do not freeze, protect from light. Shelf life - 3 years.
