OKTRID

Active material: Octreotide
When ATH: H01CB02
CCF: Somatostatin analogues. Препарат для проведения интенсивной терапии в гастроэнтерологии
ICD-10 codes (testimony): (E) 16.1, (E) 16.3, E16.8, E22.0, E34.0, I85.0
When CSF: 11.17.02
Manufacturer: Sun Pharmaceutical Industries Ltd. (India)

Pharmaceutical form, composition and packaging

The solution for I / O and p / to the introduction clear, colorless.

Excipients: acetic acid glacial, sodium acetate trihydrate, sodium chloride, water d / and.

1 ml – colorless glass vials (1) – trays, plastic (1) – cardboard boxes.

The solution for I / O and p / to the introduction clear, colorless.

Excipients: acetic acid glacial, sodium acetate trihydrate, sodium chloride, water d / and.

1 ml – colorless glass vials (1) – trays, plastic (1) – cardboard boxes.

Pharmacological action

Somatostatin analogues. Octreotide – синтетический октапептид, which is a derivative of the natural hormone somatostatin and having similar pharmacological effects, with him, but a much larger duration.

The drug suppresses the pathologically increased secretion of growth hormone (TOWN), as well as peptides and serotonin, produced in the gastro-entero-pancreatic endocrine system.

In healthy individuals oktreotid, like somatostatinu, Suppresses the secretion of GH, called arginine, physical activity and insulin hypoglycemia; insulin secretion, glucagon, gastrin and other peptides gastro-entero-pancreatic endocrine system, caused by eating, as well as the secretion of insulin and glucagon, stimulated by arginine; secretion tireotropina, called tireoliberinom.

The overwhelming effect on secretion of GH from Octreotide, Unlike somatostatin, expressed in much more, than on insulin secretion. Introduction of Octreotide is not accompanied by the phenomenon of hypersecretion of hormones on the mechanism of negative feedback.

In patients akromegaliei introduction Octreotide provides overwhelmingly strong reduction level G and normalizing the concentration of insulin-like growth factor 1/ somatomedina with (RAF-1).

The majority of patients with acromegaly oktreotid reduces the severity of symptoms such, headache, increased perspiration, paresthesia, fatigue, pain in bones and joints, perifericheskaya neuropathy. It has been reported, oktreotidom treatment of individual patients with pituitary adenomas, differing from the GR, resulted in a decrease in tumor size.

When carcinoid tumors use of Octreotide may reduce the severity of symptoms, Firstly, such as hot flushes and diarrhea. In many cases, clinical improvement accompanied by a decrease in the concentration of serotonin in plasma and urinary excretion of 5-gidroksiindoluksusnoj acid in urine.

When tumors, characterized by overproduction of vasoactive intestinal peptide (VIPomy), application of Octreotide leads in most patients to reduce severe secretory diarrhea, that is typical for a given condition, what, in turn, leads to improved quality of life of the patient. At the same time there is a reduction of related violations elektrolitnogo balance, eg, hypokalemia, that allows you to cancel the enteral and parenteral introduction of fluids and electrolytes. According to the computed tomography in some patients slowing or stopping the progression of tumors, and even reduce its size, particularly liver metastasis. Clinical improvement is usually accompanied by a decrease in (until normal values) vazoaguogo intestinalnogo peptide concentration (VIP) plasma.

При глюкагономах применение октреотида в большинстве случаев приводит к заметному уменьшению некротизирующей мигрирующей сыпи, that is typical for a given condition. Октреотид не оказывает сколько-нибудь существенного влияния на выраженность сахарного диабета, часто наблюдающегося при глюкагономах, и обычно не приводит к снижению потребности в инсулине или пероральных гипогликемических препаратах. Patients, страдающих диареей, октреотид вызывает ее уменьшение, что сопровождается повышением массы тела. При применении октреотида часто отмечается быстрое снижение концентрации глюкагона в плазме, однако при длительном лечении этот эффект не сохраняется. В то же время симптоматическое улучшение остается стабильным длительное время.

When gastrinomah/syndrome Zollinger-Ellison oktreotid, used as monotherapy or in combination with blokatorami gistaminovykh H₂-receptor and Proton pump inhibitors, can reduce the formation of hydrochloric acid in the stomach and lead to clinical improvement, incl. and against diarrhoea. It is also possible to decrease symptoms and other symptoms, probably related to the synthesis of peptide tumor, incl. tides. In some cases, there is a decrease in plasma gastrin concentrations.

In patients with insulinomami oktreotid reduces levels of immunoreactive insulin in the blood. In patients with operable tumors oktreotid can ensure the restoration and maintenance of normoglikemii in the preoperative period. In patients with inoperable benign and malignant tumors of the control of glycemia can improve and unless it is accompanied by a prolonged decline in the level of insulin in the blood.

Rarely encountered in patients with tumors, rilizing-factor giperproduciruûŝimi GR (somatoliberinomami), oktreotid reduces the severity of symptoms of acromegaly. It, apparently, due to the Suppression of secreting rilizing-factor GR and GR. In the future, possibly reducing the size of the pituitary gland, that before treatment were increased.

Pharmacokinetics

Absorption

After p/to the introduction of the drug is rapidly and completely absorbed. T_max plasma (5.2 mg/ml dose 0.1 mg) is 30 m.

Distribution

Plasma protein binding – 65%, with shaped blood elements – extremely slightly. V_d is 0.27 l / kg.

Deduction

Total clearance – 160 ml / min. T_1/2 is 100 m. A large part of the drug excreted through the intestines, about 32% excreted unchanged to the kidneys. After the on/in the introduction of excretion is carried out in 2 phase, T_1/2 is 10 and 90 min, respectively.

Pharmacokinetics in special clinical situations

In elderly patients reduced clearance of Octreotide, a T_1/2 increases.

With severe chronic renal insufficiency clearance reduced 2 times.

Testimony

- Akromegalija (When adequate control of symptoms is achieved through subcutaneous Octreotide reference, If you do not have sufficient effect on surgical treatment and radiotherapy; in preparation for surgical treatment, to treat between courses of radiation therapy to the development of lasting effect, from inoperable patients);

— therapy of endocrine tumors of the gastrointestinal tract and pancreas: carcinoid tumors with karcinoidnogo syndrome; insulinomy; VIPomy; gastrinoma (Zollinger-Ellison); glucagonomas (to control hypoglycemia in the preoperative period, as well as for maintenance therapy);

— somatoliberinomy (tumor, characterized by overproduction of rilizing-factor G);

Prevention of complications after operations on pancreas;

-stop bleeding and prevention of re-bleeding from esophageal varices in liver cirrhosis (in combination with endoscopic therapy sclerosing).

Dosage regimen

The drug is intended for p/to the in/in the introduction and.

The initial dose is 50 µg/day p/ 1 or 2 times / day. After that, the number of injections and the dose can be gradually increased, based on portability, clinical response and effects on hormone levels, produced by tumor (in the case of carcinoid tumors – effect on the excretion of urine 5-gidroksiindoluksusnoj acid). The drug is usually used 2-3 times / day.

At akromegalii the drug is injected p/in a dose of 50-100 g, intervals 8 or 12 no. Selection of doses in the future is based on the results of the monthly monitoring of concentration in blood of GR, analysis of clinical symptoms and portable products. In most cases, the daily dose is 200-300 g. The maximum dose – 1500 mg / day. If the 3 months of treatment has not been sufficient reduction of GR and improve the clinical picture of the disease, therapy should be discontinued.

At endocrine tumors of these-pancreatic system the drug is administered to the p/to the in the initial dose of 50 g 1-2 times / day. Further, Depending on the achieved effect, influence on the concentration of hormones, produced by the tumor (in the case of carcinoid tumors – impact on the allocation of 5-gidroksiindoluksusnoj acid in urine), and portability, dose can be gradually increased to 100-200 g 3 times / day.

To Prevention of complications after operations on pancreas the drug is injected p/, the first dose 100 micrograms per 1 h to laparotomy, after operation – by 100 g 3 times / day, for 7 next days. In exceptional cases, may require higher doses. Supporting dose should be selected individually.

When, If the therapy in the maximum tolerated dose is not effective for 1 of the week, therapy should be discontinued.

To stop bleeding from esophageal varices the drug is injected in/drip in at the speed of 25 μg/h for 5 days.

Rules of the injection

When s/to the introduction should avoid repeated injections of the drug at the same place within a short time.

When in/with the introduction of the drug immediately before use, the contents of hair for a single use or reusable bottle diluted with physiological solution. The amount of dilution will depend on your infusion, and it should change, to ensure the continuous introduction of Octreotide with recommended speed. After, as the drug was diluted, the resulting solution should be used within 24 no. You must destroy any unused solution.

Before/with the introduction of a solution it is necessary to test for transparency, the presence of particles, draught, color changes and leakage, in all cases, When this makes the solution and packing material. You cannot apply, If it is muddy, contains particles, sludge, If his color changed or traces of water stains.

Side effect

From the digestive system: anorexia, nausea, vomiting, abdominal cramping, abdominal distention, excessive flatulence, loose stools, diarrhea, celiac disease; with long-term use may formation of stones in the gallbladder.

Although sebum from faeces can increase, to date there is no evidence, that long-term treatment oktreotidom may lead to the development of nutritional deficiency due to malabsorption violations (malabsorption). In rare cases, possible phenomena, resembling acute intestinal obstruction: progressive flatulence, expressed pain in epigastralna area, the tension of the abdominal wall. The frequency of side effects from the stomach can be reduced, increasing the intervals between meals and Octreotide.

Rare reported cases of acute pancreatitis, developed in the first hours or days of use of Octreotide. With long-term use, there were cases of pancreatitis, associated with holelitiazom.

There are anecdotal reports of developing human liver (acute hepatitis without cholestasis with normalization of indicators following the lifting of transaminase Octreotide); the slow development of hyperbilirubinemia, accompanied by improvements in AP, GGT, less, other transaminases.

Cardio – vascular system: in certain cases, bradycardia.

Metabolism: may decrease glucose tolerance after eating; with long-term use, c/to, in some cases may develop persistent hyperglycemia; sometimes – condition of hypoglycemia. Oktreotid may affect glucose metabolism, because it suppresses the formation of GR.

Allergic reactions: seldom-skin manifestations; in some cases, anaphylactic reaction.

Local reactions: There may be pain, the sensation of itching, or burning, redness or swelling where the p/to the injections (usually disappear within 15 m). The severity of local reactions can be reduced, If you use the solution at room temperature, or enter a smaller volume of a more concentrated solution.

Other: rarely – temporary hair loss.

Contraindications

- Hypersensitivity to the drug.

FROM caution You should apply at holelitiaze, diabetes, pregnancy and lactation.

Pregnancy and lactation

Clinical experience with Octreotide in pregnancy is limited. Oktreotid should be used during pregnancy only if, if the expected benefit to the mother outweighs the potential risk to the fetus.

Unknown, whether allocated oktreotid with breast milk, There is therefore a need for caution in the use of Octreotide for the treatment of nursing mothers.

Cautions

Pituitary tumors, secreting GR, careful monitoring of the patient, tk. perhaps increasing the size of the tumors with the development of serious complications, as the narrowing of fields of view. In these cases, you should consider the need to apply other treatments. In 15-30% patients, receiving oktreotid n/a for a long time, may cause gallstones. The prevalence in the general population (age 40-60 years) is 5-20%.

Long-term care experience oktreotidom prolonged action patients akromegaliei and tumors of the DIGESTIVE TRACT and pancreas suggests, that oktreotid prolonged action, compared to short-acting oktreotidom, does not increase the frequency of gallbladder stones education.

In patients with diabetes mellitus type 1 oktreotid may affect glucose metabolism and, Consequently, reduce the need for insulin units. For patients with diabetes mellitus type 2 and patients without a concomitant violation of carbohydrate metabolism p/Octreotide injections may lead to postprandial glycemia. In this regard, it is recommended that you regularly monitor the level of glycemia and if necessary correct hypoglycemic therapy.

In patients with insulinomami treatment oktreotidom may be increasing the severity and duration of hypoglycemia (This is due to the more pronounced by an overwhelming effect on the secretion of GH and glucagon, than on insulin secretion, as well as with the lesser duration of inhibitory effects on insulin secretion). Shows the systematic monitoring of the sick.

Until the appointment of Octreotide in all patients should undertake an initial ULTRASOUND of the gallbladder. During treatment oktreotidom should be repeated ULTRASOUND of the gallbladder, preferably, intervals 6-12 Months. Gallstones, If they are detected, usually, asymptomatic. If there are clinical symptoms shown conservative treatment (eg, application of bile acids) or surgery.

If the gallbladder stones are detected even before the start of treatment, There is a need to evaluate the potential benefits of therapy compared with oktreotidom possible risk, associated with the presence of gallstones.

Currently, there is no evidence, that oktreotid adversely affects existing or forecast for cholelithiasis.

Keeping patients, whose gall bladder stones are formed in the course of treatment oktreotidom

and) Asymptomatic stones gall bladder: application of Octreotide can be terminated or continue – in accordance with the assessment of the risk/benefit ratio. In any case do not require any other measures, In addition to the continuation of the inspections, making them, if necessary, more frequent.
to) Gall bladder stones with clinical symptoms: application of Octreotide can be terminated or continue – in accordance with the assessment of the risk/benefit ratio. In any case, the patient should be treated in the same way, as in other cases, the gallstone disease with clinical manifestations. Medical treatment includes the use of combinations of bile acid preparations (eg, chenodeoxycholic acid dose 7.5 mg/kg/day in combination with Ursodeoxycholic acid in the same dose) under the ultrasound control – before the complete disappearance of stones.

Currently, no data, that would indicate a need for dose adjustment in patients elderly age and patients with impaired renal function.

As evidence of increasing T_1/2 Octreotide in patients with liver cirrhosis, recommended maintenance dose correction from patients with impaired liver function.

Use in Pediatrics

Experience of application of Octreotide in children is limited.

Effects on ability to drive vehicles and management mechanisms

There are no data on the impact of the drug on Oktrid the ability to drive vehicles and to working with machinery.

Overdose

Dose Octreotide to 2000 mcg as p/to the injections 3 times postponed for several months good.

Symptoms: the maximum single dose of the on/bolusnom adult patient was 1 mg. While there have been such symptoms, How to decrease HEART RATE, flushing, abdominal pain, spastic nature, diarrhea, nausea, a feeling of emptiness in the stomach. All these symptoms were resolved within 24 h from the time of drug administration.

One method of prolonged infusions in error was introduced excessive dose Octreotide (250 mcg/h instead of 25 g / h), that was not accompanied by side effects.

In acute overdose, there have not been any life-threatening reactions.

Treatment: symptomatic therapy.

Drug Interactions

Oktreotid reduces absorption of Cyclosporine, slows down the absorption of cimetidine.

Application of Octreotide and bromokriptina bioavailability increases.

Is a correction mode simultaneously used diuretics, beta-blockers, blockers slow calcium channels, insulin, oral hypoglycemic drugs, glucagon.

There is evidence, that somatostatin analogues may decrease the metabolism of drugs, metaboliziruthan izofermentami zitohroma P450 (may be due to supressiej GR). Because it is impossible to avoid such effects of Octreotide, preparations, metaboliziruûŝiesâ of the enzyme system and have a narrow therapeutic range of doses, It should be administered with caution.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C. Shelf life – 2 year.