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

Synthetic analogue of somatostatin with a longer effect. The drug depresses the secretion somatotropic and thyrotropic hormone. Reduces the secretory activity of the pancreas, the secretion of gastrin, cholecystokinin, hydrochloric acid, secretin, vaso-intestinal peptide, digestive enzymes and other biologically active substances.

Oppression of the secretion of growth hormone and insulin-like growth factor-1 - the effect of acromegaly. Inhibition of the secretion of serotonin and gastroenteropancreatic peptides (gastrin, motilin and secretin), delay in the evacuation of intestinal contents - before operation on the pancreas, suppression of pancreatic fluid production, reducing the risk of postoperative complications. Direct influence on intestinal vessels, decreased blood flow - an effect with bleeding gastroesophageal varices. Blockade of tides caused by carcinoid syndrome.

Pharmacokinetics:

Absorption is fast and complete from the injection site. The association with plasma proteins in patients with acromegaly is moderate (41%), in the remaining patients - high (65% with lipoproteins, to a lesser extent with albumins). With subcutaneous injection, the elimination half-life is 100 minutes, with intravenous administration, the drug is withdrawn in two phases, the first half-life is 10 minutes, the second half-90 minutes (in elderly patients it can be increased). T_Cmax 30 minutes. C_max 5.2 ng / ml.Elimination by the kidneys (32%).

Indications:

Acromegaly - for controlling the main manifestations of the disease and reducing the level of growth hormone and insulin-like growth factor-1 in plasma in those cases when there is no sufficient effect from surgical treatment or radiotherapy. Octreotide It is also indicated for the treatment of patients with acromegaly who have refused surgery or who have contraindications to it, as well as for short-term treatment in between the radiotherapy courses until its effect is fully developed.

Secretory tumors of the gastroenteropancreatic system: VIPoma; glucagonomes; gastrinomas / Zollinger-Ellison syndrome - usually in combination with proton pump inhibitors and histamine H blockers₂-receptors; insulinoma (for the control of hypoglycemia in the preoperative period, as well as for maintenance therapy); somatoliberynoma (tumors characterized by hyperproduction of growth hormone releasing factor).

Carcinoid tumors with carcinoid syndrome.

Diarrhea in patients with AIDS.

Preventive maintenance of complications after operations on a pancreas.

Stop bleeding from varicose veins of the esophagus and stomach with cirrhosis of the liver.

Octreotide is used in combination with specific therapeutic measures, for example endoscopic sclerosing therapy.

ICD-10

I.B20-B24.B20 Disease caused by the human immunodeficiency virus [HIV], manifested as infectious and parasitic diseases

II.C15-C26.C25 Malignant neoplasm of pancreas

II.C15-C26.C26 Malignant neoplasm of other and inaccurately indicated digestive organs

II.C73-C75.C75.1 Malignant neoplasm of pituitary gland

II.D00-D09.D01 Carcinoma in situ of other and unspecified digestive organs

II.D10-D36.D13 Benign neoplasm of other and inaccurately designated digestive organs

II.D37-D48.D44.3 Neoplasm of the pituitary gland

IV.E15-E16.E16.1 Other forms of hypoglycemia

IV.E15-E16.E16.3 Increased secretion of glucagon

IV.E15-E16.E16.8 Other specified disorders of internal secretion of the pancreas

IV.E20-E35.E22.0 Acromegaly and pituitary gigantism

IV.E20-E35.E34.0 Carcinoid Syndrome

IX.I80-I89.I85.0 Varicose veins of the esophagus with bleeding

XI.K55-K63.K59.1 Functional diarrhea

Contraindications:

Hypersensitivity. Children under 18 years.

Carefully:

Diabetes mellitus, cholelithiasis.

Pregnancy and lactation:

Category FDA - B. The drug 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:

Dosage regimen is individual, used subcutaneously, intravenously drip, intramuscularly.

With acromegaly - subcutaneously, in a dose of 300 μg at intervals of 8 or 12 hours. This dose is used in case of ineffectiveness of initial therapy (solution for intravenous and subcutaneous 50-100 μg at intervals of 8 or 12 hours). Do not exceed the maximum dose of 1500 μg in day.

With tumors of the gastroenteropancreatic endocrine system - subcutaneously, in a dose of 300 mcg 1-2 times a day. This dose is used in case of ineffectiveness of initial therapy (solution for intravenous and subcutaneous introduction, 50 mcg 1-2 times a day with a gradual increase to 100-200 mcg 3 times a day). In exceptional cases, a dose of more than 600 μg day, the dose of the drug can be gradually increased to 300-600 μg 3 times a day.

When bleeding from varicose-dilated veins of the esophagus and stomach - intravenously drip, at a rate of 25 mcg / h for 5 days.

Side effects:

From the gastrointestinal tract and pancreas: possible - anorexia, nausea, vomiting, abdominal cramps, sensation of bloating, excessive gas formation, loose stools, diarrhea, steatorrhea, discoloration of the stool. Although the release of fat with feces may increase, there is no indication that prolonged treatment with octreotide can lead to the development of malabsorption (malabsorption). In rare cases, there may be phenomena reminiscent of acute intestinal obstruction. There are isolated cases of acute hepatitis without cholestasis, hyperbilirubinemia in combination with an increase in the activity of alkaline phosphatase, gamma-glutamyl transferase and, to a lesser extent, other transaminases.

Long-term use of octreotide can lead to the formation of stones in the gallbladder.

From the cardiovascular system: in some cases - an arrhythmia, a bradycardia.

From the endocrine system: very often hyperglycemia; often - hypothyroidism / thyroid dysfunction (lowering of levels thyrotropic hormone, a common and free thyroxine); hypoglycemia, impaired glucose tolerance.

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

Dermatological reactions: often - itching, rash, hair loss, hives.

From the respiratory system: often - shortness of breath.

Common disorders and reactions at the site of administration: very often - pain at the injection site; infrequently - dehydration.

From the immune system: anaphylactic reactions, allergic reactions / hypersensitivity.

Overdose:

Increased side effects, flushes to the face, arrhythmias, lowering blood pressure, bradycardia, dizziness, sudden cardiac arrest, hypoxia of the brain, pancreatitis, fatty liver degeneration, diarrhea, weakness, inhibition, weight loss, hepatomegaly and lactic acidosis.

Interaction:

With simultaneous administration with insulin, hypoglycemic action may be increased.

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 growth hormone). Since such octreotide effects 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:

The drug does not have antitumor activity. Before and during treatment, it is necessary to monitor the condition of the gallbladder, control the concentration of glucose in the blood.

When tumors of the pituitary gland secreting growth hormone, careful monitoring of patients receiving octreotide, as 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.

Since the decrease in the level of growth hormone and normalization of the level insulin-like growth factor-1 on the background of therapy with octreotide can lead to the restoration of fertility in women with acromegaly, when using the drug of the patient of childbearing age should use reliable methods of contraception.

With the appointment of octreotide for a long period of time, it is necessary to monitor the function of the thyroid gland.

In the case of bradycardia on the background of octreotide, if necessary, it is possible to reduce the dose of beta adrenoblockers, calcium channel blockers or drugs that affect the water-electrolyte balance.

In some patients octreotide can change the absorption of fats in the intestine.

Against the background of octreotide, a decrease in the content of cobalamin (vitamin B₁₂) and deviation from the norm of the indices of the cobalamin absorption test (Schilling test). When octreotide is used in patients with vitamin B deficiency₁₂ in the anamnesis it is recommended to control the content of cobalamin in the body.

Recommendations for managing patients during treatment with the drug for the formation of gallstones:

- before the appointment of octreotide, patients must undergo the initial ultrasonography gallbladder;

- during treatment with the drug should be repeated ultrasound examinations the gallbladder, preferably at intervals of 6-12 months;

- If gallstones are found even before the start of treatment, it is necessary to evaluate the potential benefits of octreotide therapy in comparison with 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 the drug:

- asymptomatic gallstones stones. 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;

- Gallstones with a clinical symptomatology.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 in day in combination with ursodeoxycholic acid in the same dose) under ultrasound control - until the stones disappear completely.

When treating endocrine tumors GIT and pancreas with octreotide, in rare cases, sudden recurrence of symptoms of the disease may occur. In patients with insulinomas, with the treatment with octreotide, an increase in the severity and duration of hypoglycemia can occur (this is due to a more pronounced inhibitory effect on the secretion of growth hormone and glucagon than on insulin secretion, and also with a shorter duration of inhibitory effect on insulin secretion). Careful regular monitoring of these patients should be ensured both at the beginning of treatment with the drug and at each dose change.

Significant fluctuations in the concentration of glucose in the blood can be tried to reduce by more frequent administration of octreotide in smaller doses. In patients with type 1 diabetes mellitus octreotide can reduce the need for insulin. In patients without diabetes and type 2 diabetes with partially conserved insulin secretion, the administration of octreotide may lead to postprandial hyperglycemia. When using octreotide in patients with diabetes mellitus, it is recommended to monitor blood glucose concentration and antidiabetic therapy.

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

Impact on the ability to drive vehicles and manage mechanisms

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

Instructions

Octreotide (Octreotidum)