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

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

The drug suppresses the pathologically increased secretion of growth hormone (GR), as well as peptides and serotonin produced in the gastroenteropancreatic endocrine system.

In healthy individuals octreotide, like somatostatin, suppresses the secretion of GH caused by arginine, exercise and insulin hypoglycemia; secretion of insulin, glucagon, gastrin and other peptides of the gastroenteropancreatic endocrine system caused by food intake, as well as the secretion of insulin and glucagon stimulated with arginine; secretion of thyrotropin, caused by thyroidiberin.

The suppressive effect on the secretion of GH in octreotide, in contrast to somatostatin, is expressed to a much greater extent than on the secretion of insulin. The introduction of octreotide is not accompanied by the phenomenon of hypersecretion of hormones by the mechanism of negative feedback.

In patients with acromegaly, the administration of octreotide provides, in the vast majority of cases, a persistent decrease in the level of GH and a normalization of the concentration of insulin-like growth factor 1 / somatomedin C (IGF-1).

In most patients with acromegaly octreotide significantly reduces the severity of symptoms such as headache, increased sweating, paresthesia, fatigue, pain in the bones and joints, peripheral neuropathy. It was reported that treatment with octreotide of individual patients with adenomas of the pituitary gland secreting GH led to a decrease in the size of the tumor.

In carcinoid tumors, the use of octreotide can lead to a decrease in the severity of the symptoms of the disease, primarily such as hot flashes and diarrhea. In many cases, clinical improvement is accompanied by a decrease in plasma serotonin concentration and excretion of 5-hydroxyindoleacetic acid in the urine.

In tumors characterized by hyperproduction of the vasoactive intestinal peptide (WIPOM), the use of octreotide in most patients reduces the severe secretory diarrhea that is characteristic of this condition, which in turn leads 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. According to computed tomography, in some patients, the progression of the tumor slows or stops, and even the decrease in its size, especially the metastases to the liver. Clinical improvement is usually accompanied by a decrease (up to normal values) of the concentration of vasoactive intestinal peptide (VIP) in plasma.

With glucagonomes, the use of octreotide in most cases leads to a marked decrease in the necrotizing migrating rash that is characteristic of this condition. Octreotide does not have any significant effect on the severity of diabetes mellitus, often observed in glucagonomes, and usually does not lead to a decrease in the need for insulin or oral hypoglycemic drugs. In patients with diarrhea, octreotide causes it to decrease, which is accompanied by an increase in body weight. When octreotide is used, there is often a rapid decrease in glucagon concentration in the plasma,However, with prolonged treatment, this effect is not preserved. At the same time, symptomatic improvement remains stable for a long time.

With gastrinomas / Zollinger-Ellison syndrome octreotide, used as a monotherapy or in combination with blockers H₂-receptors and proton pump inhibitors, can reduce the formation of hydrochloric acid in the stomach and lead to clinical improvement, incl. and in relation to diarrhea. It is also possible to reduce the severity and other symptoms likely associated with the synthesis of peptides by the tumor, incl. tides. In some cases, a decrease in the concentration of gastrin in the plasma.

In patients with insulinomas octreotide reduces the level of immunoreactive insulin in the blood. 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 may improve without a simultaneous prolonged decrease in insulin levels in the blood.

In patients with rare tumors, hyper-producing growth hormone releasing factor (somatoliberinomas), octreotide reduces the severity of symptoms of acromegaly. This, apparently, is due to the suppression of the secretion of the releasing factor of growth hormone and the growth hormone itself. In the future, it is possible to reduce the size of the pituitary gland, which were increased before the treatment.

Pharmacokinetics:After subcutaneous administration, the drug is quickly and completely absorbed. Time to reach the maximum concentration in the blood plasma (5.2 mg / ml at a dose of 0.1 mg) - 30 minutes. The connection with plasma proteins is 65%, with uniform elements of blood - very insignificant. The volume of distribution is 0.27 l / kg. The total clearance is 160 ml / min. The half-life (T_1/2) is 100 minutes. Most of the drug is excreted by the intestine, about 32% are excreted unchanged by the kidneys. After IV introduction, excretion is carried out in 2 phases, with T_1/2- 10 and 90 minutes respectively. In elderly patients, clearance of octreotide decreases, and T_1/2increases. In severe chronic renal failure, the clearance decreases by a factor of 2.

Indications:

Acromegaly (when adequate control of the manifestations of the disease is due to subcutaneous octreotide, in the absence of sufficient effect from surgical treatment and radiation therapy, to prepare for surgical treatment,for treatment between radiotherapy courses before the development of a persistent effect, in inoperable patients).

In therapy of endocrine tumors of the gastrointestinal tract (GIT) and pancreas:

- carcinoid tumors with the phenomena of carcinoid syndrome;

- insulinomas;

- VIPoms;

- gastrinomas (Zollinger-Ellison syndrome);

- Glukagonomy (for the control of hypoglycemia in the preoperative period, as well as for maintenance therapy).

Somatoliberinoma (tumors characterized by hyperproduction of growth hormone releasing factor).

Preventive maintenance of complications after operations on a pancreas; stop bleeding and prevent bleeding from varicose veins of the esophagus with cirrhosis of the liver (in combination with endoscopic sclerosing therapy).

Treatment of acute pancreotitis.

Contraindications:

Hypersensitivity to octreotide or other components of the drug.

Carefully:

Chololithiasis, diabetes, pregnancy and lactation.

Pregnancy and lactation:

The experience with octreotide in pregnant women is limited. Octreotide Use in 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 caution should be exercised when using octreotide for the treatment of nursing mothers.

Dosing and Administration:

The drug is intended for subcutaneous (subcutaneous) and intravenous (IV) administration.

The initial dose is 50 mcg / day p / to 1 or 2 times a day. After that, the number of injections and dosage can be gradually increased, based on tolerability, clinical response and effects on the levels of hormones produced by the tumor (in the case of carcinoid tumors, the effect on excretion of urine with 5-hydroxyindoleacetic acid). The drug is usually used 2-3 times a day.

With acromegaly the drug is administered subcutaneously in an initial dose of 50-100 μg, at intervals of 8 or 12 hours. Subsequently, the dose selection is based on monthly determinations of the concentration of growth hormone in the blood, the analysis of clinical symptoms and the tolerability of the drug. In most patients, the daily dose is 200-300 μg. Do not exceed the maximum dose of 1500 μg / day. If after 3 months. treatment is not marked a sufficient reduction in growth hormone and improve the clinical picture of the disease, therapy should be discontinued.

With endocrine tumors of the gastroenteropancreatic system - The drug is given SC in the initial dose of 50 mcg 1-2 times a day. Further, depending on the 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 in the urine) and tolerability, the dose can be gradually increased to 100-200 μg 3 times a day.

To prevent complications after operations on the pancreas - SC, the first dose of 100 μg for 1 hour before laparotomy, after surgery - 100 μg 3 times a day, for 7 consecutive days. In exceptional cases, higher doses may be required. Supportive doses of the drug should be selected individually.

In the event that therapy in the maximum tolerated dose is not effective within 1 week, therapy should be discontinued.

To stop bleeding from varicose veins of the esophagus - in / in the drip at a rate of 25 mcg / h for 5 days.

For the treatment of acute pancreatitis - The drug is given SC at a dose of 100 mcg 3 times / day for 5 days. It is possible to administer up to 1200 μg / day using an intravenous route of administration.

With n / to the introduction multiple injections of the drug should be avoided in the same place for a short period of time.

With iv introduction of the preparation immediately before use, the contents of the single-use vial or the reusable vial should be diluted in physiological saline. The dilution volume will depend on the infusion system used, and it should be modified to ensure continuous administration of octreotide at the recommended rate. After the drug has been diluted, the resulting solution should be used within 24 hours. It is necessary to destroy the unused solution.

Before applying to / in the solution, it must be checked for transparency, presence of particles, sediment, discoloration and leakage, in all cases when the solution and material of the package permit.

Do not use the drug if it is cloudy, contains particles, sediment, if its color has changed or traces of streaks are visible.

Use in selected patient groups

Currently, there is no data that would indicate the need to adjust the dose of the drug in the elderly and in patients with impaired renal function.

Since there are data on the increase in the half-life of octreotide in patients with cirrhosis of the liver, correction of the maintenance dose in patients with impaired liver function is recommended.

The experience with octreotide in children is limited.

Side effects:

Local Reactions: pain, itching, or burning, redness, or swelling in the injection site (usually within 15 minutes) are possible.

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.

From the digestive tract: anorexia, nausea, vomiting, abdominal cramps, bloating, excessive gas, loose stools, diarrhea, steatorrhea. 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 (malabsorption). In rare cases, there may be phenomena reminiscent of acute intestinal. obstruction: progressive bloating, severe pain in the epigastric region, tension of the abdominal wall.Long-term use of octreotide can lead to the formation of stones in the gallbladder. 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 side of the pancreas: reported rare cases of acute pancreatitis that developed during the first hours or days of octreotide. With prolonged use, there have been cases of pancreatitis associated with cholelithiasis.

From the side of the liver: there are some reports of the development of violations of liver function (acute hepatitis without cholestasis with normalization of transaminases after abolition of octreotide); the slow development of hyperbilirubinemia, accompanied by an increase in the parameters of alkaline phosphatase, gamma-glutamyltransferase and, to a lesser extent, other transaminases.

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

From the side of metabolism: because the octreotide has an overwhelming effect on the formation of GH, glucagon and insulin, it can affect the exchange of glucose. Perhaps, a decrease in glucose tolerance after eating.With prolonged use of octreotide s / c in some cases, persistent hyperglycemia may develop. There were also conditions of hypoglycemia.

Other: In rare cases, a temporary hair loss after octreotide administration has been reported. There are separate reports on the development of reactions of hypersensitivity: rarely - skin allergic reactions; in some cases - anaphylactic reactions.

Overdose:

Doses of octreotide up to 2000 mcg in the form of SC injection 3 times for several months were tolerated well.

The maximum single dose for IV bolus administration to an adult patient was 1 mg. Symptoms such as a decrease in heart rate, blood flushes to the face, abdominal pain of a spastic nature, diarrhea, nausea, a feeling of emptiness in the stomach were noted. All these symptoms resolved within 24 hours from the time of administration of the drug.

One patient, using the long infusion method, was mistakenly given an excessive dose of octreotide (250 μg / h instead of 25 μg / h), which was not accompanied by side effects.

In acute overdose, there were no life-threatening reactions.

In case of an overdose, treatment is symptomatic.

Interaction:

Octreotide reduces the absorption of cyclosporine, slows the absorption of cimetidine.

With the simultaneous use of octreotide and bromocriptine, the bioavailability of the latter increases.

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

There is evidence that somatostatin analogues can reduce the metabolism of drugs metabolized by cytochrome P450 enzymes (may be due to suppression of growth hormone). Since it is impossible to exclude such effects of the ocreotide, drugs that are metabolized by the enzymes of the cytochrome P450 system and having a narrow therapeutic range of doses should be administered with caution.

Special instructions:

With tumors of the pituitary gland secreting GH, careful monitoring of patients is necessary, since it is possible to increase the size of tumors with the development of such serious complications as narrowing of the visual fields. In these cases, consideration should be given to the need for other treatments. In 15-30% of patients receiving octreotide s / c for a long time, possibly the appearance of stones in the gallbladder. The prevalence in the general population (age 40-60 years) is 5-20%. The experience of prolonged treatment with octreotide of the prolated effect of patients with acromegaly and tumors of the gastrointestinal tract and pancreas suggests that octreotide prolological action, in comparison with short-acting octreotide, does not lead to an increase in the frequency of gallbladder stones formation. Nevertheless, it is recommended to have an ultrasound of the gallbladder before starting treatment with octreotide and approximately every 6 months during treatment. Stones in the gallbladder, if nevertheless they are found, as a rule, are asymptomatic. In the presence of clinical symptoms, conservative treatment (eg, administration of bile acid preparations) or surgical intervention is indicated.

In patients with type 1 diabetes mellitus octreotide can affect the exchange of glucose and, consequently, reduce the need for injected insulin. For patients with type 2 diabetes mellitus and patients without concomitant disturbance of carbohydrate metabolism, subcutaneous octreotide injections can lead to postprandial glycemia.In this regard, it is recommended to regularly monitor the level of glycemia and, if necessary, correct hypoglycemic therapy.

In patients with insulinomas on the background of treatment with octreotide, there may be an increase in the severity and duration of hypoglycemia (this is associated with a more pronounced inhibitory effect on GH and glucagon secretion than on insulin secretion, and also with a shorter duration of inhibitory effect on insulin secretion). A systematic observation of these patients is shown.

Before the appointment of octreotide, patients should undergo an initial ultrasound of the gallbladder. During treatment with octreotide, repeated ultrasound of the gallbladder should be performed, preferably at intervals of 6-12 months.

If gallbladder stones 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 the presence of gallstones.

At the present time, there is no evidence that octreotide adversely affects the course or prognosis of an already existing cholelithiasis.

Management of patients, in which stones of the gallbladder form during the treatment with octreotide

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, no other measures are required, except to continue inspections, making them, if necessary, 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 / 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:

There is no data on the effect of octreotide on the ability to drive a car and work with mechanisms.

Form release / dosage:

Solution for intravenous and subcutaneous administration, 50, 100 μg / ml.

Packaging:

1 ml per ampoule, made of colorless glass of hydrolytic class 1,Marked above the place of the ampoule napkin in the form of a blue point and a blue ring (for a dosage of 50 μg) or a blue point and an orange ring (for a dosage of 100 μg).

1 ampoule in a plastic pallet along with instructions for use in a cardboard box.

Storage conditions:

Store in a place protected from light and inaccessible to children at a temperature of 2-8 ° C.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000588/09

Date of registration:29.01.2009 / 17.06.2014

Expiration Date:Unlimited

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp02.06.2017

Illustrated instructions

Instructions

Octreotide San (Octreotide Sun)