Octreotide-depo Lyophilisate prolonged 30mg vial, 1pc

Composition

One bottle contains

the Active ingredient-octreotide 30.0 mg,

excipients:  copolymer of DL-lactic and glycolic acids, D-Mannitol, carboxymethylcellulose sodium salt, polysorbate-80.

Solvent:  D-Mannitol, water for injection.

Pharmacological action

Pharmacotherapeutic group: Hypothalamic-pituitary hormones and their analogues. Hypothalamic hormones. Growth-slowing hormones. Octreotide.

ATX code: H 01 SV 02

Pharmacological properties

Pharmacokinetics

When used intramuscularly, octreotide is completely absorbed.

The therapeutic concentration in the blood is reached in about 30 minutes.

Protein binding is about 65%. The binding of octreotide to blood cells is extremely insignificant. The volume of distribution is 0.27 l / kg. Octreotide is metabolized in the liver.

The total clearance is 160 ml / min. T 1/2 is 100 min. About 32% is excreted unchanged by the kidneys. In elderly patients, clearance decreases and T 1/2 increases. In severe renal insufficiency, clearance is halved.

Pharmacodynamics

Octreotide depot is a synthetic octapeptide that is a derivative of the natural hormone somatostatin and has similar pharmacological effects, but a longer duration of action. The drug suppresses pathologically increased secretion of growth hormone (GH), as well as peptides and serotonin produced in the gastro-entero-pancreatic endocrine system.

In carcinoid tumors, the use of Octreotide leads to a decrease in the severity of symptoms such as flushing sensations and diarrhea, which in many cases is accompanied by a decrease in plasma serotonin concentration and urinary excretion of 5-hydroxyindoleacetic acid.

In tumors characterized by hyperproduction of vasoactive intestinal peptide (VIPoma), the use of Octreotide leads to a reduction in severe secretory diarrhea. At the same time, there is a decrease in concomitant electrolyte balance disorders. In some patients, the progression of the tumor slows down or stops, and even reduces its size, especially liver metastases. Clinical improvement is usually accompanied by a decrease (up to normal values) in the concentration of vasoactive intestinal peptide (VIP) in plasma.

In glucagonomics, the use of Octreotide depot in most cases leads to a noticeable decrease in necrotizing migrating rash. Octreotide depot does not have any significant effect on the severity of diabetes mellitus, which is often observed with glucagonomics, and usually does not lead to a decrease in the need for insulin or oral hypoglycemic drugs. In patients suffering from diarrhea, Octreotide causes its decrease, which is accompanied by an increase in body weight. When using Octreotide, a rapid decrease in the concentration of glucagon in plasma is often noted, but this effect does not persist with long-term treatment. At the same time, the symptomatic improvement remains stable for a long time.

For gastrinomas/Zollinger-Ellison syndrome Octreotide depot, used as monotherapy or in combination with H2-receptor blockers, can reduce acid production in the stomach and lead to clinical improvement, including in relation to diarrhea. The severity of other symptoms, including hot flashes, also decreases. In some cases, there is a decrease in the concentration of gastrin in plasma.

In patients with insulinomas Octreotide depot reduces the level of immunoreactive insulin in the blood (this effect can be short-lived – about 2 hours). In patients with operable tumors, Octreotide depot can provide restoration and maintenance of normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, glycemic control may improve even without a simultaneous long-term decrease in blood insulin levels.

For refractory diarrhea in patients with acquired immunodeficiency syndrome (AIDS) the use of Octreotide leads to complete or partial normalization of stool in approximately 1/3 of patients suffering from diarrhea, uncontrolled by adequate therapy with antimicrobial and/or antidiarrheal agents.

In patients undergoing pancreatic surgery, the use of Octreotide during and after surgery reduces the frequency of typical postoperative complications (for example, pancreatic fistulas, abscesses, sepsis, postoperative acute pancreatitis).

When bleeding from esophageal and gastric varicose veins in patients with cirrhosis of the liver, the use of Octreotide-depot in combination with specific treatment (for example, sclerosing therapy) leads to more effective stopping of bleeding and early re-bleeding, reducing the volume of transfusions and improving 5-day survival. The drug reduces organ blood flow by suppressing vasoactive hormones such as VIP and glucagon.

Indications

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

-carcinoid tumors with the phenomena of carcinoid syndrome

-insulinomas

-VIPomas

– gastrinomas (Zollinger-Ellison syndrome)

– glucagonomies (for controlling hypoglycemia in the preoperative period, as well as for maintenance therapy)

– somatoliberinomas (tumors characterized by hyperproduction of the releasing factor of growth hormone)

In the treatment of hormone-resistant prostate cancer

– as part of a combination therapy with surgical or medical castration

In the prevention of acute postoperative pancreatitis

-with extensive surgical operations on the abdominal cavity and thoracoabdominal interventions (including for cancer of the stomach, esophagus, colon, pancreas, primary and secondary liver cancer).

Contraindications

-hypersensitivity to octreotide or other components of the drug.

With caution:

– cholelithiasis

– diabetes mellitus

-pregnancy and lactation

Side effects

Adverse reactions are presented based on the frequency of occurrence in the following order: very common (≥1/10); common (≥1/100,  1/10); sometimes (≥1/1000, 1/100); rare (=≥1/10000, 1/1000); very rare (1/10000), including individual reports.

Very common

-headache

Often

-spastic abdominal pain, bloating, constipation, diarrhea

-local reactions in case of subcutaneous injection (pain, swelling, redness, irritation and burning)

– hypothyroidism, thyroid dysfunction

– dizziness, dyspnoea, asthenia

Sometimes

– bradycardia, tachycardia, cholecystitis, hair loss

Rarely

– allergic rash, itching

, nausea, vomiting, formation of gallstones (long-term use of Octreotide-depo), cholecystitis, biliary sludge, steatorrhea (although the release of fat in the feces may increase, there is no indication that long-term treatment with Octreotide-depo can cause a power shortage as a result of violations of absorption (malabsorption)), a phenomenon reminiscent of acute intestinal obstruction: progressive abdominal distension, severe epigastric pain, tension of the abdominal wall, muscle protection.

Very rare

– anaphylactic reactions

-hypoglycemia, hyperglycemia

-shortness

of breath-acute pancreatitis, anorexia, frequent stools, acute hepatitis without cholestasis, hyperbilirubinemia, increased alkaline phosphatase, gammaglutamyltransferase, transaminases, thrombocytopenia, hyperkalemia

-arterial hypertension (with prolonged use)

The severity of local reactions can be reduced by using a solution at room temperature, or by introducing a smaller volume of a more concentrated solution.

Post-marketing reports of side effects

-anaphylaxis, allergic reactions, urticular rash

-acute pancreatitis, acute hepatitis, cholestatic hepatitis, cholestasis, bile spillage, cholestatic jaundice

-arrhythmia

Interaction

Octreotide reduces the absorption of cyclosporine, slows down the absorption of cimetidine. It is necessary to adjust the dosage regimen of simultaneously used diuretics, beta-blockers, slow calcium channel blockers, insulin, and oral hypoglycemic drugs.

Concomitant use of octreotide and bromocriptine increases the bioavailability of the latter.

Drugs that are metabolized by cytochrome P450 enzymes and have a narrow therapeutic dose range should be administered with caution.

How to take it, course of administration and dosage

Octreotide depot should only be administered by deep intramuscular injection into the gluteal muscle. For repeated injections, the left and right sides should be alternated. The suspension should be prepared immediately before injection. On the day of injection, the vial with the drug and the ampoule with the solvent can be kept at room temperature.

In the treatment of endocrine tumors of the gastrointestinal tract and pancreas

In patients for whom subcutaneous administration of Octreotide provides adequate control of disease manifestations, the recommended initial dose of Octreotide depot is 20 mg every 4 weeks. Subcutaneous administration of Octreotide should be continued for another 2 weeks after the first administration of Octreotide depot.

In patients who have not previously received Octreotide subcutaneously, it is recommended to start treatment with subcutaneous administration of Octreotide at a dose of 0.1 mg 3 times a day for a relatively short period of time (approximately 2 weeks) in order to assess its effectiveness and overall tolerability. Only after that, Octreotide depot is prescribed according to the above scheme.

If Octreotide-depo therapy for 3 months provides adequate control of clinical manifestations and biological markers of the disease, it is possible to reduce the dose of Octreotide-depo to 10 mg, prescribed every 4 weeks. In cases where only partial improvement was achieved after 3 months of treatment with Octreotide depot, the dose of the drug can be increased to 30 mg every 4 weeks. Against the background of treatment with Octreotide-depot on some days, it is possible to increase the clinical manifestations characteristic of endocrine tumors of the gastrointestinal tract and pancreas. In these cases, additional subcutaneous use of Octreotide at the dose used before starting treatment with Octreotide-depot is recommended. This may occur mainly in the first 2 months of treatment, until therapeutic plasma concentrations of octreotide are reached.

In the treatment of hormone-resistant prostate cancer The recommended starting dose of Octreotide depot is 20 mg every 4 weeks for 3 months. In the future, the dose is adjusted taking into account the dynamics of PSA concentration in serum, as well as clinical symptoms. If after 3 months of treatment it was not possible to achieve an adequate clinical and biochemical effect (PSA reduction), the dose can be increased to 30 mg, administered every 4 weeks.

Treatment with octreotide-depot is combined with the use of dexamethasone, which is prescribed orally according to the following scheme: 4 mg per day for 1 month, then 2 mg per day for 2 weeks, then 1 mg per day (maintenance dose).

Treatment with octreotide-depo and dexamethasone in patients who have previously received medical antiandrogenic therapy is combined with the use of an analog of gonadotropin-releasing hormone (GnRH). In this case, the injection of an analog of GnRH (depot form) is carried out 1 time in 4 weeks.

Patients receiving Octreotide Depot should have their PSA concentrations determined every month.

In patients with impaired renal, hepatic and elderly function, there is no need to adjust the dosage regimen of Octreotide depot.

For the prevention of acute postoperative pancreatitis

The drug Octreotide-depot in a dose of 10 or 20 mg is administered once not earlier than 5 days and not later than 10 days before the proposed surgical intervention.

Rules for suspension preparation and drug use

• The drug is administered only intramuscularly.

• The suspension for intravenous injection is prepared using the supplied solvent immediately prior to use.

• The drug should only be prepared and administered by trained medical personnel.

• Before injection, the ampoule with the solvent and the vial with the drug must be removed from the refrigerator and brought to room temperature (it takes 30-50 minutes).

• Keep the bottle of Octreotide depot strictly vertical. By tapping the bottle lightly, make sure that all the lyophilizate is at the bottom of the bottle.

• Open the package with the syringe, attach a 1.2 mm x 50 mm solvent extraction needle to the syringe.

• Open the ampoule with solvent and fill the syringe with all the contents of the ampoule with solvent, set the syringe to a dose of 3.5 ml.

• Remove the plastic cap from the lyophilizate bottle. Disinfect the rubber stopper of the bottle with an alcohol swab. Insert the needle into the lyophilizate bottle through the center of the rubber stopper and carefully insert the solvent along the inner wall of the bottle, without touching the contents of the bottle with the needle. Remove the syringe from the bottle.

• The vial should remain stationary until the lyophilizate is completely soaked in the solvent and a suspension is formed (approximately 3 to 5 minutes). After that, without turning the bottle over, you should check for the presence of dry lyophilizate at the walls and bottom of the bottle. If dry lyophilizate remains are found, leave the bottle until it is completely soaked.

• After making sure that there are no dry lyophilizate residues, the contents of the bottle should be carefully mixed in a circular motion for 30 to 60 seconds until a homogeneous suspension is formed. Do not turn or shake the bottle, as this may cause flakes to fall out and make the suspension unusable.

• Quickly insert the needle through the rubber stopper into the bottle. Then lower the needle section down and, tilting the bottle at an angle of 45 degrees, slowly fill the suspension completely into the syringe. Do not turn the bottle over when typing. A small amount of the drug may remain on the walls and bottom of the bottle. Consumption for the remainder on the walls and bottom of the bottle is taken into account.

• Immediately after the suspension set, replace the pink pavilion needle with the green pavilion needle (0.8 x 40 mm), carefully turn the syringe over and remove the air from the syringe.

• Octreotide depot suspension should be administered immediately after preparation.

• Octreotide depot suspension should not be mixed with any other drug in the same syringe.

• Use an alcohol swab to disinfect the injection site. Insert the needle deep into the gluteal muscle, then pull the plunger of the syringe back slightly to make sure that there is no damage to the vessel. Enter the suspension intramuscularly slowly with constant pressure on the plunger of the syringe.

• In case of contact with a blood vessel, the injection site and needle should be changed.

• If the needle is clogged, replace it with another needle of the same diameter.

• For repeated injections, the left and right sides should be alternated.

Overdose

Symptoms: short-term decrease in heart rate, a feeling of “rush” of blood to the face, spastic abdominal pain, diarrhea, nausea, a feeling of emptiness in the stomach.

Treatment: symptomatic.

Description

Lyophilized powder or porous, compacted into a tablet, white or white mass with a faint yellowish tinge of color.

Solvent: colorless transparent liquid

Reconstituted suspension: When the solvent is added and shaken, a homogeneous suspension of white or white with a faint yellowish tinge of color is formed. The reconstituted suspension should not exfoliate for at least 5 minutes. When standing, the suspension is deposited, but it is easily resuspended when shaken. The suspension must pass freely into the syringe through needle No. 0840.

Special instructions

For pituitary tumors that secrete GH, careful monitoring of patients receiving Octreotide depot 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, other treatment options should be considered.

Thyroid function should be monitored in patients undergoing long-term treatment with Octreotide depot.

There have been rare reports of bradycardia with octreotide. In this regard, it may be necessary to adjust the dose for drugs such as beta-blockers, calcium channel blockers, or drugs used to control the water-electrolyte balance.

In 10-20% of patients receiving Octreotide depot for a long time, gallstones may appear, so the following recommendations should be taken into account.

Recommendations for the management of patients during treatment with Octreotide-depot in relation to the formation of gallstones.

• prior to the appointment of Octreotide-depo patients should undergo initial ultrasound examination of the gallbladder;

• during treatment with Octreotide-depo should be repeated ultrasound examination of the gallbladder, preferably at intervals of 6-12 months;

• if stones are detected before the treatment, you must assess the potential benefits of therapy with Octreotide-depo compared to the possible risk associated with the presence of gallstones. There are no data on any negative effect of Octreotide-depot on the course or prognosis of pre-existing cholelithiasis.

Management of patients who develop gallbladder stones during treatment with Octreotide-depo.

a) Asymptomatic gallstones.

The use of Octreotide-depo can be discontinued or continued – in accordance with the assessment of the benefit/risk ratio. In any case, there is no need to do anything other than continue monitoring, making it more frequent if necessary.

b) Gallbladder stones with clinical symptoms.

The use of Octreotide-depo can be discontinued or continued – in accordance with the assessment of the benefit/risk ratio. 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, henodeoxycholic acid at a dose of 7.5 mg / kg per day in combination with ursodeoxycholic acid at the same dose) under ultrasound control – until the stones completely disappear.

Patients with insulinomas treated with Octreotide-depot may experience an increase in the severity and duration of hypoglycemia (this is due to a more pronounced suppressive effect on the secretion of GH and glucagon than on insulin secretion, as well as a shorter duration of inhibitory effects on insulin secretion). Such patients should be carefully monitored at the beginning of treatment with Octreotide depot, as well as with each change in the dose of the drug. Significant fluctuations in the concentration of glucose in the blood can be tried to reduce by more frequent use of Octreotide-depot.

During bleeding from varicose veins of the esophagus and stomach in patients with cirrhosis of the liver, the risk of developing insulin-dependent diabetes mellitus is increased, and changes in the need for insulin in patients with diabetes mellitus are also possible; therefore, in these cases, systematic monitoring of blood glucose concentration is necessary.

In patients with type I diabetes, Octreotide depot may reduce the need for insulin. In patients without diabetes mellitus and with type 2 diabetes mellitus with partially preserved insulin secretion, the introduction of Octreotide-depot can lead to a postprandial increase in blood glucose.

In some patients, octreotide may alter intestinal fat absorption, reduce blood vitamin B12 levels, and cause abnormalities in the Shilling test.

Pregnancy and lactation

There is no experience of using the drug during pregnancy, in such cases the drug is prescribed only for absolute indications. Breast-feeding should be discontinued during treatment with Octreotide depot.

Application in pediatrics

There is no experience of using Octreotide-depo in children.

Features of the drug’s effect on the ability to drive a vehicle or potentially dangerous mechanisms

Some side effects of Octreotide depot may negatively affect the ability to drive vehicles and other mechanisms that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in a dry place protected from light at a temperature of 2 C to 8 C.

Keep out of the reach of children!

Expiration date

Lyophilizate – 3 years

Solvent -3 years

Do not use after the expiration date indicated on the package.

Conditions of release from pharmacies

Prescription