Composition, form of production and packaging
Lyophilizate for the preparation of a suspension for the / m administration of prolonged action of white or white with a weak yellowish hue, in the form of a powder or a porous, tablet-packed mass; the applied solvent is a colorless transparent liquid; the prepared suspension is white or white with a weak yellowish hue of color, homogeneous.
1 f.
octreotide 10 mg
Excipients: DL-lactic and glycolic acid copolymer 270 mg, D-mannitol 85 mg, carboxymethyl cellulose sodium salt 30 mg, polysorbate 80 mg 2 mg.
Solvent: mannitol, solution for injection 0.8% - 2 ml.
Vials of dark glass with a capacity of 10 ml (1) complete with a solvent (1 pc.), Disposable syringe, needles (2 pcs.) And alcohol swabs (2 pcs.) - packings, cardboard.
Lyophilizate for the preparation of a suspension for the / m administration of prolonged action of white or white with a weak yellowish hue, in the form of a powder or a porous, tablet-packed mass; the applied solvent is a colorless transparent liquid; the prepared suspension is white or white with a weak yellowish hue of color, homogeneous.
1 f.
octreotide 20 mg
Excipients: DL-lactic and glycolic acid copolymer - 560 mg, D-mannitol - 85 mg, carboxymethyl cellulose sodium salt - 30 mg, polysorbate-80 - 2 mg.
Solvent: mannitol, solution for injection 0.8% - 2 ml.
Vials of dark glass with a capacity of 10 ml (1) complete with a solvent (1 pc.), Disposable syringe, needles (2 pcs.) And alcohol swabs (2 pcs.) - packings, cardboard.
Lyophilizate for the preparation of a suspension for the / m administration of prolonged action of white or white with a weak yellowish hue, in the form of a powder or a porous, tablet-packed mass; the applied solvent is a colorless transparent liquid; the prepared suspension is white or white with a weak yellowish hue of color, homogeneous.
1 f.
octreotide 30 mg
Excipients: DL-lactic and glycolic acid copolymer 850 mg, D-mannitol 85 mg, carboxymethyl cellulose sodium salt 30 mg, polysorbate 80 mg 2 mg.
Solvent: mannitol, solution for injection 0.8% - 2 ml.
Vials of dark glass with a capacity of 10 ml (1) complete with a solvent (1 pc.), Disposable syringe, needles (2 pcs.) And alcohol swabs (2 pcs.) - packings, cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
The drug Octreotide Depot is a long-acting octreotide dosage form for intramuscular injection, which ensures the maintenance of stable therapeutic concentrations of octreotide in the blood for 4 weeks. Octreotide is a pathogenetic therapy for tumors that actively express somatostatin receptors. 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 (GH), as well as peptides and serotonin produced in the gastrointestinal pancreatic 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 gastro-entero-pancreatic 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 the depot form of octreotide provides, in the vast majority of cases, a persistent decrease in the concentration of GH and the normalization of the concentration of insulin-like growth factor 1 / somatomedin C (IGF-1).
In most patients with acromegaly, the depot form of octreotide significantly reduces the severity of such symptoms as headache, increased sweating, paresthesia, fatigue, pain in the bones and joints, peripheral neuropathy. It was reported that treatment with the depot form of octreotide of individual patients with pituitary adenomas secreting GH led to a decrease in tumor size.
When secreting endocrine tumors of the gastrointestinal tract (GIT) and pancreas, the use of the depot form of octreotide provides a constant control of the main symptoms of these diseases.
The depot form of octreotide at a dose of 30 mg every 4 weeks slows tumor growth in patients with secreting and non-secretive common (metastatic) neuroendocrine tumors of lean, iliac, blind,
ascending colon, transverse colon and vermiform appendage, or metastases of neuroendocrine tumors without a primary focus. The drug was effective in increasing the time to progression, both for secreting and for non-secreting neuroendocrine tumors.
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
reduction of serotonin concentration in plasma and excretion of 5-hydroxyindoleacetic acid in 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 with glucagonomes, and usually does not lead to
to reduce 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 plasma glucagon concentration, but this effect does not persist with long-term treatment. At the same time, symptomatic improvement remains stable for a long time.
In gastrinomas / Zollinger-Ellison syndrome, octreotide, used as a monotherapy or in combination with Hg-histamine receptor blockers 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
In cases with insulinomas, octreotide reduces the concentration of immunoreactive insulin in the blood. In patients with operable tumors, octreotide can provide restoration and maintenance of normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, glycemic control can be improved without simultaneous
a continuous decrease in the concentration of insulin in the blood.
In patients with rare tumors, hyper-producing growth hormone releasing factor (somatoliberinomas), octreotide reduces the severity of the symptoms of acromegaly.This, apparently, is due to the suppression of the secretion of the releasing factor of growth hormone and the GH itself. In the future, it is possible to reduce the size of the pituitary gland, which was increased before the start of treatment.
In patients with hormone-resistant prostate cancer (HRHR), a pool of neuroendocrine cells expressing somatostatin receptors, affinity to octreotide (SS2 and SS5 types) increases, which determines the sensitivity of the tumor to octreotide. The use of Octreotide Depot in combination with dexamethasone against the background of androgen blockade (medication or surgical castration) in patients with PGRM restores sensitivity to hormone therapy and leads to a decrease in prostate specific antigen (PSA) in more than 50% of patients.
In patients with PGRD with metastases in the bone, this therapy is accompanied by a pronounced and prolonged analgesic effect. In this case, all patients who responded to combination therapy with Octreotide Depot significantly improve quality of life and median disease-free survival.
PHARMACOKINETICS
Data on the pharmacokinetics of Octreotide Depot is not available.
INDICATIONS
In the therapy of acromegaly:
- when adequate control of the manifestations of the disease is realized due to the / o introduction of octreotide;
- in the absence of sufficient effect from surgical treatment and radiation therapy;
- for preparation for surgical treatment;
- for treatment between radiotherapy courses before the development of a persistent effect;
- in inoperable patients.
In the therapy of endocrine tumors of the gastrointestinal tract 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);
- somatoliberynomas (tumors characterized by hyperproduction of growth hormone releasing factor);
- treatment of patients with secreting and non-secretive widespread (metastatic) neuroendocrine tumors of lean, iliac, blind, ascending colon, transverse colon and appendix, or metastases of neuroendocrine tumors without a primary focus.
In the treatment of hormone-resistant prostate cancer:
- as part of a combination therapy on the background of surgical or drug 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 tumor lesions of the liver).
DOSING MODE
The drug Octreotide Depot should be administered only deep intramuscularly (IM), in the gluteal muscle. With repeated injections, the left and right sides should alternate. Suspension should be prepared immediately before injection. On the day of injection, the vial with the preparation and the ampoule with the solvent can be kept at room temperature.
In the treatment of acromegaly in patients for whom the octreotide administration provides adequate control of the manifestations of the disease , the recommended initial dose of Octreotide Depot is 20 mg every 4 weeks for 3 months. You can start treatment with Octreotide Depot by the next day after the last SC administration of octreotide. In the future, the dose is adjusted taking into account the concentration in the serum of GH and IGF-1, as well as clinical symptoms. If after 3 months of treatment an adequate clinical and biochemical effect could not be achieved (in particular, if the GH concentration remains above 2.5 Ојg / L), the dose can be increased to 30 mg administered every 4 weeks.
In those cases when after 3 months of treatment with Octreotide Depot at a dose of 20 mg there is a persistent decrease
serum GH concentration below 1 Ојg / l, normalization of IGF-1 concentration and disappearance of reversible symptoms of acromegaly, it is possible to reduce the dose of Octreotide Depot to 10 mg. However, in these patients receiving a relatively small dose of Octreotide Depot, serum concentrations of GH and IGF-1, as well as the symptoms of the disease, should be carefully monitored.
Patients receiving a stable dose of Octreotide Depot, the determination of the concentrations of GH and IGF-1 should be performed every 6 months.
Patients in whom surgical treatment and radiotherapy are not effective or generally ineffective, as well as patients who need short-term treatment between the radiotherapy courses and the time of its full effect, it is recommended that a trial of treatment with octreotide supplements be made to evaluate it efficiency and general tolerability, and only after this switch to the use of Octreotide Depot according to the above scheme.
In the treatment of endocrine tumors of the gastrointestinal tract and pancreas in patients to whom SC administration of octreotide provides adequate control of the manifestations of the disease, the recommended initial dose of Octreotide Depot is 20 mg every 4 weeks. S / o administration of octreotide should continue for another 2 weeks after the first administration of Octreotide Depot.
In patients who have not received octreotide earlier, it is recommended to start treatment with octreotide at a dose of 0.1 mg 3 times a day for a relatively short period of time (about 2 weeks) to assess its effectiveness and overall tolerance. Only after this, the Octreotide Depot is prescribed according to the above scheme.
In the case when therapy with Octreotide Depot for 3 months provides adequate control of clinical manifestations and biological markers of the disease, it is possible to reduce the dose of Octreotide Depot up to 10 mg,
appointed every 4 weeks. In those cases when, after 3 months of treatment with Octreotide Depot, only partial improvement was achieved, the dose of the drug can be increased to 30 mg every 4 weeks. On the background of treatment with the drug Octreotide Depot on certain days, it is possible to increase the clinical manifestations characteristic of endocrine tumors of the gastrointestinal tract and pancreas. In these cases, an additional SC administration of octreotide is recommended in the dose used before the beginning of treatment with Octreotide Depot. This can occur mainly in the first 2 months of treatment, until the therapeutic concentrations of octreotide in plasma are reached.
Secreting and non-secretive common (metastatic) neuroendocrine tumors of lean, iliac, blind, ascending colon, transverse colon and appendix, or metastases of neuroendocrine tumors without a primary focus: the recommended dose of Octreotide Depot is 30 mg every 4 weeks. Therapy with Octreotide Depot should be continued until signs of tumor progression.
In the treatment of hormone-resistant prostate cancer, the recommended initial dose of Octreotide Depot is 20 mg every 4 weeks for 3 months. In the future, the dose is corrected taking into account the dynamics of serum PSA concentration, as well as clinical symptoms. If after 3 months of treatment it was not possible to reach
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 by mouth as follows: 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 Depot and dexamethasone in patients who had previously undergone drug and anti-androgen therapy are combined with the use of a gonadotropin-releasing hormone (GnRH) analogue. In this case, an injection of the GnRH analogue (depot form) is carried out once every 4 weeks.
Patients receiving the Octreotide Depot drug should be assessed every month.
In patients with impaired renal, hepatic and elderly patients, there is no need to correct the dosage regimen of Octreotide Depot.
For the prevention of acute postoperative pancreatitis , Octreotide Depot in a dose of 10 or 20 mg is administered only once, not more than 5 days and no later than 10 days before the proposed surgical intervention.
Rules for the preparation of suspension and drug administration
The drug is administered only in / m. The suspension for the IM injection is prepared with the help of the applied solvent immediately before administration. The drug should be prepared and administered only by specially trained medical personnel.
Before the injection, the ampoule with the solvent and the vial with the drug must be removed from the refrigerator and brought to room temperature (30-50 min is required). Vial Octreotide depot hold vertically. Easily tapping the vial until you get to the whole lyophilisate was at the bottom of the vial.
Unpack attach a syringe to the syringe needle size 1.2 mm MMX 50 for collecting the solvent. Open the solvent vial and syringe type in the entire contents of the vial with the solvent, set the syringe per dose 2.0 ml. Remove plastic cap from the vial containing the lyophilisate. Disinfect the rubber stopper of the vial with an alcohol swab. Insert the needle into the vial with lyophilisate through the center of the rubber stopper and carefully enter the solvent on the inner wall of the vial without touching the contents of the bottle needle.
Remove the syringe from the vial. The bottle must remain stationary until complete impregnation solvent lyophilizate and form a suspension (approximately 3-5 minutes). Then, without turning the bottle, check the presence of dry lyophilisate in the walls and bottom of the vial. Upon detection of dry residues left lyophilisate vial until complete impregnation.
Once you have seen in the absence of residual dry lyophilisate, the vial contents should gently mix in a circular motion for 30-60 seconds to form a uniform suspension. Do not turn and shake the bottle, it can lead to flocculation and the unsuitability of the suspension.
Quickly insert the needle through the rubber stopper into the vial. Then the needle is lowered down cut and bent vial at 45 degrees, to slowly enter the syringe completely suspension. Do not invert the vial when typing. A small amount of the drug can remain on the walls and bottom of the vial. Consumption for the rest of the walls and bottom of the vial is taken into account.
Immediately after dialing slurry replace the needle with the needle pink pavilion with green pavilion (0.8 x 40 mm), gently invert the syringe and remove air from the syringe.
The suspension of the drug Octreotide depot should be administered immediately after preparation. The suspension of the drug Octreotide depot should not be mixed with any other drug in the same syringe.
With the help of an alcohol swab disinfect the injection site. Insert the needle deep into the gluteal muscle, then lightly pull the plunger back, to make sure that there is no damage to the vessel. Enter suspension intramuscularly slowly with constant pressure on the plunger of the syringe.
When injected into the blood vessel to be changed and the injection needle. When plugging of the needle is replaced it with another needle of the same diameter.
With repeated injections of the left and right side should be alternated.
SIDE EFFECT
Local reactions: when i / m administration of Octreotide depot may be a pain, less swelling and a rash at the injection site (usually mild, short-lived).
On the part of the digestive tract:anorexia, nausea, vomiting, abdominal cramping, bloating, excessive gas, loose stools, diarrhea, steatorrhea. Although fat excretion in feces can be increased, to date there is no evidence that long-term treatment with octreotide may lead to deficiency of certain nutrients due to malabsorption (malabsorption). In rare cases, it can be observed phenomena resemble acute intestinal obstruction: a progressive abdominal distension, severe epigastric pain, tension of the abdominal wall. Prolonged use of Octreotide depot may result in the formation of gallstones.
On the part of the pancreas:It reported rare cases of acute pancreatitis that developed in the first hours or days of use of octreotide. With prolonged use there have been cases of pancreatitis associated with cholelithiasis.
Liver: There are some reports about the development of liver function (acute hepatitis without cholestasis with normalization of transaminase levels after discontinuation of octreotide); the slow development of hyperbilirubinemia associated with increased rates of alkaline phosphatase, GGT, and, to a lesser extent, other transaminases.
From a metabolism:Octreotide as depot has inhibitory effect on the formation of GH, glucagon and insulin, it can influence the glucose metabolism. May decrease glucose tolerance after a meal. With prolonged use of Octreotide p / c in some cases, may develop persistent hyperglycemia. There were also the state of hypoglycemia.
Other: In rare cases it was reported on the temporary hair loss after administration of octreotide occurs bradycardia, tachycardia, shortness of breath, skin rash, anaphylaxis. There are some reports about the development of hypersensitivity reactions.
CONTRAINDICATIONS
- hypersensitivity to octreotide or to other components of the drug.
With about ive should be prescribed with cholelithiasis, diabetes, pregnancy and lactation.
PREGNANCY AND LACTATION
Experience of using Octreotide depot during pregnancy and breastfeeding period is not available.
Therefore, during pregnancy the drug should be administered only if the potential benefit to the mother outweighs the potential risk to the fetus.
Not recommended for breast-feeding when used during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with renal impairment is not necessary to correct dosing regimen Octreotide depot.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with impaired hepatic function it is not necessary to correct dosing regimen Octreotide depot.
APPLICATION IN ELDERLY PATIENTS
In elderly patients there is no need to correct dosing regimen Octreotide depot.
SPECIAL INSTRUCTIONS
When tumors of the pituitary, secreting GH, the patients must be carefully monitored, since may increase the size of the tumors with the development of serious complications such as narrowing of the visual field. In these cases, consideration should be given to the need for other treatments.
In 15-30% of patients receiving octreotide n / a for a long time, may cause gallstones. The prevalence in the general population (age 40-60 years) is 5-20%.Experience of prolonged treatment with octreotide long-acting patients with acromegaly and gastrointestinal tumors and pancreas suggests that octreotide long-acting in comparison with the short-acting octreotide does not lead to an increase in the frequency of formation of gallstones. However, we recommend holding ultrasound of the gallbladder before starting treatment with octreotide depot and about 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 shown conservative treatment (e.g., use of bile acids preparations) or surgical intervention.
In patients with type 1 diabetes Octreotide depot can affect glucose metabolism and therefore reduces the need of insulin. For patients with diabetes type 2 and patients without concomitant disorders of carbohydrate metabolism p / Octreotide injection may result in postprandial glycemia. In this regard, to regularly monitor blood glucose concentration and if necessary corrected hypoglycemic therapy.
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). Displaying systematic monitoring of these patients.
Prior to the appointment of octreotide patients should undergo initial ultrasound gallbladder. During treatment with octreotide depot should be repeated ultrasound examination of the gallbladder, preferably at intervals of 6-12 months.
When the gall bladder stones are detected before the start of the treatment, it is necessary to evaluate the potential benefits of therapy with octreotide depot compared with the possible risk associated with the presence of gallstones.
Currently, there is no any evidence that octreotide depot adversely affects the course or prognosis existing cholelithiasis.
Keeping patients with gall bladder stones are formed during treatment with octreotide depot
a) Asymptomatic gallstones. The use of Octreotide depot can stop or continue - in line with the assessment of benefit / risk ratio. In any case, it does not require any other measures, in addition to the continuation of the inspections, making them more frequent if necessary.
b) Gallstones symptomatic.The use of Octreotide depot can stop or continue, in accordance 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 / day in combination with ursodeoxycholic acid at the same dose) under ultrasound guidance - until complete disappearance of stones.
Impact on the ability to drive vehicles and manage mechanisms
Currently, there are no data on the effect of Octreotide depot on the ability to control the car and work with mechanisms that require attention and speed of mental and motor responses.
OVERDOSE
Currently, the cases of drug overdose Octreotide depot were reported.
DRUG INTERACTION
Octreotide reduces absorption from the intestinal absorption of cyclosporin and slows cimetidine.
With simultaneous application of octreotide and bromocriptine increases the bioavailability of the latter.
There are literature data that the somatostatin analogs can reduce the metabolic clearance of substances metabolized by cytochrome P450 isozymes, which may be caused by suppression of GH. Since it is impossible to exclude such octreotide effects of drugs metabolized by cytochrome P450 isozymes system and having a narrow therapeutic range (quinidine and terfenadine) should be used with caution.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in a dry place, protected from light, out of reach of children at a temperature of from 2 В° to 8 В° C. Shelf life - 3 years.
