Composition, form of production and packaging
Solution for infusion and s / c of administration is transparent, colorless.
1 ml
octreotide (in the form of acetate) 50 Ојg
Excipients: mannitol - 45 mg, lactic acid - 3.6 mg, sodium hydrogen carbonate - 1.4-2.0 mg, water d / and - 964.85-965.45 mg.
1 ml - ampoules of colorless glass (10) - plastic trays (1) - packs of cardboard.
1 ml - ampoules of colorless glass (10) - plastic trays (2) - cardboard packs.
Solution for infusion and s / c of administration is transparent, colorless.
1 ml
octreotide (in the form of acetate) 100 Ојg
Excipients: mannitol - 45 mg, lactic acid - 3.6 mg, sodium hydrogen carbonate - 1.4-2.0 mg, water d / and - 964.8-965.4 mg.
1 ml - ampoules of colorless glass (10) - plastic trays (1) - packs of cardboard.
1 ml - ampoules of colorless glass (10) - plastic trays (2) - cardboard packs.
Solution for infusion and s / c of administration is transparent, colorless.
1 ml
octreotide (in the form of acetate) 500 Ојg
Excipients: mannitol - 45 mg, lactic acid - 3.6 mg, sodium hydrogen carbonate - 1.4-2.0 mg, water d / and - 964.4-965.0 mg.
1 ml - ampoules of colorless glass (10) - plastic trays (1) - packs of cardboard.
1 ml - ampoules of colorless glass (10) - plastic trays (2) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Synthetic derivative of the hormone somatostatin, which has similar pharmacological effects and significantly longer duration of action. Reduces the secretion of somatotropic hormone, thyroid-stimulating hormone, has antithyroid, spasmolytic action. Reduces acid production, motility of the gastrointestinal tract. Suppresses the pathologically increased secretion of growth hormone, peptides and serotonin produced in the gastroentero-pancreatic endocrine system.
Normally reduces the secretion of growth hormone caused by arginine, stress and insulin hypoglycemia, the secretion of insulin, glucagon, gastrin and other peptides of the gastroentero-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.
PHARMACOKINETICS
After sc administration, absorption is fast and complete. C max in blood plasma is 30 minutes. C max in blood plasma 5.2 mg / ml with a dose of 0.1 mg. 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.
T 1/2 after the SC administration - 100 minutes. About 32% of octreotide is excreted unchanged by the kidneys, the rest through the intestine. After intravenous administration, 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 1/2 increases.
In severe chronic renal failure, the clearance decreases by a factor of 2.
INDICATIONS
- Acromegaly (in the absence of sufficient effect from surgical treatment, radiation therapy and treatment with dopamine receptor agonists, in inoperable patients, as well as in patients who refused surgical treatment);
- relief of symptoms of tumors of the gastroentero-pancreatic endocrine system (carcinoid tumors with carcinoid syndrome, tumors characterized by hyperproduction of the vasoactive intestinal peptide, -VIPomas, glucagonoma, gastrinomas / Zollinger-Ellison syndrome);
- insulinoma (for the control of hypoglycemia in the preoperative, as well as as maintenance therapy);
- tumors characterized by hyperproduction of somatoliberin somatoliberinoma;
- refractory diarrhea in AIDS patients;
- prevention of complications after operations on the pancreas;
- stop bleeding and prevent bleeding from varicose veins of the esophagus with cirrhosis of the liver (in combination with endoscopic sclerosing therapy).
DOSING MODE
P / to, in / in a drip.
A / c, with acromegaly - in the initial dose of 0.05-0.1 mg, with intervals of 8 or 12 hours. Further dose selection is based on monthly determinations of the concentration of growth hormone (GH) and IGF1 in the blood (GH values ​​should be <2.5 ng / ml, and the value of IGF1 should be within the physiological norm), analysis of clinical symptoms and drug tolerability. In most patients, the optimal daily dose is 0.3 mg. Do not exceed the maximum daily dose of 1.5 MG. If after 3 months of treatment there is no sufficient reduction of growth hormone and an improvement in the clinical picture of the disease, therapy should be discontinued.
With endocrine tumors of the gastroentero-pancreatic system - sc, in the initial dose of 0.05 mg, 1-2 times per day. In the future, 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 0.1-0.2 mg 3 times a day. In some cases, a higher dose of the drug may be required. The maintenance dose should be selected individually.
If after 1 week of treatment with the drug Octreotide-Aktavis of a carcinoid tumor, when receiving the maximum tolerated dose, there is no sufficient improvement in the clinical picture of the disease, therapy should be discontinued.
With refractory diarrhea in patients with AIDS - p / k, at an initial dose of 0.1 mg 3 times a day. If after 1 week of treatment the diarrhea does not stop, the dose is increased (under condition of normal tolerability) to 0.25 mg 3 times a day. If the therapy is ineffective for 1 week (at a dose of 0.25 mg 3 times a day), the treatment is stopped.
For prophylaxis of complications after operations on the pancreas, enter 0.1 mg 3 times a day for 7 consecutive days, starting from the day of surgery (but at least 1 hour before laparotomy).
To stop bleeding from the varicose-esophageal veins of the esophagus - iv drip at a rate of 0.025 mg / h for 1-2 days. In patients with a high risk of bleeding, the infusion of the drug should be continued, but not more than 5 days. The drug Octreotide-Aktavis can be administered when diluted with saline.
Older patients do not need a dose adjustment.
Patients with impaired hepatic function
In patients with liver cirrhosis, T 1/2 may increase, which requires dose adjustment. This does not apply to patients with fatty liver degeneration.
Patients with impaired function of night
With subcutaneous administration, a decrease in renal function does not affect the area under the concentration-time curve of octreotide. In this connection, do not require dose adjustment in this group of patients.
Octreotide acetate (active substance of the drug) is not stable in preparations for parenteral nutrition.
Application rules
With n / to the introduction:
Patients who self-administer subcutaneous injection of Octreotide-Actavis should receive detailed instructions from a doctor or nurse. For the introduction of SC injections, dilution of the drug is not required.
Avoid multiple injections in the same place at short intervals. To prevent the appearance of a sense of discomfort at the injection site, the solution should have room temperature.
Ampoules should be opened immediately before the administration of the solution. Unused solution should be disposed of.
With IV introduction:
Before administration, the solution should be inspected, it should be colorless and without visible foreign particles.
The drug Octreotide-Actavis is physically and chemically stable in sterile saline or sterile 5% aqueous dextrose (glucose) solution for 24 hours. However, in view of the fact that octreotide can influence glucose metabolism, it is preferable to use saline for dilution. The prepared solution is physiologically and chemically stable at a temperature below 25 В° C for 24 hours. To avoid microbial contamination, dilute solutions should be used immediately after preparation. If the solution is not used immediately after dilution, it should be stored at 2-8 В° C until it is applied. Before administration, the solution should be held at room temperature. The period including dilution of the solution, its storage in the refrigerator and the last administration to the patient, should not exceed 24 hours.
In the case of the administration of Octreotide-Actavis in the form of infusions, a concentration solution of 0.5 mg / ml is usually used, diluted in 60 ml of saline.Infusion is repeated at the required frequency in accordance with the recommended duration of treatment. Octreotide-Actavis can also be used in lower concentrations.
SIDE EFFECT
Determination of the frequency of unwanted reactions: very often (> 1/10), often (> 1/100, <1/10), sometimes (> 1/1000, <1/100), rarely (> 1/10 000, < 1/1000), very rarely (<1/10 000), including individual messages.
From the digestive system: often - diarrhea, spastic abdominal pain, constipation, flatulence; sometimes - cholecystitis; rarely - steatorrhea, nausea, vomiting, bloating, the formation of stones in the gallbladder; very rarely - acute pancreatitis, anorexia, loose stools, acute hepatitis without the phenomena of cholestasis, hyperbilirubinemia, increased activity of alkaline phosphatase and "liver" enzymes.
Dermatological reactions: sometimes - temporary hair loss.
From the cardiovascular system: sometimes - bradycardia, tachycardia.
Allergic reactions: rarely - hypersensitivity, rash; very rarely anaphylaxis.
On the part of the endocrine system: very rarely - hypoglycemia, hyperglycemia.
From the respiratory system: very rarely - shortness of breath.
Local reactions: pain, itching or burning sensation, redness and swelling at the site of the injection (usually within 15 minutes). 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.
Other
It was reported that very rare cases of acute pancreatitis, which developed in the first hours or days of application and disappeared after drug withdrawal. In addition, with prolonged use of SC, there have been cases of pancreatitis associated with cholelithiasis.
CONTRAINDICATIONS
- Children's age till 18 years (experience of application is limited);
hypersensitivity to the components of the drug.
With caution: cholelithiasis, diabetes, pregnancy, lactation.
PREGNANCY AND LACTATION
The experience with octreotide in pregnant women is limited. Octreotide-Actavis 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 discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
With subcutaneous administration, a decrease in renal function does not affect the area under the concentration-time curve of octreotide. In this connection, do not require dose adjustment in this group of patients.
Octreotide acetate (active substance of the drug) is not stable in preparations for parenteral nutrition.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with liver cirrhosis, T 1/2 may increase, which requires dose adjustment. This does not apply to patients with fatty liver degeneration.
APPLICATION FOR CHILDREN
Contraindicated in children under 18 years.
APPLICATION IN ELDERLY PATIENTS
Older patients do not need a dose adjustment.
SPECIAL INSTRUCTIONS
Precautions for use
With tumors of the pituitary gland, careful monitoring of patients is necessary because of the possible increase in the size of tumors with the development of narrowing of the visual fields. In these cases, consideration should be given to the need for other treatments.
In patients with somatoliberinoma, in the absence of the possibility of surgery or radiation therapy may require long-term treatment.
In the treatment of gastroentero-pancreatic endocrine tumors, a sudden relapse of symptoms may occur in rare cases.
As a result of a sharp cessation of therapy, a sudden relapse of symptoms may occur.
In patients with insulinomas against the background of treatment with the drug Octreotide-Actavis, there may be an increase in the severity and duration of hypoglycemia. Before starting treatment with Octreotide-Actavis, patients with insulinoma should be hospitalized and monitored during treatment. Each dose change requires careful monitoring of the patient's condition. Fluctuations in blood glucose concentration can be reduced by more frequent administration of smaller doses.Patients with type 1 diabetes mellitus may need a reduction in insulin dose during treatment with Octreotide-Actavis. In patients not suffering from diabetes mellitus and with type 2 diabetes mellitus with partially preserved insulin secretion, the administration of the drug may lead to postprandial hyperglycemia. Long-term treatment with Octreotide-Aktavis may lead to impaired glucose tolerance or worsening of the course of diabetes mellitus. The doctor should be ready to develop the patient's symptoms of hypoglycemia. During the period of treatment, a systematic control of blood glucose concentrations (every 6 months or more, if necessary), especially in patients with bleeding from esophageal varices in cirrhosis, increases the risk of developing hyperglycemia.
During therapy with the drug Octreotide-Actavis, the fat content in the feces may increase and the exocrine function of the pancreas may be disrupted. Although the release of fat with feces may increase, there is no evidence to date that prolonged treatment with octreotide can lead to malnutrition due to malabsorption.
In the case of prolonged therapy, it is recommended to control the level of secretion of fats through the intestine.
The severity of side effects from the gastrointestinal tract decreases with the introduction of the drug in the intervals between meals or at bedtime.
For long-term treatment (acromegaly), an ultrasound examination of the gallbladder should be performed before and during treatment (every 6-12 months). Stones in the gallbladder, if nevertheless they are found, as a rule, are asymptomatic. In the presence of clinical symptoms, conservative or surgical treatment is indicated.
Impact on the ability to drive vehicles and manage mechanisms
Some of the side effects of octreotide can adversely affect the ability to drive vehicles and other mechanisms that require increased concentration and speed of the speed of psychomotor reactions. In this regard, it is recommended that when exercising these symptoms, care should be taken when driving vehicles or mechanisms requiring increased concentration of attention.
OVERDOSE
Symptoms: short-term decrease in the heart rate, "tides" of blood to the face, abdominal pain of a spastic nature, diarrhea, nausea, sensation of emptiness in the stomach.
Treatment: symptomatic.
DRUG INTERACTION
Reduces the absorption of cyclosporine, slows the absorption of cimetidine.
Octreotide can interact with fat-soluble substances.
With the simultaneous use of the drug Octreotide-Actavis and bromocriptine, the bioavailability of the latter increases.
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 similar effects of the ocreotide, drugs metabolized by enzymes of the cytochrome P450 system and having a narrow therapeutic range of doses should be administered with caution (eg, quinidine, terfenadine).
TERMS OF RELEASE FROM PHARMACY
On prescription.
TERMS AND CONDITIONS OF STORAGE
In the original packaging, in the dark place at a temperature of 2 В° to 8 В° C. Do not freeze! Keep out of the reach of children! Shelf life - 3 years.
