In healthy subjects octreotide, like somatostatin, inhibits GH secretion caused by arginine, exercise and insulin-induced hypoglycemia; insulin secretagogue, glucagon, gastrin peptides and other gastro-entero-pancreatic endocrine systems caused by eating, and the secretion of insulin and glucagon stimulated arginine; TSH secretion caused by thyrotropin-releasing hormone. In octreotide, unlike somatostatin, the inhibitory effect on the GH secretion is expressed to a greater extent than on insulin secretion. Introduction of octreotide is not accompanied by the effect hypersecretion of hormones by negative feedback.
In patients with acromegaly administration of octreotide provides the vast majority of persistent decrease in plasma concentrations of GH and normalization of the concentration of insulin-like growth factor 1 (IGF-1).
The majority of patients with acromegaly, octreotide substantially reduces the severity of symptoms such as headache, increased sweating, paresthesia, fatigue, pain in bones and joints, peripheral neuropathy. It has been reported that some patients treated with octreotide pituitary adenomas secreting GH resulted in a decrease in tumor size.
When carcinoid tumors application of octreotide may result in a decrease in severity of disease symptoms, especially such as flushing and diarrhea. In many cases, the clinical improvement is accompanied by decrease of concentration of serotonin in the blood and excretion of 5-hydroxyindoleacetic acid excretion plasma. When tumors are characterized by overproduction, vasoactive intestinal peptide (Vipom), the use of octreotide results in most patients to reduce the severe secretory diarrhea, which 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 reduction of concomitant electrolyte imbalance, eg hypokalaemia, enabling enteral and parenteral cancel the introduction of fluids and electrolytes. According to CT in some patients there is a delay or stop the progression of the tumor, and even decrease its size; metastatic foci in the liver. Clinical improvement is usually accompanied by a decrease (down to normal) concentration of vasoactive intestinal peptide (VIP) in plasma.
When Glucagonomas use of octreotide in most cases leads to a marked reduction in necrotizing erythema migrans, which is characteristic of this condition. Octreotide does not have any significant effect on the severity of diabetes, often observed in Glucagonomas, and typically does not lead to a decrease in the need for insulin or oral hypoglycemic drugs. Patients with diarrhea, octreotide causes its decrease is accompanied by an increase in body weight. In the application of octreotide often faster decrease in the plasma concentration of glucagon, but long-term effect of this treatment is not stored. At the same time, improving the clinical symptoms remains stable for a long time.
When gastrinoma / Zollinger-Ellison syndrome, octreotide, used alone or in combination with blockers of H 2 receptors and proton pump inhibitors, can reduce the formation of hydrochloric acid in the equipoise vs deca stomach and to bring clinical improvement, including and against diarrhea. It is also possible reduction in the severity and other symptoms possibly related to tumor peptide synthesis, including tides. In some cases, there is a decrease gastrin plasma levels.
Patients with insulinomas Octreotide decreases in plasma concentration of immunoreactive insulin. In patients with operable tumors, octreotide may provide restoration and maintenance of normoglycemia in the preoperative period. In patients with inoperable benign or malignant tumors, glycemic control may be improved without simultaneously prolonged decline in insulin concentration in the blood plasma.
Patients with rare tumors occurring overproducing GH releasing factor (somatoliberinomami), octreotide reduces the severity of symptoms of acromegaly. This is apparently due to the suppression of secretion of the growth hormone releasing itself and GR. In the future, may decrease the size of the pituitary gland, which prior to treatment were increased.
Approximately one third of patients with acquired immunodeficiency syndrome (AIDS), suffering from persistent diarrhea, uncontrollable adequate antimicrobial therapy and / or antidiarrheal agents, the use equipoise vs deca of octreotide results in complete or partial normalization chair.
in patients who planned to carry out operations on the pancreas, the use of octreotide during the operation and after it reduces the incidence of typical postoperative complications (eg pancreatic fistula, abscess, sepsis, postoperative acute pancreatitis).
If bleeding from varices of the esophagus and stomach in patients with liver cirrhosis octreotide use in combination with a specific treatment (for example, sclerosing therapy) results in a more effective early stopping bleeding and re-bleeding, transfusion volume reduction and improvement of the 5-day survival. It is believed that the mechanism of action of octreotide associated with reduced blood flow through the suppression of organ such as an VIP vazoaktivngh hormone and glucagon.
Pharmacokinetics. After subcutaneous administration of the drug is rapidly and completely absorbed. The time to reach maximum plasma concentration (5.2 mg / ml at a dose of 0.1 mg) – 30 min.Relationship to plasma proteins – 65%, with form elements of blood – is extremely small. The volume of distribution is 0.27 l / kg. Total clearance – 160 ml / min. The half-life (the T 1/2 ) is 100 minutes. Most of the drug is excreted intestine, about 32% is excreted unchanged by equipoise vs deca the kidneys. After the on / in the elimination is carried out in two phases, with a T 1/2 – 10 minutes and 90 minutes respectively. In elderly patients, the octreotide reduced clearance, and the T 1/2 increases. In severe chronic renal clearance is reduced by 2 times.
- Acromegaly (when adequate control of the disease manifestations is carried out by subcutaneous injection of octreotide, in the absence of a sufficient effect of surgery and radiation therapy to prepare for surgery, to treat between courses of radiation therapy to the development of resistant effect in inoperable patients).
- In the treatment of endocrine tumors of the gastrointestinal (GI) tract and pancreas, when s / c injection of the drug provides adequate control of symptoms of the disease:
• carcinoid tumors with symptoms of carcinoid syndrome;
• insulinoma (to control hypoglycemia in the preoperative period, as well as for maintenance treatment );
• gastrinoma (Zollinger-Ellison syndrome) – usually in combination with proton pump inhibitors and histamine H2 receptor;
• glucagonomas (to control hypoglycemia in the preoperative period, as well as maintenance therapy).
- Somatoliberinomy (tumors characterized by overproduction of GH releasing equipoise vs deca factor).
Genfastat ® is no anticancer agent and its use can lead to a cure of this category of patients.
- Controlling symptoms of persistent diarrhea in AIDS patients
- Prevention of complications after operations on the pancreas; stop bleeding and prevention of rebleeding from esophageal varicose veins in liver cirrhosis (in combination with endoscopic sclerotherapy).
Hypersensitivity to octreotide or other components of the preparation.
Precautions : cholelithiasis, diabetes, pregnancy and lactation.
Pregnancy and lactation
The use of octreotide in pregnant women has not been studied. There is limited experience with the use of octreotide in clinical practice in pregnant patients with acromegaly (half of pregnancy outcome was not known). The majority of patients (cases with known outcome) pregnancies ended in the birth of healthy children, but also reported several spontaneous abortions during the first trimester and in cases of abortion. In the application of octreotide during pregnancy so far no cases of birth defects in children. Pregnant women drug is prescribed only in cases of extreme necessity.
In experimental studies, octreotide had no direct or indirect negative impact on the course of pregnancy, the formation and maturation of the fetus, childbirth and the postnatal development of the animals, with the exception of the time delay of growth.
It is unknown whether octreotide is excreted in breast milk in people, animals marked isolation of the drug in breast milk. If necessary, use during lactation should stop breastfeeding
Dosing and Administration
Preparation Genfastat ® for subcutaneous (s / c) and intravenous (i / v) administration. The initial dose is 50 mg / d n / k 1 or 2 times per day. Thereafter, the number of injections and dosage may be gradually increased starting from tolerability, clinical response and the effects on the concentration of hormones in blood plasma, produced tumors (in the case of carcinoid tumors – effects on the urinary excretion of 5-hydroxyindole acetic acid). The drug is typically used 2-3 times per day. In acromegaly drug is administered subcutaneously in an initial dose of 50-100 ug at intervals of 8 or 12 h later, dose selection based on monthly concentration determinations of GH and IGF-1 in blood (target concentration.: GH <2.5 ng / ml; IGF-1 within the normal range), the analysis of clinical symptoms and tolerability.The majority of patients a daily dosage of 200-300 micrograms. Do not exceed the maximum dose of 1500 mg / day. In patients receiving a stable dose of octreotide, determination of GH concentration in plasma should be performed every 6 months! If after three months. treatment is observed a sufficient reduction in GH concentration in plasma and improving clinical disease, therapy should be discontinued.When endocrine pancreatic tumors gastroenteritis-system – preparatat injected s / c in an initial dose of 50 mg 1-2 times a day. Further, depending on the achieved effect and influence on the concentration of hormones in blood plasma, produced by the tumor (for carcinoid tumors – influence the selection of 5-hydroxyindoleacetic acid excretion), and tolerability, the dose can be gradually increased to 100-200 mg 3 times per day. In exceptional cases, may require higher doses. Supporting dose should be adjusted individually. Carcinoid tumors, if a therapy octreotide maximum tolerated dose for 1 week was not effective, the treatment should not continue. When refractory diarrhea in AIDS patients, the drug is administered s / c in the initial dose of 100 mg 3 times / day. If, after one week of treatment the diarrhea subsides, the dose should be increased individually up to 250 mg three times / day. Dose adjustment is carried out taking into account the dynamics of stool frequency and tolerability. If during a week of treatment with octreotide at a dose of 0.25 mg 3 times per day improvement does not occur, therapy should be discontinued. For the prevention of complications after surgery on the pancreas – n / a, the first dose of 100 mg for 1 h prior to laparotomy after surgery – 100 mg 3 times a day for 7 consecutive days. In exceptional cases, may require higher doses. Supporting dose should be adjusted individually. If therapy is in the maximum tolerated dose is not effective for 1 week, therapy should be discontinued. To stop bleeding from esophageal varicose veins – / drip at a rate of 25 g / h for 5 days. For n / to a avoid multiple injections of the drug in the same place in a short period of time. When i / in the introduction of the drug prior to use contents of the vial for single use or reusable bottle to be diluted in saline. The amount of dilution will depend on the infusion system used and should be modified to provide continuous administration of octreotide with the recommended rate. After the drug was dissolved, the resulting solution should be used within 24 hours. It is necessary to destroy unused solution. The bottle with the preparation for the reusable (200 ug / ml) after the first autopsy should be stored in a refrigerator at 2-8 ° C and use within 15 days. Before use, the solution must be checked for transparency, availability of particles , precipitate, discoloration and leakage, in all cases where this leads to the solution and the packaging material. Do not use the drug if it is cloudy, contains particles, sediment, if it has changed color or traces of sagging.
Use in otdelyshh patient groups
Currently, there is no data that would indicate the need for dose adjustment of the drug in the elderly and in patients with impaired renal function .
Since there is evidence of an increase in half-life of octreotide in patients with cirrhosis of the liver, it is recommended correction maintenance dose in patients with hepatic impairment .
Experience with octreotide in children is limited.
To determine the frequency of adverse reactions, the following criteria were used: very common (> 1/10); common (> 1/100, <1/10); sometimes (> 1/1000, <1/100), rare (> 1/10000, <1/1000), very rare (<1/10000), including isolated reports. From the digestive system: very often – diarrhea, pain abdominal pain, nausea, constipation, bloating; often – dyspeptic disorders, vomiting, feeling of fullness / abdominal heaviness, steatorrhea, soft stool consistency, change in stool color, anorexia; rarely – a progressive abdominal distension, severe epigastric pain, muscle tension of the abdominal wall. From the nervous system: very often – headache; . often – dizziness part of the endocrine system: very often – hyperglycemia; often – hypothyroidism / thyroid dysfunction (reduction in the concentration of thyroid-stimulating hormone, total and free thyroxine); hypoglycemia, violation (decrease) of glucose tolerance. From the hepatobiliary system: very often – cholelithiasis, ie the formation of gallstones; often – cholecystitis, a violation of the colloidal stability of bile (the formation of cholesterol microcrystals), hyperbilirubinemia, increased activity of “liver” transaminases; very rarely – acute pancreatitis; reactive pancreatitis associated with cholelithiasis; acute hepatitis without cholestasis phenomena, jaundice, elevation of blood plasma alkaline phosphatase, gamma-glutamyltransferase. Dermatological reactions:often – itching, rash, hair loss. Immune system: rarely – anaphylactic shock, hypersensitivity reactions. With the respiratory system: often – shortness of breath. On the part of the cardiovascular system:often – bradycardia, sometimes – tachycardia; rarely – arrhythmias General disorders and administration site reactions: often – pain at the injection site, often – asthenia; sometimes – dehydration. anabolic steroids online pharmacy
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