Oktreotid

Oktreotid – the drug having somatostatinopodobny effect.

Form of release and structure

Dosage form – solution for intravenous and hypodermic administration: transparent, colourless, inodorous (on 1 ml in ampoules: in a dose of 50 and 100 mkg/ml – on 5 ampoules in blister strip packagings, in a pack cardboard 1 or 2 packagings; in a dose of 300 and 600 mkg/ml – on 1, 2 or 5 ampoules in blister strip packagings, in a pack cardboard 1 (on 1, 2 or 5 ampoules) or 2 (on 5 ampoules) packagings).

Active ingredient – октреотид (in the form of acetate), its contents in 1 ml of solution makes 50, 100, 300 or 600 mkg.

Inactive components: sodium chloride and injection water.

Indications to use

• Bleeding stop from varicose expanded veins of a gullet and a stomach at patients with cirrhosis and prevention of a recurrence (in a combination with endoscopic sclerosing therapy or other specific medical actions);
• Acromegalia – for control of symptomatology of a disease and decrease in an insulinopodobny growth factor-1 (IFR-1) and a growth hormone in a blood plasma in cases when the effect of performing beam or surgical treatment is not enough; for treatment of a disease in those cases if the patient refused operation or has contraindications to its carrying out; for short-term treatment in intervals between courses of radiation therapy until obtaining effect of its carrying out;
• The cosecreting endocrine tumors of a pancreas and digestive tract (for control of symptoms): glucagonomas, somatoliberinoma, Vipoma, carcinoid tumors with existence of a carcinoid syndrome, insulinoma (for a maintenance therapy, and also for control of a hypoglycemia in the preoperative period), gastrinoma and Zollingera-Ellison's syndrome (usually in a combination with blockers histamine _{H2 receptors} and inhibitors of a proton pomp);
• Treatment of acute pancreatitis;
• Treatment and prevention of complications after surgical interventions on belly bodies;
• Bleeding stop at a peptic ulcer of a stomach and a 12-perstny gut.

Contraindications

Oktreotid's use is strictly contraindicated to children and teenagers up to 18 years, and also to all patients in the presence at them hypersensitivity to any component of drug.

With care medicine needs to be applied at treatment of patients with a diabetes mellitus and cholelithiasis (cholelithiasis).

Influence of drug on the course of pregnancy was not studied therefore its use is possible only in extreme cases if the estimated advantage exceeds possible risks.

Whether gets октреотид into breast milk, it is unknown therefore for the period of treatment it is recommended to refuse breastfeeding.

Route of administration and dosage

Oktreotid is intended for hypodermic (п / to) and intravenous (in/in) introductions.

The appointed dosing modes depending on indications and the purpose of use:

• Treatment of acute pancreatitis: on 100 mkg п / to 3 times a day within 5 days. In some cases the doctor can advise in/in administration of drug in a daily dose up to 1200 mkg;
• Prevention of complications after pancreas operation: on 100-200 mkg п / to. The first dose is entered in 1-2 hours prior to a laparotomy, after operation – 3 times a day within 5-7 days;
• Stop of ulcer bleeding: on 25-50 mkg/hour in a look in/in infusions, a course – 5 days;
• Bleeding stop from varicose expanded veins of a gullet and a stomach: on 25-50 mkg/hour in the form of long in/in infusions, a course of treatment – 5 days;
• Acromegalia: an initial dose – 50-100 mkg п / to each 8 or 12 hours. In case of inefficiency (target concentration of a growth hormone makes less than 2,5 ng/ml, and the indicator of IFR-1 is in limits of normal values) the single dose is raised to 300 mkg. The most admissible daily dose makes 1500 mkg. At the patients receiving октреотид in a stable dose, each 6 months need to be defined growth hormone level. If after 3 months of treatment there is no sufficient decrease in this indicator and improvement of a clinical course of a disease, drug should be cancelled;
• Tumors of gastroenteropankreatichesky endocrine system: an initial dose – on 50 mkg 1-2 times a day, in need of it gradually increase up to 100-200 mkg 3 times a day п / to. In case of inefficiency (it is estimated proceeding from data on the reached clinical effect, concentration of hormones which produce a tumor, and portability of drug) the dose is increased to 300 mkg п / to 1-2 times a day. In exceptional cases perhaps bigger increase in a dose – to 300-600 mkg 3 times a day. The doctor chooses maintenance doses for each patient individually. If at carcinoid tumors within 1 week therapy in the maximum tolerable dose was inefficient, drug is cancelled.

Patients with abnormal liver functions need correction of a maintenance dose.

Rules of hypodermic introduction of Oktreotid:

• It is attentive to examine an ampoule regarding existence in solution of foreign impurity and discoloration;
• To heat an ampoule to room temperature;
• To open an ampoule just before introduction;
• To throw out unused amount of solution;
• Not to do an injection to the same place through short periods.

Rules of intravenous drop administration:

• It is attentive to examine an ampoule regarding availability of foreign impurity and discoloration;
• To heat solution to room temperature;
• For cultivation to use 0,9% of sodium chloride (for example, 1 ampoule of 600 mkg is diluted with 60 ml of physical solution);
• To prepare injection solution just before introduction;
• If necessary to store no more than 24 hours after cultivation in the refrigerator (at a temperature from 2 to 8 ºС).

Side effects

Criteria for evaluation of frequency of development of side effects: very often – is not more often than in 1 case from 10, it is frequent – ≥1/100, but <1/10, sometimes – ≥1/1000, but <1/100.

The undesirable reactions revealed during clinical trials of drug:

• From the alimentary system: very often – diarrhea or locks, abdominal distention, nausea, an abdominal pain; often – a steatorrhea, chair discoloration, feeling of filling or weight of a stomach, a soft consistence of a chair, dispepsichesky disturbances, anorexia, vomiting;
• From gepatobiliarny system: stones in a gall bladder (cholelithiasis); often – increase in activity of hepatic transaminases, cholecystitis, a hyperbilirubinemia, formation of microcrystals of cholesterol owing to disturbance of colloid stability of bile;
• From cardiovascular system: often – bradycardia; sometimes – tachycardia;
• From endocrine system: very often – a hyperglycemia; often – a hypoglycemia, disturbance of tolerance to glucose, a hypothyroidism, dysfunction of a thyroid gland (it is shown by decrease in levels of thyritropic hormone, general and free thyroxine);
• From respiratory system: often – an asthma;
• From a nervous system: very often – a headache; often – dizziness;
• Dermatological reactions: often – rash, an itch, a hair loss;
• Local reactions: very often – pain in the place of an injection;
• Others: sometimes – dehydration.

Relationship of cause and effect of the following side effects using Oktreotid is not established:

• From gepatobiliarny system: a cholestasia, jaundice, cholestatic hepatitis, an acute hepatitis without the cholestasia phenomena, cholestatic jaundice, acute pancreatitis, increase in level gamma глутамилтрансферазы and an alkaline phosphatase;
• From immune system: hypersensitivity reactions, anaphylactic reactions;
• From cardiovascular system: arrhythmias;
• Dermatological reactions: small tortoiseshell.

Special instructions

Women of childbearing age with an acromegalia during therapy should use reliable methods of contraception since at decrease in level of a growth hormone and normalization of the IFR-1 level under the influence of an oktreotid recovery of genital function is possible.

At prolonged treatment it is necessary to control function of a thyroid gland.

At patients with anamnestic data on existence of deficit _{of B12 vitamin} it is necessary to control the content of cobalamine in an organism.

Before Oktreotid's appointment of patients it is necessary to direct to ultrasound examination of a gall bladder. In case of detection of stones drug can be appointed after careful assessment of the expected advantage of therapy and possible risks. Repeated inspections it is necessary to spend each 6-12 months during treatment.

If stones come to light during treatment:

• Asymptomatic: it is possible to cancel drug or to continue therapy after ratio assessment advantages/risks. To undertake any measures there is no need, more frequent observation is required;
• With clinical symptomatology: it is possible to cancel drug or to continue treatment after ratio assessment advantages/risks. Patients need standard therapy of the cholelithiasis (including drugs of bile acids) and regular ultrasonic control.

Patients with the hypophysis tumors cosecreting a growth hormone need careful medical observation during treatment as drug can promote increase in a tumor in a size and to development of a serious complication, such as narrowing of fields of vision. If it occurs, it is necessary to resolve an issue of use of other methods of treatment.

Drug can influence absorption of fats in intestines.

At development of bradycardia it is necessary to consider the possibility of a dose decline of blockers of calcium channels, beta adrenoblockers or drugs which influence water and electrolytic balance.

It is necessary to remember that Oktreotid is not antineoplastic means therefore does not promote treatment of the cosecreting endocrine tumors of a pancreas and digestive tract.

At treatment of endocrine tumors of digestive tract and pancreas the sudden recurrence is in some cases possible. At development of an insulinoma during use of an oktreotid increase in duration and expressiveness of a hypoglycemia is possible. Such patients have to be under careful observation, especially at each change of a dose of drug.

Oktreotid influences concentration of glucose in blood. It is possible to reduce fluctuations thanks to more frequent administration of drug in smaller doses. At a diabetes mellitus of 1 type medicine can reduce the need for insulin, at diabetes 2 types (with partially safe secretion of insulin) and at patients without diabetes – to lead to development of a postprandialny hyperglycemia. For this reason a sick diabetes mellitus control of level of glucose in blood and performing antidiabetic therapy is necessary.

It is also necessary to control concentration of glucose in blood to patients after bleedings from varicose expanded veins of a stomach or a gullet as in this case the risk of development of a diabetes mellitus of 1 type increases.

Due to the risk of development of side effects from the central nervous system it is recommended to be careful when driving the car and performing any works requiring special attention and speed of reactions.

Medicinal interaction

It is necessary to use at the same time with care drugs which are metabolized by system _{of P450 cytochrome} and have the narrow range of therapeutic concentration (for example, quinidine or терфенадин) since the probability of development of side effects increases.

Oktreotid reduces cyclosporine absorption, increases bioavailability of Bromocriptinum, slows down absorption of Cimetidinum, reduces metabolism of medicines which are metabolized with the participation of enzymes of system _{of P450 cytochrome}.

In case of simultaneous use of the following medicines correction of their doses is required: insulin, peroral hypoglycemic drugs, glucagon, blockers of calcium channels, beta adrenoblockers and diuretics.

Terms and storage conditions

To store in the place unavailable to children and protected from light, in the temperature range 8-25 ºС.

Period of validity – 5 years.