Somatulin аутожель

General characteristics. Structure:

Active agent: lanreotida acetate of 149.4 mg
in terms of ланреотид * 125.5 mg
the entered dose of a lanreotid ** 120 mg
lump - 510 mg / the syringe
the weight entered at an injection *** - 488 mg / the syringe

Excipients: water for and - 357.8 mg / the syringe, acetic acid ice **** - to pH 6.1±0.3.

510 mg - syringes one-time polypropylene (1) complete with a needle - packages three-layered (1) - packs cardboard.

* the average content of a lanreotid of the basis in a lanreotid acetate of 82-84%, concentration of a lanreotid of the basis in the oversaturated solution of 24.6% (mom).
** quantity of the lanreotid coming to the central blood stream at an injection.
*** loss of weight in the syringe makes 22 mg.
**** acetic acid ice can be added or not, depending on the level of content of anhydrous acetate in active substance.

Pharmacological properties:

Synthetic analog of natural somatostatin, synthetic peptide.
Like natural somatostatin, ланреотид suppresses a number of endocrine, exocrine and paracrine mechanisms. The expressed tropnost of a lanreotid to somatostatinovy receptors of the person (SSR)-2, 3 and 5, and a low tropnost to SSR-1 and 4 is revealed. As believe, activation of SSR-2 and 5 is the main mechanism which is the cornerstone of suppression of secretion of the growth hormone (GH).
Lanreotid, like somatostatin, has the systemic exocrine anti-secretory effect. It suppresses basal secretion of the inhibiting peptides of a stomach and polypeptides of a pancreas, but has no effect on secretion of digestive enzymes or gastric secretion. Lanreotid significantly suppresses strengthening of a blood-groove induced by food in an upper mezenterialny artery and a portal vein. Lanreotid significantly reduces the secretion of water, sodium, potassium and chlorides stimulated by E1 prostaglandin in a jejunum.
Lanreotid reduces prolactin level at the patients with an acromegalia receiving treatment for a long time.

Pharmacokinetics. Unlike indicators at in introduction, profiles of pharmacokinetics of a lanreotid in a dosage form of the prolonged action, the entered in oil or it is deep п / to, showed duration of effect of drug within 28 days.
The way of administration of drug (п / to or in oil) does not exert any impact on pharmacokinetic parameters of a lanreotid. Level of concentration of drug in plasma showed dozozavisimy linearity with the small deviations connected with specific features of participants of researches.

Absorption. After single deep п / to administration of the drug Somatulin® Аутожель® 120 of mg to healthy volunteers of Cmax in blood serum made 6.79 ng/ml and it was reached in 7 h, with the subsequent slow decrease (T1/2 averaged 30.1 days). In 4 weeks average concentration of drug in serum made 1.69 ng/ml. Absolute bioavailability made 78.4%.
After single deep п / to administration of the drug Somatulin® Аутожель® 120 of mg to patients with an acromegalia of Cmax value made 3.1 ng/ml and it was reached in 23:52 h, with the subsequent slow decrease. In 4 weeks average concentration of drug in serum made 1.4 ng/ml.
On average after 4 injections entered each 4 weeks Css of a lanreotid in plasma was reached. At the same time average Cssmax value made 7.7 ng/ml at a dose of 120 mg. Average Cmin value made 3.8 ng/ml.

Distribution. Pharmacokinetic parameters of a lanreotid in/in introductions to healthy volunteers revealed later limited extravasated distribution with Vd in an equilibrium condition of 13 l.

Removal. Later in/in introductions to healthy volunteers the general clearance - 20 l/h, T1/2 - 2.5 h, the average time of definition of drug in plasma – 0.68 h.
After injections of the drug Somatulin® Аутожель® 120 of mg to healthy volunteers of T1/2 made about 28 days.

Indications to use:

Acromegalia (for the purpose of decrease in the GR level and an insulinopodobny growth factor-1/IFR-1/and, whenever possible, their normalization):
— long therapy of patients who have a GR level and/or an insulinopodobny growth factor-1 (IFR-1) remains raised after operational treatment and/or radiation therapy;
— long therapy of patients to whom performing medicamentous therapy is shown (the purpose of therapy of an acromegalia decrease in GR and IFR-1 and, whenever possible, normalization of these indicators is).
Therapy of symptoms of carcinoid tumors.

Route of administration and doses:

Acromegalia
The recommended initial dose makes 120 mg each 28 days.
To patients at whom against the background of therapy by analogs of somatostatin will reach effective control over a disease Somatulin® Autozhel® in a dose of 120 mg with the increased interval - can be appointed each 42-56 days. At these patients it is necessary regularly and in the long term to monitorirovat clinical symptoms and the GR and IFR-1 level.
Regular control of clinical symptoms, the GR and IFR-1 level is shown to all patients.

Carcinoid tumors
The recommended initial dose makes 120 mg each 28 days. Further the dose should be selected depending on the reached reduction of symptomatology.
To patients at whom against the background of therapy by analogs of somatostatin will reach effective control over a disease Somatulin® Autozhel® in a dose of 120 mg with the increased interval - can be appointed each 42-56 days.

Rules of administration of drug
Gel for п / to introduction of the prolonged action is delivered in previously filled syringe supplied with the protection device which automatically closes a needle right after carrying out an injection that helps to prevent an accidental prick a needle after use.

The drug should be administered deeply п / to immediately after packaging opening.
1 syringe with drug is intended only for single introduction.
The drug is administered by medical personnel in an upper lateral quadrant of a buttock.
If the patient receives a stable dose of the drug Somatulin® Autozhel®, patients or his relatives after the preliminary corresponding training at the doctor can carry out injections in house conditions. At independent carrying out an injection by the patient the drug should be administered in an upper part of a hip.
At administration of drug it is necessary to observe the following instructions.
1. To get Somatulin® Autozhel® from the refrigerator in 30 min. prior to use.
2. To be convinced available the pure place for preparatory actions and to wash up hands.
3. Before opening to check integrity of a package in which the syringe with drug is placed. Also, it is necessary to be convinced that at drug the period of validity did not expire. Expiration date of a period of validity is present at the label of a package. Not to use drug in case of disturbance of integrity of a package or after a period of validity.
4. To open a package and to take from it the syringe with the protection device.
5. To choose the place for an estimated injection. To disinfect the place of an estimated injection (an upper part of a hip or an upper lateral quadrant of a buttock), avoiding grinding of skin. The injection becomes every time alternately, in left, in the right buttock or a hip.
6. To turn and pull the protection device of a piston stroke, then to remove it.
7. To remove a cap from a needle.
8. Enter a needle into an upper part of a hip or an upper lateral quadrant of a buttock without capture of a skin fold, but holding skin big and index fingers.
The needle has to be entered quickly, at all length, perpendicular to the surface of skin (a deep subcutaneous injection).
9. To slowly administer all drug, putting the constant uniform pressure upon the piston, leaving at the same time a needle in a motionless state (usually for full introduction drug is required about 20 sec.). Against that the moment when the piston completely passes all body of the syringe and will rest against the opposite end, the click is heard.
Note: it is necessary to continue to hold the piston in the pressed state in order to avoid operation of the protection device.
10. Holding the piston, to take out a needle from the place of an injection.
11. After that, to release the piston, the needle will automatically be involved in a tube of the protection device and will be blocked in it.
12. To accurately put a dry wadded disk or a sterile napkin to the place of an injection to avoid bleeding. Not to pound and not to mass a drug injection site after an injection.
13. To utilize the used syringe according to instructions.

Features of use:

Pharmacological researches on animals and people showed what ланреотид, like somatostatin and its analogs, can cause passing inhibition of secretion of insulin and a glucagon. Therefore, at the patients with a diabetes mellitus receiving treatment by the drug Somatulin® Autozhel® minor short-term changes of level of glucose in blood can be observed. For definition of need of correction of antidiabetic therapy, it is necessary to control glucose level in blood.

In the course of treatment of patients with an acromegalia perhaps insignificant depression of function of a thyroid gland, however a clinical hypothyroidism is observed seldom (<1%). In this regard control of function of a thyroid gland is shown.

Lanreotid can cause formation of stones in a gall bladder therefore performing ultrasonography of a gall bladder is shown both in an initiation of treatment, and in its process. The cholelithiasis proceeds usually asymptomatically. At emergence of symptoms of cholelithiasis treatment is required.

At patients with heavy renal failures reduction approximately twice of the general clearance of a lanreotid in plasma with the caused this increase in T1/2 and AUC is observed. At an abnormal liver function increase in volume of distribution and average time of definition of a lanreotid in plasma is observed, but there are no changes of the general clearance or AUC. At elderly patients increase in an elimination half-life and average time of definition of a lanreotid in plasma in comparison with young healthy faces is revealed. Thanks to the big therapeutic width of a lanreotid, in these cases there is no need to change its dose.

Influence on ability to driving of motor transport and to control of mechanisms
It is improbable that during treatment by the drug Somatulin® Autozhel® ability to manage motor transport worsens and to work with mechanisms.

Side effects:

The side reactions revealed in the course of clinical trials against the background of use of the drug Somatulin® Autozhel® are similar to those which are observed at use of other dosage forms of a lanreotid of the prolonged action, and, generally are disturbances from the alimentary system.
In clinical trials of the drug Somatulin® Autozhel® at treatment of patients with an acromegalia, at 80% of patients, at least, 1 undesirable phenomenon was observed. More than 50% of these undesirable phenomena were carried to disturbances from the alimentary system. These side effects are usually poorly expressed and is passing.
From the alimentary system: very often (> 10%) - diarrhea, abdominal pain, nausea, a cholelithiasis or a sladzh-syndrome in a gall bladder; often (> 5%, but <10%) - a lock, a meteorism, anorexia; seldom (> 1%, but <5%) - increase in concentration of bilirubin; very seldom (<1%) - tenesmus, vomiting, acute pancreatitis, a steatorrhea.
From cardiovascular system: often (> 5%, but <10%) - a sinus bradycardia.
From a metabolism: often (> 5%, but <10%) - a hypoglycemia; very seldom (<1%) - deterioration in a current of a diabetes mellitus, disturbance of tolerance to glucose, a hyperglycemia.
Dermatological reactions: very seldom (<1%) - a hair loss, an itch, the increased sweating, skin reactions (nonspecific).
Local reactions: very seldom (<1%) - pain in an injection site, cutaneous swelling. In 30 min. after a deep p / to an injection of the drug Somatulin® Autozhel® in the field of introduction pain, reddening, an itch and consolidation respectively at 8%, 5%, 5% and 19% of patients can be observed. After the 3rd injection the frequency of these symptoms decreases and observed at 6%, 2%, 3% and 9% of patients. In all cases symptoms were poorly expressed.
Others: often (> 5%, but <10%) - dizziness, allergic skin reactions; seldom (> 1%, but <5%) - weakness, fatigue; very seldom (<1%) - feeling of heat, an onychalgia, an indisposition, a headache, decrease in a libido, drowsiness.

Interaction with other medicines:

At simultaneous use of a lanreotid and cyclosporine reduction of concentration of cyclosporine in a blood plasma therefore it is necessary to control its concentration in blood is possible.

Interaction with medicines which are characterized by high linkng with proteins of plasma is improbable, in view of weak linkng of a lanreotid with proteins of plasma (on average 78%).

Contraindications:

— the complicated, not treated choledocholithiasis;
— pregnancy;
— lactation;
— children's age (in connection with insufficiency of clinical data);
— hypersensitivity to a lanreotid or to related peptides.

Use of the drug SOMATULIN® AUTOZhEL® at pregnancy and feeding by a breast
Adequate and strictly controlled clinical trials of safety of use of drug at pregnancy were not conducted.
In pilot studies on studying of influence on reproductibility at rats and rabbits of drug in the doses, by 33 times exceeding the doses applied at the person the risk for a fruit is not revealed. As researches on studying of reproductibility at animals not always predict influence on reproductibility at the person, this drug is contraindicated at pregnancy.
Use of drug in the period of a lactation (breastfeeding) is contraindicated.

Overdose:

Symptoms: in clinical trials ланреотид applied in the doses exceeding 15 mg/days, at the same time in the course of treatment serious by-effects are not revealed. The description of overdose of a lanreotid in a dosage form of the prolonged action at people is limited to one case, when as it was reported, to the patient entered ланреотид in oil 30 mg in a dose in a dosage form of the prolonged release daily within 2 months (instead of 1 injection each 7 or 14 days). In 1 week after the end of therapy at the 52-year-old man with an acromegalia, a diabetes mellitus and arterial hypertension the myocardial infarction with a lethal outcome developed.

Treatment: in case of overdose performing symptomatic therapy is shown.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature from 2 °C to 8 °C (in the refrigerator); not to freeze.

Issue conditions:

According to the recipe