Somatulin Autozhel - instructions for use, doses, side effects, contraindications

Active substanceLanreotideLanreotide

Similar drugsTo uncover

Somatulin®

lyophilizate w / m

IPSEN PHARMA France

Somatulin® Autologel®

gel PC

IPSEN PHARMA France

Dosage form: & nbspcontinuous-release gel for subcutaneous administration

Composition:

Somatulin® Autologel® 60 mg:

Content:

Active substance:

Lanreotide acetate - 77.9 mg / syringe converted to lanreotide - 65.4 * mg / syringe

Excipients:

Water for injection - 186.6 mg / syringe

Acetic acid ice **** - to a pH of 6.1 ± 0.3

Total weight - 266.0 mg / syringe

Weight, injected ** - 244.0 mg / syringe

The injected dose of lanreotide *** is 60.0 mg / syringe

Somatulin® Autogel 90 mg:

Content:

Active substance:

Lanreotide acetate - 113.6 mg / syringe converted to lanreotide - 95.4 * mg / syringe

Excipients:

Water for injection - 272.3 mg / syringe

Acetic acid ice **** - to pH 6.1 ± 0,3

Total weight - 388.0 mg / syringe

Weight, injected ** - 366.0 mg / syringe

The injected dose of lanreotide *** is 90.0 mg / syringe

Somatulin® Autologel® 120 mg:

Content:

Active substance:

Lanreotide acetate - 149.4 mg / syringe converted to lanreotide - 125.5 * mg / syringe

Excipients:

Water for injection - 357.8 mg / syringe

Acetic acid ice **** - to a pH of 6.1 ± 0.3

Total weight - 510.0 mg / syringe

Weight injected ** - 488.0 mg / syringe

The injected dose of lanreotide *** is 120.0 mg / syringe

* The average content of base lanreotide in lanreotide acetate is 82-84%, the concentration of base lanreotide in the supersaturated solution is 24.6% (m / m).

** Mass loss in the syringe is 22.0 mg.

*** The amount of lanreotide entering the central bloodstream when injected.

**** Acetic acid ice can be added or not, depending on the level of anhydrous acetate in the active substance.

Description:Gel from whitish to yellowish color.

Pharmacotherapeutic group:Somatostatin analogue synthetic

ATX: & nbsp

H.01.C.B Hormones that slow growth

H.01.C.B.03 Lanreotide

Pharmacodynamics:

Lanreotide is a synthetic peptide, an analogue of natural somatostatin. Like natural somatostatin, lanreotide suppresses a number of endocrine, exocrine, neuroendocrine and paracrine mechanisms. The expressed tropicity of lanreotide to human somatostatin receptors (SSR) - 2 and 5, and low tropicity to SSR - 1, 3, and 4 were recognized. Activation of CCP-2 and 5 is believed to be the main mechanism underlying the suppression of growth hormone secretion ). Lanreotide, like somatostatin, has a common exocrine antisecretory effect. It suppresses the basal secretion of motilin, gastroinhibitory peptide and pancreatic polypeptide, but does not affect the secretion of digestive enzymes or gastric secretion. Lanreotide significantly suppresses the food-induced increase in blood flow in the upper mesenteric artery and portal vein. Lanreotide significantly reduces the secretion of water, sodium, potassium and chloride in the jejunum stimulated by prostaglandin E1. Lanreotide reduces the concentration of prolactin in patients with acromegaly, who receive treatment for a long time.

Lanreotide is much more active than natural somatostatin and has a longer period of exposure.

Pharmacokinetics:

Pharmacokinetic parameters of lanreotide after intravenous administration to healthy volunteers revealed a limited extravascular distribution with an equilibrium volume distribution of 16.1 liters. The total clearance was 23.7 l / h, the elimination half-life was 1.14 h, and the mean time of the drug determination in plasma was 0.68 h.

Studies evaluating the excretion of the drug showed that less than 5% of the lanreotide is excreted by the kidneys, and less than 0.5% of the unaltered lanreotide was found in the stool, indicating a certain proportion of biliary excretion.

After three deep subcutaneous injections of Somatulin® Autogel® every 28 days at a dose of 60 mg,90 mg or 120 mg in patients with acromegaly, the concentration of plasma lanreotide in plasma was similar to the steady-state concentration of plasma lanreotide in patients with acromegaly who received injections of Somatulin® 30 mg every 14, 10 or 7 days, respectively.

Deep subcutaneous injections of Somatulin® Autologel® at a dose of 60 mg, 90 mg, or 120 mg in patients with acromegaly showed a linear pharmacokinetic release profile.

After single deep subcutaneous administration of the drug Somatulin® Autologel® at a dose of 60 mg, 90 mg or 120 mg in healthy maximum concentration of the drug in the blood plasma (Cmoh) 4.25 ng / ml, 8.39 ng / ml and 6.79 ng / ml were achieved after 8, 12 and 7 hours, respectively, followed by a slow decrease (the average half-life was 23.3, 27, 4 and 30.1 days, respectively). After four weeks, the average plasma concentrations of the drug were 0.9; 1.11 and 1.69 ng / ml, respectively. Absolute bioavailability was 73.4; 69.0 and 78.4%, respectively.

After single-entry deep subcutaneous administration of the drug Somatulin® Autologel® at a dose of 60 mg, 90 mg or 120 mg in patients with acromegaly with a Cm1.6 ng / ml, 3.5 ng / ml and 3.1 ng / ml were achieved at 6; 6 and 24 hours, respectively, followed by a slow decline. After four weeks, the average plasma concentrations of the drug were 0.7; 1.0 and 1.4 ng / ml, respectively.

On average, after 4 injections administered every four weeks, the concentration of lanreotide in plasma reached a constant value. The average values of Cmah were 3.8; 5.7 and 7.7 ng / ml for dosages of 60 mg, 90 mg and 120 mg, respectively. Mean values Cmin were 1.8; 2.5 and 3.8 ng / ml, respectively. Vibrations between the maximum and minimum concentrations of the drug in equilibrium (PTF) were moderate: from 81% to 108%.

Indications:

Long-term therapy of patients with acromegaly, in whom the concentration of GH and / or insulin-like growth factor-1 (IGF-1) remains elevated after surgical treatment and / or radiation therapy; or patients who are shown to conduct drug therapy.

Therapy of clinical symptoms of acromegaly.

Therapy of clinical symptoms of carcinoid tumors.

Contraindications:

Hypersensitivity to lanreotid or related peptides. Due to the lack of clinical data, the drug is contraindicated for use in children and adolescents.

Carefully:Choledocholithiasis, pregnancy and the period of breastfeeding, diabetes mellitus, at the beginning of therapy - in patients with bradycardia.

Pregnancy and lactation:

Studies in animals have shown that there is no evidence of a teratogenic effect associated with the use of lanreotide during organogenesis in the fetus. A decrease in fertility in female rats was found due to inhibition of growth hormone secretion at doses exceeding therapeutic doses in humans.

A limited amount of data on the development of pregnancy in patients shows that lanreotide does not affect the course of pregnancy or the health of the fetus / newborn. There are no other data at the moment.

Since animal studies do not always predict the effect of the drug in humans, lanreotide should be used in pregnant women only in case of emergency.

There are no data on the penetration of the drug into breast milk.

Since a large number of drugs penetrates into breast milk, breastfeeding during therapy with lanreotide is only possible in case of emergency.

Dosing and Administration:

Acromegaly

The recommended initial dose is 60-120 mg every 28 days. For example, in patients who received Somatulin® injections, lyophilizate to prepare a suspension for intramuscular administration of a 30 mg dose every 14 days, the initial dose of Somatulin® Autologel®, a subcutaneous gel prolonged action, should be 60 mg every 28 days. In patients who received injections of Somatulin®, a lyophilizate to prepare a suspension for intramuscular administration of a prolonged effect, at a dose of 30 mg every 10 days, the initial dose of Somatulin® Autologel®, a long-acting subcutaneous gel, should be 90 mg every 28 days. In patients who received Somatulin® injections, a lyophilizate to prepare a suspension for intramuscular long-acting administration, at a dose of 30 mg every 7 days, the initial dose of Somatulin® Autologel®, a sustained-release subcutaneous gel, should be 120 mg every 28 days.

In the future, on average after 3 injections with an interval of 28 days,the dose should be selected individually depending on the patient's response (which is evaluated based on the severity of clinical symptoms and / or decrease in the concentration of GH and / or IGF-1):

- Increase the dose of the drug to 120 mg every 28 days, with a GH concentration above 2.5 ng / ml, maintain a high concentration of IGF-1 and / or in the absence of control over clinical symptoms;

- keep the dose unchanged, if the concentration of GH is 1-2.5 ng / ml, the concentration of IGF-1 is normal and control over clinical symptoms is achieved;

- should reduce the dose of the drug to 60 mg every 28 days, when the concentration of GH is below 1 ng / ml, the normalization of IGF-1 concentration and the control of clinical symptoms. Patients who have achieved effective control of the disease with somatostatin analogues can be assigned Somatulin® Autologel® at a dose of 120 mg with an increased interval every 42-56 days. These patients need to monitor regularly and in the long term clinical symptoms and concentrations of GH and IGF-1.

All patients are shown regular monitoring of clinical symptoms, the concentration of GH and IGF-1.

Carcinoid tumors

The recommended initial dose is 60-120 mg every 28 days.

In the future, the dose should be selected depending on the attained symptom reduction.

Patients who have achieved effective control of the disease with somatostatin analogues can be assigned Somatulin® Autologel® at a dose of 120 mg with an increased interval every 42-56 days.

The dosage regimen of the drug in specific patient groups.

Impaired liver / kidney function: In patients with severe renal dysfunction, the total clearance of lanreotide in plasma is approximately halved, with the increase in the half-life and AUC (area under the pharmacokinetic curve of the concentration of lanreotide in the blood plasma versus time). In patients with impaired hepatic function from moderate to severe, a decrease in clearance by 30% is observed. In patients with impaired liver function of any degree, the volume of distribution and the average retention time of lanreotide in the body increases. There is no need to adjust the initial dose for patients with hepatic or renal dysfunction, since it is assumed that the plasma lanreotide concentration in this patient population is in the same range and is also well tolerated in healthy patients.

In elderly patients revealed an increase in the half-life and the average time of determination of lanreotide in plasma in comparison with young healthy individuals.

There is no need to adjust the initial dose for elderly patients, since it is assumed that the concentration of lanreotide in the blood plasma for a given patient population is in the same range, and is also well tolerated as in healthy patients.

Rules of drug administration

The gel for subcutaneous administration of prolonged action is supplied in a pre-filled syringe equipped with a protective device that automatically closes the needle immediately after the injection, thereby helping to prevent accidental needle pricking after use.

The drug is administered deep subcutaneously immediately after opening the package.

1 syringe with the drug is intended for single administration only. The drug is injected by medical personnel into the upper lateral quadrant of the buttock.

If the patient receives a stable dose of Somatuline® Autogel®, injections can be carried out at home by the patient or his loved ones after preliminary appropriate training with a doctor. If the patient carries out the injection himself, the drug should be injected into the upper part of the thigh.

When administering the drug, observe the following instructions:

1. Take Somatuline® Autogel® from the refrigerator 30 minutes before use.

2. Make sure there is a clean place for the preparations and wash your hands.

3. Before opening, check the integrity of the package in which the syringe containing the drug is placed. Also, you need to make sure that the drug has not expired. Expiration date is on the package label.

DO NOT USE THE PREPARATION IN THE EVENT OF VIOLATION OF THE PACKAGE'S INTEGRITY OR ON THE EXPIRATION OF THE YEAR.

4. Open the bag and remove the syringe from the protective device.

5. Choose a place for the proposed injection (option A - if injected with medical personnel or a close patient by the patient, option B - in case of self-injection). Disinfect the site of the proposed injection, avoiding rubbing the skin. The injection is done every time alternately, then to the left, then to the right buttock or thigh.

6. Turn and pull the safety device of the piston stroke as shown in the figure, then remove it.

7. Remove the cap from the needle.

8. Insert the needle into the upper thigh or upper lateral quadrant of the buttock without grasping the skin fold, but keeping the skin large and forefinger, as shown in the figure. The needle should be inserted quickly, the entire length, perpendicular to the skin surface (deep subcutaneous injection).

9. Slowly insert the entire preparation, applying constant even pressure to the piston, leaving the needle stationary (usually about 20 seconds is required to completely inject the drug). At the moment when the piston completely passes the entire body of the syringe and rests against the opposite end, you will hear a click.

Note: Keep the piston held down to prevent the protective device from tripping.

10. While holding the piston, remove the needle from the injection site.

11. After this, release the piston, the needle automatically retracts into the tube of the protective device and locks into it.

12. Carefully apply a dry cotton pad or sterile cloth to the injection site to avoid bleeding. DO NOT rub or massage the injection site after injection.

Dispose of the used syringe in accordance with the instructions you received from your doctor.

Side effects:

The adverse reactions described in this section are distributed according to the system-organ classes and have the following classification: very often (≥1 / 10), often (≥1 / 100 - <1/10), infrequently (≥1 / 1,000 to <1/100). The adverse reactions identified during the clinical trials against the background of the use of the Somatulin® Autologel® are similar to those observed with other dosage forms of long-acting lanreotide, and are mainly disorders of the gastrointestinal tract (diarrhea and pain in the abdomen, usually mild to moderate and transient), cholelithiasis (often asymptomatic), and reactions at the injection site (pain, nodular thickening and densification).

Laboratory and instrumental data:

Often: increase in ALT level, ALT level deviation, level deviation ACT, increased blood bilirubin levels, increased blood glucose levels, increased glycosylated hemoglobin, and decreased body weight.

Infrequently: increase in ACT, an increase in the level of alkaline phosphatase in the blood, a deviation of the level of bilirubin in the blood, a decrease in the level of sodium in the blood.

From the heart:

Often: sinus bradycardia.

From the nervous system:

Often: dizziness, headache.

From the gastrointestinal tract:

Often: diarrhea, loose stool, abdominal pain.

Often: nausea, vomiting, constipation, flutulenia, bloating, abdominal discomfort, dyspepsia.

Infrequently: change in the color of feces.

From the skin and subcutaneous tissues:

Often: alopecia, hypotrichosis.

From the side of metabolism and nutrition:

Often: hypoglycemia.

Infrequently: diabetes mellitus, hyperglycemia.

From the side of the vessels:

Infrequently: "tides".

General disorders and disorders at the site of administration:

Often: fatigue, reactions at the injection site (pain, swelling, tightening, nodular thickening, itching).

Infrequently: asthenia.

Disorders from the liver and bile ducts:

Often: cholelithiasis.

Often: expansion of the bile ducts.

From the side of the psyche:

Infrequently: insomnia.

Post-event application experience:

The experience of using the drug during the post-registration period did not reveal any new side effects, except for individual cases of pancreatitis.

Overdose:

In case of an overdose, symptomatic therapy is indicated.

Interaction:

The pharmacological effect of lanreotide on the gastrointestinal tract can reduce absorption in the intestine of concurrently taken drugs, including cyclosporine. With the simultaneous use of lanreotide and cyclosporine, the concentration of cyclosporine in the blood can decrease, so monitoring of this indicator is necessary.

Interaction with drugs that have a pronounced relationship with blood plasma proteins is unlikely, due to weak binding of lanreotide to plasma proteins.

There are limited published data indicating that simultaneous use of somatostatin and bromocriptine analogs may increase the bioavailability of bromocriptine.

With the simultaneous use of lanreotide and a means of reducing the heart rate (such as beta-blockers), the effect of a slight additional reduction in the heart rate associated with the use of lanreotide may occur. Therefore, in this case, you may need to adjust the dose of the drug taken at the same time.

There are limited published data indicating that somatostatin analogues can reduce metabolic clearance of drugs,metabolized with the help of cytochrome P450 enzymes, this can occur due to oppression of GH secretion. Since it can not be ruled out that the use of lanreotide can cause such an effect, caution should be exercised in the joint administration of lanreotide and drugs metabolized mainly by CYP3A4, and having a low therapeutic index (such as quinidine, terfenadine).

Special instructions:

Lanreotide, like somatostatin and its analogs, can cause inhibition of the secretion of insulin and glucagon. Therefore, patients receiving therapy with Somatulin® Autologel® may develop hypoglycemia or hyperglycaemia. After the start of treatment, it is necessary to monitor the concentration of glucose in the blood, and in patients with diabetes it is necessary to adjust the dosages of hypoglycemic drugs.

In the treatment of patients with acromegaly, there may be a slight decrease in thyroid function, but clinical hypothyroidism is rarely observed. Depending on the clinical picture, the control of thyroid function is recommended.

Lanreotide can reduce the motility of the gallbladder and this can cause the formation of gallstonesa bubble. Therefore, the conduct of ultrasound of the gallbladder is shown both at the beginning of treatment and in its process. Chololithiasis usually is asymptomatic. When symptoms of cholelithiasis appear, treatment is required.

In patients who do not have severe cardiac problems, lanreotide can lead to a decrease in the heart rate without necessarily reaching the threshold of a bradycardia. In patients with heart disease before starting therapy with lanreotide, sinus bradycardia may develop. Care should be taken when starting therapy with lanreotide in patients with bradycardia.

In patients with carcinoid tumors lanreotide It should not be administered until the patient has an obturating intestinal tumor. The use of lanreotide therapy does not relieve patients with acromegaly and primary thyroid-mediated pituitary adenoma from monitoring the size of the pituitary tumor.

Patients with severe and prolonged steatorrhea need the appointment of pancreatic enzymes.

In elderly patients revealed an increase in the half-life and the average time of determination of lanreotide in plasma in comparison with young healthy individuals.

Effect on the ability to drive transp. cf. and fur:

Despite the fact that during the treatment with the drug Somatulin® Autogel®, the effect of the drug on the ability to drive vehicles and work with mechanisms has not been established, dizziness may develop on the background of drug therapy. If this side effect occurs, do not drive vehicles and work with mechanisms.

Form release / dosage:

Gel for subcutaneous administration of prolonged action 60 mg, 90 mg, 120 mg.

Packaging:

266 mg (for a dosage of 60 mg), 388 mg (for a dosage of 90 mg) or 510 mg (for a dosage of 120 mg) of the drug in a disposable polypropylene syringe of 0.5 ml with a protective device complete with a silanized needle mm x 20 mm) made of stainless steel, closed with a plastic cap.

A syringe packed in a bag of polyethylene terephthalate / aluminum / polyethylene, together with the instruction for use is placed in a cardboard pack.

Storage conditions:

At a temperature of 2 ° to 8 ° C (in the refrigerator), out of the reach of children.

Do not freeze!

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003497/09

Date of registration:08.05.2009

The owner of the registration certificate:IPSEN PHARMA IPSEN PHARMA France

Manufacturer: & nbsp

IPSEN PHARMA BIOTECH France