Sandostatin Lar - instructions for use, dose, side effects, contraindications

1 syringe with solvent (2.5 ml) contains: sodium carmellose (sodium carboxymethyl cellulose) 12.5 mg, mannitol 15 mg, water for injection up to 2.5 ml.

Description:

The powder is white or almost white.

Pharmacotherapeutic group:somatostatin analogue synthetic

ATX: & nbsp

H.01.C.B.02 Octreotide

Pharmacodynamics:

The drug Sandostatin® LAR is a synthetic octapeptide, which is a derivative of the natural somatostatin hormone and possesses similar pharmacological effects, but a much longer duration of action. Octreotide the depot form suppresses the pathologically increased secretion of growth hormone (GH), as well as the release of GH caused by arginine, exercise and insulin hypoglycemia. The drug also inhibits the secretion of peptides of the gastroenteropancreatic system (for example, food-induced secretion of insulin, glucagon, gastrin) and serotonin. Also octreotide The depot form suppresses the secretion of insulin and glucagon stimulated by arginine. Besides, octreotide The depot form suppresses the secretion of thyrotropin, caused by thyroidiberin.

In contrast to somatostatin, octreotide suppresses the secretion of GH more than insulin secretion, and its administration is not accompanied by a ricochet effect in the form of hypersecretion of hormones (eg, GH in patients with acromegaly).

Have patients with acromegaly application of octreotide depot form ensures the maintenance of stable therapeutic concentrations of octreotide in the serum when the drug is administered once every 4 weeks. Introduction of octreotide depot form provides in the overwhelming majority of cases a persistent decrease in serum GH concentration and normalization of serum concentrations of insulin-like growth factor-1 (IGF-1).

In most patients with acromegaly octreotide depot form significantly reduces the severity of such symptoms as headache, increased sweating, paresthesia, a feeling of fatigue, pain in the bones and joints, carpal tunnel syndrome. In some clinical cases, treatment with octreotide depot form patients with pituitary adenomas, secreting GH, led to a decrease in tumor size.

When secreting endocrine tumors of the gastrointestinal tract (GIT) and pancreas the use of octreotide depot forms provides a constant control of the main symptoms of these diseases.

Octreotide depot form in a dose of 30 mg every 4 weeks slows tumor growth in patients with secreting and non-secretive common (metastatic) neuroendocrine tumors of lean, iliac, blind, ascending colonic,transverse colon and appendix, or metastases of neuroendocrine tumors without a primary focus. The drug significantly increased the time to progression in this category of patients: the median time to progression was 14.3 months compared with 6 months in the placebo group. After 6 months of treatment, stabilization was observed in 66% of patients in the group octreotide depot form and 37% of patients in the placebo group. The drug was effective in increasing the time to progression for both secreting and non-secreting neuroendocrine tumors.

When carcinoid tumors the use of octreotide may lead to a decrease in the severity of the symptoms of the disease, primarily such as hot flashes and diarrhea. In many cases, clinical improvement is accompanied by a decrease in plasma serotonin concentration and excretion of 5-hydroxyindoleacetic acid in the urine.

When tumors characterized by hyperproduction of the vasoactive intestinal peptide (Wipomy), the use of octreotide in most patients leads to a reduction in 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 decrease in associated electrolyte imbalance, for example, hypokalemia, which allows to cancel enteral and parenteral administration of fluid and electrolytes. According to computed tomography, in some patients there is a slowing or stopping of tumor progression and a decrease in its size, and especially of metastatic foci in the liver. Clinical improvement is usually accompanied by a decrease (up to normal values) of the concentration of vasoactive intestinal peptide (VIP) in plasma.

When glucagonomes the use of octreotide in most cases leads to a significant decrease in necrolytic migratory erythema, which is characteristic of this condition. Octreotide does not have any significant effect on the severity of diabetes mellitus, often observed with glucagonomes, and its use usually does not lead to a decrease in the need for insulin or oral hypoglycemic drugs. In patients with diarrhea, octreotide causes it to decrease, which is accompanied by an increase in body weight.When octreotide is used, there is often a rapid decrease in plasma glucagon concentration, but this effect does not persist with long-term treatment. At the same time, the improvement of clinical symptoms persists for a long time.

When gastrinomas / Zollinger-Ellison syndrome when octreotide is used as monotherapy or in combination with blockers H₂receptors and proton pump inhibitors, it is possible to reduce the formation of hydrochloric acid in the stomach and the development of clinical improvement, including a reduction in diarrhea. It is also possible to reduce the severity and other symptoms likely associated with the synthesis of peptides by a tumor, including tides. In some patients there is a decrease in the concentration of gastrin in the plasma.

In patients with insulinomas octreotide reduces the level of immunoreactive insulin in the blood.

In patients with operable tumors octreotide can provide recovery and maintenance of normoglycemia in the preoperative period. In patients with inoperable benign and malignant tumors, glycemic control can be improved without a simultaneous steady decrease in insulin levels in the blood.

In patients with rare tumors, hyper-producing growth hormone releasing factor (somatoliberinomas), octreotide reduces the severity of symptoms of acromegaly. This, apparently, is due to the suppression of the secretion of the releasing factor of growth hormone and the growth hormone itself. In the future, it is possible to reduce the size of the pituitary gland, which was increased before the treatment.

Pharmacokinetics:

After intramuscular (IM) administration of depot octreotide, serum octreotide concentration reaches a short-term initial peak for 1 hour, after which it progressively decreases within 24 hours to undetectable values. After the initial peak, observed on the first day, the concentration of octreotide in the next 7 days in most patients remains within the subtherapeutic values.

After that, the octreotide concentrations increase again, reach the "plateau" by about the 14th day and remain relatively constant over the next 3-4 weeks. The peak concentration value on the 1st day is lower than the levels noted in the "plateau" phase. On the 1st day, no more than 0.5% of the total amount of active substance is released.Approximately after the 42nd day, the concentrations of octreotide slowly decrease, which occurs simultaneously with the final stage of degradation of the polymer matrix of the dosage form.

After administration of acromegaly, octreotide depot form in single doses of 10 mg, 20 mg and 30 mg of octreotide concentration in the "plateau" phase was 358 ng / l, 926 ng / l and 1710 ng / l, respectively. The equilibrium serum octreotide concentrations achieved after three injections of octreotide depot formulations at doses of 20 mg and 30 mg at 4-week intervals were approximately 1.6-1.8 times higher and were 1557 ng / L and 2384 ng / l, respectively.

In patients with carcinoid tumors who received multiple injections of Sandostatin® LAR at doses of 10, 20 and 30 mg at 4-week intervals, the mean (and median) values of the equilibrium serum octreotide concentration increased linearly with increasing dose and amounted to 1231 (894 ) ng / l, 2620 (2270) ng / l and 3928 (ZOUS) ng / l, respectively. With the use of depot octreotide for 28 months (1 injection per month), no cumulation of octreotide was found beyond what one would expect due to partial overlapping of the pharmacokinetic curves.The pharmacokinetic profile of octreotide after depot octreotide injection reflects its release profile from the polymer matrix and its biodegradation. After release into the systemic circulation, the distribution of octreotide occurs in accordance with its pharmacokinetic properties, which are described for the dosage form for the SC administration. The volume of distribution of octreotide in the equilibrium state is 0.27 l / kg. The total plasma clearance is 160 ml / min. The connection with plasma proteins is 65%. With the shaped elements of the blood octreotide does not communicate.

Indications:

Acromegaly. In the absence of sufficient effect, complete inefficiency or in the presence of contraindications to surgical treatment or radiotherapy, treatment in the period after radiation therapy to the development of its maximum effect.

Secreting endocrine tumors of the gastrointestinal tract and pancreas - to provide adequate control of clinical symptoms of the disease:

- carcinoid tumors with manifestations of carcinoid syndrome;

- VIPoms;

- Glucagon;

- gastrinomas / Zollinger-Ellison syndrome;

- Isisulinoma - to control hypoglycemia in the preoperative period, as well as for maintenance therapy.

Somatoliberinoma (tumors characterized by hyperproduction of growth hormone releasing factor).

Neuroendocrine secretion and non-secretory widespread tumors originating from the lean, iliac, blind, ascending colon, transverse colon and appendix, as well as metastatic tumors with an unspecified primary focus.

Contraindications:Hypersensitivity to octreotide or other components of the drug.

Carefully:

Use with caution the drug Sandostatin® LAR for cholelithiasis, diabetes mellitus; with simultaneous use with drugs with a narrow therapeutic index, the metabolism of which is carried out with the participation of the isoenzyme CYP3A4 (for example, quinidine, terfenadine), during pregnancy and during breastfeeding.

With pituitary tumors secreting GH, careful monitoring of patients is necessary, since it is possible to increase the size of the tumor with the development of such serious complications as narrowing of the visual fields.In these cases, consideration should be given to the need for other treatments.

Against the background of the use of octreotide a decrease in the concentration of vitamin B₁₂ and the deviation of the cyanocobalamin absorption test (Schilling test) from the norm. When using Sandostatin® LAR in patients with vitamin B deficiency₁₂ in the anamnesis it is recommended to control its concentration.

Pregnancy and lactation:

The use of octreotide in pregnancy has not been studied. There is limited experience with the drug in pregnant women with acromegaly in clinical practice (in half the cases, the outcome of pregnancy is unknown). Most pregnant patients received octreotide therapy in the first trimester of pregnancy (Sandostatin® preparation 100-300 μg / day subcutaneously or Sandostatin® LAR 20-30 mg per month). Approximately 70% of cases with a known outcome of the patient independently decided to continue therapy with the drug during pregnancy. In most patients (cases with a known outcome), the pregnancy ended with the birth of healthy children, but there were also reported several spontaneous abortions in the first trimester and cases of abortion.

When octreotide was used during pregnancy, there were no cases of congenital malformations in children.

Use the drug during pregnancy should only be in case of emergency.

In studies in animals, reproductive toxicity has not been identified. Some individuals of rats had a transient growth retardation, possibly a feature of the endocrine profile of the species.

It is not known whether the octreotide in human milk. In studies in animals, the penetration of octreotide into milk was noted. If you need to use the drug during breastfeeding, breast-feeding should be discontinued.

Dosing and Administration:

The drug Sandostatin® LAR should be administered only deep intramuscularly (IM), in the gluteal muscle. With repeated injections, the left and right sides should alternate. In order to minimize the risk of developing adverse reactions from the gastrointestinal tract, injections should be administered as soon as possible after ingestion, i.e. between meals or at bedtime.

Acromegaly

The recommended initial dose of Sandostatin® LAR is 20 mg every 4 weeks for 3 months. In patients who have previously received SC injections of Sandostatin®, treatment with Sandostatin® LAR can be started the day after the last administration of Sandostatin®. In the future, the dose is adjusted taking into account the concentration of GH and IGF-1 in blood plasma, as well as clinical symptoms. If after 3 months of treatment failed to achieve adequate clinical and biochemical control (in particular, if the concentration of GH remains above 2.5 μg / l), the dose can be increased to 30 mg administered every 4 weeks. If after 3 months of treatment failed to achieve adequate clinical and biochemical control (increased concentration of GH and IGF-1), the dose can be increased to 40 mg, administered every 4 weeks.

In those cases where after a 3-month treatment with Sandostatin® LAR at a dose of 20 mg there is a persistent decrease in serum GH concentration below 1 μg / L, normalization of IGF-1 concentration and disappearance of reversible symptoms of acromegaly, it is possible to reduce the dose of Sandostatin® LAR to 10 mg every 4 weeks.Nevertheless, these patients should carefully monitor the clinical manifestations of the disease and the concentration of GH and IGF-1 in blood plasma.

In patients receiving a stable dose of Sandostatin® LAR, every 6 months, the concentration of GR and IGF-1 should be determined.

Endocrine tumors of the gastrointestinal tract and pancreas

The initial dose of Sandostatin® LAR is 20 mg every 4 weeks. In the case of prior treatment with Sandostatin®, the injection should be given within 2 weeks after the first injection of Sandostatin® LAR.

If there is adequate control of clinical symptoms and biochemical parameters after 3 months of treatment dose can be reduced to 10 mg every 4 weeks.

With insufficient control of the disease after 3 months of treatment, the dose of the drug can be increased to 30 mg once every 4 weeks.

With increasing symptoms characteristic of endocrine tumors gastrointestinal tract and pancreas, on separate days on the background of treatment Sandostatin® LAR may Sandostatin® additional introduction of medication in the dose applied until the transition or treatment with Sandostatin® LAR.This increase in symptoms most often develops in the first 2 months of treatment until the therapeutic concentration of octreotide is reached.

Neuroendocrine secretion and non-secretive common tumors originating from the lean, iliac, blind, ascending colon, transverse colon and appendix, as well as metastatic tumors with an unspecified primary foci

The recommended dose of Sandostatin® LAR is 30 mg once every 4 weeks.

The drug should be continued only if there is no evidence of tumor progression.

Use in patients with impaired renal function

With the administration of the drug Sandostatin®, there was no change in the AUC (area under the concentration-time curve) in patients with impaired renal function. Thus. It is not necessary to correct the dose of Sandostatin® LAR in this category of patients.

Use in patients with impaired liver function

According to the study, with intravenous administration of the drug Sandostatin® excretion can be disrupted in patients with cirrhosis of the liver, in contrast to patients with fatty liver dystrophy.Due to the wide therapeutic range of Sandostatin® LAR, there is no need for correction of its dose in patients with cirrhosis of the liver.

Use in patients> 65 years of age

According to the study, when the administration of the drug Sandostatin® is not required dose adjustment in patients aged> 65 beds. Thus. It is not necessary to correct the dose of Sandostatin® LAR in this category of patients.

Use in children (under 18 years)

There is limited experience with the use of Sandostatin LAR in children.

Application rules

Suspension should be prepared immediately before injection.

The drug Sandostatin® LAR should be stored in the refrigerator at a temperature of 2 to 8 ° C. On the day of injection, the vial with the preparation and the syringe with the solvent can be kept at a temperature below 25 ° C.

See also "Instructions for intramuscular injection of Sandostatin® LAR".

Side effects:

The main undesirable phenomena (AEs) observed with the use of octreotide were disorders of the gastrointestinal tract and nervous system, violations of the liver and bile ducts, as well as disorders of metabolism and nutrition.

In clinical studies, diarrhea, abdominal pain, nausea, bloating, headache, cholelithiasis, hyperglycemia and constipation were most frequently observed with the use of the drug. Also, dizziness, pain of different localization, violation of colloidal bile stability (formation of cholesterol microcrystals), thyroid dysfunction (decrease in thyroid-stimulating hormone concentration, total and free thyroxin), soft stool consistency, decreased glucose tolerance, vomiting, asthenia and hypoglycemia were often noted.

When applying the drug in rare cases, there may be phenomena reminiscent of acute intestinal obstruction: progressive bloating, severe pain in the epigastric region, abdominal wall tension and muscular dysfunction.

Despite the fact that excretion of fats with feces may increase, there is no evidence that prolonged treatment with octreotide can lead to the development of nutritional deficiencies due to malabsorption (malabsorption). The likelihood of such side effects can be reduced by administering the drug between meals or at bedtime.

There were reported very rare cases of acute pancreatitis in the first hours or days after octreotide application (preparation Sandostatin®), which was resolved on its own after the drug was withdrawn. In addition, with prolonged use of the drug Sandostatin®, there were cases of development of pancreatitis caused by cholelithiasis.

According to the ECG data, prolongation of the QT interval, deviation of the electric axis of the heart, early repolarization, low-ECG type, displacement of the transition zone, early tooth P and nonspecific changes in the ST segment and the T wave were observed in patients with acromegaly and carcinoid syndrome, This category of patients had concomitant heart disease, a causal relationship between the use of octreotide and the development of these undesirable phenomena has not been established.

AEs are grouped according to the classification of organs and systems of organs of MedDRA, listed in order of decreasing frequency of occurrence.

The following criteria were used to determine the incidence of adverse events identified in clinical trials: very often (≥ 1/10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000),including individual messages.

Disorders from the gastrointestinal tract: very often - diarrhea, abdominal pain, nausea, constipation, bloating; often - indigestion, vomiting, feeling of filling / heaviness in the abdomen, steatorrhea, soft stool consistency, discoloration of the stool; rarely soreness in palpation of the abdomen.

Disturbances from the nervous system: very often - headache; often - dizziness.

Disorders from the endocrine system: often - hypothyroidism / thyroid dysfunction (decrease in thyroid-stimulating hormone, total and free thyroxine).

Disorders from the metabolism and nutrition: very often hyperglycemia: often - hypoglycemia, impaired glucose tolerance, anorexia; infrequently - dehydration.

Disturbances from the liver and bile ducts: very often - cholelithiasis; often - cholecystitis, violation of the colloidal stability of bile (formation of microcrystals of cholesterol), hyperbilirubinemia.

Disturbances from the skin and subcutaneous tissues: often - itching, rashes, alopecia.

Disturbances from the respiratory system, chest and mediastinal organs: often - shortness of breath.

Heart Disease: often bradycardia; infrequently - a tachycardia.

General disorders and disorders at the site of administration: very often - reactions at the site of injection: tingling, burning, flushing, pain and swelling at the injection site (usually lasting no more than 15 minutes after the injection and less pronounced with a suspension of the preparation at room temperature or with a smaller volume of suspension with a larger concentration); often - asthenia.

Laboratory and instrumental data: often - an increase in the activity of "liver" transaminases.

Since data on undesirable phenomena in the postmarketing period were obtained on the basis of voluntary spontaneous messages from a population of unknown numbers, it is impossible to estimate the frequency of their occurrence (the frequency is unknown).

Undesirable phenomena are classified according to the systems of organs, within each system of organs, undesirable phenomena are arranged in order of decreasing importance.

Immune system disorders: anaphylactic reactions, allergic reactions / hypersensitivity reactions.

Disturbances from the skin and subcutaneous tissues: hives.

Disturbances from the liver and bile ducts: acute pancreatitis, acute hepatitis without the phenomena of cholestasis, cholestatic hepatitis, cholestasis, jaundice, cholestatic jaundice.

Laboratory and instrumental data: an increase in the activity of alkaline phosphatase and gamma-glutamyltransferase.

Heart Disease: arrhythmia.

Overdose:

Data on the overdose of Sandostatin® LAR are absent. When using Sandostatin® LAR in a dose of 90 mg every 2 weeks, in patients with malignant neoplasms, no undesirable adverse events were noted. With a single intravenous bolus administration of 1 mg octreotide to an adult patient, such symptoms as a short-term bradycardia, flushes to the face, spastic pains in the abdomen, diarrhea, a feeling of emptiness in the stomach and nausea. All described symptoms resolved within 24 hours after the administration of the drug.

Treatment symptomatic.

Interaction:

It may be necessary to correct the dose of beta-adrenoblockers, blockers of "slow" calcium channels, drugs to correct the water-electrolyte balance when they are used simultaneously with octreotide.

It may be necessary to correct the dose of insulin or hypoglycemic drugs when they are used simultaneously with octreotide.

Octreotide reduces intestinal absorption of cyclosporine and slows the absorption of cimetidine.

The simultaneous use of octreotide and bromocriptine increases the bioavailability of the latter.

There is evidence that somatostatin analogues can reduce the metabolic clearance of substances metabolized with enzymes of the cytochrome P450 system, which may be due to the suppression of GH. Since it can not be ruled out that octreotide may also have this effect, caution should be exercised when using drugs metabolized with the participation of the CYP3A4 isoenzyme and having a narrow range of therapeutic concentrations (for example, quinidine, terfenadine).

Special instructions:

General recommendations

With pituitary tumors secreting GH, careful monitoring of patients is necessary, since it is possible to increase the size of the tumor with the development of such serious complications as narrowing of the visual fields. In these cases, consideration should be given to the need for other treatments.

Since the decrease in the concentration of growth hormone and the normalization of IGF-1 concentration against the background of octreotide therapy can lead to restoration of reproductive function in women with acromegaly, when using the drug for patients with preserved reproductive potential, reliable contraceptive methods should be used. It is not known whether octreotide on fertility in humans. In studies in animals, no negative effect on the fertility of male and female rats with octreotide at a dose of 1 mg / kg body weight per day was found.

When using the drug Sandostatin® LAR for a long period of time, it is necessary to monitor the function of the thyroid gland.

Disorders from the cardiovascular system

When using the drug, bradycardia was often noted.

On the background of therapy with octreotide, it may be necessary to reduce the dose of beta-adrenoblockers, calcium channel blockers or drugs that affect the water-electrolyte balance.

In 15-30% of patients treated with Sandostatin ® for a long time, gallstones appeared in the gall bladder.The prevalence in the general population (age 40-60 years) is 5-20%. The long-term use of Sandostatin® LAR in patients with acromegaly and tumors of the gastrointestinal tract and pancreas suggests that the use of Sandostatin® LAR, compared with the administration of Sandostatin®, does not increase the incidence of gallbladder stones. Nevertheless, all patients should undergo ultrasound examination of the gallbladder before starting treatment with Sandostatin® LAR, and every 6 months during treatment. As a rule, the appearance of gallstones in the use of the drug is asymptomatic. In the presence of clinical symptoms, conservative treatment (eg, administration of bile acid preparations) or surgical intervention is indicated.

Disturbance of nutrition

In some patients octreotide can change the absorption of fats in the intestine.

Against the background of the use of octreotide a decrease in the concentration of vitamin B₁₂ and the deviation of the cyanocobalamin absorption test (Schilling test) from the norm. When using Sandostatin® LAR in patients with vitamin B deficiency₁₂in the anamnesis it is recommended to control its concentration.

Metabolism of glucose

In connection with the inhibitory effect of the drug on GH, glucagon and insulin, the development of glucose metabolism disorders in the form of postprandial impairment of glucose tolerance, and in some cases, the development of persistent hyperglycemia as a result of prolonged use of the drug, is possible. There have also been cases of development of hypoglycemia.

In patients with type 1 diabetes, the drug Sandostatin® LAR can affect glucose metabolism and reduce the need for insulin.

In patients with type 2 diabetes mellitus and patients without carbohydrate metabolism disorders, s / s injections of Sandostatin® can lead to an increase in postprandial glycemia. In this regard, it is recommended to monitor the concentration of glucose in the blood and, if necessary, to correct hypoglycemic therapy.

In patients with insulinomas, treatment with octreotide may show an increase in the severity and duration of hypoglycemia (this is associated with a more pronounced effect on the secretion of GH and glucagon than on insulin secretion, and also with a shorter duration of inhibitory effect on insulin secretion). Such patients should be carefully observed.

Recommendations for the timely detection of gallstones and the management of patients during treatment with Sandostatin® LAR

1. All patients should undergo ultrasound examination of the gallbladder before treatment.

2. During the treatment with Sandostatin® LAR, repeated ultrasound examination of the gall bladder should be performed, preferably at an interval of 6 months.

3. In the presence of gallstones before the start of therapy with the drug, the possibility of conducting therapy should be assessed individually, based on the ratio of possible risk to potential benefit. There is no evidence of worsening of the course of the existing cholelithiasis with the use of Sandostatin® LAR.

Recommendations for the formation of gallstones with Sandostatin® LAR

a) Asymptomatic stones of the gallbladder.

Continuation of drug therapy with a reassessment of the benefit / risk ratio. No treatment is required; follow-up is recommended.

b) Stones of the gallbladder with clinical symptoms.

Depending on the benefit / risk ratio, discontinue or continue therapy with the drug.Treatment of a patient with gall bladder stones, accompanied by clinical symptoms, must meet the accepted standards of therapy. Drug treatment includes the use of combinations of bile acid preparations (eg, chenodeoxycholic acid in combination with ursodeoxycholic acid or monotherapy with ursodeoxycholic acid) with ultrasound control until the stones disappear completely.

Effect on the ability to drive transp. cf. and fur:There is no evidence of the effect of Sandostatin® LAR on the ability to drive vehicles and mechanisms.

Form release / dosage:

Microspheres for suspension for intramuscular administration, 10 mg, 20 mg and 30 mg.

Packaging:

In bottles of glass hydrolytic class I with a capacity of 5 ml, sealed with gray rubber stoppers with a snap-off aluminum cover. Cover color: 10 mg - dark blue, 20 mg - orange, 30 mg - dark red.

For 2.5 ml of solvent in syringes of colorless glass of hydrolytic class I, volume 3 ml, sealed with two gray rubber stoppers.

Set: 1 vial with the drug, 1 pre-filled with a solvent syringe, 2 Sterile needles together with instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of 2-8 ° C (in the refrigerator).

Keep out of the reach of children.

Shelf life:3 years.

The drug should not be used after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N012891 / 01

Date of registration:07.12.2007

The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland

Manufacturer: & nbsp

NOVARTIS PHARMA STEIN, AG Switzerland

Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC

Information update date: & nbsp15.08.2015

Illustrated instructions

Instructions

Sandostatin® Lar (Sandostatin® LAR)