Sandostatina

Package leaflet: Information for the patient

Sandostatina ® 50 micrograms/1 mL, injectable solution/infusion, ® 100 micrograms/1 mL, injectable solution/infusion, ® 500 micrograms/1 mL, injectable solution/infusion

octreotide
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Sandostatina is and what it is used for
2. What you need to know before using Sandostatina
3. How to use Sandostatina
4. Possible side effects
5. How to store Sandostatina
6. Contents of the pack and other information

1. What Sandostatin is and what it is used for

Sandostatin is a synthetic compound analogous to somatostatin. Somatostatin is naturally present
in the human body, where it inhibits the release of certain hormones such as growth hormone. The advantages of
Sandostatin over somatostatin are that it is more potent and its effect lasts longer.
Sandostatin is used

• in acromegaly, a condition in which the body produces an excessive amount of growth hormone. Normally, growth hormone regulates the growth of tissues, organs and bones. When present in excessive amounts, it causes an increase in the size of bones and tissues, particularly in the hands and feet. Sandostatin significantly reduces the symptoms of acromegaly, including headache, excessive sweating, numbness in the hands and feet, fatigue and joint pain.

• to relieve symptoms associated with certain gastrointestinal tract tumours (e.g. carcinoid tumours, VIPomas, glucagonomas, gastrinomas, insulinomas). In these conditions, there is excessive production of specific hormones and other related substances in the stomach, intestine or pancreas. This overproduction disrupts the body's natural hormonal balance and causes a variety of symptoms, such as hot flushes, diarrhoea, hypotension, skin rashes and weight loss. Treatment with Sandostatin helps control these symptoms.

• to prevent complications following pancreatic surgery. Treatment with Sandostatin helps reduce the likelihood of complications (e.g. abdominal abscess, inflammation of the pancreas) after surgery.

• to stop bleeding and prevent re-bleeding from ruptured gastro-oesophageal varices in patients with cirrhosis (chronic liver disease). Treatment with Sandostatin helps control bleeding and reduce the need for blood transfusions.

• to treat pituitary adenomas that produce excessive amounts of thyroid-stimulating hormone (TSH). Excessive levels of thyroid-stimulating hormone (TSH) lead to hyperthyroidism.
  Sandostatin is used to treat people with pituitary tumours that produce too much thyroid-stimulating hormone (TSH):

• when other treatments (surgery or radiotherapy) are not indicated or have not been effective;

• after radiotherapy, to cover the period required for radiotherapy to achieve maximum effectiveness

2. What you need to know before taking Sandostatin

Do not take Sandostatin:

• if you are allergic to octreotide or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before taking Sandostatin:

• if you know you have gallstones, have had them in the past, or if complications occur such as fever, chills, abdominal pain, or yellowing of the skin or eyes; inform your doctor, as prolonged use of Sandostatin may lead to gallstone formation. Your doctor may ask you to have periodic gallbladder monitoring.
• if you know you have blood sugar level problems, either too high (diabetes) or too low (hypoglycemia). When Sandostatin is used to treat gastro-oesophageal variceal bleeding, blood sugar levels must be monitored.
• if you have previously experienced episodes of vitamin B12 deficiency, your doctor may ask you to periodically check your vitamin B12 levels.
• Octreotide may reduce heart rate and, at very high doses, may cause an irregular heartbeat. Your doctor may monitor your heart rate during treatment.

Tests and monitoring
If you are receiving Sandostatin treatment for a long period, your doctor may ask you to periodically check
thyroid function.
Your doctor will monitor liver function.
Children
Experience with the use of Sandostatin in children is limited.
Other medicines and Sandostatin
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines.
In general, you can continue taking other medicines while being treated with Sandostatin. However,
it has been reported that Sandostatin may interact with certain drugs, such as cimetidine, cyclosporine,
bromocriptine, quinidine, and terfenadine.
If you are taking medicines to control blood pressure (such as beta-blockers or calcium
antagonists) or agents affecting water and electrolyte balance, your doctor may decide to adjust
the dosage.
If you are diabetic, your doctor may decide to adjust your insulin dosage.
If you are about to receive lutetium (Lu) oxodotreotide, a radiopharmaceutical therapy, your doctor may interrupt
and/or modify Sandostatin treatment.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding,
consult your doctor before taking this medicine.
Sandostatin may be used during pregnancy only if clearly necessary.
Women of childbearing potential should use adequate contraception during treatment.
Women must not breastfeed during treatment with Sandostatin. It is not known whether Sandostatin is excreted in human milk.
Driving and using machines
Sandostatin does not affect or affects negligibly the ability to drive vehicles or operate machinery.
However, during treatment with Sandostatin, some adverse effects such as headache and fatigue may occur, which could impair your ability to drive or operate machinery safely.
Sandostatin contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. is practically 'sodium-free'.

3. How to take Sandostatin

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Depending on the condition being treated, Sandostatin may be administered as:

• a subcutaneous injection (under the skin), or
• an intravenous infusion (into a vein).

If you are a patient with cirrhosis (chronic liver disease), your doctor may need to adjust the
maintenance dose.
Your doctor or nurse will explain how to inject Sandostatin under the skin; however, intravenous infusion must
always be performed by a healthcare professional.

• Subcutaneous injection

The most suitable sites for subcutaneous injection are the arms, thighs, and abdomen.
Choose a different injection site each time to avoid irritating a specific area. Patients who are to perform self-injection must receive clear instructions from their doctor or nurse.
If you store the medicine in the refrigerator, it is recommended to bring it to room temperature before use.
This reduces the risk of pain at the injection site. You may bring it to room temperature by holding it in your hand, but it must not be heated.
Some people may experience pain at the subcutaneous injection site. This pain usually lasts only briefly. If this occurs, it can be relieved by gently massaging the injection site for a few seconds afterwards.
Before using the Sandostatin vial, check for particles or changes in colour. Do not use the medicine
if you notice anything unusual.

If you take more Sandostatin than you should
Symptoms of overdose may include: irregular heartbeat, low blood pressure, cardiac arrest, reduced oxygen supply to the brain, severe upper abdominal pain, yellowing of the skin and eyes, nausea, loss of appetite, diarrhoea, weakness, fatigue, lack of energy, weight loss, abdominal swelling, discomfort, elevated blood lactate levels, and irregular heart rhythm.
If you think you are experiencing symptoms of an overdose, inform your doctor immediately.

If you forget to take Sandostatin
Take the missed dose as soon as you remember, then continue your treatment as usual. If you miss a dose, there may not be serious consequences, but you might experience a temporary return of symptoms until treatment is resumed.
Do not inject a double dose of Sandostatin to make up for a forgotten dose.

If you stop taking Sandostatin
If you stop treatment with Sandostatin, symptoms may return. Therefore, do not stop treatment with Sandostatin unless instructed to do so by your doctor.

If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Some adverse effects may be serious. Inform your doctor immediately if you experience any of the
following:
Very common (may affect more than 1 in 10 users):

• Gallstones, which may cause sudden back pain.
• High blood sugar levels.

Common (may affect up to 1 in 10 users):

• Decreased thyroid activity (hypothyroidism), with changes in heart rate, appetite, or weight, fatigue, feeling cold, or swelling in the front of the neck.
• Changes in thyroid function tests.
• Inflammation of the gallbladder (cholecystitis); symptoms may include pain in the upper right abdomen, fever, nausea, yellowing of the skin and eyes (jaundice).
• Low blood sugar.
• Impaired glucose tolerance.
• Slow heart rate.

Uncommon (may affect up to 1 in 100 users):

• Thirst, low urine output, dark urine, flushed and dry skin.
• Fast heart rate.

Other serious adverse effects

• Hypersensitivity reactions (allergy), including skin rash.
• A type of allergic reaction (anaphylaxis) that may cause difficulty swallowing or breathing, swelling and tingling, possibly with a drop in blood pressure leading to dizziness or loss of consciousness.
• Inflammation of the pancreas (pancreatitis); symptoms may include sudden pain in the upper abdomen, nausea, vomiting, diarrhoea.
• Inflammation of the liver (hepatitis); symptoms may include yellowing of the skin and eyes (jaundice), nausea, vomiting, loss of appetite, general malaise, itching, pale-coloured urine.
• Irregular heartbeat.
• Low platelet count in the blood; this may lead to increased bleeding or bruising.

Inform your doctor immediately if you notice any of the above adverse effects.
Other adverse effects:
Inform your doctor, pharmacist, or nurse if you notice any of the following adverse effects. These are usually mild in intensity and tend to resolve with continued treatment.
Very common (may affect more than 1 in 10 users):

• Diarrhoea.
• Abdominal pain.
• Nausea.
• Constipation.
• Flatulence.
• Headache.
• Local injection site pain.

Common (may affect up to 1 in 10 users):

• Stomach discomfort after meals (dyspepsia).
• Vomiting.
• Feeling of stomach fullness.
• Fatty stools.
• Soft stools.
• Pale stools.
• Dizziness.
• Loss of appetite.
• Changes in liver function tests.
• Hair loss.
• Shortness of breath.
• Weakness.

If you experience any of these adverse effects, inform your doctor, nurse, or pharmacist.
A few people may experience pain at the subcutaneous injection site. This pain usually lasts only a short time. If it occurs, it can be relieved by gently massaging the injection site for a few seconds.
If you are taking Sandostatin for subcutaneous injection, avoid injecting close to mealtimes, as this may help reduce the risk of gastrointestinal adverse effects. It is therefore recommended to administer the injection between meals or at bedtime.
Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report adverse effects directly via the national reporting system at the website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store Sandostatina

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from light.
Store in a refrigerator (2°C to 8°C). Do not freeze.
Vials may be stored at temperatures below 30°C for up to a maximum of 2 weeks.
Vials must be used immediately after opening.
The diluted solution must be used immediately after preparation.
Do not use this medicine after the expiry date stated on the label and on the carton after "EXP". The expiry date refers to the last day of that month.
Do not use the medicine if you notice any change in colour or the presence of particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Sandostatina contains

• The active substance is octreotide.
  Sandostatina 50 micrograms/1 ml, solution for injection/infusion
  Sandostatina 100 micrograms/1 ml, solution for injection/infusion
  Sandostatina 500 micrograms/1 ml, solution for injection/infusion
• The other components are: lactic acid, mannitol (E421), sodium bicarbonate, water for injections.

Description of the appearance of Sandostatina and contents of the pack
Colourless glass vial with two rings of different colours, containing a clear, colourless solution.
Sandostatina 50 micrograms/1 ml: one blue ring and one yellow ring
Sandostatina 100 micrograms/1 ml: one blue ring and one green ring
Sandostatina 500 micrograms/1 ml: one blue ring and one pink ring
Packs containing three, five, six, ten, twenty or fifty vials.
Multiple packs of ten packs, each containing three vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Novartis Farma S.p.A.
Largo Umberto Boccioni, 1
21040 Origgio (VA)
Italy

Manufacturer
Novartis Farma SpA
L.go U. Boccioni, 1
21040 Origgio (VA)
Italy
Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes, 764
08013 Barcelona,
Spain

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Austria, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Malta, Norway, Poland, Romania, Slovak Republic, Slovenia, Spain, Sweden, United Kingdom (Northern Ireland)	Sandostatin
Belgium, France, Luxembourg, Netherlands	Sandostatine
Italy, Portugal	Sandostatina

Other sources of information
Detailed information on this medicinal product is available on the website of the Italian Medicines Agency.
The following information is intended exclusively for physicians or healthcare professionals:

• Intravenous infusion (for healthcare professionals)

Visually inspect the medicinal product before administration to check for changes in colour and for the presence of particles. Do not use if anything unusual is observed. For intravenous infusion, dilute the product prior to administration. Sandostatin (octreotide acetate) is physically and chemically stable for 24 hours in sterile physiological saline or in sterile aqueous 5% dextrose (glucose) solutions. However, since Sandostatin may interfere with glucose balance, physiological saline is recommended rather than dextrose solution. Diluted solutions are physically and chemically stable for at least 24 hours below 25°C. From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, the times and conditions of storage are the responsibility of the user.
The contents of a 500 microgram vial must be dissolved in 60 mL of physiological saline and the resulting solution must be administered using an infusion pump. This procedure must be repeated with the necessary frequency for the prescribed duration of treatment.
Amount of Sandostatin to use
The dose of Sandostatin depends on the condition being treated.

• Acromegaly Treatment is normally initiated at 0.05 – 0.1 mg every 8 or 12 hours by subcutaneous injection. The dose may subsequently be adjusted based on effect and symptom control (such as fatigue, sweating and headache). In most patients, the optimal daily dose is 0.1 mg three times daily. It is recommended not to exceed the maximum dose of 1.5 mg per day.
• Gastrointestinal tract tumours Treatment is normally initiated at a dose of 0.05 mg once or twice daily by subcutaneous injection. Based on response and tolerability, the dose may be gradually increased to 0.1 – 0.2 mg three times daily. In carcinoid tumours, therapy should be discontinued if no benefit is obtained after 1 week of treatment at the maximum tolerated dose.
• Complications following pancreatic surgery The usual dose is 0.1 mg three times daily by subcutaneous injection for 1 week, starting at least 1 hour before surgery.
• Gastro-oesophageal variceal bleeding The recommended dose is 25 micrograms/hour by continuous intravenous infusion for 5 days. Blood glucose levels must be monitored during treatment.
• Treatment of TSH-secreting pituitary adenomas The generally most effective dose is 100 micrograms three times daily by subcutaneous injection. The dose may be adjusted according to TSH and thyroid hormone responses. At least 5 days of treatment will be necessary to assess efficacy.

Patient Information Leaflet: Information for the patient

Sandostatina LAR 10 mg powder and solvent for injectable suspension, LAR 20 mg powder and solvent for injectable suspension, LAR 30 mg powder and solvent for injectable suspension

octreotide
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Sandostatina LAR is and what it is used for
2. What you need to know before using Sandostatina LAR
3. How to use Sandostatina LAR
4. Possible side effects
5. How to store Sandostatina LAR
6. Contents of the pack and other information

1. What Sandostatina LAR is and what it is used for

Sandostatina LAR is a synthetic compound analogous to somatostatin. Somatostatin is naturally
present in the human body, where it inhibits the release of certain hormones such as growth hormone. The advantages
of Sandostatina LAR compared to somatostatin are that it is more potent and its action lasts longer over time.
Sandostatina LAR is used

• to treat acromegaly. Acromegaly is a condition in which the body produces an excessive amount of growth hormone. Normally, growth hormone controls the growth of tissues, organs, and bones. When present in excessive amounts, it causes an increase in the size of bones and tissues, particularly in the hands and feet. Sandostatina LAR significantly reduces the symptoms of acromegaly, which include headache, excessive sweating, numbness in the hands and feet, fatigue, and joint pain. In most cases, the excessive production of growth hormone is caused by enlargement of the pituitary gland (pituitary adenoma); treatment with Sandostatina LAR can reduce the size of the adenoma. Sandostatina LAR is used to treat people with acromegaly:
• when other types of treatment for acromegaly (surgery or radiotherapy) are not suitable or have not been effective;
• after radiotherapy, to cover the transition period until radiotherapy reaches maximum effectiveness.
• to relieve symptoms associated with the excessive production of certain specific hormones and other related substances in the stomach, intestine, and pancreas. The excessive production of specific hormones and other related natural substances may be caused by rare conditions affecting the stomach, intestine, and pancreas. This situation disrupts the body's natural hormonal balance and leads to a variety of symptoms, such as hot flashes, diarrhea, hypotension, skin rashes, and weight loss. Treatment with Sandostatina LAR helps control these symptoms.
• to treat neuroendocrine tumours located in the intestine (e.g. appendix, small intestine, or colon). Neuroendocrine tumours are rare tumours that can occur in various parts of the body. Sandostatina LAR is also used to control the growth of these tumours when they are located in the intestine (e.g. appendix, small intestine, or colon).
• to treat pituitary adenomas that produce an excessive amount of thyroid-stimulating hormone (TSH). An excessive amount of thyroid-stimulating hormone (TSH) leads to hyperthyroidism. Sandostatina LAR is used to treat people with pituitary tumours that produce too much thyroid-stimulating hormone (TSH):
• when other treatments (surgery or radiotherapy) are not indicated or have not been effective;
• after radiotherapy, to cover the period required for radiotherapy to reach maximum effectiveness.

2. What you should know before taking Sandostatina LAR

Carefully follow all instructions given by your doctor. These may differ from the information contained in this leaflet.
Read the following instructions before using Sandostatina LAR.

Do not take Sandostatina LAR:

• if you are allergic to octreotide or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before taking Sandostatina LAR:

• if you know you have gallstones, have had them in the past, or if complications occur such as fever, chills, abdominal pain, or yellowing of the skin or eyes; inform your doctor, as long-term use of Sandostatina LAR may lead to gallstone formation. Your doctor may ask you to have periodic gallbladder examinations.
• if you have diabetes, since Sandostatina LAR may affect blood sugar levels. If you are diabetic, your blood sugar levels should be monitored regularly.
• if you have previously experienced episodes of vitamin B12 deficiency, your doctor may ask you to periodically monitor your vitamin B12 levels.

Tests or monitoring
If you are receiving long-term treatment with Sandostatina LAR, your doctor may periodically check your thyroid function.
Your doctor will monitor your liver function.

Children
Experience with the use of Sandostatina LAR in children is limited.

Other medicines and Sandostatina LAR
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In general, you may continue taking other medicines while being treated with Sandostatina LAR.
However, it has been reported that Sandostatina LAR may interact with certain drugs such as cimetidine, cyclosporine, bromocriptine, quinidine, and terfenadine.
If you are taking medications to control blood pressure (such as β-blockers or calcium antagonists) or agents affecting fluid and electrolyte balance, your doctor may decide to adjust the dosage.
If you are diabetic, your doctor may decide to adjust your insulin dosage.
If you are about to receive lutetium (Lu) oxodotreotide, a radiopharmaceutical therapy, your doctor may temporarily interrupt and/or modify treatment with Sandostatina LAR.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
Sandostatina LAR may be used during pregnancy only if clearly necessary.
Women of childbearing potential must use adequate contraception during treatment.
Patients must not breastfeed during treatment with Sandostatina LAR.
It is not known whether Sandostatina LAR is excreted in human milk.

Driving and using machines
Sandostatina LAR does not affect or affects negligibly the ability to drive vehicles or operate machinery. However, during treatment with Sandostatina LAR, some side effects such as headache and fatigue may occur, which could reduce your ability to drive or use machinery safely.

Sandostatina LAR contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is practically ‘sodium-free’.

3. How to take Sandostatina LAR

Sandostatina LAR must always be administered by deep intramuscular injection into the gluteal site.
The injection site for repeated administrations should be alternated between the left and right gluteus.
If you take more Sandostatina LAR than you should
No life-threatening reactions have been reported following overdose of Sandostatina LAR.
Symptoms of overdose include: flushing, frequent urination, fatigue, depression, anxiety, and difficulty concentrating.
If you think you are experiencing symptoms of an overdose, inform your doctor immediately.
If you forget to take Sandostatina LAR
If you miss an injection, it is recommended to administer it as soon as you remember, then continue treatment as usual.
A delay of a few days in administration is not harmful, but may temporarily cause symptoms to reappear until normal treatment is resumed.
If you stop taking Sandostatina LAR
If treatment with Sandostatina LAR is stopped, symptoms may reappear. Therefore, do not interrupt therapy with Sandostatina LAR unless instructed by your doctor.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some side effects can be serious. Inform your doctor immediately if you experience any of the
following:
Very common (may affect more than 1 in 10 people):

• Gallstones, which may cause sudden back pain.
• High blood sugar levels.

Common (may affect up to 1 in 10 people):

• Reduced thyroid activity (hypothyroidism), with changes in heart rate, appetite, or weight, fatigue, feeling cold, or swelling in the front of the neck.
• Changes in thyroid function tests.
• Inflammation of the gallbladder (cholecystitis); symptoms may include pain in the upper right part of the abdomen, fever, nausea, yellowing of the skin and eyes (jaundice).
• Low blood sugar.
• Impaired glucose tolerance.
• Slow heart rate.

Uncommon (may affect up to 1 in 100 people):

• Thirst, low urine output, dark urine, flushed and dry skin.
• Fast heart rate.

Other serious side effects

• Hypersensitivity reactions (allergy) including skin rash.
• A type of allergic reaction (anaphylaxis) which may cause difficulty swallowing or breathing, swelling and tingling, possibly with a drop in blood pressure leading to dizziness or loss of consciousness.
• Inflammation of the pancreas (pancreatitis). Symptoms may include sudden pain in the upper part of the abdomen, nausea, vomiting, diarrhoea.
• Inflammation of the liver (hepatitis); symptoms may include yellowing of the skin and eyes (jaundice), nausea, vomiting, loss of appetite, general feeling of being unwell, itching, pale-coloured urine.
• Irregular heartbeat.
• Low platelet count in the blood; this could lead to increased bleeding or bruising.

Inform your doctor immediately if you notice any of the above-mentioned side effects.
Other side effects:
Inform your doctor, pharmacist or nurse if you notice any of the following side effects. These are usually mild in intensity and tend to disappear with continued treatment.
Very common (may affect more than 1 in 10 people):

• Diarrhoea.
• Abdominal pain.
• Nausea.
• Constipation.
• Flatulence.
• Headache.
• Local injection site pain.

Common (may affect up to 1 in 10 people):

• Stomach discomfort after meals (dyspepsia).
• Vomiting.
• Feeling of fullness in the stomach.
• Fatty stools.
• Soft stools.
• Pale stools.
• Dizziness.
• Loss of appetite.
• Changes in liver function tests.
• Hair loss.
• Shortness of breath.
• Weakness.

If you experience any of these side effects, inform your doctor, nurse or pharmacist.
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sandostatina LAR

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from light.
Store in a refrigerator (2°C-8°C). Do not freeze.
Sandostatina LAR must be stored at a temperature below 25°C on the day of administration.
Do not store Sandostatina LAR after reconstitution (it must be used immediately).
Do not use this medicine after the expiry date stated on the label and packaging after "EXP". The expiry date refers to the last day of that month.
Do not use the medicine if particles are visible or if there is any change in colour.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sandostatina LAR contains
The active substance is octreotide.
One vial contains 10 mg, 20 mg, or 30 mg of octreotide (as octreotide acetate).
The other ingredients are:
in the powder (vial): poly(DL-lactide-co-glycolide), mannitol (E421).
in the solvent (pre-filled syringe): sodium carmellose, mannitol (E421), poloxamer 188, water for
injections.

Description of the appearance of Sandostatina LAR and contents of the pack
One pack contains a 6 ml glass vial closed with a rubber stopper (bromobutyl rubber), sealed with an aluminium seal with a tear-off strip, containing the powder for injectable suspension, and a 3 mL colourless glass pre-filled syringe with a plunger and a front cap (chlorobutyl rubber), containing 2 mL of solvent, packed in a sealed blister tray together with a vial adapter and a safety needle for injection.

Multiple packs containing three single packs, each containing: a 6 mL glass vial closed with a rubber stopper (bromobutyl rubber), sealed with an aluminium seal with a tear-off strip, containing the powder for injectable suspension, and a 3 mL colourless glass pre-filled syringe with a plunger and a front cap (chlorobutyl rubber) containing 2 mL of solvent, packed in a sealed blister tray together with a vial adapter and a safety needle for injection.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Novartis Farma S.p.A.
Origgio (VA)

Manufacturer
Novartis Farma S.p.A
Torre Annunziata (NA)
Novartis Farma SpA
L.go U. Boccioni, 1
21040 Origgio (VA)
Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain

This medicinal product is authorized in the European Economic Area Member States and in the United Kingdom (Northern Ireland) under the following names:

Austria, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Malta, Norway, Poland, Romania, Slovak Republic, Slovenia, Spain, Sweden, United Kingdom (Northern Ireland)	Sandostatin LAR
Belgium, Luxembourg, Netherlands	Sandostatine LAR
Italy, Portugal	Sandostatina LAR
France	Sandostatine L.P.

Other sources of information
Detailed information on this medicinal product is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco).

The following information is intended exclusively for physicians or healthcare professionals:

Amount of Sandostatina LAR to use

Acromegaly
Treatment should be initiated with Sandostatina LAR 20 mg administered every 4 weeks for 3 months. Patients previously treated with subcutaneous Sandostatina may start Sandostatina LAR the day after the last subcutaneous dose.

Subsequent dose adjustments should be based on blood levels of growth hormone (GH) and insulin-like growth factor-1/somatomedin C (IGF-1), as well as clinical symptoms.

In patients in whom, within the first 3-month period, both clinical symptoms and biochemical parameters (GH; IGF-1) have not been adequately controlled (GH concentrations still above 2.5 micrograms/L), the dose may be increased to 30 mg every 4 weeks. If, after 3 months, GH, IGF-1, and/or clinical symptoms are still not adequately controlled at the 30 mg dose, the dose may be increased to 40 mg every 4 weeks.

In patients in whom GH concentrations remain consistently below 1 microgram/L, serum IGF-1 concentrations normalize, and most reversible signs/symptoms of acromegalia have disappeared after 3 months of treatment with 20 mg, Sandostatina LAR 10 mg every 4 weeks may be administered. However, particularly in this group of patients receiving this low dose of Sandostatina LAR, adequate monitoring of serum GH and IGF-1 concentrations and clinical signs and symptoms is recommended.

In patients on a stable dose of Sandostatina LAR, GH and IGF-1 should be monitored every 6 months.

Gastro-entero-pancreatic endocrine tumors

• Treatment of patients with symptoms associated with functioning gastro-entero-pancreatic neuroendocrine tumors
  Treatment should be initiated with Sandostatina LAR 20 mg administered every 4 weeks. Patients previously treated with subcutaneous Sandostatina should continue treatment at the previously effective dose for 2 weeks after the first Sandostatina LAR injection. In patients in whom both clinical symptoms and biochemical parameters are well controlled after 3 months of treatment, the dose may be reduced to Sandostatina LAR 10 mg every 4 weeks.

In patients in whom both clinical symptoms and biochemical parameters are only partially controlled after 3 months of treatment, the dose may be increased to Sandostatina LAR 30 mg every 4 weeks.

In cases where symptoms associated with gastro-entero-pancreatic tumors worsen during Sandostatina LAR treatment, additional subcutaneous Sandostatina should be administered at the dose previously used before initiating Sandostatina LAR therapy. This may occur particularly during the first 2 months of treatment, until therapeutic octreotide concentrations are achieved.

• Treatment of patients with advanced midgut neuroendocrine tumors or tumors of unknown primary origin, with exclusion of extramidgut sites
  The recommended dose of Sandostatina LAR is 30 mg administered every 4 weeks. Treatment with Sandostatina LAR for tumor control should be continued even in the absence of tumor progression.

Treatment of TSH-secreting pituitary adenomas
Treatment with Sandostatina LAR should be initiated at a dose of 20 mg every 4 weeks for 3 months before considering any dose adjustment. The dose should then be adjusted based on TSH and thyroid hormone response.

Instructions for preparation and intramuscular injection of Sandostatina LAR
FOR DEEP INTRAMUSCULAR INJECTION ONLY

Contents of the injection kit:

a. A vial containing Sandostatina LAR powder,
b. A pre-filled syringe containing the diluent solution for reconstitution,
c. A vial adapter for reconstitution of the medicinal product,
d. A safety needle for injection.

Carefully follow the instructions below to ensure correct reconstitution of Sandostatina LAR prior to deep intramuscular injection.
There are 3 critical steps in the reconstitution of Sandostatina LAR. Failure to follow these steps may result in inappropriate leakage of the medicinal product.

• The injection kit must reach room temperature. Remove the kit from the refrigerator and allow it to stand at room temperature for at least 30 minutes before reconstitution, but not longer than 24 hours.
• After adding the diluent solution, ensure the powder is completely saturated by allowing the vial to stand for 5 minutes.
• After saturation, gently agitate the vial horizontally for at least 30 seconds until a uniform suspension is formed. The Sandostatina LAR suspension must be prepared immediately before administration.

It is recommended that Sandostatina LAR administration be performed only by trained healthcare personnel.

Step 1

• Remove the Sandostatina LAR injection kit from the refrigerator.

WARNING: It is essential to begin the reconstitution process only after the kit has reached room temperature. Allow the kit to stand at room temperature for at least 30 minutes before reconstitution, but not longer than 24 hours.
Note: The injection kit may be refrigerated again if necessary.

Step 2

• Remove the plastic cap from the vial and clean the rubber stopper with an alcohol swab.
• Remove the foil from the package containing the vial adapter, but DO NOT remove the vial adapter from its packaging.
• Holding the packaging of the vial adapter, place the adapter onto the top of the vial and push down firmly until it clicks into place with an audible "click".

• Lift off the outer packaging of the vial adapter with a vertical motion.

Step 3

• Remove the cap from the pre-filled syringe containing diluent and screw the syringe into the vial adapter.
• Gently push the plunger fully to transfer all the diluent into the vial.

Step 4

WARNING: It is essential to let the vial stand for 5 minutes to allow complete saturation of the powder.
Note: It is normal for the plunger to move slightly due to slight overpressure in the vial.

• At this point, prepare the patient for injection.

Step 5

• After the saturation time, ensure the plunger is fully depressed in the syringe. WARNING: While keeping the plunger depressed, gently agitate the vial horizontally for at least 30 seconds to ensure the powder is completely suspended (uniform milky suspension). Repeat gentle agitation for another 30 seconds if the powder is not fully suspended.

Step 6

• Invert the syringe and vial, slowly pull back the plunger, and transfer the entire contents from the vial into the syringe.
• Unscrew the syringe from the vial adapter.

Step 7

• Screw the safety injection needle onto the syringe.
• If immediate administration is delayed, gently re-agitate the syringe to ensure a uniform milky suspension.
• Prepare the injection site with an alcohol swab.

Remove the protective needle cap.

• Gently tap the syringe to remove any visible air bubbles and expel them from the syringe.
• Proceed immediately to Step 8 for administration to the patient. Any delay may cause sedimentation.

Step 8

• Sandostatina LAR must be administered only by deep intramuscular injection; NEVER by intravenous route.
• Insert the needle fully into the left or right gluteal muscle at a 90° angle to the skin.
• Slowly pull back the plunger to check whether a blood vessel has been entered (reposition if a vessel is punctured).
• Push the plunger steadily until the syringe is empty. Remove the needle from the injection site and activate the safety device (as shown in Step 9).

Step 9

• Activate the safety device over the needle using one of the two methods shown:
• Press the hinged part of the safety device downward onto a hard surface (Figure A)
• Or push the hinged part forward with your finger

(Figure B).

• An audible "click" confirms proper activation.
• Dispose of the syringe immediately in the appropriate sharps container.