Package Insert: Information for the Patient

SANDOSTATIN 100 micrograms/mL injectable solution and for infusion

octreotide

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
  If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1. What is Sandostatin and how is it used

2. What you need to know before starting to use Sandostatin

3. How to use Sandostatin

4. Possible adverse effects

5. Storage of Sandostatin

6. Contents of the package and additional information

Sandostatin is a synthetic compound derived from somatostatin, a substance that is normally found in the human body that inhibits the effects of some hormones such as growth hormone. The advantages of Sandostatin compared to somatostatin are that it is more potent and its effects are longer-lasting.

Sandostatin is used

• foracromegaly, a disease in which the body produces too much growth hormone. Normally, growth hormone controls the growth of tissues, organs, and bones. An excess of growth hormone means an increase in the size of bones and tissues, especially in the hands and feet. Sandostatin significantly reduces the symptoms of acromegaly, which include headache, excessive sweating, numbness in the hands and feet, fatigue, and joint pain.
• to alleviate symptoms associated with somegastrointestinal tract tumors(e.g. carcinoid tumors, VIPomas, glucagonomas, gastrinomas, insulinomas, GRFomas). In these diseases, there is an overproduction of certain hormones and other related substances by the stomach, intestine, or pancreas. This overproduction alters the body's natural hormonal balance and produces various symptoms, such as hot flashes, diarrhea, low blood pressure, urticaria, and weight loss. Sandostatin treatment helps control these symptoms.
• to preventcomplications after pancreatic gland surgery. Sandostatin treatment helps reduce the likelihood of complications after surgery (e.g. abdominal abscesses, pancreatitis inflammation).
• to stop bleeding and to protect against arepetition of bleeding due to esophageal varices rupturein patients with cirrhosis (chronic liver disease). Sandostatin treatment helps control bleeding and reduce transfusion needs.
• to treat pituitary tumors that produce too much thyroid-stimulating hormone (TSH). An excess of thyroid-stimulating hormone (TSH) causes hyperthyroidism.

Sandostatin is used to treat people with pituitary tumors that produce too much thyroid-stimulating hormone (TSH):

• when other types of treatment (surgery or radiation therapy) are not suitable or have not worked;
• after radiation therapy, to cover the period until radiation therapy is fully effective.

No use Sandostatin:

• If you are allergic to octreotide or any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctor before starting to use Sandostatin:

• If you know you currently have gallstones, or have had them in the past, or have complications such as fever, chills, abdominal pain, or yellowing of the skin or eyes; inform your doctor, as prolonged use of Sandostatin may cause the formation of gallstones. Your doctor may want to monitor your gallbladder periodically.

• If you have problems with blood sugar levels, either too high (diabetes) or too low (hypoglycemia). When Sandostatin is used to treat bleeding due to esophageal varices; blood sugar level control is mandatory.

• If you have a history of vitamin B12 deficiency, your doctor may monitor your B12 levels periodically.

• Octreotide may reduce heart rate and at very high doses may cause an abnormal heart rhythm. Your doctor may monitor your heart rate during treatment.

Analysis and controls

If you receive treatment with Sandostatin for a prolonged period, your doctor may monitor your thyroid function periodically.

Your doctor will monitor your liver function.

Your doctor may check the functioning of your pancreatic enzymes.

Children

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

Other medications and Sandostatin

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

You can usually continue taking other medications while on Sandostatin treatment. However, some medications such as cimetidine, cyclosporine, bromocriptine, quinidine, and terfenadine have been affected by Sandostatin.

If you are taking a medication to control blood pressure (e.g. a beta blocker or a calcium channel blocker) or a medication to control fluid and electrolyte balance, your doctor may need to adjust the dose.

If you are diabetic, your doctor may need to adjust your insulin dose.

If you are to receive treatment with lutetium (177Lu) oxodotreotide, a radioactive agent, your doctor may interrupt or adapt Sandostatin treatment.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

Sandostatin should only be used during pregnancy if absolutely necessary.

Women of childbearing age should use an effective contraceptive method during treatment.

You should not breastfeed during Sandostatin treatment. It is unknown whether Sandostatin passes into breast milk.

Driving and operating machinery

Sandostatin has no effects or insignificant effects on the ability to drive or operate machinery. However, some of the adverse effects you may experience during Sandostatin treatment, such as headaches and fatigue, may reduce your ability to drive and operate machinery safely.

Sandostatin contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per vial; it is essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Depending on the disease being treated, Sandostatin is administered through:

• subcutaneous injection (under the skin) or
• intravenous infusion (in the vein).

If you have cirrhosis of the liver (chronic liver disease), your doctor may need to adjust your maintenance dose.

Your doctor or nurse will explain how to inject Sandostatin under the skin, but intravenous infusion always has to be performed by a healthcare professional.

• Subcutaneous injection

The upper arms, thighs, and abdomen are suitable areas for subcutaneous injection.

A new location should be chosen for each subcutaneous injection to avoid irritating a specific area. Patients who will administer the injection themselves should receive specific instructions from their doctor or nurse.

If the medication is stored in the refrigerator, it is recommended to let it reach room temperature before using it. This will reduce the risk of pain at the injection site. It can be tempered in the hand, but not heated.

Only a few patients experience pain at the subcutaneous injection site. This pain usually only lasts for a short period of time. If this happens to you, you can relieve it by gently massaging the injection site for a few seconds afterwards.

Before using a Sandostatin vial, check for the presence of particles or a color change. Do not use it if you detect anything abnormal.

If you use more Sandostatin than you should

The symptoms of overdose are: irregular heartbeat, low blood pressure, cardiac arrest, decreased oxygen supply to the brain, intense pain in the upper stomach, yellow color on the skin and eyes, nausea, loss of appetite, diarrhea, weakness, fatigue, lack of energy, weight loss, abdominal swelling, abdominal discomfort, high lactic acid level in the blood, and abnormal heart rhythm.

If you think you have overdosed and are experiencing any of these symptoms, inform your doctor immediately.

In case of overdose or accidental ingestion, you can also contact the Toxicological Information Service, Tel. 91 5620420.

If you forgot to use Sandostatin

Administer a dose as soon as you remember and then continue with the usual schedule. Missing a dose will not cause any harm, but symptoms may temporarily reappear until you return to the usual treatment schedule.

Do not inject a double dose to compensate for missed individual doses.

If you interrupt treatment with Sandostatin

If you interrupt your treatment with Sandostatin, your symptoms may reappear. Therefore, do not interrupt treatment with Sandostatin unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor, nurse, or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some side effects could 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 can cause sudden back pain.
• High blood sugar.

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

• Decreased activity of the thyroid gland (hypothyroidism) that causes changes in heart rhythm, 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).
• Very low blood sugar.
• Alteration of glucose tolerance
• Slow heart rate.

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

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

Other serious side effects

• Allergic reactions (hypersensitivity) including skin hives.
• A type of allergic reaction (anaphylaxis) that can cause difficulty swallowing or breathing, swelling, and tingling, possibly with a drop in blood pressure and dizziness or loss of consciousness.
• Inflammation of the pancreas (pancreatitis); symptoms may include sudden pain in the upper abdomen, nausea, vomiting, diarrhea.
• Inflammation of the liver (hepatitis); symptoms that may include yellowing of the skin and eyes (jaundice), nausea, vomiting, loss of appetite, general feeling of discomfort, itching, lightly colored urine.
• Irregular heart rate.
• Low platelet count in the blood; this may increase the risk of bleeding or bruising.

Inform your doctor immediately if you notice any of the previous side effects.

Other side effects:

Inform your doctor, pharmacist, or nurse if you notice any of the following side effects. They are usually mild and tend to disappear as treatment progresses.

Very common(may affect more than 1 in 10people):

• Diarrhea.
• Abdominal pain.
• Nausea.
• Constipation.
• Flatulence (gas).
• Headache.
• Pain at the injection site.

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

• Discomfort in the stomach after eating (dyspepsia).
• Vomiting.
• Feeling of having a full stomach.
• Fatty stools.
• Watery stools.
• Change in stool color.
• Dizziness.
• Loss of appetite.
• Changes in liver function tests.
• Hair loss.
• Difficulty breathing.
• Weakness.

If you experience any type of side effect, consult your doctor, nurse, or pharmacist.

A few patients experience pain at the subcutaneous injection site. This pain usually only lasts for a short period of time. If this happens to you, you can relieve it by gently massaging the injection site for a few seconds.

If you are administered Sandostatin via subcutaneous injection, you can help reduce the risk of gastrointestinal side effects by avoiding meals near the time of injection. Therefore, it is recommended that you administer Sandostatin between meals or before going to bed.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: http://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Store in the original packaging to protect it from light.

Store in the refrigerator (between2°Cand8°C). Do not freeze.

Prepared vials can be stored below 30°C for two weeks. Vials must be used immediately after opening.

Diluted solutions must be used immediately after preparation.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not use this medication if it contains visible particles or if you observe a change in color.

Medications should not be disposed of through drains or trash. Dispose of packaging and unused medications at the SIGREpoint at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and unused medications. This will help protect the environment.

Active Ingredient Content of Sandostatin

• The active ingredient is octreotide. 1 ml of solution contains 100 micrograms of octreotide.
• The other components are: lactic acid, mannitol (E421), sodium bicarbonate, water for injection.

Appearance of the Product and Contents of the Package

Colourless glass vial with two coloured rings (one blue and one green) containing a transparent and colourless solution.

Packages of three, five, six, ten, twenty and fifty vials.

Multi-pack of 10 packages, each containing three vials.

Only some package sizes may be marketed.

Marketing Authorization Holder

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes, 764

08013 Barcelona

Responsible for Manufacturing

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes, 764

08013 Barcelona

Novartis Pharma GmbH

Jakov-Lind-Straße 5, Top 3.05 1020 Wien Austria

Novartis Pharma NV

Medialaan 40/Bus 1, 1800 Vilvoorde, (Belgium).

Novartis Healthcare A/S

Edvard Thomsens vej 14, DK-2300 Copenhagen S, (Denmark).

Novartis Finland Oy

Metsänneidonkuja 10, 02130 Espoo, (Finland)

Novartis Pharma SAS

8-10 rue Henri Sainte-Claire Deville, 92500 Rueil-Malmaison (France)

Novartis Pharma GmbH

Roonstrasse 25, 90429 Nürnberg, (Germany).

Novartis Pharma GmbH

Sophie-Germain-Strasse 10, 90443 Nürnberg (Germany).

Novartis Farma-Produtos Farmacéuticos, SA

Avenida Professor Doutor Cavaco Silva nº10E, Taguspark, 2740-255 Porto Salvo, (Portugal).

Novartis Farma S.p.A.

Via Provinciale Schito 131, 80058 Torre Annunziata, NA, (Italy).

Novartis Sverige AB

Torshamnsgatan 48, 164 40 Kista (Sweden)

Novartis (Hellas) S.A.

12th km National Road Athinon-Lamia 14451 Metamorphosis Attiki, (Greece).

Novartis Pharma B.V.

Haaksbergweg 16, 1101 BX Amsterdam (Netherlands).

Novartis Poland Sp. z o.o.

15 Marynarska Street, 02-674 Warsaw (Poland).

Novartis Hungária Kft.

Vasút u.13, 2040 Budaörs (Hungary).

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Last review date of this leaflet:12/2023

Other sources of information

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

• Intravenous infusion (for healthcare professionals)

Check visually if the medicinal product presents a change in colour or visible particles before administration. Do not use it if you observe anything abnormal. For intravenous infusion, dilute the medicinal product before administration.

Sandostatin (octreotide acetate) is physically and chemically stable for 24 hours in physiological saline solution or sterile dextrose (glucose) solutions at 5% in water. However, since Sandostatin may affect glucose homeostasis, it is recommended to use physiological saline solutions instead of dextrose.

The diluted solutions are physically and chemically stable for at least 24 hours below 25°C. From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, the storage time and conditions before use are the responsibility of the user.

The content of a 500 microgram vial is usually dissolved in 60 ml of saline solution, and the resulting solution is administered by infusion pump. This should be repeated as necessary to achieve the prescribed treatment duration.

How much Sandostatin should be used

The dose of Sandostatin depends on the disease being treated.

• Acromegaly

Typically, treatment is initiated at doses of 0.05 to 0.1 mg every 8 or 12 hours by subcutaneous injection. Subsequently, it is adjusted according to its effects and relief of symptoms (such as fatigue, sweating, and headache). In most patients, the optimal daily dose will be 0.1 mg 3 times a day. Do not exceed the maximum daily dose of 1.5 mg.

• Gastrointestinal tract tumors

Treatment is usually initiated at a dose of 0.05 mg once or twice a day by subcutaneous injection. Depending on the response and tolerability, the dose can be gradually increased to 0.1 mg to 0.2 mg 3 times a day. In carcinoid tumors, treatment should be discontinued if no improvement is observed after 1 week of treatment at the maximum tolerated dose.

• Complications after pancreatic surgery

The usual dose is 0.1 mg 3 times a day by subcutaneous injection for 1 week, starting at least 1 hour before surgery.

• Gastroesophageal variceal hemorrhage

The recommended dose is 25 micrograms/hour for 5 days by continuous intravenous infusion. Blood glucose levels should be monitored during treatment.

• Pituitary adenomas secreting TSH

The usual effective dose is 100 micrograms 3 times a day by subcutaneous injection. The dose can be adjusted according to TSH response and thyroid hormone levels. At least 5 days are needed to evaluate efficacy.