Package Insert: Information for the Patient

SANDOSTATIN LAR 20 mg powder and solvent for injectable suspension

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 who 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.

Sandostatin LAR is a synthetic compound derived from somatostatin. Somatostatin is normally found in the human body, where it inhibits the release of certain hormones such as growth hormone. The advantages of Sandostatin LAR over somatostatin are that it is more potent and its effects are longer-lasting.

Sandostatin LAR is used

• to treat acromegaly,

Acromegaly is 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 results in an increase in the size of bones and tissues, especially in the hands and feet. Sandostatin 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 overproduction of growth hormone is caused by an increase in the size of the pituitary gland (pituitary adenoma); treatment with Sandostatin LAR can reduce the size of the adenoma.

Sandostatin LAR is used to treat individuals who suffer from acromegaly:

• when other types of treatment for acromegaly (surgery or radiation therapy) are not suitable or have not been effective;
• after radiation therapy, to cover the intermediate period until radiation therapy is completely effective.

• to alleviate symptoms associated with the overproduction of certain specific hormones and other related substances in the stomach, intestine, or pancreas.

The overproduction of certain specific hormones and other natural substances related can be caused by some rare alterations of the stomach, intestine, or pancreas. This alters the natural hormonal balance and causes a series of symptoms such as hot flashes, diarrhea, low blood pressure, skin rash, and weight loss. Treatment with Sandostatin LAR helps to control these symptoms.

• to treat localized neuroendocrine tumors in the intestine (e.g. appendix, small intestine, or colon)

Neuroendocrine tumors are rare tumors that can be found in different parts of the body. Sandostatin LAR is also used to control the growth of these tumors when they are localized in the intestine (e.g. appendix, small intestine, or colon)

• to treat pituitary tumors that produce too much thyroid-stimulating hormone (TSH).

An excess of thyroid-stimulating hormone (TSH) causes hyperthyroidism. Sandostatin LAR is used to treat individuals 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 been effective;

after radiation therapy, to cover the period until radiation therapy is completely effective.

Follow all the instructions given by your doctor carefully. They may be different from the information contained in this prospectus.

Read the following instructions before using Sandostatin LAR.

Do not use Sandostatin LAR:

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

Warnings and precautions

Consult your doctor before starting to use Sandostatin LAR:

• if you know that you currently have gallstones, or have had them in the past, or if you have any complications such as fever, chills, abdominal pain, or yellowing of the skin or eyes;inform your doctor, as prolonged use of Sandostatin LAR may cause the formation of gallstones. Your doctor may want to monitor your gallbladder periodically.
• if you know that you have diabetes, as Sandostatin LAR may affect blood sugar levels. If you are diabetic, you must regularly control your blood sugar levels.
• if you have a history of vitamin B12 deficiency, your doctor may monitor your B12 levels periodically.

Analysis and controls

If you receive treatment with Sandostatin LAR for a prolonged period of time, 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 LAR in children.

Use of Sandostatin LAR with other medications

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 you are being treated with Sandostatin LAR. However, some medications such as cimetidine, cyclosporine, bromocriptine, quinidine, and terfenadine have been reported to be affected by Sandostatin LAR.

If you are taking a medication to control blood pressure (e.g. a beta blocker or a calcium channel blocker) or an agent 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 radiopharmaceutical, your doctor may interrupt and/or adapt the treatment with Sandostatin LAR for a short period of time.

Pregnancy and lactation

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

Sandostatin LAR should only be used during pregnancy if it is strictly necessary.

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

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

Driving and operating machinery

Sandostatin LAR has no effects or they are insignificant on the ability to drive or operate machinery. However, some of these adverse effects that you may experience during treatment with Sandostatin LAR, such as headache 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".

Sandostatin LAR must be administered always as an injection into the gluteal muscle. With repeated administration, the right and left gluteal muscles should be used alternately.

If you use more Sandostatin LAR than you should

No fatal reactions have been reported after an overdose of Sandostatin LAR.

The symptoms of an overdose are: hot flashes, frequent urination, fatigue, depression, anxiety, and lack of concentration.

If you think you have had an overdose and are experiencing any of these symptoms, inform your doctor immediately. You can also call the Toxicology Information Service, Tel. 91 562 0420.

If you forgot to use Sandostatin LAR

If you have forgotten your injection, it is recommended that you administer it as soon as you remember, and then continue with your usual schedule. Not receiving a dose a few days later will not cause any harm, but your symptoms may temporarily return until you return to your regular treatment schedule.

If you interrupt treatment with Sandostatin LAR

If you interrupt your treatment with Sandostatin LAR, your symptoms may return. Therefore, do not interrupt treatment with Sandostatin LAR 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 medications, this medication may 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 10 people:

• 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).
• Low blood sugar.
• Alteration of glucose tolerance.
• Slow heart rate.

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

• Thirst, decreased 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 may cause difficulty swallowing or breathing, swelling, and tingling, possibly with a decrease 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 10 people):

• 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.

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 the 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 medication.

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 (between 2°C and 8°C). Do not freeze.

Sandostatin LAR can be stored below 25°C on the day of injection.

Do not store Sandostatin LAR after reconstitution (it must be used immediately).

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 you observe the presence of particles or a change in color.

Medications should not be disposed of through drains or in the trash. Dispose of the containers and medications you no longer need at the SIGRE point of the pharmacy.Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Composition of Sandostatin LAR

• The active ingredient is octreotide.

One vial contains 20 mg of octreotide (as octreotide acetate).

• The other components are:

In the powder (vial): poly(DL-lactide-co-glycolide), mannitol (E421).

In the solvent (pre-filled syringe): carboxymethylcellulose sodium, mannitol (E421), poloxamer 188, water for injection.

Appearance of Sandostatin LAR and packaging contents

Single-unit containers containing a 6 ml glass vial with a rubber stopper (bromobutyl), sealed with an aluminum flip-off seal, containing the powder for injectable suspension and a pre-filled syringe of colorless glass with a front stopper and a piston stopper (chlorobutyl rubber) with 2 ml of solvent, packaged together in a blister pack sealed with an adapter to the vial and a safety injection needle.

Multi-unit containers of three single-unit containers, each containing: a 6 ml glass vial with a rubber stopper (bromobutyl), sealed with an aluminum flip-off seal, containing the powder for injectable suspension and a pre-filled syringe of colorless glass with a front stopper and a piston stopper (chlorobutyl rubber) with 2 ml of solvent, packaged together in a blister pack sealed with an adapter to the vial and a safety injection needle.

Only some sizes of packaging may be commercially available.

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 Farma S.p.A.

Viale Luigi Sturzo 43, 20154 - Milan (MI) (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).

Abbot Biologicals B.V.

Veerweg, 12. 8121 AA Olst (Netherlands)

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

The 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:

How much Sandostatin LAR should be used

Acromegaly

It is recommended to start treatment with the administration of 20 mg of Sandostatin LAR at intervals of 4 weeks for 3 months. Patients on treatment with Sandostatin s.c. can start treatment with Sandostatin LAR the day after the last dose of Sandostatin s.c. The subsequent dose adjustment should be based on serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) concentrations and clinical symptoms.

For patients in whom the clinical symptoms and biochemical parameters (GH; IGF-1) are not fully controlled after 3 months (GH concentrations still above 2.5 micrograms/L), the dose can be increased to 30 mg every 4 weeks. If after 3 months, the clinical symptoms and biochemical parameters (GH; IGF-1) are not adequately controlled at a dose of 30 mg, the dose can be increased to 40 mg every 4 weeks.

For patients with GH concentrations consistently below 1 microgram/L, and with normalized serum IGF-1 concentrations, and in whom most reversible signs/symptoms of acromegaly have disappeared after 3 months of treatment with 20 mg, 10 mg of Sandostatin LAR can be administered every 4 weeks. However, especially in this group of patients, it is recommended to closely monitor serum GH and IGF-1 concentrations and clinical symptoms at this low dose of Sandostatin LAR.

For patients on a stable dose of Sandostatin LAR, serum GH and IGF-1 concentrations should be evaluated every 6 months.

Gastroenteropancreatic neuroendocrine tumors

• Treatment of patients with symptoms associated with functional gastroenteropancreatic neuroendocrine tumors

It is recommended to start treatment with the administration of 20 mg of Sandostatin LAR at intervals of 4 weeks. Patients on treatment with Sandostatin s.c. should continue at the previously effective dose for 2 weeks after the first injection of Sandostatin LAR.

For patients in whom symptoms and biological markers are well controlled after 3 months of treatment, the dose can be reduced to 10 mg of Sandostatin LAR every 4 weeks.

For patients in whom symptoms are only partially controlled after 3 months of treatment, the dose can be increased to 30 mg of Sandostatin LAR every 4 weeks.

For days when symptoms associated with gastroenteropancreatic tumors may increase during treatment with Sandostatin LAR, additional administration of Sandostatin s.c. at the dose used before treatment with Sandostatin LAR is recommended. This may occur mainly in the first 2 months of treatment until therapeutic concentrations of octreotide are reached.

• Treatment of patients with advanced neuroendocrine tumors of the intestine or of unknown origin where the sites of origin other than the intestine have been excluded

The recommended dose of Sandostatin LAR is 30 mg administered every 4 weeks. Treatment with Sandostatin LAR to control the tumor should be continued in the absence of tumor progression.

Treatment of TSH-secreting adenomas

Treatment with Sandostatin LAR should be started at a dose of 20 mg at intervals of 4 weeks for 3 months before considering dose adjustment. After that, the dose is adjusted based on TSH and thyroid hormone response.

Instructions for preparation and intramuscular injection of Sandostatin LAR.

ONLY FOR INTRAMUSCULAR INJECTION

Components of the injection kit:

1. A vial containing the powder of Sandostatin LAR
2. A pre-filled syringe containing the solvent for reconstitution
3. An adapter to the vial for reconstitution of the medication
4. A safety injection needle

Follow the instructions carefully below to ensure the reconstitution of Sandostatin LAR before intramuscular injection.

There are three critical steps in the process of reconstituting Sandostatin LAR. If they are not performed correctly, it may mean that the medication is not administered properly.

• The injection kit must reach room temperature. Remove the injection kit from the refrigerator and let the kit reach room temperature for at least 30 minutes before reconstitution, but not exceeding 24 hours.
• After adding the solvent solution, leave the vial to stand for 5 minutesto ensure that the powder is completely saturated.
• After saturation,gently agitate the vial horizontally for at least 30 secondsuntil a uniform suspension is formed. The Sandostatin LAR suspension should only be preparedimmediately before administration.

Sandostatin LAR should only be administered by a healthcare professional.