Sandostatin LAR 10 mg powder and solvent for injectable suspension

Patient Information Leaflet

Introduction

Package Leaflet: Information for the Patient

SANDOSTATIN LAR 10 mg powder and solvent for injectable suspension

Octreotide

Read this entire leaflet carefully before you start using this medicine, as it contains important information for you.

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

Leaflet Contents

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

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

Sandostatin LAR is a synthetic compound derived from 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 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 condition in which the body produces too much growth hormone. Normally, growth hormone regulates the growth of tissues, organs, and bones. Excess growth hormone leads to an increase in the size of bones and tissues, especially in the hands and feet. Sandostatin LAR significantly reduces the symptoms of acromegaly, including headache, excessive sweating, numbness in the hands and feet, fatigue, and joint pain. In most cases, the overproduction of growth hormone is caused by enlargement of the pituitary gland (pituitary adenoma); treatment with Sandostatin LAR may reduce the size of the adenoma.

Sandostatin LAR is used to treat people with acromegaly:

• when other types of treatment for acromegaly (surgery or radiotherapy) are not suitable or have not worked effectively;

• after radiotherapy, to cover the interim period until radiotherapy becomes fully effective.

• to relieve 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 related natural substances may be caused by rare disorders of the stomach, intestine, or pancreas. This disrupts the natural hormonal balance and causes a range of symptoms such as flushing, diarrhea, low blood pressure, skin rash, and weight loss. Treatment with Sandostatin LAR helps control these symptoms.

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

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

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

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

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

2. What you need to know before starting Sandostatin LAR

Follow all instructions given to you by your doctor carefully. They may differ from the information contained in this leaflet.

Please read the following information before using Sandostatin LAR.

Do not use Sandostatin 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 starting Sandostatin LAR:

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

Tests and monitoring

If you are receiving long-term treatment with Sandostatin LAR, your doctor may periodically monitor your thyroid function.

Your doctor will monitor your liver function.

Your doctor may check the activity of your pancreatic enzymes.

Children

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

Using Sandostatin LAR with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

You can usually continue taking other medications while being treated with Sandostatin LAR. However, it has been reported that some medicines such as cimetidine, cyclosporine, bromocriptine, quinidine, and terfenadine may be affected by Sandostatin LAR.

If you are taking a medicine to control blood pressure (e.g. a beta-blocker or a calcium channel antagonist) 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 adjust your Sandostatin LAR treatment for a short period of time.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

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

Women of childbearing potential should use an effective method of contraception during treatment.

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

Driving and using machines

Sandostatin LAR has no or negligible effects on the ability to drive or use machines. However, some of the adverse effects you may experience during treatment with Sandostatin LAR, such as headache and fatigue, may reduce 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., essentially “sodium-free”.

3. How to use Sandostatin LAR

Sandostatin LAR must always be administered as an intramuscular injection in 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 life-threatening adverse reactions have been reported following an overdose of Sandostatin LAR.

Symptoms of overdose include: flushing, frequent urination, fatigue, depression, anxiety, and difficulty concentrating.

If you think you have taken an overdose and experience any of these symptoms, inform your doctor immediately. You may also call the Toxicology Information Service at Tel. 91 562 0420.

If you forget to use Sandostatin LAR

If you have forgotten your injection, it is recommended that you receive it as soon as you remember, and then continue with your regular dosing schedule. Receiving the dose a few days later will not cause you harm, but your symptoms may temporarily reappear until you return to your regular treatment schedule.

If you stop using Sandostatin LAR

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

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

4. Possible adverse effects

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

Some adverse reactions 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, causing sudden back pain.
• Too much sugar in the blood.

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

• Decreased activity of the thyroid gland (hypothyroidism), causing 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).
• Too little sugar in the blood.
• Impaired glucose tolerance.
• Slow heart rate.

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

• Thirst, reduced urine output, dark-colored urine, dry red skin.
• Rapid heartbeat.

Other serious adverse reactions:

• Hypersensitivity (allergic) reactions including skin hives.
• 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 abdomen, nausea, vomiting, diarrhea.
• 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, lightly colored 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 reactions.

Other adverse effects:

Inform your doctor, pharmacist, or nurse if you notice any of the following adverse effects listed below. These are usually mild and tend to disappear as treatment continues.

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

• Diarrhea.
• Abdominal pain.
• Nausea.
• Constipation.
• Flatulence (gas).
• Headache.
• Local injection site pain.

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

• Stomach discomfort after eating (dyspepsia).
• Vomiting.
• Feeling of fullness in the 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 adverse effect, consult your doctor, nurse, or pharmacist.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: http://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Sandostatin LAR

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

Store in the original packaging to protect from light.

Store in a refrigerator (between 2°C and 8°C). Do not freeze.

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

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Do not use this medicine if you notice the presence of particles or any change in colour.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused containers and medicines at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Sandostatin LAR

• The active substance is octreotide. One vial contains 10 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): sodium carboxymethylcellulose, mannitol (E421), poloxamer 188, water for injections.

Appearance of Sandostatin LAR and contents of the pack

Single packs containing a 6 ml glass vial with a rubber stopper (bromobutyl), sealed with an aluminium cap, containing the powder for injectable suspension, and a 3 ml colourless glass pre-filled syringe with a front plug and a plunger stopper (chlorobutyl rubber) containing 2 ml of solvent, packed together in a sealed blister tray with a vial adapter and a safety injection needle.

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

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes, 764

08013 Barcelona

Manufacturer

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 SAS

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

Novartis Pharma GmbH

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

Novartis Farma-Produtos Farmacêuticos, 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 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 European Economic Area member states under the following names:

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

Date of the most recent review of this leaflet: 12/2023

Other sources of information

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Dosage of Sandostatin LAR

Acromegaly

Treatment should be initiated with 20 mg of Sandostatin LAR administered every 4 weeks for 3 months. Patients receiving Sandostatin s.c. may start Sandostatin LAR the day after the last dose of Sandostatin s.c. Subsequent dose adjustments should be based on serum levels of growth hormone (GH) and insulin-like growth factor-1/somatomedin C (IGF-1), as well as clinical symptoms.

For patients in whom clinical symptoms and biochemical parameters (GH; IGF-1) are not adequately controlled within a 3-month period (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 symptoms are not adequately controlled at the 30 mg dose, the dose may be increased to 40 mg every 4 weeks.

In patients with consistently GH concentrations below 1 microgram/L, normalized serum IGF-1 levels, and in whom most reversible signs/symptoms of acromegaly have disappeared after 3 months of treatment with 20 mg, administration of 10 mg of Sandostatin LAR every 4 weeks may be considered. However, especially in this group of patients, close monitoring of serum GH and IGF-1 levels and clinical signs/symptoms is recommended at this lower dose of Sandostatin LAR.

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

Gastroenteropancreatic endocrine tumors

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

Treatment should be initiated with 20 mg of Sandostatin LAR administered every 4 weeks. Patients receiving Sandostatin s.c. should continue on their 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 may 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 may be increased to 30 mg of Sandostatin LAR every 4 weeks.

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

• Treatment of patients with advanced neuroendocrine tumors of intestinal origin or of unknown origin where non-intestinal primary sites have been excluded

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

Treatment of TSH-secreting adenomas

Treatment with Sandostatin LAR should be initiated at a dose of 20 mg every 4 weeks for 3 months before considering any dose adjustment. Subsequently, the dose should be adjusted based on TSH levels and thyroid hormone response.

Instructions for the preparation and intramuscular injection of Sandostatin LAR

FOR INTRAMUSCULAR USE ONLY

Components of the injection kit:

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

Carefully follow the instructions below to ensure proper reconstitution of Sandostatin LAR prior to deep intramuscular injection.

There are three critical steps in the reconstitution process of Sandostatin LAR. Failure to perform these steps correctly may result in improper administration of the medication.

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

Sandostatin LAR must be administered only by an experienced healthcare professional.

	STEP 1 Remove the Sandostatin LAR injection kit from the refrigerator. WARNING: It is essential to begin the reconstitution process only after the injection kit has reached room temperature. Allow the kit to reach room temperature for a minimum of 30 minutes before reconstitution, but do not exceed 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 protective film from the wrapper containing the vial adapter. DO NOT remove the vial adapter from its wrapper. Holding the vial adapter by its wrapper, place it on top of the vial and press it down firmly until it clicks into place, confirming it is securely attached. Remove the wrapper from the vial adapter with a vertical motion.
	STEP 3 Remove the cap from the pre-filled syringe containing the solvent and screw the syringe into the vial adapter. Slowly push the plunger fully down to transfer all of the diluent solution into the vial.
	STEP 4 WARNING: It is essential to let the vial stand for 5 minutes to ensure the solvent has completely saturated the powder. Note: It is normal for the plunger to move upward due to possible overpressure in the vial. At this point, prepare the patient for administration of the injection.
	STEP 5 After the saturation period, ensure the plunger is fully depressed. WARNING: Keep the plunger depressed and shake the vial moderately in a horizontal motion for at least 30 seconds to ensure the powder is completely suspended in the solvent (uniform milky consistency). Repeat moderate shaking for another 30 seconds if the powder is not fully suspended.
	STEP 6 Prepare the injection site with an alcohol swab. Turn the syringe and vial upside down, and slowly pull back the plunger to transfer the entire contents of the vial into the syringe. Unscrew the syringe from the vial adapter.
	STEP 7 Screw the safety injection needle onto the syringe. Reshake the syringe moderately to ensure uniform suspension with a milky consistency. Remove the protective needle cover. Gently tap the syringe to dislodge any visible air bubbles and expel them from the syringe. Ensure the injection site has not been contaminated. Proceed immediately to Step 8 for patient administration. Any delay in administration may result in sedimentation.
	STEP 8 Sandostatin LAR must be administered only by deep intramuscular injection; NEVER administer intravenously. Insert the needle completely into the right or left gluteal muscle at a 90º angle to the skin. Slowly aspirate using the plunger to ensure a blood vessel has not been entered (if so, change the injection site). Using constant pressure on the plunger, slowly administer the full dose until the syringe is empty. Withdraw the needle from the injection site and activate the safety mechanism (as shown in Step 9 below).
	STEP 9 Activate the safety mechanism on the needle using one of the following two methods: either press the hinged section of the safety device downward onto a rigid surface (Figure A). or press the hinged section with a finger (Figure B). A "click" sound confirms proper activation. Dispose of the syringe immediately (in a sharps container).