SIROCTID

Package leaflet: Information for the patient

Siroctid 50 micrograms/ml, solution for injection in pre-filled syringe, 100 micrograms/ml, solution for injection in pre-filled syringe, 500 micrograms/ml, solution for injection in pre-filled syringe

Octreotide
Please read all of this leaflet carefully before taking 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, because it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Siroctid is and what it is used for

Siroctid 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 Siroctid over somatostatin are that it is more potent and its effect lasts longer.
Siroctid is used:

• in the treatment of acromegaly, a condition in which the body produces excessive amounts of growth hormone. Normally, growth hormone regulates the growth of tissues, organs, and bones. When present in excess, it causes an increase in the size of bones and tissues, especially in the hands and feet. Siroctid 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 leads to a variety of symptoms,

such as hot flushes, diarrhoea, hypotension, skin rashes, and weight loss. Treatment with Siroctid helps control these symptoms.

• to prevent complications following pancreatic surgery. Treatment with Siroctid helps reduce the likelihood of complications (e.g. abdominal abscess, inflammation of the pancreas) after surgery.
• to stop bleeding and prevent rebleeding from ruptured gastro-oesophageal varices in patients with cirrhosis (chronic liver disease). Treatment with Siroctid helps control bleeding and reduce the need for blood transfusions.
• to treat pituitary adenomas that produce excessive amounts of thyroid-stimulating hormone (TSH). Excess thyroid-stimulating hormone (TSH) leads to hyperthyroidism. Siroctid is used to treat patients 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 its maximum effectiveness.

2. What you need to know before taking Siroctid

Do not take Siroctid:

• 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 Siroctid:

• if you have gallstones or have had them in the past; inform your doctor, as prolonged use of Siroctid may lead to gallstone formation. Your doctor may ask you to have periodic checks of your gallbladder.
• if you have problems with your blood sugar levels, either too high (diabetes) or too low (hypoglycaemia). When Siroctid is used to treat gastro-oesophageal variceal bleeding, your blood sugar levels must be monitored.
• if you have previously experienced episodes of vitamin B deficiency, your doctor may ask you to periodically monitor your vitamin B levels.

Tests and monitoring
If you are receiving Siroctid treatment for a prolonged period, your doctor may ask you to periodically monitor thyroid function.
Your doctor will monitor liver function.

Children
Experience with the use of Siroctid in children is limited.

Other medicines and Siroctid
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 Siroctid. However, it has been reported that Siroctid may interact with certain drugs such as cimetidine, cyclosporine, bromocriptine, quinidine, and terfenadine.
If you are taking medicines to control your blood pressure (such as β-blockers or calcium antagonists) or agents to control fluid and electrolyte balance, your doctor may decide to adjust the dosage.
If you are diabetic, your doctor may decide to adjust your insulin dose.

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

Driving and using machines
Siroctid does not affect or has a negligible effect on the ability to drive or use machines. However, during treatment with Siroctid, some side effects such as headache and fatigue may occur, which could reduce your ability to drive or use machinery safely.

Siroctid contains sodium
Siroctid contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to take Siroctid

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, Siroctid 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 Siroctid 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 new injection site each time to avoid irritating a specific area. Patients who wish to self-inject 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 injection site pain. You can bring it to room temperature by holding it in your hands, but it must not be heated.
A small number of people experience pain at the subcutaneous injection site. This pain usually lasts only a short time. If this occurs, it can be relieved by gently massaging the injection site for a few seconds afterwards.
Before using Siroctid, check for the presence of particles or changes in colour.
Do not use if you notice anything unusual.

If you take more Siroctid than you should
No life-threatening reactions have been reported following overdose with Siroctid.
Symptoms of overdose may include: irregular heartbeat, low blood pressure, cardiac arrest, reduced oxygen supply to the brain, severe pain in the upper stomach, yellowing of the skin and eyes, nausea, loss of appetite, diarrhoea, weakness, fatigue, lack of energy, weight loss, abdominal swelling, malaise, and high levels of lactic acid in the blood.
If you think you have symptoms of an overdose, inform your doctor immediately.

If you forget to take Siroctid
Take a dose as soon as you remember, then continue your treatment as usual.
Missing a dose is unlikely to have serious consequences, but you may experience a temporary return of symptoms until normal treatment resumes.
Do not inject a double dose of Siroctid to make up for a forgotten dose.

If you stop taking Siroctid
If you stop treatment with Siroctid, symptoms may return. Therefore, do not stop treatment with Siroctid unless instructed by your doctor.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody 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 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 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 users):

• 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) 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-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 as treatment continues.
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 side effects, inform your doctor, nurse, or pharmacist.
A few people experience pain at the site of subcutaneous injection. This pain usually lasts only a short time. If this occurs, it can be relieved by gently massaging the injection site for a few seconds.
If you are taking Siroctid by subcutaneous injection, avoid injecting close to mealtimes, as this may help reduce the risk of gastrointestinal side effects. It is therefore recommended to administer the injection between meals or at bedtime.
Reporting of side effects
If you experience any side effect, 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 the following website:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-
avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Siroctid

Store in a refrigerator (2°C - 8°C).
During daily use, the product may be stored at a temperature below 30°C for a period of 30 days.
Do not freeze. Keep in the original packaging to protect the medicine from light.
After dilution in 0.9% sodium chloride, when stored in glass bottles: chemical and physical stability of the product has been demonstrated for 24 hours at 25°C.
From a microbiological standpoint, the product should be used immediately.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "Exp". The expiry date refers to the last day of that month.
Do not use this medicine if you notice any particles or anything unusual.
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 Siroctid contains
Each pre-filled syringe containing 1 ml of injectable solution contains 50 micrograms of
octreotide as octreotide acetate.
Each pre-filled syringe containing 1 ml of injectable solution contains 100 micrograms of
octreotide as octreotide acetate.
Each pre-filled syringe containing 1 ml of injectable solution contains 500 micrograms of
octreotide as octreotide acetate.
The active substance is octreotide as octreotide acetate.
The excipients are: (S) lactic acid, sodium chloride, sodium hydroxide and water for
injections.

Description of the appearance of Siroctid and contents of the pack
The medicinal product is available in pre-filled syringes containing 1 ml of a clear, colourless injectable solution.
Packs containing 5, 6 or 30 pre-filled syringes in white thermoformed PVC blisters sealed with an aluminium foil.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Chemi S.p.A.
Via dei Lavoratori 54
20092 Cinisello Balsamo (MI)
Tel: +39.02.64431
Fax: +39.02.6128960
e-mail: [email protected]

Manufacturer
Italfarmaco S.p.A.
Viale Fulvio Testi, 330
20126 Milano
Italy
Tel. +39 02 64431
Fax. +39 02 644346
e-mail: [email protected]

This medicinal product is authorised in the European Economic Area Member States under the following names:
Italy: Siroctid 50 – 100 – 500 micrograms/ml, solution for injection in pre-filled syringe
Austria: Siroctid 0.05 mg/ml - 0.1 mg/ml - 0.5 mg/ml Injektionslösung in einer Fertigspritze
Greece: Siroctid 50 – 100 - 500 μικρογραμμάρια/ml, ενέσιμο διάλυμα σε προγεμισμένη σύριγγα
France: SIROCTID® 0.05 mg/ml - 0.1 mg/ml - 0.5 mg/ml solution injectable ou solution à diluer pour perfusion en seringue préremplie
Poland: Siroctid, 50 – 100 – 500 mikrogramów/ml, roztwór do wstrzykiwań w ampułkostrzykawce

The following information is intended exclusively for physicians or healthcare professionals:
The following is an extract from the SmPC and should be used for the correct administration of Siroctid.

• For parenteral use only: subcutaneous (SC) or intravenous (IV).

Storage
Store in a refrigerator (2°C - 8°C). Do not freeze. Keep pre-filled syringes in their blister and outer packaging to protect from light.

Use:
To reduce injection site discomfort, allow the solution to reach room temperature before administration. Avoid repeated injections at short intervals into the same injection site.
Before administration, the solution should be visually inspected for any change in colour or presence of particles.
Do not use unless the solution is clear and free from visible solid particles.

• Intravenous infusion (for healthcare professionals): When Siroctid is to be administered by intravenous infusion, the contents of one 500 microgram pre-filled syringe should be dissolved in 60 mL of physiological saline and the resulting solution administered using an infusion pump. This procedure should be repeated as frequently as required for the prescribed duration of treatment.

Disposal:
Any solution or material used (or that has come into contact) with Siroctid injectable solution must be disposed of in accordance with local regulations for injectable waste.

Amount of Siroctid to use
The dose of Siroctid depends on the condition being treated.

• Acromegaly
  Treatment is usually initiated at a dose of 0.05–0.1 mg every 8 or 12 hours by subcutaneous route. The dose may subsequently be adjusted based on therapeutic effects and symptom control (such as fatigue, sweating and headache). In most patients, the optimal daily dose is 0.1 mg three times daily. A maximum daily dose exceeding 1.5 mg is not recommended.

• Gastrointestinal tract tumours
  Treatment is usually 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 observed after 1 week of treatment at the highest tolerated dose.

• Complications following pancreatic surgery
  The usual dose is 0.1 mg three times daily by subcutaneous administration for 1 week, starting at least 1 hour before surgery.

• Bleeding from gastro-oesophageal varices
  The recommended dosage is 25 micrograms/hour by continuous intravenous infusion for 5 days. Blood glucose levels should be monitored during treatment.

• Treatment of TSH-secreting pituitary adenomas
  The generally most effective dosage 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 are required to assess efficacy.