Octreotide Teva

Package leaflet: Information for the patient

Octreotide Teva 10 mg powder and solvent for prolonged-release injectable suspension, 20 mg powder and solvent for prolonged-release injectable suspension, 30 mg powder and solvent for prolonged-release injectable suspension

Generic medicine
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 others, even if their symptoms are the same as yours, as it may 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 Octreotide Teva is and what it is used for
2. What you need to know before using Octreotide Teva
3. How to use Octreotide Teva
4. Possible side effects
5. How to store Octreotide Teva
6. Contents of the pack and other information

1. What is Octreotide Teva and what is it used for

Octreotide Teva 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 Octreotide Teva over somatostatin are that it is more potent and its action lasts
longer.
Octreotide Teva 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, especially in the hands and feet. Octreotide Teva significantly reduces the symptoms of acromegaly, including 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 Octreotide Teva can reduce the size of the adenoma.

Octreotide Teva is used to treat people with acromegaly:

• when other types of treatment for acromegaly (surgery or radiotherapy) are not suitable or have not worked;
• after radiotherapy, to cover the period required for radiotherapy to reach its maximum effectiveness.
• to relieve symptoms associated with the excessive production of certain specific hormones and related substances in the stomach, intestine, and pancreas. Excessive production of specific hormones and other related natural substances may be caused by rare conditions affecting the stomach, intestine, and pancreas. This condition disrupts the body's natural hormonal balance and leads to a variety of symptoms, such as hot flashes, diarrhoea, hypotension, skin rashes, and weight loss. Treatment with Octreotide Teva 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. Octreotide Teva 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 tumours that produce an excessive amount of thyroid-stimulating hormone (TSH). An excessive amount of thyroid-stimulating hormone (TSH) leads to hyperthyroidism. Octreotide Teva 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 its maximum effectiveness.

2. What you need to know before taking Octreotide Teva

Follow your doctor's instructions carefully. These may differ from the information contained in this leaflet.
Read the following instructions before using Octreotide Teva.

Do not take Octreotide Teva

• 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 Octreotide Teva:

• if you know you have gallstones or have had them in the past; inform your doctor, as long-term use of Octreotide Teva may lead to gallstone formation. Your doctor may ask you to have periodic gallbladder checks;
• if you have diabetes, since Octreotide Teva can 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 and monitoring
If you are receiving long-term treatment with Octreotide Teva, your doctor may ask you to have periodic thyroid function tests.
Your doctor will monitor your liver function.

Children
Experience with the use of Octreotide Teva in children is limited.

Other medicines and Octreotide Teva
Inform 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 Octreotide Teva.
However, interactions have been reported between Octreotide Teva and certain drugs such as cimetidine, cyclosporine, bromocriptine, quinidine, and terfenadine.
If you are taking medicines to control blood pressure (e.g. beta-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.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you might be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before taking this medicine.
Octreotide Teva should be used during pregnancy only if clearly necessary.
Women of childbearing potential must use adequate contraception during treatment.
Do not breastfeed during treatment with Octreotide Teva. It is not known whether Octreotide Teva is excreted in human milk.

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

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

3. How to take Octreotide Teva

Octreotide Teva must always be administered by injection into the gluteal muscle.
The injection site for repeated injections should be alternated between the left and right buttock.
If you take more Octreotide Teva than you should
No life-threatening reactions have been reported following overdose with Octreotide Teva.
Symptoms of overdose include: hot flushes, 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 Octreotide Teva
If you miss an injection, it is recommended to administer it as soon as you remember, and then continue your treatment as usual.
A delay of a few days in administration is not harmful but may result in a temporary return of symptoms until normal control is restored.
If you stop taking Octreotide Teva
If you stop treatment with Octreotide Teva, symptoms may reappear. Therefore, do not stop Octreotide Teva treatment unless instructed by your doctor.
If you have any doubts 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 everyone gets them.
Some side effects may 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):

• 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 people):

• Thirst, reduced urine output, dark urine, flushed and dry skin.
• Tachycardia.

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 abdomen, nausea, vomiting, diarrhoea.
• Inflammation of the liver (hepatitis); symptoms may include yellowing of the skin and eyes (jaundice), nausea, vomiting, loss of appetite, feeling generally 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 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 (excess intestinal gas).
• Headache.
• Local injection site pain.

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

• 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.
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: 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 Octreotide Teva

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.
Octreotide Teva may be stored at temperatures below 25°C on the day of administration.
Use immediately after reconstitution.
Do not use this medicine after the expiry date stated on the label and carton 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 a change in colour.
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 Octreotide Teva contains

• The active substance is octreotide. One vial contains 10 mg, 20 mg, or 30 mg of octreotide (as octreotide acetate).
• The other components are:
  in the powder (vial): poly (DL-lactide-co-glycolide) and mannitol (E 421).
  in the solvent (pre-filled syringe): sodium carmellose, mannitol (E 421), poloxamer, and water for injections.

Description of the appearance of Octreotide Teva and contents of the pack
Octreotide 10 mg: Each pack contains one glass vial with 10 mg of octreotide closed with a rubber stopper sealed with an aluminium cap with a dark blue tear-off strip, one pre-filled glass syringe with 2 ml of solvent, one safety needle for injection, and one vial adapter; or three glass vials with 10 mg of octreotide, three pre-filled syringes with 2 ml of solvent, three safety needles for injection, and three vial adapters.
Octreotide 20 mg: Each pack contains one glass vial with 20 mg of octreotide closed with a rubber stopper sealed with an aluminium cap with an orange tear-off strip, one pre-filled glass syringe with 2 ml of solvent, one safety needle for injection, and one vial adapter; or three glass vials with 20 mg of octreotide, three pre-filled syringes with 2 ml of solvent, three safety needles for injection, and three vial adapters.
Octreotide 30 mg: Each pack contains one glass vial with 30 mg of octreotide closed with a rubber stopper sealed with an aluminium cap with a dark red tear-off strip, one pre-filled glass syringe with 2 ml of solvent, one safety needle for injection, and one vial adapter; or three glass vials with 30 mg of octreotide, three pre-filled syringes with 2 ml of solvent, three safety needles for injection, and three vial adapters.
Not all pack sizes may be marketed.

Marketing Authorization Holder
TEVA B.V.
Swensweg 5,
2031 GA Haarlem
The Netherlands

Manufacturer
Teva Pharmaceuticals Europe B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands
Merckle GmbH
Ludwig-Merckle-Strasse 3,
Blaubeuren 89143
Germany
Actavis Group PTC ehf.
Reykjavíkurvegur 76-78, Hafnarfjörður IS-220
Iceland
PLIVA HRVATSKA d.o.o. (PLIVA CROATIA Ltd.)
Prilaz baruna Filipovića 25,
Zagreb 10000
Croatia

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

Amount of Octreotide Teva to use

Acromegaly
It is recommended to initiate treatment with Octreotide Teva 20 mg administered every 4 weeks for 3 months. Patients previously treated with subcutaneous octreotide may start treatment with Octreotide Teva the day after the last dose of subcutaneous octreotide.
Subsequent dose adjustments should be based on serum growth hormone (GH) and insulin-like growth factor-1/somatomedin C (IGF-1) levels, as well as clinical symptoms.
In patients who, within the 3-month period, do not achieve satisfactory control of both clinical symptoms and biochemical parameters (GH; IGF-1) (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 still not adequately controlled at the 30 mg dose, the dose may be increased to 40 mg every 4 weeks.
In patients in whom serum GH concentrations remain consistently below 1 microgram/L, serum IGF-1 levels normalize, and most reversible signs/symptoms of acromegalia disappear after 3 months of treatment with 20 mg, Octreotide Teva 10 mg every 4 weeks may be administered. However, particularly in this group of patients receiving this low dose of Octreotide Teva, adequate monitoring of serum GH and IGF-1 levels and clinical signs and symptoms is recommended.
In patients on a stable dose of Octreotide Teva, GH and IGF-1 levels should be monitored every 6 months.

Gastro-entero-pancreatic endocrine tumours

• Treatment of patients with symptoms associated with functional gastro-entero-pancreatic neuroendocrine tumours
  It is recommended to initiate treatment with Octreotide Teva 20 mg administered every 4 weeks. Patients previously treated with subcutaneous octreotide should continue treatment at the previously effective dose for 2 weeks after the first injection of Octreotide Teva.

In patients in whom both clinical symptoms and biological parameters are well controlled after 3 months of treatment, the dose may be reduced to Octreotide Teva 10 mg every 4 weeks.
In patients in whom clinical symptoms are only partially controlled after 3 months of treatment, the dose may be increased to Octreotide Teva 30 mg every 4 weeks.
In cases where symptoms associated with gastro-entero-pancreatic tumours worsen during treatment with Octreotide Teva, additional subcutaneous octreotide administration at the dose previously used before starting Octreotide Teva is recommended. This may occur particularly during the first 2 months of treatment, until therapeutic octreotide concentrations are achieved.

• Treatment of patients with advanced midgut neuroendocrine tumours or with unknown primary tumour site, after exclusion of extramidgut sites
  The recommended dose of Octreotide Teva is 30 mg administered every 4 weeks. Treatment with Octreotide Teva for tumour control should be continued even in the absence of tumour progression.

Treatment of TSH-secreting pituitary adenomas
Treatment with Octreotide Teva 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 the response of TSH and thyroid hormone levels.

Instructions for the preparation and intramuscular injection of Octreotide Teva
FOR DEEP INTRAMUSCULAR INJECTION ONLY.

Contents of the injection kit:

a. One vial containing Octreotide Teva powder,
b. One pre-filled syringe containing the vehicle solution for reconstitution,
c. One vial adapter for reconstitution of the medicinal product,
d. One safety needle for injection.

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

• The injection kit must reach room temperature. Remove the injection 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 shake the vial horizontally for at least 30 seconds until a uniform suspension is formed. The Octreotide Teva suspension must be prepared immediately before administration.

Octreotide Teva must be administered only by trained healthcare personnel.

Step 1
Remove the Octreotide Teva 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 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 blister and take out the vial adapter from its packaging, holding it by the white cap and its sheath. DO NOT touch the tip of the access device to any surface.
Place the vial on a flat surface. Place the vial adapter on top of the vial and press down firmly until it clicks into place.
Clean the tip of the vial adapter with an alcohol swab.

Step 3

Remove the smooth white 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 by the diluent.
Note: It is normal for the plunger rod to rise slightly due to slight overpressure in the vial.
At this point, prepare the patient for injection.

Step 5

After the saturation period, ensure the plunger is fully depressed.
WARNING: Hold the plunger down and gently shake the vial horizontally for at least 30 seconds until the powder is completely suspended (uniform milky suspension). Gently shake for an additional 30 seconds if the powder has not yet formed a complete suspension.

Step 6
Turn the syringe and vial upside down, slowly pull back the plunger, and withdraw the entire contents of the vial into the syringe.
Unscrew the syringe from the vial adapter.

Step 7

Prepare the injection site with an alcohol swab.
Screw the safety injection needle onto the syringe.
If immediate administration is delayed, gently re-shake the syringe to ensure a uniform milky suspension.
Remove the needle protective cap.
Gently tap the syringe to remove any visible air bubbles and expel them from the syringe.
Proceed immediately to step 8 for patient administration.
Any delay may cause sedimentation.

Step 8

Octreotide Teva must be administered only by deep intramuscular injection, NEVER intravenously.
Insert the needle fully into the left or right gluteal muscle at a 90° angle to the skin surface.
Gently pull back the plunger to check whether a blood vessel has been punctured (reposition if a vessel is hit).
Push the plunger with constant pressure 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 needle safety device using one of the two procedures described below:

• Firmly press the hinged part of the safety device downward onto a hard surface (Figure A)
• or push forward the hinged part with your finger (Figure B). An audible "click" confirms proper activation.

Note: Record the injection site in the patient's medical record and alternate the site monthly.
Immediately dispose of the syringe in a sharps container.