Okteva

Package leaflet: information for the patient

Okteva, 10 mg, powder and solvent for suspension for injection with prolonged release
Okteva, 20 mg, powder and solvent for suspension for injection with prolonged release
Okteva, 30 mg, powder and solvent for suspension for injection with prolonged release
octreotide
Please read carefully the entire leaflet before using the medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What Okteva is and what it is used for
Okteva is a synthetic analogue of somatostatin, a substance naturally occurring in the human body that inhibits the action of certain hormones, such as growth hormone. Okteva acts more strongly than somatostatin and has a longer duration of action.
Okteva is used

• in the treatment of acromegaly. Acromegaly is a disease in which the body produces too much growth hormone. In healthy individuals, growth hormone affects the growth of tissues, organs, and bones. Excess growth hormone causes enlargement of bones and tissues, especially in the hands and feet. Okteva significantly alleviates symptoms of acromegaly, such as headache, excessive sweating, numbness in hands and feet, fatigue, and joint pain. In most cases, excessive production of growth hormone is caused by enlargement of the pituitary gland (pituitary adenoma); treatment with Okteva may reduce the size of the adenoma.

Okteva is used in the treatment of patients with acromegaly:

• when other treatments for acromegaly (surgery or radiotherapy) are contraindicated or ineffective;
• after radiotherapy, during the interim period before the full effect of radiotherapy is achieved;
• to alleviate symptoms associated with excessive production of certain specific hormones and related substances by the stomach, intestines, and pancreas; Excessive production of hormones and related natural substances may be caused by certain rare diseases of the stomach, intestines, or pancreas. This disrupts the body's natural hormonal balance and causes various symptoms such as facial flushing, diarrhea, low blood pressure, skin rash, and weight loss. Treatment with Okteva helps to alleviate these symptoms;
• in the treatment of neuroendocrine tumors located in the intestine (e.g. in the appendix, small intestine, or colon); Neuroendocrine tumors are rare tumors occurring in various parts of the body. Okteva is also used to inhibit the growth of such tumors when they are located in the intestine (e.g. in the appendix, small intestine, or colon);
• in the treatment of pituitary tumors producing excessive amounts of thyroid-stimulating hormone (TSH); Excess thyroid-stimulating hormone (TSH) leads to hyperthyroidism. Okteva is used in patients with pituitary tumors producing excessive amounts of thyroid-stimulating hormone (TSH):
  • when other treatments (surgery or radiotherapy) are inappropriate or ineffective;
  • after radiotherapy during the interim period before radiotherapy achieves full effectiveness.

2. Important information before using Okteva

Follow all your doctor's instructions. They may differ from the information contained in this leaflet.
Please review the following information before using Okteva.
When not to use Okteva:

• if you are allergic to octreotide or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Okteva, discuss with your doctor:

• if you know you have or have previously had gallstones; 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 Okteva may lead to the formation of gallstones. Your doctor may recommend periodic monitoring of the gallbladder;
• if you have diabetes, because Okteva may affect blood glucose levels. If you have diabetes, your blood glucose levels should be monitored regularly;
• if you have previously had reduced vitamin B levels, your doctor may recommend periodic monitoring of vitamin B levels.

Monitoring and follow-up visits
If you are receiving long-term treatment with Okteva, your doctor may recommend periodic monitoring of thyroid function.
Your doctor will monitor your liver function.
Your doctor may recommend checking pancreatic enzyme activity.
Children
Experience with the use of Okteva in children is limited.
Okteva and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Treatment with other medicines can generally be continued during therapy with Okteva.
However, interactions have been reported between Okteva and certain drugs such as cimetidine, cyclosporine, bromocriptine, quinidine, and terfenadine.
If you are taking a medicine that lowers blood pressure (e.g. an adrenergic blocker - so-called beta-blocker, or a calcium antagonist) or a medicine affecting water-electrolyte balance, your doctor may adjust the dosage.
In patients with diabetes, adjustment of insulin dosage by the doctor may be necessary.
If you are to receive lutetium oxodotreotide (Lu) therapy, a radiopharmaceutical treatment, your doctor may temporarily interrupt and/or adjust treatment with Okteva.
Pregnancy, breastfeeding, and fertility
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.
Okteva may be used during pregnancy only if clearly necessary.
Women of childbearing potential should use effective contraception methods during treatment.
Do not breastfeed while using Okteva. It is not known whether Okteva passes into human milk.
Driving and operating machinery
Okteva has no effect or a negligible effect on the ability to drive and operate machinery. However, certain adverse reactions that may occur during treatment with Okteva, such as headache and fatigue, may reduce the patient's ability to drive safely or operate machinery.
Okteva contains sodium
Okteva contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially "sodium-free".

3. How to use Okteva

Okteva must be administered only as an intramuscular injection into the buttock.
When administering long-term, injections should be alternated between the left and right buttock.

Use of a higher than recommended dose of Okteva
Following overdose of Okteva, no life-threatening reactions have been reported.
Symptoms of overdose include: hot flushes, frequent urination, fatigue, depression, anxiety, and lack of concentration.
If you suspect an overdose and the patient experiences any of these symptoms, inform the doctor immediately.

Missed dose of Okteva
If an injection has not been administered on time, it should be given as soon as possible, and then treatment should continue as previously scheduled. Administering the dose several days later is not harmful, but may result in a temporary recurrence of disease symptoms until the regular treatment schedule is resumed.

Stopping treatment with Okteva
After discontinuation of treatment with Okteva, disease symptoms may recur. Therefore, do not stop using Okteva without consulting your doctor.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Some adverse reactions may be serious. You must immediately inform the doctor
if the patient experiences any of the following symptoms:

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

• Gallstones causing sudden back pain
• High blood sugar levels

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

• Hypothyroidism (underactive thyroid) affecting heart rhythm, appetite, or body weight changes; fatigue, feeling cold, or swelling in the front of the neck
• Changes in thyroid function test results
• Inflammation of the gallbladder; symptoms may include pain in the upper right part of the abdomen, fever, nausea, yellowing of the skin and eyes (jaundice)
• Low blood sugar levels
• Impaired glucose tolerance
• Slow heart rate

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

• Thirst, reduced urine output, dark-coloured urine, dry, red skin
• Fast heart rate

Other serious adverse reactions

• Hypersensitivity reactions (allergic reactions), including skin rash
• A type of allergic reaction (anaphylaxis) which may cause difficulty in swallowing or breathing, swelling and tingling, possibly with low blood pressure leading to dizziness or loss of consciousness
• Inflammation of the pancreas; symptoms may include sudden pain in the upper abdomen, nausea, vomiting, diarrhoea
• Inflammation of the liver; 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; this may cause increased bleeding or bruising

If the patient notices any of the above-mentioned symptoms, they should immediately
inform their doctor.

Other adverse reactions:
If the patient notices any of the following adverse reactions, they should
inform their doctor, pharmacist, or nurse. These reactions are usually mild and tend to
resolve as treatment progresses.

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

• Diarrhoea
• Abdominal pain
• Nausea
• Constipation
• Bloating with gas
• Headache
• Pain at injection site

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

• Stomach discomfort after meals (dyspepsia)
• Vomiting
• Feeling of fullness in the stomach
• Fatty stools
• Loose stools
• Pale-coloured stools
• Dizziness
• Loss of appetite
• Changes in liver function test results
• Hair loss
• Shortness of breath
• Weakness

If any adverse reactions occur, the patient should inform their doctor, nurse, or
pharmacist.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, the patient should inform their doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: 22 49-21-301
Fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Okteva

Keep this medicine out of sight and reach of children.
Store in the original packaging to protect from light.
Store in a refrigerator (2°C – 8°C). Do not freeze.
On the day of injection, Okteva may be stored at temperatures below 25°C.
Do not store Okteva after reconstitution. The prepared suspension must be used immediately.
Do not use this medicine after the expiry date stated on the label and packaging after "EXP" and "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Do not use this medicine if foreign particles or changes in colour are observed.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the Package and Other Information

What Okteva Contains

• The active substance is octreotide. Each vial contains 10 mg, 20 mg, or 30 mg of octreotide (as octreotide acetate).
• Other ingredients are: in the powder (vial): D,L-lactide and glycolide copolymer (55:45) and mannitol (E 421). in the solvent (pre-filled syringe): sodium carmellose, mannitol (E 421), poloxamer 188, and water for injections.

What Okteva Looks Like and Contents of the Pack
Okteva 10 mg
Each single pack contains: 1 glass vial containing 10 mg of octreotide, closed with a rubber stopper and an aluminium cap with a dark blue flip-off cap, 1 glass pre-filled syringe containing 2 ml of solvent, 1 safety needle for injections, and 1 vial connector, or
3 glass vials each containing 10 mg of octreotide, 3 pre-filled syringes each containing 2 ml of solvent, 3 safety needles for injections, and 3 vial connectors.
Okteva 20 mg
Each single pack contains: 1 glass vial containing 20 mg of octreotide, closed with a rubber stopper and an aluminium cap with an orange flip-off cap, 1 glass pre-filled syringe containing 2 ml of solvent, 1 safety needle for injections, and 1 vial connector, or
3 glass vials each containing 20 mg of octreotide, 3 pre-filled syringes each containing 2 ml of solvent, 3 safety needles for injections, and 3 vial connectors.
Okteva 30 mg
Each single pack contains: 1 glass vial containing 30 mg of octreotide, closed with a rubber stopper and an aluminium cap with a dark red flip-off cap, 1 glass pre-filled syringe containing 2 ml of solvent, 1 safety needle for injections, and 1 vial connector, or
3 glass vials each containing 30 mg of octreotide, 3 pre-filled syringes each containing 2 ml of solvent, 3 safety needles for injections, and 3 vial connectors.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands

Manufacturer
PLIVA HRVATSKA d.o.o. (PLIVA CROATIA Ltd.)
Prilaz baruna Filipovića 25
Zagreb 10000
Croatia
Merckle GmbH,
Ludwig-Merckle-Str. 3
Blaubeuren
Germany
Pharmathen International S.A
Industrial Park Sapes
Rodopi Prefecture, Block No 5
Rodopi 69300
Greece

For further information about the medicine and its names in other European Economic Area countries, please contact the representative of the marketing authorisation holder:
Teva Pharmaceuticals Polska Sp. z o.o., ul. Emilii Plater 53, 00-113 Warsaw, tel. (22) 345 93 00.

Information intended exclusively for healthcare professionals:

What Dose of Okteva Should Be Administered

Acromegaly
Treatment should be initiated with Okteva at a dose of 20 mg every 4 weeks for 3 months. Patients previously receiving subcutaneous (sc.) octreotide may start treatment with Okteva the day after the last subcutaneous dose. The dose should then be adjusted based on serum growth hormone (GH) and insulin-like growth factor-1/somatomedin C (IGF-1) levels, as well as clinical symptoms.

In patients in whom clinical symptoms and biochemical parameters (GH; IGF-1) are not fully controlled after 3 months (GH levels still >2.5 micrograms/l), the dose may be increased to 30 mg every 4 weeks. If after another 3 months GH, IGF-1, and (or) other symptoms remain inadequately controlled during treatment with 30 mg, the dose may be increased to 40 mg every 4 weeks.

In patients in whom GH levels remain consistently below 1 microgram/l, serum IGF-1 has normalized, and the most rapidly regressing objective and subjective symptoms of acromegaly have improved after 3 months of treatment with 20 mg, Okteva at a dose of 10 mg every 4 weeks may be used. However, particularly in this group of patients, close monitoring of treatment efficacy is recommended by measuring serum GH and IGF-1 levels and assessing objective and subjective clinical symptoms during treatment with this lower dose of Okteva.

In patients receiving a stable dose of Okteva, GH and IGF-1 levels should be determined every 6 months.

Gastrointestinal, Pancreatic, and Gastric Hormone-Active Tumours

• Treatment of patients with symptoms related to hormone-active neuroendocrine tumours of the stomach, intestine, and pancreas
  Treatment should be initiated with Okteva at a dose of 20 mg every 4 weeks. Patients previously receiving subcutaneous octreotide should continue this treatment at the previously effective dose for 2 weeks after the first injection of Okteva.
  In patients in whom satisfactory symptom relief and improvement in biological markers have been achieved after 3 months of treatment, the dose of Okteva may be reduced to 10 mg every 4 weeks.
  In patients in whom only partial symptom relief has occurred after 3 months of treatment, the dose of Okteva may be increased to 30 mg every 4 weeks.
  On days when symptoms related to tumours of the stomach, intestine, and pancreas are exacerbated despite treatment with Okteva, additional subcutaneous octreotide at the dose previously used before initiation of Okteva is recommended. This may occur particularly during the first 2 months of treatment, before therapeutic octreotide concentrations are achieved.

• Treatment of patients with advanced neuroendocrine tumours originating from the midgut or of unknown primary site, when a primary site outside the midgut has been excluded
  The recommended dose of Okteva is 30 mg administered every 4 weeks. Treatment with Okteva to inhibit tumour progression should be continued in the absence of tumour progression.

• Treatment of TSH-secreting adenomas
  Treatment with Okteva should be initiated at a dose of 20 mg every 4 weeks and continued for 3 months before any dose adjustment. The dose may then be adjusted according to TSH and thyroid hormone secretion.

Instructions for Preparation and Intramuscular Administration (Injection) of Okteva Medicinal Product
FOR DEEP INTRAMUSCULAR INJECTION INTO THE BUTTOCK ONLY – NEVER INTRAVENOUS

Kit Contents:

a One vial containing Okteva powder
b One pre-filled syringe containing solvent for suspension preparation
c One vial connector for reconstitution of the medicinal product
d One safety needle for injections

Follow the instructions below carefully to properly reconstitute Okteva before deep intramuscular injection into the buttock.
Proper reconstitution of Okteva depends critically on meeting three requirements.
Failure to meet these requirements may result in improper administration of the medicine.

• 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, but no longer than 24 hours before reconstitution.
• After adding the solvent, allow the vial to stand for 5 minutes to ensure complete wetting of the powder by the solution.
• After wetting, shake the vial moderately in a horizontal plane for at least 30 seconds until a uniform suspension is formed. The suspension of Okteva must be prepared immediately before administration.

Okteva must be administered only by trained healthcare professionals.

Step 1

• Remove the Okteva injection kit from the refrigerator where it was stored. 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 returned to the refrigerator if necessary.

Step 2

• Remove the plastic cap from the vial and wipe the rubber stopper with an alcohol-impregnated swab.
• Peel off the foil covering the vial connector package, remove the vial connector from the package, holding it between the white Luer connector and the collar. DO NOT TOUCH the tip of the connector at any point.
• Place the vial on a flat surface. Place the vial connector onto the vial and press down firmly until it clicks into place.
• Wipe the tip of the vial connector with an alcohol-impregnated swab.

Step 3

• Remove the tip cap from the pre-filled syringe

containing the solvent and screw the syringe onto the vial connector.

• Slowly push the plunger fully down to transfer all the solvent into the vial.

Step 4
WARNING: It is essential to allow the vial to stand for 5 minutes

to ensure complete wetting of the powder by the solvent.
Note: The plunger may be pushed back upwards due to slight overpressure in the vial. This is normal. At this stage, prepare the patient for injection.

Step 5

• After sufficient time for wetting the powder, check that the plunger is fully depressed to the bottom of the syringe. WARNING: While holding the plunger fully depressed, shake the vial moderately in a horizontal plane for at least 30 seconds to ensure the entire powder forms a suspension (a uniform milky suspension). If part of the powder has not mixed with the solution, repeat moderate shaking for another 30 seconds.

Step 6

• Turn the syringe and vial upside down and slowly withdraw the entire contents of the vial into the syringe by pulling back the plunger.
• Unscrew the syringe from the vial connector.

Step 7

• Prepare the injection site by wiping it with an alcohol-impregnated

swab.

• Screw the safety needle onto the syringe.
• If immediate administration is not possible, gently shake the syringe again just before administration to obtain a milky, uniform suspension.
• Remove the protective needle cap with a straight upward motion.
• Gently tap the syringe with fingers to move any visible air bubbles to the top, then expel air from the syringe. Proceed immediately to Step 8. Any delay may cause sedimentation.

Step 8

• Okteva must be administered exclusively by deep intramuscular injection into the buttock, NEVER intravenously.

• Insert the entire needle into the left or right buttock at a 90° angle to the skin surface.
• Slowly pull back the plunger of the pre-filled syringe to ensure the needle is not in a blood vessel (reposition the needle if it is within a blood vessel).
• Slowly and steadily push the plunger until the syringe is empty. Remove the needle from the injection site and activate the needle safety shield (according to instructions in Step 9).

Step 9

• Activate the needle safety shield using one of the following two methods:
  • Press the folding part of the shield against a hard surface (Figure A)
  • Or press the folding part of the shield with a finger (Figure B).
• Proper activation will be confirmed by an audible click.
• Note: Record the injection site on the patient's chart, rotating sites monthly.
• Immediately dispose of the syringe in an appropriate sharps container.