PACKAGE LEAFLET: INFORMATION FOR THE USER

MONIYOT-131 14.8 – 3700 MBq/ml oral solution for therapeutic use Sodium Iodide (131I)

Read all of this leaflet carefully before you start using this medicine because it contains important information for you. • Keep this leaflet. You may need to read it again. • If you have any further questions, ask your Nuclear Medicine doctor who will supervise the procedure. • If you get any side effects, talk to your Nuclear Medicine doctor who has supervised the procedure. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet: 1. What MONIYOT-131 is and what it is used for 2. What you need to know before you take MONIYOT-131 is administered 3. How to take MONIYOT-131 4. Possible side effects 5. How to store MONIYOT-131 6. Contents of the pack and other information

1. What MONIYOT-131 is and what it is used for

This medicine is a radiopharmaceutical product for therapeutic use only. MONIYOT-131 use can be used for: • Treatment of thyroid diseases like increased activity of the thyroid gland (Graves’ disease) and enlargement of the thyroid gland (toxic multinodular goitre or autonomous nodules) • Treatment of thyroid cancer including metastasis (papillary and follicular thyroid carcinoma)

The use of MONIYOT-131 does involve exposure to radioactivity. Your doctor and the nuclear medicine doctor have considered that the clinical benefit that you will obtain from the procedure with the radiopharmaceutical overcomes the risk due to radiation.

2. What you need to know before you take MONIYOT-131

Do not use MONIYOT-131 • if you are allergic to Sodium Iodide (131I) or any of the other ingredients of this medicine (listed in section 6). • if you are pregnant or breast-feeding your child • if you have difficulties in swallowing (dysphagia, oesophageal stricture, oesophagal stenosis, oesophagus diverticulum) • if you suffer from stomach disorders like inflammation (gastritis) and peptic ulcer • if you suffer from reduced abdominal or bowel movements • if your gullet is obstructed if the product is intended solely for making the thyroid gland visible. Usually other products containing sodium iodide (I-123) or Technetium (Tc-99m) are used for this. Exceptions to this advice are if these products are not available in the clinic where you are treated or if you are being treated for cancer.

Warnings and precautions

Take special care with MONIYOT-131 • If you receive therapy for your thyroid, you should be re-examined regularly to check thyroid hormone levels and to identify possible late complications. • After treatment you are encouraged to drink plenty and to void frequently to prevent accumulation of sodium iodide (131I) in the bladder. If you have bladder voiding problems you will be catheterized after high dose administration • Directly after swallowing the solution you have radioactive material in you. You will be shielded from your surroundings for some time. Also stools, urine or vomit that leaves your body are considered radioactive and should be disposed with care so they will not come into contact with others. • If you have a stomach disease. Concomittant use of medicines to treat ulcer disease and gastritis (H2 antagonists or proton pump inhibitors) is advised. • If you have a significantly reduced kidney function which requires dose adjustment. To avoid inflammation of the salivary glands, you are advised to take sweets or drinks containing citric acid which will stimulate saliva flow. Before treatment you will be advised to take food that contains little iodine to increase the uptake in the thyroid gland. • If you use thyroid hormones. Thyroid replacement therapy should be stopped prior to administration to ensure adequate uptake. A period of 14 days is recommended for triiodothyronine and 4-5 weeks for thyroxine. They should be restarted two weeks after treatment. Similarly carbimazole and propythiouracil should be stopped 1 week prior to treatment of increased activity of the thyroid gland (hyperthyroidism) and restarted several days later. • If protruding eyes is part of the symptoms of the disease you are suffering from (Graves’ disease-induced ophthalmopathy). In this case you should receive simultaneous medication to reduce inflammation (corticosteroids). • After treatment women should use contraception for a time period of 6-12 months. Men should use contraception for a time period of 6 months after treatment. • Your doctor will inform you which special precautions that have to be taken. • The receipt, storage, use, transfer and disposal of radiopharmaceuticals are subject to the regulations and/or appropriate licences of the local competent official organization. As a result MONIYOT-131 will always be administered in a hospital or other designated clinical setting.

Before MONIYOT-131 administration you should: • Drink plenty of water and to be well hydrated before the start of the administration in order to urinate as often as possible during the first hours after the study • Fast (no food) for at least 4 hours

Talk to your Nuclear Medicine doctor before using MONIYOT-131: • If you are pregnant or believe you may be pregnant • If you are breastfeeding • If you are under 18 years old

Other medicines and MONIYOT-131 Please tell your Nuclear Medicine doctor who will supervise the procedure if you are taking or have recently taken any other medicines, including medicines obtained without prescription.

Please tell your Nuclear Medicine doctor if you are taking or have been administered any of the following medicines/substances, since they may interfere with your physician’s interpretation of the images. Your doctor may recommend that you stop the following medicines before treatment: • Medicines used to reduce thyroid gland function such as: - carbimazole, methimazole, propyluracil - perchlorate. These medicinal products are to be withheld 1 week before treatment with sodium iodide (131I) until several days after.

• The medicinal products listed below, used for various clinical situations, are to be withheld 1 week before treatment: - salicylates: medicines to reduce pain, fevers or inflammation such as acetylsalicylic acid. - cortisone: medicines to reduce inflammation or prevent organ transplantat rejection. - sodium nitroprusside: a medicine to reduce high blood pressure, and also during an operation. - sodium sulfobromophthalein: a medicine to test liver function - Certain drugs: • to reduce blood coagulation • to treat parasitic infestation • antihistamines : used to treat allergies • penicillins and sulphonamides: antibiotics, • tolbutamide: a medicine to reduce blood sugar • thiopentone: used while under anaesthetic to reduce brain pressure, and also to treat extreme epileptic seizures

• phenylbutazone (a medicine to reduce pain and imflammation) is to be withheld 1-2 week before treatment.

• iodine containing medicines to help free the airways of sputum, are to be withheld 2 weeks before treatment.

• vitamins containing iodine salts are to be withheld 2 weeks before treatment.

• medicines containing thyroid hormones such as, thyroxine, liothyronine, triiodothyronine, thyroid extract are to be withheld 2-5 weeks before treatment.

• benzodiazepines (medicines which calm and initiate sleep and relax muscles) are to be withheld 4 weeks before treatment.

• lithium (a medicine to treat depression) is to be withheld 4 weeks before treatment.

• iodide containing medicines (which are used only on a restricted area of the body) are to be withheld 1 – 9 months before treatment.

• amiodarone (a medicine to treat heart rhythm disorders) is to be withheld several months before treatment.

• iodine containing contrast media are to be withheld up to 1 year before treatment.

MONIYOT-131 with food and drink MONIYOT-131 should be taken fasting (on an empty stomach) and with plenty of liquid.

Pregnancy, breast-feeding and fertility You must inform the Nuclear medicine doctor before the administration of MONIYOT-131 if there is a possibility you might be pregnant, if you have missed your period or if you are breast-feeding. When in doubt, it is important to consult your Nuclear medicine doctor who will supervise the procedure.

• If you are pregnant Do not take MONIYOT-131 if you are pregnant. Any possibility of pregnancy must be ruled out before using this medicine. Additionally, you are advised not to become pregnant within 6- 12 months after taking MONIYOT-131. The Nuclear medicine doctor will only administer this product during pregnancy if a benefit is expected which would outweigh the risks.

• If you are breast-feeding Tell your doctor if you are breast-feeding as he may delay treatment until breast-feeding is finished. He may also ask you to stop breast-feeding after taking MONIYOT-131.

• Fertility Women are advised to use contraception for a time period of 6 -12 months. As a precaution, men should not father a child for a time period of 6 months after radioiodine treatment.

If you are pregnant, think you may be pregnant or are planning to have a baby, or if you are breast-feeding ask your Nuclear Medicine doctor for advice before taking this medicine.

Please ask your Nuclear Medicine doctor before taking any medicine.

Driving and using machines It is considered unlikely that MONIYOT-131 will affect your ability to drive or to operate machinery.

MONIYOT-131 contains sodium • This medicinal product contains 5.7 mg sodium per ml. This must be taken into consideration by patients on a controlled sodium diet.

3. How to take MONIYOT-131

There are strict laws on the use, handling and disposal of radiopharmaceutical products. MONIYOT-131 will only be used in special, controlled areas. This product will only be handled and given to you by people who are trained and qualified to use it safely. These persons will take special care for the safe use of this product and will keep you informed of their actions.

The Nuclear Medicine doctor supervising the procedure will decide on the quantity of MONIYOT-131 to be used in your case. It will be the minimal quantity necessary to get the desired effect.

Use in children and adolescents In children and adolescents, the quantity to be administered will be adapted to the child’s body mass.

Administration of MONIYOT-131 and conduct of the procedure MONIYOT-131 is intended for oral use. • Your stomach should be empty when taking MONIYOT-131. • You will receive a heavy lead pot, with a glass container. • Your health care provider will open the pack as appropriate and measure the activity. • You will be asked to drink the solution with some water. • You will then need to drink plenty to ensure the solution enters your stomach as quickly as possible.

Duration of procedure Your Nuclear Medicine doctor will inform you about the usual duration of the procedure.

Doses for the treatment of hyperthyroidism MONIYOT-131 is usually given once as a single oral dose in a hospital. Occasionally a second does is given. The dose for radioactive therapeutic medicinal products can be expressed as MBq, this is the amount of radioactivity in the solution at the moment you take it or it can be expressed in Gy this is the amount of radiation that is expected to be absorbed by the tissue that is being targeted for treatment (e.g. the thyroid gland). It can be calculated from a test dose you can receive before the actual treatment and from an estimation of the amount of tissue that must be taken away. There are several ways to calculate this; for some the data of additional test procedures involving ultrasound procedures and/or an injection with radioactive sodium pertechnetate (Tc-99m) are necessary.

The usual dose in radioactivity for the treatment of hyperthyroidism is usually in the range of 200-800 MBq but repeated treatment may be necessary. These doses are given for adults. The calculations for children may yield lower doses of radioactivity. The dose expressed in Gy may vary between 150 – 400 Gy in the tissue that needs to be treated.

Doses for the treatment of cancer: When used after surgical removal of the tumour doses are usually between 1850-3700 MBq. In subsequent treatment for metastases, administered activity is in the range 3700-11100 MBq.

After administration of MONIYOT-131 has been performed, you should: • Urinate frequently in order to eliminate the product from your body.

If you have been administered more MonIyot-131 than you should An overdose is almost impossible because you will receive MONIYOT-131 precisely controlled by the Nuclear Medicine doctor supervising the procedure. However in the case of an overdose, you will receive the appropriate treatment.

If you unintentionally receive too high a dose the measures taken are directed at removing the radioactive iodide (131I) from your body as quickly as possible. The measures involve: • Taking substances that make you throw up (vomit) the rest of the solution. • Drinking as much as possible so that you urinate more and so remove more of the radioactive iodide (131I). It is also possible to take substances that will prevent the radioactive iodide (131I from accumulating in tissues as the thyroid gland. (e.g. the substance potassium perchlorate).

Should you have any further questions on the use of MONIYOT-131, please ask Nuclear Medicine doctor in Nuclear Medicine who supervises the procedure.

4. Possible side effects

Like all medicines, MONIYOT-131 can cause side effects, although not everybody gets them.

Your doctor has considered that the clinical benefit that you will obtain from the procedure with the radiopharmaceutical overcomes the risk due to radiation. Side effects can occur with the following frequencies and are grouped below, according to the therapies:

Treatment of non-cancerous diseases

• Very common, occurs in more than 1 per 10 users - underactive thyroid

• Common, occurs in 1 to 10 per 100 users - certain eye inflammation, called endocrine ophthalmopathy (after treatment of Graves`disease) - temporarily overactive thyroid - salivary gland inflammation

• Very rare, occurs in less than 1 per 10.000 users - vocal cord paralysis

• Frequency unknown, from the data available - serious allergic reaction which causes difficulty in breathing or dizziness - severe overactive thyroid crisis - thyroid inflammation - reduced gland function characterised with dry eyes - reduction or loss of parathyroid hormone production - local swelling

Treatment of cancers

• Very common, occurs in more than 1 per 10 users − severe reduction in blood cells which can cause weakness, bruising or make infections more likely − lack of red blood cells − bone marrow failure − disturbance or loss of the sense of smell or taste − nausea − decreased appetite − failure of function of the ovaries − flu-like illness − headache, neck pain − extreme tiredness or drowsiness − inflammation causing red, watery and itchy eyes − salivary gland inflammation with symptoms such as dry mouth, nose and eyes; tooth decay, tooth loss Stimulate the salivary glands by eating or drinking acidic foods to reduce the frequency of this side effect.

• Common, occurs in 1 to 10 per 100 users − abnormal, cancerous increase of white blood cells − lack of white blood cells or platelets − increased streaming − breathing difficulty − vomiting − local swelling of tissue

• Rare, occurs in 1 to 10 per 10.000 users − severe or temporarily overactive thyroid

• Frequency unknown, from the data available − serious allergic reaction which causes difficulty in breathing or dizziness − cancer, such as on the bladder, large bowel, stomach − permanent or severe bone marrow suppression − thyroid inflammation − reduction or loss of parathyroid hormone production − underactive thyroid − inflammation of the trachea and/or throat narrowing − proliferation of connective tissue in the lungs − difficulty or wheezy breathing − lung inflammation − vocal cord paralysis, hoarseness, reduced ability to produce voice sounds using the vocal organs − mouth/throat pain − fluid accumulation in the brain − inflammation of the stomach lining − difficulty in swallowing − inflammation of the bladder − disturbed menstrual cycle − decreased male fertility, low or loss of sperm − thyroid hormone deficiency

Reporting of side effects If you get any side effects, talk to your doctor or Nuclear Medicine doctor who supervises the procedure. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V*. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store MONIYOT-131

You will not have to store this medicine. This medicine is stored under the responsibility of the specialist in appropriate premises. Storage of radiopharmaceuticals will be in accordance with national regulation on radioactive materials. The information is intended for the specialist only. MONIYOT-131 will not be used after the expiry date which is stated on the label after “EXP”.

6. Contents of the pack and other information

What MONIYOT-131 contains • The active substance is Sodium Iodide (131I). One ml contains 131I as sodium iodide: 14.8-3700 MBq at activity reference date and time. Iodine-131 has a half-life of 8.02 days. It decays by emission of gamma radiations of 365 keV (81%), 637 keV (7.3%) and 284 keV (6.0%) and beta radiations of maximal energy of 606 keV to stable Xenon-131.

• Other ingredients are: Sodium thiosulphate Sodium carbonate decahydrate Sodium hydrogen carbonate Hydrochloric acid Sodium hydroxide Water for injections

What MonIyot-131 looks like and contents of the pack MonIyot-131 is packaged in glass vials. The product is provided in lead shield for prevention from radiation. MonIyot-131 is a clear and colourless solution.

Pack sizes: Glass vials 5 ml or 10 ml Not all pack sizes may be marketed.

Marketing Authorisation Holder Monrol Europe S.R.L. Pantelimon, Str. Gradinarilor, nr.1 Ilfov Romania

Manufacturer Institute of Isotopes Co., Ltd. Konkoly Thege M. str. 29 – 33 H-1121 Budapest Hungary

This medicinal product is authorised in the Member States of the EEA under the following names: Denmark: Moniyot-131 Germany: MONIYOT-131 zur Therapie 14.8-3700 MBq/ml Lösung zum Einnehmen Romania: MONIYOT-131 soluţie orală 14.8-3700 MBq Bulgaria: MONIYOT-131 Greece: MONIYOT-131

This leaflet was last revised in {MM/YYYY}. [To be completed nationally]

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

The following information is intended for medical or healthcare professionals only:

The complete SmPC of MONIYOT-131 is provided in the product package, with the objective to provide healthcare professionals with other additional scientific and practical information about the administration and used of this radiopharmaceutical.