Thromboreductin

Package Leaflet: Information for the User

Thromboreductin, 0.5 mg hard capsules

Anagrelide

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the package leaflet

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

1. What is Thromboreductin and what is it used for

Thromboreductin is indicated for the treatment of essential thrombocythemia. The decision to treat should be made individually for each patient, depending on the platelet count, patient age, clinical symptoms, and history, as well as the rate of increase in platelet count after diagnosis, concomitant diseases, and risk factors for thrombosis, and current treatment, such as hydroxyurea or interferon alpha.

2. Important information before taking Thromboreductin

When not to take Thromboreductin

Warnings and precautions

Before starting treatment with Thromboreductin, you should consult your doctor:

• In case of heart problems;
• If you have a congenital or family history of prolonged QT interval (visible on ECG, recording of the electrical activity of the heart) or if you are taking other medicines that affect the ECG or if you have decreased electrolyte levels, such as potassium, magnesium, or calcium (see "Thromboreductin and other medicines");
• In case of liver or kidney problems.

Thromboreductin should be taken in the exact dose prescribed by your doctor. Do not stop taking the medicine without consulting your doctor first. Do not suddenly stop taking this medicine without consulting your doctor. Sudden withdrawal of the medicine may increase the risk of stroke or heart attack.
Symptoms of stroke may include sudden numbness or weakness of the face, arm, or leg, especially on one side of the body, sudden confusion, difficulty speaking or understanding speech, sudden problems with vision in one or both eyes, sudden problems with walking, dizziness, loss of balance or coordination, and sudden severe headache with no known cause. Medical help should be sought immediately.
Symptoms of heart attack may include pain or discomfort in the chest, feeling of weakness, dizziness or fainting, pain or discomfort in the jaw, neck, back, or arms, shortness of breath. Medical help should be sought immediately.
Elderly patients
Caution should be exercised in elderly patients with cardiovascular disease.

Children and adolescents

Anagrelide has been given to a small number of children under 16 years of age. It seems that there are no major differences in dosing compared to adult treatment.

Thromboreductin and other medicines

Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
The following medicines have been used in combination with Thromboreductin:
acetylsalicylic acid - used to treat pain and fever, also anti-inflammatory
acetaminophen, also known as paracetamol - used as a pain reliever and antipyretic
beta-blocker - used, among other things, to treat high blood pressure
angiotensin-converting enzyme inhibitors - used to treat high blood pressure
clopidogrel - used as an antiplatelet agent
coumarin - used as an anticoagulant
folic acid, vitamin B
amlodipine - used to treat high blood pressure
carbamazepine - used to treat epilepsy
hydrochlorothiazide - a diuretic used to treat high blood pressure
indapamide - a diuretic used to treat high blood pressure
furosemide - a diuretic used to treat high blood pressure
iron preparations - used in case of iron deficiency,
isosorbide mononitrate - used in coronary artery disease to interrupt an angina attack
levothyroxine - used to treat hypothyroidism
simvastatin - a medicine that regulates blood fat levels
tiklopidine - an antiplatelet agent
ranitidine - used to treat stomach and duodenal ulcers
hydroxyurea - used to treat blood diseases such as polycythemia vera
allopurinol - used to treat gout
digoxin - used to treat heart failure.
Except for acetylsalicylic acid (increased risk of bleeding), no significant interactions have been observed.
Tell your doctor if you are taking medicines that may affect heart rhythm.
Theoretical interactions with medicines such as fluvoxamine (used to treat depression) and omeprazole (used to treat stomach and duodenal ulcers) may have an unfavorable effect on the elimination of anagrelide from the body. Anagrelide has some limited inhibitory activity against the CYP1A2 enzyme, which may theoretically pose a risk of interaction with other concomitantly administered medicines that use the same elimination mechanism from the body, such as theophylline (used to treat asthma).
Anagrelide may enhance the effect of medicines with similar properties, such as inotropic agents (stimulating heart activity): milrinone, enoximone, amrinone, olprinone, or cilostazol - a medicine used to treat peripheral artery occlusion.
Anagrelide may cause gastrointestinal disturbances in some patients and limit the absorption of oral hormonal contraceptives.

Thromboreductin with food and drink

Food delays the absorption of anagrelide, but does not significantly affect its potency.
It has been shown that grapefruit juice may delay the elimination of anagrelide from the body.

Pregnancy and breastfeeding

There are insufficient data on the use of anagrelide in pregnant women. Animal studies with very high doses of the medicine have shown a harmful effect on reproduction.
Therefore, Thromboreductin should not be used during pregnancy. If Thromboreductin is used during pregnancy or if pregnancy is detected during treatment, the patient should be informed of the potential risk to the fetus.
Women of childbearing age should use effective contraceptive methods during treatment with Thromboreductin.
It is not known whether anagrelide passes into breast milk. Considering that many medicines pass into human milk, and the possibility of side effects in breastfed infants, patients should stop breastfeeding during treatment with Thromboreductin.

Driving and using machines

Patients should be informed not to drive vehicles or operate machinery if they experience dizziness during treatment.

Thromboreductin contains lactose

If you have been diagnosed with an intolerance to some sugars, you should contact your doctor before taking the medicine.

3. How to take Thromboreductin

Treatment with anagrelide should be initiated by doctors with experience in the treatment of essential thrombocythemia.
Thromboreductin is dosed individually for each patient. The doctor will start treatment with a dose of 0.5 mg per day for the first week, and then increase the dose by 0.5 mg per day every week until the desired response to treatment is achieved.
Usually, a response to treatment occurs within 2 weeks of taking doses from 1 mg to 3 mg per day. The total daily dose should be given in two (every 12 hours) or three (every 8 hours) divided doses.
The total daily dose should not exceed 5 mg.
The doctor will regularly monitor the treatment results. During the initiation of treatment, the doctor will check the platelet count every week until optimal response is achieved (normalization of platelet count or reduction to <600,000/microliter, or a 50% reduction); then the doctor will check the platelet count at regular intervals.
The switch from previously used medicines (e.g., hydroxyurea or interferon alpha) to anagrelide or combination treatment with anagrelide should be done by the doctor in such a way that the new medicine (medicines) is started before the previous medicines are stopped.
Anagrelide is intended for long-term use.
After withdrawal of the medicine, the platelet count returns to pre-treatment levels within a few days.
In case of resistance to anagrelide treatment, the doctor will consider other treatment methods. During treatment, the platelet count should be regularly monitored.
Caution is recommended in patients with cardiovascular disease.
There is limited data available on patients with renal and hepatic impairment, so the doctor will use anagrelide only after careful analysis of the risk-to-benefit ratio.
Use in elderly patients: anagrelide has been used in a small number of elderly patients. The doctor will use anagrelide with caution in elderly patients with cardiovascular disease.

Use in children and adolescents

Use in children: anagrelide has been used in a small number of children under 16 years of age. It seems that there are no major differences in dosing compared to adult treatment.

Overdose of Thromboreductin

In case of overdose, close clinical monitoring of the patient is required, which includes monitoring the platelet count to detect thrombocytopenia. The dose should be reduced or the medicine withdrawn, depending on the situation, until the platelet count returns to normal.

Missed dose of Thromboreductin

A double dose should not be taken to make up for a missed dose.

Withdrawal of Thromboreductin

Within a few days, the platelet count returns to pre-treatment levels.
If you feel that the effect of the medicine is too strong or too weak, you should consult your doctor.

4. Possible side effects

Like all medicines, Thromboreductin can cause side effects, although not everybody gets them.
If you experience any worrying symptoms, you should consult your doctor.

You should contact your doctor or go to the nearest hospital emergency department immediately if you experience any of the following symptoms:

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

• heart failure (symptoms include severe chest pain and shortness of breath);
• ventricular tachycardia (symptoms include very rapid heartbeat and severe chest pain with accompanying shortness of breath);
• pulmonary hypertension (symptoms include shortness of breath, swelling of the legs or ankles, and possible blue discoloration of the lips and skin).

Rare (may affect up to 1 in 1000 people):

• heart attack (symptoms include severe chest pain or discomfort and shortness of breath; see section 2);
• atrial fibrillation (symptoms include very rapid heartbeat and severe chest pain with accompanying shortness of breath);
• angina pectoris (symptoms include severe chest pain due to insufficient blood flow to the heart).

Other side effects that may occur

Very common (may affect more than 1 in 10 people):
headache.
Common (may affect up to 1 in 10 people):
anemia (slight decrease in red blood cell count and iron deficiency), bruising;
localized swelling with fluid (edema);
dizziness (rarely when getting up or standing up from bed), numbness or tingling in the fingers of the hands and feet, insomnia;
palpitations (feeling strong heartbeats, which can be rapid or irregular), tachycardia, hypertension;
nosebleeds;
nausea, diarrhea, indigestion;
rash;
back pain, fatigue.
Uncommon (may affect up to 1 in 100 people):
decrease in platelet count, bleeding, subcutaneous hemorrhages;
weight gain;
depression; nervousness, dryness of the mucous membranes of the mouth, migraine;
vision disturbances, conjunctivitis;
tinnitus;
heart failure (including congestive heart failure), irregular heartbeat, supraventricular tachycardia, ventricular tachycardia, fainting;
shortness of breath, respiratory tract inflammation, pulmonary hypertension (symptoms include shortness of breath, swelling of the legs or ankles, and possible blue discoloration of the lips and skin);
vomiting, bloating, constipation, abdominal pain;
hair loss, itching;
muscle pain, joint pain;
renal failure, urinary tract infection;
pain, weakness.
Rare (may affect up to 1 in 1000 people):
atrial fibrillation, angina pectoris, heart attack, orthostatic hypotension, chest pain at rest (Prinzmetal's angina);
pleural effusion, pneumonia, asthma;
gastritis, loss of appetite;
rash;
nocturia;
increased liver enzyme activity;
flu-like symptoms, chills, malaise.
Frequency not known (cannot be estimated from the available data):
Torsades de pointes(a potentially life-threatening condition with rapid, irregular heartbeat);
pulmonary fibrosis;
interstitial nephritis;
decreased sensation and feeling (hypoesthesia);
stroke (see section 2).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should inform your doctor. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides of the Office for Registration of Medicinal Products, Medical Devices, and Biocides, Al. Jerozolimskie 181C, 02-222 Warsaw, Poland, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Thromboreductin

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
Do not store above 30°C.
Store in the original packaging to protect from light.

6. Contents of the pack and other information

What Thromboreductin contains

• The active substance is anagrelide in the form of anagrelide hydrochloride. One hard capsule contains 0.5 mg of anagrelide.
• The other ingredients are: lactose monohydrate, povidone, crospovidone (type A), microcrystalline cellulose (type 102), magnesium stearate, capsule shell: titanium dioxide (E 171), indigo carmine (E 132), gelatin, purified water.

What Thromboreductin looks like and contents of the pack

Blue hard capsules filled with white powder.
A container with a screw cap contains 100 capsules, in a cardboard box.

Marketing authorization holder and manufacturer

AOP Orphan Pharmaceuticals GmbH
Leopold-Ungar-Platz 2
1190 Vienna, Austria
For more detailed information, please contact the representative of the marketing authorization holder:
AOP Orphan Pharmaceuticals Poland Sp. z o.o.
ul. Olkuska 7
02-604 Warsaw, Poland

Date of last revision of the leaflet: