Hydrea 500 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Hydrea 500 mg hard capsules

hydroxycarbamide

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Hydrea is and what it is used for

Hydrea is a cytostatic drug, that is, a medication that inhibits cell multiplication in rapidly dividing cells, such as cancer cells. It causes cell death. Hydrea is used to treat blood cancers (chronic leukemia, myelofibrosis) and other types of blood disorders. It is used in combination with radiotherapy to treat certain types of cervical, head and neck cancer, excluding cancers of the lips.

2. What you need to know before taking Hydrea

Do not take Hydrea

• if you are allergic to hydroxycarbamide or any of the other ingredients of this medicine (listed in section 6).
• if you have a low number of white blood cells (leucopenia), platelets (thrombocytopenia), or red blood cells (severe anaemia).
• if you have had or currently have skin or vascular ulcers.
• if you are pregnant or breastfeeding.

Warnings and precautions

Talk to your doctor or pharmacist before starting Hydrea.

While taking this medicine, your doctor may advise you to drink more fluids to ensure adequate diuresis (urine elimination).

Taking hydroxycarbamide may temporarily reduce the number of white blood cells (leucocytes) in your blood, increasing your risk of infections. It may also reduce the number of platelets, which are the cells needed for blood clotting, and the number of red blood cells. In such cases, certain precautions should be taken, especially when blood cell counts are low, to reduce the risk of infection or bleeding. Treatment with hydroxycarbamide should not be started if bone marrow function is suppressed. Severe anaemia should be corrected before starting treatment with hydroxycarbamide.

Haemoglobin levels and counts of white blood cells and platelets should be checked at least once a week during treatment with hydroxycarbamide. If the white blood cell or platelet count is too low, treatment should be interrupted until normal values are restored. In the case of anaemia, even if severe, it may be treated without interrupting hydroxycarbamide therapy.

If laboratory tests indicate haemolytic anaemia (a blood disorder in which red blood cells are destroyed faster than they are produced), your doctor will stop treatment with Hydrea.

Long-term administration of this medicine may worsen skin lesions caused by arterial or venous diseases, such as diabetes, hypertension, or vasculitis (inflammation of the arteries). Hydroxycarbamide itself may cause skin ulcers, particularly in the legs.

If you have previously received or are currently receiving radiotherapy or other medications that affect cell growth, hydroxycarbamide should be administered with caution due to the possible occurrence of adverse effects. Hydrea may cause pain or discomfort due to inflammation of the mucous membranes in the irradiated area (mucositis). If the reaction is severe, your doctor may temporarily interrupt treatment with Hydrea. If the reaction is very severe, radiotherapy dose may also need to be temporarily postponed.

In particular, skin ulcer-type effects have been reported more frequently in patients treated with hydroxycarbamide who were also receiving or had previously received interferon alfa. In some of these cases, ulcers on the fingers may worsen and lead to gangrene. If your doctor considers there is a risk of this occurring, it may be a reason to discontinue this treatment.

If you have liver impairment, although there are no data justifying dose adjustment, close monitoring of blood parameters is recommended.

If you have severe renal impairment, elimination of hydroxycarbamide will be slower, so the dose of this medicine should be reduced. Close monitoring of blood parameters is also recommended.

Hydroxycarbamide may alter the results of blood tests for urea, uric acid, and lactic acid.

Talk to your doctor before taking Hydrea if you plan to be vaccinated.

In some cases, treatment with Hydrea may mask a deficiency in folic acid, so your doctor may recommend periodic monitoring of your folic acid levels.

Cases of skin cancer have been reported in patients receiving long-term hydroxycarbamide treatment. You should protect your skin from sunlight and perform frequent skin checks during and after treatment with hydroxycarbamide. Your doctor will also examine your skin during routine follow-up visits.

If you have diabetes and are using a continuous glucose monitor (CGM) to check your blood glucose levels, be aware that hydroxycarbamide (also known as hydroxyurea) may cause falsely elevated glucose readings in certain sensors. This could lead to the use of more insulin than needed, resulting in low blood sugar (hypoglycaemia). Talk to the doctor who prescribed your CGM about whether it is safe to use while taking Hydrea.

Children and adolescents

The safety and efficacy of hydroxycarbamide in children and adolescents have not been established.

Other medicines and Hydrea

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

The therapeutic effect may be affected if this medicine is taken at the same time as other medicines. Your doctor needs to know if you are taking other medicines concurrently.

Concomitant use of Hydrea with other medicines that affect the bone marrow (e.g., cytostatics) or radiotherapy may increase the risk of certain side effects.

Hydrea may increase blood uric acid levels. Therefore, it may be necessary to adjust the dose of medicines used to treat high uric acid levels, such as allopurinol.

Concomitant use of Hydrea and vaccines made with live microorganisms is not recommended, as it may increase vaccine-related side effects and pose a higher risk of serious infection, since normal body defence mechanisms may be altered by Hydrea treatment.

In patients treated with Hydrea in combination with HIV infection medications (didanosine, stavudine), pancreatitis and liver damage have occurred (in some cases, these side effects were fatal), as well as damage to nerves in the hands and feet (peripheral neuropathy).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. Women of childbearing potential are advised to avoid becoming pregnant while being treated with Hydrea and to inform their doctor immediately if pregnancy occurs.

Hydroxycarbamide may cause fetal harm if administered to pregnant women. Women of childbearing potential are advised to use effective contraception during treatment and for at least 6 months after treatment ends.

It may also cause fetal harm if the man is undergoing treatment at the time of conception. Men undergoing treatment with hydroxycarbamide are advised to use reliable contraception during treatment and for at least 3 months after treatment ends.

Hydroxycarbamide is excreted in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, a decision must be made whether to discontinue Hydrea treatment or to discontinue breastfeeding, taking into account the importance of the treatment to the mother.

Changes in semen quality (absence or low sperm count), sometimes reversible, have been observed. Men should be informed about the possibility of sperm preservation before starting treatment with hydroxycarbamide.

Driving and using machines

Do not drive or operate machinery, as Hydrea may cause drowsiness.

Hydrea contains lactose and sodium

If your doctor has informed you that you have an intolerance to certain sugars, consult him before taking this medicine.

This medicine contains 11.7 mg of sodium (main component of table/cooking salt) per capsule. This corresponds to 0.6% of the maximum daily recommended sodium intake for an adult.

3. How to take Hydrea

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, consult your doctor or pharmacist again.

Remember to take your medicine.

Your doctor will determine your daily dose of Hydrea based on your body weight and the individual characteristics of your condition. Follow these recommendations carefully and do not change the dose yourself. Your doctor will advise you on how long your treatment with Hydrea should last. Do not stop treatment without first consulting your doctor.

The recommended dose is:

Adults: A single daily dose is generally administered, but this regimen may be modified at the doctor's discretion depending on the individual case.

Elderly patients: Elderly patients may be more sensitive to the effects of hydroxycarbamide and may therefore require a reduced dose.

Renal impairment: Since Hydrea is primarily eliminated in the urine, determining the optimal dose requires periodic monitoring of blood and urine parameters. The dose should be reduced in these patients.

All dose adjustments and monitoring must be carried out under medical supervision.

Hydrea is taken orally. If you are unable to swallow the capsule, or if you prefer, the contents of the capsule may be dispersed in a glass of water and taken immediately. It is normal for some particles of the powder not to dissolve and to remain on the surface.

Hydrea capsules should be handled with care. The following precautions may help prevent exposure:

• Wash your hands thoroughly with soap and water before and after handling the product, or use protective gloves.
• If the capsule powder is spilled, clean it up immediately using a moist disposable towel, and dispose of it in a closed container together with the empty capsule shell.
• Wash your hands thoroughly with water if the capsule breaks or dissolves.
• DO NOT inhale the contents of the capsules.
• People who are not taking Hydrea should not be exposed to the medicine. Keep Hydrea out of the reach of children and pets.

If you take more Hydrea than you should

If you have taken more Hydrea than you should, contact your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, it is recommended to go immediately to the nearest Hospital Emergency Department or contact the Toxicology Information Service at telephone (91) 562 04 20. It is advisable to bring the medicine packaging and leaflet to the healthcare professional.

If you forget to take Hydrea

If you miss a dose, consult your doctor. If you vomit shortly after taking a dose of hydroxycarbamide, consult your doctor. He or she will advise you whether you should take another dose or wait until your next scheduled dose. Do not take a double dose to make up for missed doses.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Contact your doctor immediately if you experience any of the following symptoms:

• Severe infection
• Tiredness or paleness
• Unexplained bruising or bleeding

These symptoms may be a sign of reduced activity of blood-producing organs, a very common side effect (may affect more than 1 in 10 people).

• Skin ulcers

These symptoms may be a sign of inflammation in the blood vessels of the skin, a very common side effect (may affect more than 1 in 10 people).

• In some cases, high fever (>39 °C) induced by this medicine has been reported, together with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological, and cardiovascular manifestations, requiring hospitalization. These symptoms usually occurred within the first 6 weeks after starting treatment and resolved rapidly after discontinuation of hydroxyurea. When treatment was resumed, fever reappeared within 24 hours (frequency cannot be estimated from the available data).

• Breathing difficulties, such as shortness of breath, especially during exertion, persistent dry cough, tiredness, or chest discomfort, may be signs of lung involvement, a common side effect (may affect up to 1 in 10 people). If respiratory problems occur due to allergic inflammation of lung tissue, fever may occur at an unknown frequency (cannot be estimated from the available data).

Other possible side effects:

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

• anemia
• loss of appetite
• pancreatitis (may be fatal)
• nausea and vomiting
• diarrhea
• mucositis
• stomatitis
• constipation
• abdominal and/or gastrointestinal tract irritation
• skin rash, including peeling and spots, along with inflamed skin rash
• hair loss
• inflammation of the skin, dermis, and adjacent muscles
• redness of the face or arms and legs/hands and feet
• skin peeling
• hyperpigmentation
• skin and nail atrophy
• increased uric acid
• increased blood urea
• increased blood creatinine
• dysuria
• reduced or absent sperm production
• fever
• chills
• weakness
• malaise

Common (may affect up to 1 in 10 people)

• skin cancer
• disorientation
• hallucination
• seizures
• dizziness
• headache
• nerve problems in hands and feet
• somnolence
• increased levels of liver enzymes in blood
• impaired bile flow
• liver inflammation (hepatitis)
• liver damage (may be fatal)

Rare (may affect up to 1 in 1,000 people)

• abnormal blood values caused by tumor breakdown products, which may sometimes lead to irregular heartbeats and impaired kidney function (tumor lysis syndrome)
• local tissue death resulting from inflammation of blood vessels in the skin with recurrent ulcers (usually associated with concomitant or prior interferon treatment)

Frequency not known (cannot be estimated from the available data)

• skin inflammation causing red, scaly patches, which may occur simultaneously with joint pain
• pigmented (colored) nails
• hemolytic anemia (a condition in which red blood cells are destroyed faster than they are produced)

Adverse reactions observed when hydroxycarbamide is administered together with radiotherapy are of the same type as those observed when hydroxycarbamide is given alone. These adverse reactions include mainly: decreased numbers of red and white blood cells (anemia and leucopenia) and stomach irritation. Most patients who have received hydroxycarbamide together with radiotherapy have experienced a decrease in white blood cells (leucopenia). Rarely, and only in cases of severe decrease in white blood cells (severe leucopenia), a decrease in platelets has occurred. Hydrea may enhance some adverse reactions normally associated with radiotherapy, such as stomach pain and mucosal inflammation.

Although radiotherapy alone produces the same adverse reactions as hydroxycarbamide, combination therapy may lead to an increase in the frequency and severity of these adverse reactions.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Hydrea

Keep this medicine out of the sight and reach of children.

Do not store above 25 ºC. Store in the original packaging.

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at a SIGRE collection point at your pharmacy. If you are in doubt, ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Hydrea

• The active substance is hydroxycarbamide. Each hard capsule contains 500 mg of hydroxycarbamide.
• The other components are: anhydrous sodium hydrogen phosphate, anhydrous citric acid, monohydrate lactose, and magnesium stearate. The capsule shell contains: gelatin, titanium dioxide (E171), yellow iron oxide (E172), erythrosine (E127), and indigo carmine (E132). Black printing ink: Opacode S-1-277002 (shellac, black iron oxide (E172), propylene glycol (E1520), ammonium hydroxide).

Appearance of the product and pack contents

Hydrea hard capsules are pink and green in colour. Each pack contains 20 hard capsules presented in two blisters of 10 capsules each.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

CHEPLAPHARM Arzneimittel GmbH
Ziegelhof 24
17489 Greifswald
Germany

Manufacturer

Latina Pharma S.p.A.
Via Murillo, 7
04013 Sermoneta (LT)
Italy

or

Haupt Pharma Amareg GmbH
Donaustaufer Straße 378
93055 Regensburg
Germany

Local Representative

Laboratorios Rubió, S.A.
Industria, 29 – Pol. Ind. Comte de Sert
08755 Castellbisbal (Barcelona)
Spain

Handling instructions

Handling of a cytotoxic agent by healthcare personnel requires precautions to ensure protection of the handler and the working environment.

Patients who choose to disperse the capsule contents in water (see sections 4.2 and 6.6 of the Summary of Product Characteristics) should be advised to handle the medicine with care.

Precautions should be taken to avoid contact of the powder with the skin and mucous membranes, including inhalation of the powder once the capsule is opened. Individuals not taking Hydrea should not be exposed to the medicine. To reduce the risk of exposure, wear disposable gloves when handling Hydrea or blisters containing Hydrea. Anyone handling Hydrea should wash their hands before and after contact with the capsules or blister pack. If capsule powder is spilled, it should be cleaned up immediately with a damp cloth and both the cloth and the empty capsule should be disposed of in a closed container.

Any broken container must be handled with the same precautions and considerations as contaminated waste. Contaminated waste must be incinerated in appropriate, rigid, and properly labelled containers.

This medicine, particularly opened capsules, must be kept out of the sight and reach of children and pets. Pregnant women should avoid handling this medicine.

As with all cytotoxic drugs, treatment with Hydrea should be initiated by a specialist physician and handled with caution under aseptic conditions.

To minimize the risk of dermal exposure, always wear impermeable gloves when handling blisters containing Hydrea capsules. This includes all handling activities in clinics, pharmacies, warehouses, and home healthcare facilities, including those performed during unpacking and inspection, transport within a facility, and dose preparation and administration.

If hydroxycarbamide comes into contact with the skin or mucous membranes, immediately wash thoroughly and abundantly with water.

Appropriate guidelines for the safe handling and disposal of antineoplastic drugs should be followed.

Date of the latest revision of this leaflet: December 2025.

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/