Prescription Information for the Patient

Hydrea 500 mg Hard Capsules

Hydroxycarbamide

Read this entire leaflet carefully before you start taking this medicine, as 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 must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Hydrea is a compound belonging to a group of medications called antimetabolites, indicated in the treatment of certain proliferative diseases of the bone marrow (e.g. polycythemia vera, essential thrombocythemia), and as supportive treatment in certain cervical, head, and neck diseases.

Do not take Hydrea

• if you are allergic to hydroxyurea or any of the other ingredients of this medication (listed in section 6).
• if you have a reduced number of white blood cells (leucopenia), platelets (trombocytopenia), or red blood cells (severe anemia).
• if you have suffered or suffer from skin ulcers or vasculitis.
• if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Hydrea.

When taking this medication, your doctor may advise you to drink more liquids to ensure adequate urine output.

Hydroxyurea may temporarily reduce the number of white blood cells (leucocytes) in the blood, increasing the risk of infections. It may also decrease the number of platelets, which are necessary for blood clotting, and the number of red blood cells. In these cases, take some precautions, especially when the blood cell count is low, to reduce the risk of infection or bleeding. Do not start treatment with hydroxyurea if the bone marrow function is depressed. Severe anemia must be corrected before starting treatment with hydroxyurea.

Blood hemoglobin and white blood cell and platelet counts must be determined at least once a week during hydroxyurea treatment. If the white blood cell or platelet count is too low, treatment must be interrupted until normal values are restored. In the event of the appearance of anemia, even if it is severe, it may be treated without interrupting hydroxyurea treatment.

If laboratory tests determine that there is hemolytic anemia (a blood disorder in which red blood cells are destroyed faster than they are produced), your doctor will suspend treatment with Hydrea.

Prolonged administration of this medication may exacerbate skin lesions caused by arterial or venous diseases, such as diabetes, hypertension, or vasculitis. Hydroxyurea itself may cause the appearance of skin ulcers, especially on the legs.

If you have ever received or are receiving radiation therapy or other medications that act on cell growth, the administration of hydroxyurea will be done with caution due to the possible appearance of adverse effects.

Particularly, skin ulcer effects were reported more frequently in patients treated with hydroxyurea and who were also receiving or had previously received interferon-alpha treatment. In some of these cases, leg ulcers may worsen to the point of gangrene. If your doctor considers that there may be a risk of this occurring, it may be a reason to suspend treatment with this medication.

If you have liver insufficiency, although there are no data to justify adjusting the medication dose, it is recommended to closely monitor blood parameters.

If you have severe renal insufficiency, the elimination of hydroxyurea will be slower, so the dose of this medication should be reduced, and it is also recommended to closely monitor blood parameters.

Hydroxyurea may alter the results of urea, uric acid, and lactic acid in your blood tests.

Cancer of the skin has been reported in patients receiving hydroxyurea for a prolonged period. Protect your skin from the sun and have your skin checked frequently during treatment with hydroxyurea and after treatment is completed. Your doctor will also check your skin during your regular check-ups.

If you have diabetes and are using a continuous glucose monitor (CGM) to check your blood glucose level. Hydroxyurea (also known as hydroxyurea) may cause falsely elevated glucose readings in certain sensors. This could lead to using too much insulin, resulting in low blood sugar (hypoglycemia). Talk to the doctor who prescribed the CGM about whether it is safe to use while taking Hydrea.

Children and adolescents

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

Other medications and Hydrea

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

If you are being treated with medications used to treat gout (uricosuric), consult your doctor.

Inform your doctor if you need to use a live virus vaccine during treatment with hydroxyurea.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication. Women of childbearing age are advised to avoid becoming pregnant while taking Hydrea and to inform their doctor immediately if this occurs.

Hydroxyurea may cause damage to the fetus if administered to pregnant women. Women of childbearing age are advised to use effective contraceptive methods during treatment and for at least 6 months after treatment.

It may also cause damage to the fetus if the man is being treated at the time of conception. Men being treated with hydroxyurea are advised to use safe contraceptive methods during treatment and for at least 3 months after treatment.

Hydroxyurea is excreted in breast milk. Due to the potential for severe adverse reactions in the infant, it should be decided whether to interrupt treatment with Hydrea or interrupt breastfeeding, taking into account the importance of the treatment for the mother.

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

Driving and operating machinery

Do not drive or operate machinery, as Hydrea may make you feel drowsy.

Hydrea contains lactose

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Remember to take your medication.

Your doctor will determine your daily dose of Hydrea based on your weight and the individual characteristics of your disease. Follow these recommendations closely and do not modify the dose yourself. Your doctor will inform you of the duration of your treatment with Hydrea. Do not discontinue treatment without consulting your doctor first.

The recommended dose is:

Adults:Generally, a single daily dose will be administered, but this regimen will be subject to changes that your doctor may consider necessary in each case.

Seniors:Elderly patients may be more sensitive to the effects of hydroxyurea, so they may require a reduction in dose.

Renal insufficiency:Since Hydrea is primarily eliminated through urine, periodic monitoring of blood and urine parameters is required to determine the optimal dose. The dose should be reduced in these patients.

All dose modifications and monitoring will be performed under medical supervision.

Hydrea is taken orally. If you cannot swallow the capsule or prefer not to, the contents of the capsule can be dispersed in a glass of water and taken immediately. It is normal for certain particles of the powder not to dissolve and remain on the surface. Precautions should be taken to avoid contact of the powder with the skin and mucous membranes, avoiding breathing the powder once the capsule is opened. Disposable gloves should be worn, and hands should be washed before and after contact with the capsules or blister pack. In the event of the powder from the capsule spilling, it should be immediately cleaned with a damp cloth and discarded, along with the empty capsule, in a closed container, such as a plastic bag. This medication, particularly opened capsules, should be kept out of sight and reach of children and domestic animals.

If you take more Hydrea than you should

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

In case of overdose or accidental ingestion, it is recommended to go quickly to the nearest Hospital Emergency Service or consult the Toxicological Information Service, phone (91) 562 04 20. It is recommended to bring the packaging and the medication leaflet to the healthcare professional.

If you forget to take Hydrea

In case of forgetting a dose, consult your doctor. If you vomit shortly after taking a dose of hydroxyurea, consult your doctor. He will tell you if you should take the dose again or if you should wait until the next dose. Do not take a double dose to compensate for missed doses.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The following adverse reactions have been reported: temporary reduction in the number of white blood cells, red blood cells, or platelets in the blood (leucopenia, anemia, thrombocytopenia, and hemolytic anemia), mouth and lip sores, loss of appetite, nausea, vomiting, diarrhea, constipation, skin rash, skin redness and face, and vascular ulcers.

In some patients, after several years of long-term daily maintenance treatment with Hydrea, hyperpigmentation, nail pigmentation, skin redness, skin atrophy, and nail atrophy have been observed, as well as skin peeling, violaceous skin lesions, and ulcers that may evolve into gangrene.

In rare cases, hair loss and skin cancer have been observed.

Somnolence and renal alterations (elevated levels of uric acid, urea, and creatinine) have also been described. Exceptionally, headaches, dizziness, disorientation, hallucinations, seizures, and dysuria (painful or difficult urination) have been reported.

Hypersensitivity reactions have been described.

In some cases, high fever (> 39°C) induced by this medicine has been reported, concurrently with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological, or cardiovascular manifestations that have required hospitalization. Normally, they occurred within 6 weeks of starting treatment and resolved rapidly after discontinuing treatment with hydroxyurea. After re-administration, fever appeared again within 24 hours.

Other reported adverse reactions include: fever, chills, malaise, weakness, absence or low sperm count in semen, liver alteration (elevated levels of liver enzymes), cholestasis, hepatitis, tumor lysis syndrome (a metabolic complication due to the breakdown of cancer cells), skin inflammation causing red and scaly plaques, and possibly accompanied by joint pain. In rare cases, acute pulmonary reactions have been reported.

Inform your doctor immediately if you experience symptoms such as:

-fever, cough, or respiratory problems; this could be a sign of a severe lung disease (unknown frequency).

Adverse reactions observed when administering hydroxicarbamide with radiation therapy are of the same type as those observed when administering hydroxicarbamide alone. These adverse reactions include mainly: a decrease in the number of red and white blood cells (anemia and leucopenia) and stomach irritation. Most patients who have received hydroxicarbamide with radiation therapy have experienced a decrease in white blood cells (leucopenia). Rarely, and only in cases of severe white blood cell decrease (severe leucopenia), a decrease in platelets has been produced. Hydrea may potentiate some adverse reactions normally associated with radiation therapy, such as stomach pain and mucous membrane inflammation.

Although radiation therapy as a single treatment produces the same adverse reactions as hydroxicarbamide, combined therapy may lead to an increase in the frequency and severity of these adverse reactions.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

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

Do not store at a temperature above25°C. Store in the original packaging.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Hydrea

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

Appearance of the product and contents of the package

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

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Responsible 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

The handling of a cytostatic agent by healthcare personnel requires taking precautions to ensure the protection of the handler and their work area.

Patients who choose to disperse the contents of the capsules in water (see sections 4.2 and 6.6 of the Technical Dossier) should handle the medication 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. People not taking Hydrea should not be exposed to the medication. 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. In the event of capsule powder spilling, it should be cleaned immediately with a damp cloth and discarded, along with the empty capsule, in a closed container, such as a plastic bag.

Any broken container should be treated with the same precautions and considerations as contaminated waste. Contaminated waste should be incinerated in suitable, rigid, and properly labeled containers.

This medication, particularly opened capsules, should be kept out of the sight and reach of children and domestic animals. Pregnant women should avoid handling this medication.

As with all cytostatic drugs, Hydrea treatment should be initiated by a specialist doctor and handled with caution, in aseptic conditions.

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

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

The guidelines for correct handling and disposal of antineoplastic drugs should be observed.

Last review date of this leaflet:December 2024.

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/