HYDREA 500 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the Patient

Hydrea 500 mg Hard Capsules

Hydroxycarbamide

Read all of this leaflet carefully before you start taking 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 doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Hydrea and what is it used for

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

2. What you need to know before you take 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 reduced number of white blood cells (leukopenia), platelets (thrombocytopenia), or red blood cells (severe anemia).
• if you have suffered or are suffering from cutaneous or vascular ulcers.
• if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with 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 (leukocytes) in the blood, increasing the risk of infections. It may also decrease the number of platelets, which are the cells required for blood coagulation, and the number of red blood cells. In these cases, some precautions should be taken, especially when the blood cell count is low, to reduce the risk of infection or bleeding. Treatment with hydroxycarbamide should not be initiated if bone marrow function is depressed. Severe anemia should be corrected before starting treatment with hydroxycarbamide.

Hemoglobin determination and leukocyte and platelet counts should be performed at least once a week during treatment with hydroxycarbamide. If the leukocyte or platelet count is too low, treatment should be interrupted until normal values are recovered. In case of anemia, even if severe, it can be treated without interrupting treatment with hydroxycarbamide.

In case 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 discontinue treatment with Hydrea.

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

If you have ever received or are receiving treatment with X-rays or other types of medicines that affect cell growth, the administration of hydroxycarbamide will be done with caution due to the possible appearance of side effects.

In particular, cutaneous ulcer-like effects were more frequently reported in patients treated with hydroxycarbamide who were also receiving or had previously received treatment with alpha-interferon. In some of these cases, ulcers on the fingers may worsen until gangrene appears. If your doctor considers that there may be a risk of this happening, it may be a reason to decide to discontinue this treatment.

If you have liver failure, since there is no data to justify adjusting the dose of the medicine, it is recommended to closely monitor blood parameters.

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

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

Skin cancer has been reported in patients who received hydroxycarbamide for a prolonged period. The skin should be protected from the sun and checked frequently during treatment with hydroxycarbamide and after treatment. Your doctor will also check your skin during routine check-ups.

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

Children and adolescents

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

Other medicines and Hydrea

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

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

Tell your doctor if you need to use a live virus vaccine during treatment with hydroxycarbamide.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Women of childbearing age are advised to avoid becoming pregnant while taking Hydrea and to inform their doctor immediately if this happens.

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

Hydroxycarbamide is excreted in breast milk. Due to the potential serious side effects of hydroxycarbamide on the infant, a decision should be made to either discontinue treatment with Hydrea or discontinue breastfeeding, taking into account the importance of the treatment for the mother.

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

Driving and using machines

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

Hydrea contains lactose

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

3. How to take Hydrea

Follow exactly the administration instructions of this medicine given by your doctor. 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 weight and the individual characteristics of your disease. Follow these recommendations carefully and do not change the dose yourself. Your doctor will indicate the duration of your treatment with Hydrea. Do not stop 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 the doctor considers appropriate in each case.

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

Renal failure:Since Hydrea is mainly eliminated by urine, determining the optimal dose requires periodic monitoring of blood and urine parameters. The dose should be decreased in these patients.

All modifications and dose control 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 some powder particles 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 inhalation of the powder at all times after opening the capsule. Disposable gloves should be worn, and hands should be washed before and after contact with the capsules or blister. In case the powder from the capsule spills, it should be cleaned immediately with a damp cloth and disposed of, along with the empty capsule, in a closed container, such as a plastic bag. This medicine, particularly opened capsules, should be kept out of the sight and reach of children and pets.

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 Emergency Service of the nearest Hospital or consult the Toxicology Information Service, phone (91) 562 04 20. It is recommended to take the packaging and the leaflet of the medicine 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 will tell you if you should take the dose again or wait until the next dose. Do not take a double dose to make up for missed doses.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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 (leukopenia, anemia, thrombocytopenia, and hemolytic anemia), mouth and lip sores, loss of appetite, nausea, vomiting, diarrhea, constipation, skin rash, skin redness and flushing, and vasculitic ulcers.

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

Loss of hair and skin cancer have been reported rarely.

Somnolence and kidney alterations (increased 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.

High fever (> 39°C) induced by this medicine has been reported, concurrently with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological, or cardiovascular manifestations, which have required hospitalization. They usually occurred within 6 weeks of starting treatment and resolved quickly after discontinuing treatment with hydroxyurea. After re-administration, the fever reappeared within 24 hours.

The following have also been reported: fever, chills, malaise, weakness, absence or low amount of sperm in the semen, liver alteration (increased levels of liver enzymes), cholestasis, hepatitis, tumor lysis syndrome (a metabolic complication due to the breakdown of cancer cells), skin inflammation that causes red and scaly plaques, which may be accompanied by joint pain. Acute pulmonary reactions have been reported rarely.

Tell your doctor immediately if you have symptoms such as:

- fever, cough, or respiratory problems; this could be a sign of a serious lung disease (frequency not known).

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

Although radiotherapy as a single treatment produces the same adverse reactions as hydroxycarbamide, combination therapy may result in an increase in the frequency and severity of these adverse reactions.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side 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°C. Store in the original packaging.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicine in the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Content and Additional Information

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 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 Container Content

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

Marketing Authorization Holder and Manufacturer

Marketing Authorization 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 a cytostatic agent by healthcare personnel requires precautions to ensure the protection of the handler and their workspace.

Patients who choose to disperse the contents of the capsules in water (see sections 4.2 and 6.6 of the Technical Sheet) should be informed to 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 who are not taking Hydrea should not be exposed to the medication. To decrease 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 case the powder from the capsule spills, 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 pets. Pregnant women should avoid handling this medication.

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

To minimize the risk of dermal exposure, always wear impermeable gloves when handling blisters that contain Hydrea capsules. This includes all handling 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 the correct handling and disposal of antineoplastic drugs should be taken into account.

Date of the Last Revision of this Prospectus:December 2024.

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