Hidroxiurea medac

Package Leaflet: Information for the Patient

HYDROXYUREA medac, 500 mg, hard capsules

Hydroxycarbamidum

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

• Keep this package 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 symptoms 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 package leaflet

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

1. What is Hydroxyurea medac and what is it used for

One of the most important effects of hydroxyurea is the inhibition of ribonucleotide reductase, which leads to the inhibition of DNA synthesis.

Indications for use

Treatment of chronic myeloid leukemia (CML) in the chronic or accelerated phase.
Treatment of primary thrombocythemia or polycythemia vera with a high risk of thromboembolic complications.

2. Important information before taking Hydroxyurea medac

When not to take Hydroxyurea medac:

Warnings and precautions

Before starting treatment with Hydroxyurea medac, discuss it with your doctor or pharmacist.
Treatment with hydroxyurea may cause bone marrow suppression (resulting in leukopenia, thrombocytopenia, and anemia).
After determining the individual optimal dose, your doctor will also determine the frequency of necessary follow-up tests (hemoglobin level, total white blood cell count, and platelet count). If the white blood cell count is less than 2.5 x 10/L or the platelet count is less than 100 x 10/L, your doctor may recommend stopping treatment with hydroxyurea until these values return to near-normal levels.
You should inform your doctor if you have ever had a gout attack.
You should inform your doctor if you have a folic acid deficiency.
In case of a decrease in the number of red blood cells (anemia) before or during treatment, your doctor may recommend, if necessary, the administration of red blood cells. If hemolytic anemia (a disorder in which red blood cells are destroyed faster than they can be produced) is detected during follow-up blood tests, your doctor will discontinue treatment with Hydroxyurea medac.
Patients with renal and/or hepatic impairment should inform their doctor before starting treatment with this medicine.
In patients taking hydroxyurea chronically, secondary leukemia may develop.
The relationship with treatment or underlying disease is currently unknown.
Spontaneous megaloblastic erythropoiesis is often observed at the beginning of hydroxyurea treatment. Morphological changes resemble megaloblastic anemia but are not dependent on vitamin B or folic acid deficiency.
During treatment with Hydroxyurea medac, liver and kidney function parameters should be frequently monitored.
Uric acid levels in the serum may increase, which may require appropriate dose modification.
In patients taking hydroxyurea for a long time, malignant skin cancer has been reported. During and after treatment with hydroxyurea, the skin should be protected from the sun and regularly self-examined. Additionally, the attending physician will perform skin examinations during routine follow-up visits.
Patients may experience leg ulcers. In such cases, the attending physician will decide whether the patient should continue taking this medicine. After discontinuation of this medicine, ulcers usually heal slowly, within a few weeks.
If the patient has diabetes and uses a continuous glucose monitoring system (CGM) to test blood glucose. Hydroxyurea (also known as hydroxycarbamide) may cause falsely high glucose readings from some sensors. This may lead to the administration of a higher dose of insulin than necessary, resulting in low blood sugar levels (hypoglycemia). You should discuss with your doctor who prescribed the CGM system whether it can be used safely while taking Hydroxyurea medac.

Children

These diseases rarely occur in children, so dosing for this age group has not been established.

Hydroxyurea medac and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
Hydroxyurea should be administered with caution to patients currently or previously treated with anticancer medicines or radiation, as adverse reactions occur more frequently and are more severe than with hydroxyurea alone, anticancer medicines, or radiation. Primary bone marrow suppression may occur, as well as mucositis, stomatitis, and gastrointestinal disturbances.
The severity of radiation dermatitis may increase in patients irradiated during treatment with hydroxyurea or before starting treatment.
Studies have shown that hydroxyurea may enhance the cytotoxic effects of both ara-C (cytarabine) and fluoropyrimidines.
Hydroxyurea may increase the activity of nucleoside reverse transcriptase inhibitors (NRTIs), which are used to treat HIV infections (e.g., didanosine, stavudine). It has been shown that hydroxyurea in combination with didanosine, stavudine, and indinavir reduces the number of white blood cells (reduction of CD4 lymphocytes). Hydroxyurea in combination with NRTIs may increase the risk of adverse reactions to NRTIs.
Patients who have been vaccinated recently or plan to be vaccinated should inform their doctor.

Renal and/or hepatic impairment

No dosage recommendations can be made for patients with renal or hepatic impairment.

Elderly patients

Elderly patients may be more sensitive to the effects of hydroxyurea and may require lower doses.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine.
Women of childbearing age/Contraception in women and men
Women of childbearing age should use effective contraception during treatment with Hydroxyurea medac and for 6 months after treatment.
Men are advised to use effective contraception and not to father a child during treatment with Hydroxyurea medac and for 3 months after treatment.
Pregnancy
Hydroxyurea medac should not be used during pregnancy unless your doctor recommends it.
Breastfeeding
Hydroxyurea medac should not be used during breastfeeding. The active substance of Hydroxyurea medac passes into human milk. You should ask your doctor for advice.
Fertility
You should ask your doctor about the possibility of freezing sperm before starting treatment for the first time.
Genetic counseling is recommended for patients planning offspring after treatment.

Driving and using machines

Reaction ability may be impaired during treatment with Hydroxyurea medac. This should be taken into account when increased concentration is required, e.g., when driving a car.

Hydroxyurea medac contains lactose and sodium

If you have been diagnosed with intolerance to some sugars, you should contact your doctor before taking this medicine.
The medicine contains less than 1 mmol (23 mg) of sodium per capsule, which means it is considered "sodium-free".

3. How to take Hydroxyurea medac

This medicine should always be taken exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Treatment should be carried out under the supervision of a doctor experienced in oncology or hematology. Dosing is based on the patient's actual or ideal body weight, choosing the lower one.
The initial dose in the treatment of chronic myeloid leukemia (CML) is 40 mg/kg body weight per day, depending on the white blood cell count. The dose is chosen by the doctor individually for each patient so that the white blood cell count remains between 5 and 10 x 10/L.
The doctor may reduce the dose by 50% (20 mg/kg body weight) if the white blood cell count is less than 20 x 10/L. If the white blood cell count is less than 2.5 x 10/L or the platelet count is less than 100 x 10/L, the doctor may discontinue treatment until these values return to near-normal levels.
The initial dose in the treatment of primary thrombocythemia is 15 mg/kg body weight per day and is adjusted to maintain the platelet count below 600 x 10/L and the white blood cell count above 4 x 10/L.
Treatment of polycythemia vera starts with an initial dose of 15-20 mg/kg body weight per day.
The dose is adjusted individually to keep the hematocrit value below 45% and the platelet count below 400 x 10/L.
Capsules should be swallowed whole without opening them.
It is recommended to drink plenty of fluids during treatment.
If you feel that the effect of Hydroxyurea medac is too strong or too weak, you should consult your doctor.

Taking a higher dose of Hydroxyurea medac than prescribed

If you have taken more of this medicine than prescribed by your doctor, you should always contact your doctor or hospital. Patients may experience symptoms in the mucous membranes and skin.
In patients who have taken multiple daily doses, acute mucocutaneous symptoms have been observed. The following have also been observed: pain, purple spots, swelling on the palms and soles, leading to skin peeling, general skin discoloration, and stomatitis.
Immediate treatment includes gastric lavage, followed by the use of supportive measures and monitoring of the hematopoietic system.

Missing a dose of Hydroxyurea medac

Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should immediately inform your doctor if you experience any of the following symptoms:

• Fever, cough, or difficulty breathing, as they may be related to a severe lung disease (frequency unknown)
• High fever (>39°C) with gastrointestinal, pulmonary, muscular, hepatic, skin, and cardiac symptoms within 6 weeks of taking Hydroxyurea medac (frequency: rare)

Bone marrow suppression is a dose-limiting adverse reaction.

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

• Absence or low number of sperm in the semen (azoospermia or oligospermia)
• Decreased number of blood cells (bone marrow suppression), especially white blood cells (leukopenia), including the type of white blood cells that help the body fight infections (reduction of CD4 lymphocytes), red blood cells (anemia), and platelets (thrombocytopenia)
• Nausea, vomiting, loss of appetite, stomatitis, diarrhea, constipation, abdominal pain, gastritis, and digestive problems (dyspepsia)
• Black tarry stools or blood in the stool
• In combination with some HIV medicines: pancreatitis with abdominal or stomach pain
• Drug fever, chills, malaise, weakness, fatigue
• Skin ulcers, especially leg ulcers
• Skin rash with spots and blisters (maculopapular rash), facial erythema, palmar-plantar erythrodysesthesia syndrome
• Skin changes, such as purple rash and skin thinning; discoloration and damage to nails and skin; itching, small, purple spots on the skin; skin peeling, discoloration, and necrosis of the skin
• Hair loss
• Transient renal impairment with increased blood parameters, such as uric acid, urea, and creatinine
• Difficulty urinating

Common (may affect up to 1 in 10 people)

• Megaloblastic erythropoiesis
• Skin cancer
• Increased liver enzyme activity
• Hepatitis, which can cause flu-like symptoms, including fatigue, loss of appetite, fever, pain, and nausea/vomiting, feeling of pressure or pain under the right rib cage, and may also include yellowing of the skin or eyes
• Bile flow problems (cholestasis). Bile produced by the liver to aid in digestion may not flow properly. Bile buildup can cause itching, yellow skin, very dark urine, and very light stools
• Neurological disorders, including headache, dizziness, drowsiness, disorientation, hallucinations, and seizures
• Acute and chronic pulmonary reactions with changes in lung tissue observed in X-rays and shortness of breath, as well as fever in acute reactions and dry cough in chronic reactions
• In combination with some HIV medicines: peripheral neuropathy and hepatotoxicity

Uncommon (may affect up to 1 in 100 people)

• Thick and peeling skin rashes (actinic keratosis)
• High levels of bilirubin in the blood

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

• Allergic reactions
• Metabolic disorders due to tumor cell breakdown (tumor lysis syndrome)
• Skin ulcers with severe infection

Very rare (may affect up to 1 in 10,000 people)

• Skin inflammation causing red, peeling spots that may occur with joint pain
• Kidney dysfunction

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

• High levels of potassium in the blood, which can cause irregular heartbeat
• Fever, cough, or difficulty breathing, which may be a sign of severe lung disease, allergic alveolitis
• Hemolytic anemia
• Dry skin

After the medicine has been on the market, cases of low sodium levels in the blood have been observed, which can cause feelings of tiredness, confusion, tremors, seizures, or coma.
During treatment with hydroxyurea, megaloblastic erythropoiesis may occur, which does not respond to treatment with folic acid or vitamin B.
However, bone marrow suppression resolves when treatment is discontinued.
Severe gastrointestinal disturbances (nausea, vomiting, loss of appetite) resulting from combined treatment with hydroxyurea and radiation can usually be alleviated by temporarily discontinuing hydroxyurea.
Hydroxyurea may exacerbate radiation-induced mucositis. This may resemble erythema and discoloration of previously irradiated tissues.
Erythema, skin atrophy, and nail changes, as well as desquamation, have been observed, as have fungal skin changes, radiation keratosis, leg ulcers, vasculitis, itching, skin discoloration, and dryness after years of long-term daily maintenance treatment with hydroxyurea.
Hydroxyurea may decrease serum iron levels and iron utilization by red blood cells. However, this does not affect the lifespan of red blood cells.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C, PL-02-222 Warsaw, tel.: +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.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hydroxyurea medac

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after: Expiry date. The expiry date refers to the last day of the month stated.
Do not store above 25°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Hydroxyurea medac contains

• The active substance is hydroxyurea (Hydroxycarbamidum). One capsule contains 500 mg of hydroxyurea.
• Other ingredients are:
• capsule contents: calcium citrate, disodium citrate, magnesium stearate, lactose monohydrate.
• capsule shell: titanium dioxide (E 171), gelatin.

What Hydroxyurea medac looks like and contents of the pack

White, hard capsules.
The packaging is an aluminum and PVC/PVCD blister pack with a titanium dioxide coating.
Pack sizes: 50 or 100 capsules in a cardboard box.

Marketing authorization holder and manufacturer

medac
Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Phone:
+48 22 43000-30
Fax:
+48 22 43000-31
e-mail: [email protected]

Date of last revision of the leaflet: