Hidroxicarbamid Teva

Package Leaflet: Information for the Patient

Hydroxycarbamid Teva, 500 mg, Capsules

Hydroxycarbamidum

Read the Package Leaflet Carefully Before Taking the Medication, 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 or pharmacist.
• This medication has been prescribed for a specific person. 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, tell your doctor. See section 4.

Table of Contents of the Package Leaflet

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

1. What is Hydroxycarbamid Teva and what is it used for

Hydroxycarbamid Teva contains the active substance hydroxycarbamide, which is an anticancer medication with cytostatic and antimitotic effects. It inhibits the growth of cancer cells and thus the progression of cancer.

Sickle cell anemia is a congenital blood disorder in which red blood cells take on an abnormal sickle shape and become rigid, leading to anemia and blockage of blood vessels, resulting in acute painful episodes and organ damage. The hydroxycarbamide in the medication helps prevent the formation of red blood cells with an abnormal shape, reduces the frequency of acute painful episodes, and the need for hospital treatment due to the disease.

Indications for use:

• Chronic myeloproliferative syndromes, such as:
• Chronic myeloid leukemia (CML);
• True erythrocytosis with a high risk of thromboembolic complications;
• Essential thrombocythemia;
• Myelofibrosis.
• Sickle cell anemia:
• Prevention of painful crises in patients with sickle cell disease, including acute chest syndrome, in adults, adolescents, and children over 2 years of age with a body weight of ≥ 33 kg and symptomatic sickle cell anemia.

2. Important information before taking Hydroxycarbamid Teva

When not to take Hydroxycarbamid Teva

• If you are allergic to hydroxycarbamide or any of the other ingredients of this medication (listed in section 6),
• If you have severe bone marrow suppression; reduced white blood cell count (below 2.5 x 10^9/L), reduced platelet count (below 100 x 10^9/L), or severe anemia,
• In pregnant or breastfeeding women,
• If you have severe liver disease,
• If you have severe kidney disease.

Warnings and precautions

Before starting treatment with Hydroxycarbamid Teva, consult your doctor, pharmacist, or nurse:

• If you have leg ulcers,
• If you are to be vaccinated with certain vaccines.

If you have diabetes and use a continuous glucose monitoring system (CGM) to check your blood glucose levels. Hydroxycarbamide (also known as hydroxyurea) may cause falsely high glucose readings with some sensors. This may lead to the administration of a higher dose of insulin than necessary, resulting in low blood sugar (hypoglycemia). You should discuss with your doctor who prescribed the CGM system whether it can be used safely while taking Hydroxycarbamid Teva.

Before starting treatment and during treatment, your doctor will regularly check the following parameters:

• Blood parameters (morphology, white blood cell count, platelet count, differential count). Hemoglobin concentration, total white blood cell count, and platelet count - at least once a week.
• Kidney function parameters (creatinine concentration, urea concentration, diuresis)
• Blood uric acid concentration
• Liver function parameters.

If hemolytic anemia (a disorder in which red blood cells are destroyed faster than they can be produced) is detected during routine blood tests, your doctor will discontinue treatment with Hydroxycarbamid Teva.

In cases of severe anemia, before starting or during treatment, your doctor may decide to correct it by blood transfusion.

When taking hydroxycarbamide, caution should be exercised in patients who have undergone radiation therapy, previous chemotherapy, patients with kidney tumors, and patients with kidney and/or liver dysfunction (especially at the beginning of treatment).

In patients undergoing long-term treatment with hydroxycarbamide for myeloproliferative disorders, such as true erythrocytosis or essential thrombocythemia, secondary leukemia may develop. The patient should report to the doctor the occurrence of symptoms such as weakness, fever, bone and joint pain, pallor, mucosal ulcers, nosebleeds or gum bleeding. The doctor will then prescribe blood tests.

If you are taking other medications that suppress bone marrow function (other anticancer medications administered simultaneously or previously, reducing the production of red blood cells, white blood cells, or platelets), you should consult your doctor, pharmacist, or nurse.

In patients taking hydroxycarbamide for a long time, cases of malignant skin cancer have been reported. During and after treatment with hydroxycarbamide, you should protect your skin from the sun and regularly self-examine your skin. Additionally, your attending doctor will perform skin examinations during routine check-ups.

You should report any skin changes to your doctor.

You should inform your doctor if you are taking antiretroviral medications (used to treat HIV infection, e.g., didanosine, stavudine, and indinavir). Concurrent use of these medications with hydroxycarbamide may increase toxic effects. Cases of acute pancreatitis, sometimes fatal, liver damage and failure, sometimes fatal, and peripheral neuropathy (in some cases severe) have been reported in HIV patients.

Children and adolescents

Chronic myeloproliferative syndromes

Due to the rare occurrence of these conditions in children, no dosage regimen has been established for this age group.

Sickle cell anemia

The medication is indicated for use in adolescents and children over 2 years of age with a body weight of 33 kg or more (see "Information intended for healthcare professionals only").

Hydroxycarbamid Teva and other medications

Tell your doctor about all medications you are currently taking or have recently taken, as well as any medications you plan to take.

Concomitant administration of hydroxycarbamide with other medications that suppress bone marrow function (other anticancer medications administered simultaneously or previously, reducing the production of red blood cells, white blood cells, or platelets) or radiation therapy may enhance the suppressive effect and increase the risk of immune system damage. In irradiated patients, the symptoms of radiation dermatitis may worsen.

The use of hydroxycarbamide in patients with HIV infection, treated with antiretroviral medications (i.e., medications that inhibit or destroy retroviruses, such as HIV), e.g., didanosine, stavudine, and indinavir, may increase toxic effects. Cases of acute pancreatitis, sometimes fatal, liver damage and failure, sometimes fatal, and peripheral neuropathy have been reported.

Concomitant use of hydroxycarbamide with live virus vaccines may enhance the replication of the vaccine virus and/or increase the adverse effects of the vaccine virus, due to the weakening of normal defense mechanisms as a result of hydroxycarbamide treatment.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before taking this medication.

Women of childbearing age/Contraception in women and men

Women of childbearing age should use effective contraception during treatment with hydroxycarbamide and for 6 months after treatment.

Men are advised to use effective contraception and not to father a child during treatment with hydroxycarbamide and for 3 months after treatment.

Pregnancy

Hydroxycarbamid Teva is contraindicated during pregnancy.

Inform your doctor if you become pregnant or think you may be pregnant while taking Hydroxycarbamid Teva.

Breastfeeding

Hydroxycarbamide passes into human milk, therefore, Hydroxycarbamid Teva is contraindicated during breastfeeding.

Fertility

Patients should be informed about the possibility of preserving sperm in men or ova in women before starting treatment.

Hydroxycarbamide may have a genotoxic effect, therefore, if a patient plans to become pregnant after treatment with hydroxycarbamide, genetic counseling is recommended.

If you plan to have children, consult your doctor to decide whether to continue treatment with Hydroxycarbamid Teva. Patients planning to have children should stop treatment for 3 months (men) or 6 months (women) before possible conception.

Hydroxycarbamid Teva may reduce sperm production in men during treatment and thus may affect fertility. Discuss this with your doctor before starting treatment. Also, if your partner becomes pregnant or plans to become pregnant, discuss this with your doctor.

The doctor will assess the risk-benefit ratio individually, considering the risk associated with hydroxycarbamide treatment versus switching the patient to a blood transfusion program.

Driving and using machines

During treatment with hydroxycarbamide, especially when taking high doses, it is not recommended to drive vehicles or operate machinery, as it may cause dizziness, disorientation, and hallucinations.

Hydroxycarbamid Teva contains E 124 (carmoisine)

The medication may cause allergic reactions.

3. How to take Hydroxycarbamid Teva

Take this medication always exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.

The dosage depends on the type of disease being treated. The doctor determines the dose of the medication based on the patient's current body weight or ideal body weight if the current weight is lower.

Detailed information on the dosage of the medication is provided at the end of the package leaflet, in the section "Information intended for healthcare professionals only".

Use in children and adolescents

Chronic myeloproliferative syndromes

Due to the rare occurrence of these conditions in children, no dosage regimen has been established for this age group.

Sickle cell anemia

The medication is indicated for use in adolescents and children over 2 years of age with a body weight of 33 kg or more (see "Information intended for healthcare professionals only").

Use in elderly patients

Elderly patients often require lower doses due to increased sensitivity to hydroxycarbamide.

Use in patients with kidney and/or liver dysfunction

Chronic myeloproliferative syndromes

There are no data available. There are no dosage recommendations for patients with kidney and/or liver dysfunction.

Sickle cell anemia

Kidney dysfunction

In patients with kidney dysfunction, the doctor should consider reducing the dose of Hydroxycarbamid Teva, as kidney excretion is the main route of elimination of the medication. In this patient population, close monitoring of blood parameters is recommended. Hydroxycarbamid Teva is contraindicated in patients with severe kidney dysfunction (creatinine clearance <30 ml min).< p>

Liver dysfunction

In this patient population, close monitoring of blood parameters is recommended. For safety reasons, Hydroxycarbamid Teva is contraindicated in patients with severe liver dysfunction.

Method of administration

The medication is taken orally.

The capsules should be swallowed whole, without being broken or crushed in the mouth.

Monitoring during treatment for sickle cell anemia

Your doctor will inform you how long you should take Hydroxycarbamid Teva.

During treatment with Hydroxycarbamid Teva, regular blood tests and liver and kidney function tests will be performed. Depending on the dose taken,

these tests may be performed every two weeks or every two months.Your doctor will adjust the dose of Hydroxycarbamid Teva according to the results of these tests.

Your doctor should regularly monitor the development of children treated with Hydroxycarbamid Teva.

Overdose of Hydroxycarbamid Teva

In case of ingestion of a hydroxycarbamide dose several times higher than recommended, acute mucocutaneous symptoms have been observed, such as pain, redness, swelling of the hands and feet, followed by skin peeling, severe generalized hyperpigmentation, and oral mucositis.

In case of overdose, the doctor will perform gastric lavage and then administer supportive treatment and monitor the hematopoietic system.

In case of overdose or accidental ingestion of the medication by a child, seek medical attention immediately, as urgent medical attention may be necessary.

Missed dose of Hydroxycarbamid Teva

Take the missed dose as soon as possible. Do not take a double dose to make up for the missed dose.

If you have any doubts about taking this medication, consult your doctor or pharmacist.

4. Possible side effects

Like all medications, Hydroxycarbamid Teva can cause side effects, although not everybody gets them.

If you experience any of the following, go to the hospital. Medical attention may be necessary:

• Pain that does not go away after taking ordinary painkillers
• High fever (above 38.5°C) without pain
• Vomiting
• Sudden pallor, fatigue, or worsening of general condition, or sudden splenomegaly (your doctor will inform you how to palpate the spleen), in men, unwanted, painful erection lasting more than three hours (priapism)
• Thrombosis of blood vessels affecting the lungs (acute chest syndrome) characterized by chest pain, fever, and difficulty breathing (shortness of breath) or cough. These symptoms may be associated with severe lung disease and may occur in both adults and children. If they occur, seek medical attention immediately.
• Severe infection
• Unexplained bruising (blood accumulation in tissues) or bleeding
• Headache
• Or any other symptoms that may indicate painful crises related to the disease.

Additionally, inform your doctor as soon as possible if you experience any of the following side effects of Hydroxycarbamid Teva:

• Fever or chills
• Nausea, weakness, lack of energy, or general malaise
• Rash (itching, red skin lesions)
• Ulcers or sores on the legs
• Ulcers (open infection) of the skin
• Disorientation (confusion) and dizziness.

At the beginning of treatment, megaloblastic erythropoiesis (production of a certain type of red blood cells) may occur. Hydroxycarbamide may decrease iron levels in the blood.

• Megaloblasts (multinucleated bone marrow cells from which red blood cells are produced in megaloblastic anemia).

There may be an exacerbation of radiation dermatitis caused by previous or concurrent radiation therapy.

During treatment with hydroxycarbamide, blood uric acid levels may increase (risk of developing gout or uric acid nephropathy). You should drink plenty of fluids, and your doctor will prescribe appropriate treatment.

Bone marrow suppression is an adverse effect that requires dose reduction. Adverse reactions from the gastrointestinal tract occur frequently, but rarely require dose reduction or discontinuation of treatment.

Sickle cell anemia

The most commonly reported adverse effect is bone marrow suppression, and the most common symptom is neutropenia. Bone marrow suppression is a toxic effect of hydroxycarbamide, which can be limited by dose reduction.

Gradual dose escalation may help reduce the occurrence of adverse effects.

The following are possible adverse effects of hydroxycarbamide, classified by frequency:

Very common(may occur in more than 1 in 10 patients):

Bone marrow suppression, low white blood cell count, large red blood cells, decreased immunity to infections.

Absence or low sperm count in semen (azoospermia or oligospermia). The medication may therefore limit the ability of men to father children.

Common(may occur in up to 1 in 10 patients):

Decreased white blood cell count, increased megaloblasts (multinucleated bone marrow cells from which red blood cells are produced in megaloblastic anemia), thrombocytopenia, anemia.

Diarrhea, constipation.

Uncommon(may occur in up to 1 in 100 patients):

Nausea, vomiting, loss of appetite, oral mucositis, drug fever, chills, malaise.

Papular rash, facial erythema, palmar-plantar erythrodysesthesia.

Increased liver enzyme activity and bilirubin concentration.

Transient renal tubular dysfunction, accompanied by increased uric acid, urea, and creatinine levels in the blood.

Rare(may occur in up to 1 in 1,000 patients):

Hypersensitivity reactions.

Hair loss.

Acute pulmonary reactions in the form of diffuse pulmonary infiltrates, dyspnea, allergic alveolitis.

Difficult and painful urination.

Headache, dizziness, disorientation, hallucinations.

Very rare(may occur in up to 1 in 10,000 patients):

Skin changes resembling dermatomyositis, hyperpigmentation, or atrophic skin changes and nail changes, skin ulcers (especially leg ulcers), pruritus, hyperkeratosis, skin cancer (squamous cell, basal cell), erythema multiforme, skin peeling, dermatitis causing red, peeling patches that may occur with joint pain.

Kidney dysfunction.

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

Gastrointestinal ulcer, significant decrease in blood magnesium levels, interstitial lung disease, dry skin, amenorrhea, parvovirus B19 infection, bleeding, weight gain, hemolytic anemia.

Isolated cases of malignant blood cancer (leukemia).

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 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 medication.

5. How to store Hydroxycarbamid Teva

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

Do not use this medication after the expiry date stated on the packaging. The expiry date refers to the last day of the month stated.

Store in a temperature below 25°C.

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Hydroxycarbamid Teva contains

• The active substance is hydroxycarbamide. One capsule contains 500 mg of hydroxycarbamide.
• The other ingredients are: potato starch; capsule: gelatin, titanium dioxide (E 171), indigo carmine (E 132), carmoisine (E 124), quinoline yellow (E 104), iron oxide red (E 172).

What Hydroxycarbamid Teva looks like and contents of the pack

The capsules are cylindrical in shape with rounded edges. The capsule cap is green, and the body is light pink.

The pack contains:

100 capsules in a PE bag, heat-sealed, packed with a patient leaflet and silica gel (in a small sachet) in an aluminum box with an aluminum membrane and cap. The silica gel serves as a desiccant to protect the capsules from moisture and should not be ingested.

or

100 capsules in a 250 ml PE bottle with a PP cap, packed with a patient leaflet in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder

Teva Pharmaceuticals Polska Sp. z o.o.

ul. Emilii Plater 53, 00-113 Warsaw

tel.: (22) 345 93 00

Manufacturer

Teva Czech Industries s.r.o.

Ostravská 29, č.p. 305

747 70 Opava-Komárov

Czech Republic

Teva Operations Poland Sp. z o.o.

ul. Mogilska 80

31-546 Kraków

Date of last revision of the package leaflet: October 2024

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Information intended for healthcare professionals only:

Dosage and administration of Hydroxycarbamid Teva

Chronic myeloproliferative syndromes

Chronic myeloid leukemia

Initial treatment with hydroxycarbamide is usually given at a daily dose of 40 mg/kg body weight, depending on the white blood cell count. The dose is reduced by 50% (20 mg/kg body weight per day) when the white blood cell count is less than 20 x 10^9/L. The dose is then adjusted individually to maintain the white blood cell count between 5 and 10 x 10^9/L. The hydroxycarbamide dose should be reduced if the white blood cell count is less than 5 x 10^9/L and increased if the white blood cell count is greater than 10 x 10^9/L.

If the white blood cell count is less than 2.5 x 10^9/L or the platelet count is less than 100 x 10^9/L, treatment should be discontinued until the counts return to near-normal values.

The anticancer effect of hydroxycarbamide is assessed by the doctor after six weeks of treatment. If the disease progresses significantly, treatment is discontinued. If treatment is effective, it can be continued indefinitely.

Essential thrombocythemia

Treatment of essential thrombocythemia usually starts with a dose of 15 mg/kg body weight per day and is adjusted to maintain a platelet count below 600 x 10^9/L and a white blood cell count above 4 x 10^9/L.

True erythrocytosis

Treatment of true erythrocytosis usually starts with a daily dose of 15-20 mg/kg body weight. The doctor adjusts the dose of hydroxycarbamide individually to maintain the hematocrit value below 45% and the platelet count below 400 x 10^9/L. In most patients, the average dose is between 500 mg and 1000 mg per day in continuous therapy.

If the hematocrit value and platelet count can be adequately controlled, treatment should be continued indefinitely.

Myelofibrosis

Treatment usually involves a dose of 5 to 20 mg/kg body weight per day in initial treatment, 10 mg/kg body weight per day in maintenance treatment.

Special populations

Children and adolescents

Due to the rare occurrence of these conditions in children, no dosage regimen has been established for this age group.

Elderly patients

Elderly patients often require lower doses due to increased sensitivity to hydroxycarbamide.

Kidney and/or liver dysfunction

There are no data available. There are no dosage recommendations for patients with kidney and/or liver dysfunction.

Sickle cell anemia

Treatment should be initiated by a doctor with experience in treating sickle cell anemia.

Dosage

Adults, adolescents, and children over 2 years of age

The initial dose of hydroxycarbamide is 15 mg/kg body weight; the standard dose is between 15 and 30 mg/kg body weight per day.

The dose of hydroxycarbamide should be maintained without change as long as the patient responds to treatment clinically or hematologically (e.g., increased fetal hemoglobin concentration [HbF], mean corpuscular volume [MCV], neutrophil count).

If there is no response (recurrence of crises or no reduction in their frequency), the daily dose can be gradually increased by 2.5 to 5 mg/kg body weight per day.

In exceptional circumstances, a maximum dose of 35 mg/kg body weight per day may be justified, provided that close hematological monitoring is performed.

If the patient still does not respond to treatment with the maximum dose of hydroxycarbamide (35 mg/kg body weight per day) within 3-6 months, consideration should be given to permanent discontinuation of the medication.

If the blood count is in the toxic range, hydroxycarbamide should be temporarily discontinued until the blood count returns to normal. Hematological normalization usually occurs within two weeks. Treatment can then be resumed at a lower dose. The dose of hydroxycarbamide can be increased later with close hematological monitoring. It is not recommended to attempt to administer a dose that causes hematological toxicity more than twice.

The toxic range can be characterized by the following blood test results:

Neutrophils <2,000/mm^3

Platelets <80,000/mm^3

Hemoglobin <4.5 g/dL

Reticulocytes <80,000/mm^3, if hemoglobin concentration <9 g dl< p>

For patients with a body weight less than 33 kg, it is possible to start treatment with one of the available hydroxycarbamide medications with a lower strength, registered for use in sickle cell anemia in patients over 2 years of age.

For children who cannot swallow capsules, it is recommended to administer hydroxycarbamide in a different pharmaceutical form.

For adults who have no problems with swallowing, fixed-dose oral pharmaceutical forms may be more suitable and convenient.

Long-term data are available on the long-term use of hydroxycarbamide in patients with sickle cell anemia for children and adolescents; observation was carried out for 12 years in children and adolescents and over 13 years in adults. Currently, it is not known how long patients should be treated with hydroxycarbamide. The duration of treatment is determined by the attending doctor based on the assessment of the patient's clinical and hematological condition.

Special populations

Children under 2 years of age

Due to the limited amount of long-term data on the treatment of children under 2 years of age with hydroxycarbamide, no dosage regimens have been established for this age group, and therefore, hydroxycarbamide is not recommended for use in this population.

Kidney dysfunction

In patients with kidney dysfunction, the doctor should consider reducing the dose of Hydroxycarbamid Teva, as kidney excretion is the main route of elimination of the medication. In this patient population, close monitoring of blood parameters is recommended. Hydroxycarbamid Teva is contraindicated in patients with severe kidney dysfunction (creatinine clearance <30 ml min).< p>

Liver dysfunction

There are no data available indicating a specific dose modification in patients with liver dysfunction. In this patient population, close monitoring of blood parameters is recommended. For safety reasons, Hydroxycarbamid Teva is contraindicated in patients with severe liver dysfunction.

Method of administration

The medication is taken orally.

The dosage depends on the type of disease being treated. The dose of the medication is determined based on the patient's current body weight or ideal body weight if the current weight is lower.

The capsules should be swallowed whole, without being broken or crushed in the mouth.