Hydroxycarbamide

Hydroxycarbamide (Hydroxyurea, hydroxyurea) is a medication that is used to treat several diseases, including cancer and hematologic conditions.

The main indications for the use of hydroxycarbamide include:

1. Chronic myeloid leukemia (CML): Hydroxycarbamide may be used in the treatment of chronic myeloid leukemia along with other anticancer drugs.
2. Hoffmann's disease: This is a genetic disorder characterized by hyperplasia of red blood cells. Hydroxycarbamide can be used to reduce red blood cell hyperplasia and reduce the risk of thrombosis.
3. Spinal cyst (Meningioma): Hydroxycarbamide may be used to reduce tumor size or decrease tumor growth in patients with brain tumors.
4. True polycythemia: Hydroxycarbamide may be used to reduce the number of red blood cells in patients with true polycythemia.

The action of hydroxycarbamide is based on its ability to inhibit DNA synthesis, which helps to slow down the growth and reproduction of abnormal cells. It is important to note that hydroxycarbamide should be administered under medical supervision, as it can cause various side effects, including myelosuppression (reduction in the number of blood cells), skin ulcers, nausea, vomiting and others.

Indications Hydroxycarbamide

Hydroxycarbamide, also known as hydroxyurea, has a variety of medical indications, including the following:

1. Chronic myeloid leukemia (CML): Hydroxycarbamide may be prescribed as drug therapy for patients with chronic myeloid leukemia to reduce the number of abnormal cells in the blood and improve the patient's condition.
2. Spinal cyst (Meningioma): The drug is used to treat spinal cysts, as monotherapy or in combination with other drugs or treatments.
3. True polycythemia: This drug may be used to reduce the number of red blood cells in the blood in patients with itin polycythemia.
4. Gout: Hydroxycarbamide can sometimes be used to treat gout, especially when other treatments have not been effective enough.
5. Chronic myelomonocytic leukemia (CMML): Hydroxycarbamide may also be used in the treatment of this rare type of leukemia.

In addition, hydroxycarbamide may be used as a preventive measure to reduce the risk of thrombosis in high-risk patients.

Release form

Hydroxycarbamide (hydroxyurea) is usually available in the following dosage forms:

1. Tablets: Hydroxycarbamide may be available in the form of oral tablets. Tablets usually contain a specific dosage of the active ingredient and may be taken one or more times a day, depending on your doctor's instructions.
2. Capsules: Sometimes hydroxycarbamide is manufactured as capsules containing powder for oral administration. Like tablets, capsules usually have a specific dosage and are taken according to your doctor's instructions.
3. Solution: In some cases, hydroxycarbamide may be available as an oral solution. This is usually used when a more precise dosage is needed or when patients have difficulty taking solid forms of the medication.
4. Powder: Some forms of hydroxycarbamide may be presented as a powder that can be diluted in liquid for ingestion.

The dosage form of hydroxycarbamide may vary depending on the manufacturer, country, and individual patient needs. Dosage and recommendations for use may also vary depending on the specific medical condition and physician's instructions.

Pharmacodynamics

Here are the main pharmacodynamic aspects of hydroxycarbamide:

1. Ribonucleotide reductase inhibition: Hydroxycarbamide is an inhibitor of ribonucleotide reductase, an enzyme that plays a key role in the synthesis of deoxyribonucleoside triphosphates (dNTPs) from nucleoside triphosphates (NTPs). This process is essential for the availability of nucleotides for DNA synthesis. Suppression of ribonucleotide reductase activity by hydroxycarbamide leads to a decrease in the level of dNTPs, which may have an inhibitory effect on DNA synthesis.
2. Stimulation of cell differentiation: Some studies suggest that hydroxycarbamide may contribute to the induction of tumor cell differentiation. This may be due to its ability to affect the cell cycle and regulation of gene expression.
3. Anti-angiogenic effects: Some studies have also noted the anti-angiogenic effects of hydroxycarbamide, that is, its ability to inhibit the formation of new blood vessels, which is important for tumor development.
4. Immunomodulatory action: Some evidence suggests that hydroxycarbamide may affect the immune system by altering the activity of immunocompetent cells.
5. Anti-inflammatory effects: Hydroxycarbamide also exhibits anti-inflammatory effects, which may be helpful in some inflammatory conditions.

The common result of these pharmacodynamic effects is the inhibition of tumor cell growth and development, making hydroxycarbamide a valuable tool in the treatment of various cancers.

Pharmacokinetics

The main aspects of the pharmacokinetics of hydroxycarbamide are summarized below:

1. Absorption: After oral administration hydroxycarbamide is rapidly and completely absorbed from the gastrointestinal tract.
2. Distribution: Hydroxycarbamide is distributed throughout the tissues of the body. It penetrates the blood-brain barrier and the placental barrier.
3. Metabolism: Hydroxycarbamide undergoes metabolic transformations in the liver. The main metabolite is urea, which can also be formed in other tissues.
4. Excretion: Hydroxycarbamide and its metabolites are excreted mainly through the kidneys. A small part of the drug is excreted with bile.
5. Excretionhalf-life: The half-life of hydroxycarbamide from the body is approximately 3-4 hours. This means that about 3-4 hours after administration half of the drug dose is excreted from the body.
6. DoseKinetics: The dosekinetics of hydroxycarbamide are linear at standard doses.
7. Nutritional effects: Food may affect the rate and completeness of absorption of hydroxycarbamide, therefore it is recommended to take the drug on an empty stomach or 1-2 hours before a meal.
8. Factors of influence: The pharmacokinetics of hydroxycarbamide may be altered in patients with impaired renal or hepatic function and in patients with varying degrees of hypoxia.

Taking into account the pharmacokinetic features of hydroxycarbamide allows physicians to adjust the dosage and frequency of drug administration to achieve optimal therapeutic effect with minimal risk of side effects.

Dosing and administration

Dosage and regimen may vary depending on the specific disease, its severity and individual characteristics of the patient. Here are the general recommendations:

1. True polycythemia syndrome (TPS):

   • The usual starting dosage for adults is 500 to 2000 mg of hydroxycarbamide per day taken orally.
   • The dose can be individualized depending on the hematocrit level and other blood parameters.
   • In children, the dosage is determined according to their weight and health status, usually starting with a lower dose.

2. Chronic myeloid leukemia (CML):

   • For adults, it is generally recommended to start with an oral dose of 500 to 1500 mg per day.
   • The dosage may be adjusted depending on the response to treatment and tolerability of the drug.
   • In children, the dosage may also vary depending on their weight and health status.

3. Application:

   • Hydroxycarbamide is usually taken in tablet form orally, 1-2 hours before meals.
   • Hydroxycarbamide tablets should be swallowed whole, drinking enough water.

4. Duration of treatment:

   • The duration of treatment is determined by the physician depending on the characteristics of the disease and response to treatment.
   • Treatment can be lengthy, sometimes requiring you to take hydroxycarbamide for many years.

Use Hydroxycarbamide during pregnancy

The drug is FDA Category D for use during pregnancy, which means that there is evidence of risk to the fetus, but the benefits of the drug may justify its use in certain cases.

The use of hydroxycarbamide during pregnancy may be considered in the following cases:

1. Need for treatment of maternal cancer: If a woman is pregnant and suffers from cancer that requires treatment with hydroxycarbamide, the decision to use the drug should be made after careful assessment of risks and benefits to the mother and fetus.

2. Need for platelet and red blood cell control: Hydroxycarbamide may be used to reduce platelet and red blood cell counts in pregnant women with certain hematologic disorders such as polycythemia vera or thrombocythemia.

3. Sickle cell disease: In patients with sickle cell disease, hydroxycarbamide may be prescribed to reduce the risk of crises during pregnancy.

It is important to note that the decision to use hydroxycarbamide during pregnancy should be individualized and based on discussion with a medical specialist. A woman and her doctor should together assess the risks and benefits of the drug in each specific case, taking into account the mother's condition, stage of pregnancy and specific features of her disease.

Contraindications

Here are the main contraindications to the use of hydroxycarbamide:

1. Allergic reaction: People with a known allergy to hydroxycarbamide or other components of the drug should not use it.
2. Severe impairment of bone marrow function: Hydroxycarbamide may depress bone marrow, therefore its use may be undesirable in patients with severe disorders of hematopoiesis, such as aplastic anemia.
3. Pregnancy and lactation: The use of hydroxycarbamide during pregnancy or lactation may be contraindicated due to potential effects on the fetus or child.
4. Severe hepatic or renal impairment: Patients with severe hepatic or renal impairment may experience worsening of the condition when using hydroxycarbamide.
5. History of heart disease: In patients with a history of heart disease or acute heart failure, hydroxycarbamide may worsen the condition.
6. Severe bleeding disorders: In bleeding disorders such as thrombosis or embolism, the use of hydroxycarbamide may be contraindicated.
7. Severe anemia: Hydroxycarbamide may worsen anemia, which may be dangerous in patients with pre-existing severe anemia.

Before starting hydroxycarbamide or any other medication, it is important to consult your doctor and discuss any existing medical contraindications and the benefits and risks of the treatment.

Side effects Hydroxycarbamide

Here are some of the possible side effects associated with its use:

1. Hematological disorders: Hydroxycarbamide may cause a decrease in the number of white blood cells, red blood cells and platelets in the blood, which may lead to leukopenia, anemia and thrombocytopenia.
2. Hepatotoxicity: Changes in the levels of liver enzymes such as aminotransferases and alkaline phosphatase may be observed in some patients, which may indicate liver damage.
3. Gastrointestinal Disorders: Side effects may include nausea, vomiting, diarrhea, anorexia, and abdominal discomfort.
4. Skin reactions: Rash, itching, skin dryness, skin irritation or redness may occur.
5. Myelosuppression: Hydroxycarbamide may suppress bone marrow, which may result in decreased hematopoietic cell formation and increased risk of infections and bleeding.
6. Fatigueand weakness: Some patients may experience fatigue and weakness as a side effect of the drug.
7. Neurologic symptoms: May include headache, dizziness, drowsiness or irritability.
8. Possible effects on reproductive function: Women taking hydroxycarbamide may experience decreased reproductive function.
9. Hair loss: Some patients may experience hair loss.
10. Cardiotoxicity: Rarely, cardiotoxicity may occur, manifested by abnormal heart rhythm or other cardiac problems.

These side effects may occur in varying degrees of severity from patient to patient.