Hydroxycarbamide

BRAND NAMES

• Hydrea (most widely used global oncology brand) 

• Droxia (used mainly in the United States for sickle cell disease) 

• Siklos (approved in Europe and some other regions; specifically for sickle cell disease)

MECHANISM OF ACTION

Hydroxycarbamide inhibits ribonucleotide reductase, an enzyme required for DNA synthesis, leading to reduced deoxyribonucleotide production and arrest of cells in the S phase of the cell cycle. In sickle cell disease, it also increases fetal hemoglobin (HbF) levels, which reduces hemoglobin S polymerization and decreases red blood cell sickling. Additionally, it may enhance nitric oxide–mediated signaling, contributing to improved blood flow and fewer vaso-occlusive episodes.

PHARMACOKINETICS

Absorption

Hydroxycarbamide is quickly and almost completely absorbed from the gastrointestinal tract after oral intake, resulting in high bioavailability. Peak plasma levels are usually reached within 1–4 hours (often as early as 0.75–2 hours), and the drug distributes widely throughout the body, including crossing the blood–brain barrier.

Distribution

Hydroxycarbamide has a relatively high volume of distribution (Vd), approximately 0.5–0.9 L/kg, indicating wide distribution into body tissues beyond the vascular compartment. It readily penetrates tissues, including bone marrow, where it exerts its primary pharmacologic effect.

Metabolism

Hydroxycarbamide (Hydroxyurea) undergoes minimal metabolism, with a small amount processed in the liver to urea and carbon dioxide. Most of the drug is excreted unchanged by the kidneys, making renal function important for its elimination.

Elimination

Hydroxycarbamide (Hydroxyurea) occurs mainly through the kidneys, with about 40–60% of the drug excreted unchanged in urine. A small portion is eliminated as metabolites like urea and carbon dioxide, the latter being exhaled via the lungs. Its short half-life means it is cleared relatively quickly from the body.

PHARMACODYNAMICS

Hydroxycarbamide (Hydroxyurea) acts by inhibiting Ribonucleotide Reductase, an enzyme required for DNA synthesis. This reduces the production of DNA, particularly in rapidly dividing cells, leading to decreased cell proliferation. It also increases fetal hemoglobin levels, which is beneficial in conditions like Sickle Cell Disease.

ADMINISTRATION
It is usually administered orally in the form of capsules or tablets and can be taken once daily. The dose is individualized based on body weight, disease condition, and blood counts. Regular monitoring is required to adjust the dose and avoid toxicity, especially bone marrow suppression.

DOSAGE AND STRENGTH
It is available in capsule strengths such as 500 mg (most common) and sometimes 200 mg or 100 mg in certain formulations. The dosage varies by indication; in adults it is often started around 15–20 mg/kg/day orallyand adjusted based on blood counts and response. In conditions like Sickle Cell Disease, the dose may be gradually increased to a maximum tolerated dose while monitoring for bone marrow suppression.

DRUG INTERACTIONS

Hydroxycarbamide (Hydroxyurea) can interact with other drugs that suppress bone marrow, such as chemotherapy agents or radiation therapy, increasing the risk of low blood counts. It should be used cautiously with other myelosuppressive medicines, with regular monitoring of blood parameters.

FOOD INTERACTIONS

Hydroxycarbamide (Hydroxyurea) has no significant food interactions, so it can be taken with or without food. However, taking it with food may help reduce stomach upset in some patients. It is important to maintain good hydration and follow regular dosing timing for best effect.

CONTRAINDICATIONS

Hydroxycarbamide (Hydroxyurea) is contraindicated in patients with hypersensitivity to the drug, severe bone marrow suppression, and during pregnancy due to risk of fetal harm. It should be used cautiously in patients with significant renal or hepatic impairment.

SIDE EFFECTS

• Bone marrow suppression (leukopenia, thrombocytopenia, anemia) 

• Nausea and vomiting 

• Diarrhea 

• Loss of appetite 

• Skin hyperpigmentation 

OVER DOSE

• Severe bone marrow suppression 

• Leukopenia 

• Anemia 

• Thrombocytopenia 

TOXICITY

Hydroxycarbamide (Hydroxyurea) toxicity is mainly characterized by dose-dependent bone marrow suppression, leading to leukopenia, anemia, and thrombocytopenia. Other toxic effects include gastrointestinal symptoms like nausea, vomiting, and diarrhea, as well as mucositis and skin changes. Rarely, it may cause liver and kidney toxicity and increase the risk of infections.