Hydroxyurea is a potent antimetabolite and ribonucleotide reductase inhibitor, classified as an antineoplastic and antiretroviral agent. It is a cornerstone in the management of chronic myelogenous leukemia (CML), essential thrombocythemia, polycythemia vera, and sickle cell disease (SCD). In the Indian context, it is a critical, cost-effective option for myeloproliferative neoplasms and for reducing the frequency of painful crises and need for blood transfusions in SCD. It works by inhibiting DNA synthesis without affecting RNA or protein synthesis.
Adult: Varies by indication. CML/Polycythemia Vera/Thrombocythemia: Initial: 15-20 mg/kg/day as a single dose or divided. Adjust based on blood counts. Sickle Cell Disease: Initial: 15 mg/kg/day as a single dose. May increase by 5 mg/kg/day every 12 weeks to a max of 35 mg/kg/day based on hematological response and toxicity.
Note: Administer orally, once daily. Capsules should be swallowed whole with a glass of water. Can be taken with or without food. If patient cannot swallow capsules, contents may be emptied into a small amount of water and consumed immediately (avoid inhalation of powder). Do not crush or chew capsules. Handle with care; caregivers should avoid direct contact with powder/capsule contents.
Hydroxyurea is a synthetic, non-alkylating antimetabolite. Its primary mechanism is the inhibition of the enzyme ribonucleotide reductase. This enzyme is crucial for the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), the building blocks of DNA. By depleting intracellular pools of deoxyribonucleotides, particularly deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), hydroxyurea selectively inhibits DNA synthesis in the S-phase of the cell cycle. It does not interfere with RNA or protein synthesis.
Pregnancy: Category D (US FDA). CONTRANDICATED. Teratogenic and embryotoxic in animals. Can cause fetal harm. Women of childbearing potential must use effective contraception during and for at least 6 months after therapy. Men should use contraception during and for at least 6 months after therapy due to risk of genotoxicity in sperm.
Driving: May cause drowsiness, dizziness, or confusion. Patients should be cautioned about operating machinery or driving until they know how the drug affects them.
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever) | Increased risk of vaccine-induced infection due to immunosuppression. | Major |
| Other Myelosuppressive Agents (e.g., Azathioprine, Clozapine, Ganciclovir, Zidovudine) | Additive bone marrow toxicity. Increased risk of severe leukopenia/pancytopenia. | Major |
| Didanosine (ddI) + Stavudine (d4T) | Increased risk of pancreatitis, peripheral neuropathy, and fatal lactic acidosis in HIV patients. | Major |
| Antiretroviral Drugs (e.g., Zidovudine) | May have synergistic antiviral activity but also synergistic hematologic toxicity. | Moderate |
| Interferon-alpha | Increased risk of cutaneous vasculitic ulcers. | Moderate |
| Lithium | May enhance the neutropenic effect of Hydroxyurea. | Moderate |
| 5-Fluorouracil (5-FU) | Hydroxyurea may enhance the toxicity of 5-FU. | Moderate |
Same composition (Hydroxyurea (500mg)), different brands: