Hydroxyurea

Hydroxyurea or hydroxycarbamide (the latter being the antineoplastic drug used in hematological malignancies. It is also used as an antiretroviral agent (e.g., against HIV).

Mechanism

Its mechanism of action is believed to be based on its inhibition of the enzyme ribonucleotide reductase by scavenging tyrosyl free radicals^[1] as they are involved in the reduction NDPs.^[2]

Uses

• Polycythemia vera
• Chronic myelogenous leukemia
• Essential thrombocytosis
• Sickle-cell disease (breaks down cells that are prone to sickle, as well as increasing fetal hemoglobin content)
• AIDS as an adjunct to ddI in combination antiretroviral therapies
• Biochemical research as a DNA replication inhibitor that causes ribonucleotide depletion and results in DNA double strand breaks near replication forks (see DNA repair)
• Moderate to severe psoriasis (slows down the rapid division of skin cells)

Dose

500 milligrams once or twice a day, or more if pancytopenia does not develop.

Side effects

Reported side-effects are: drowsiness, nausea, vomiting and diarrhea, constipation, mucositis, anorexia, stomatitis, bone marrow toxicity (which may take 7-21 days to recover after the drug has been discontinued), alopecia (hair loss), skin changes, abnormal blood urea nitrogen.

Due to its effect on the bone marrow, regular monitoring of the liver enzymes, are commonly checked.

Use in pregnancy

Category D - investigational or post-marketing data show risk to the fetus. However, potential benefits may outweigh the potential risk. Generally this rating is reserved for drugs with no safer alternatives.

Contraindications

Contraindications are: severe anemia, bone marrow depression or neutropenia.

References

1. ^ http://www.medscape.com/viewarticle/408266_8
2. ^ http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.3503