Hydroxyurea is a medication used primarily to treat sickle cell disease and certain blood cancers. It works by slowing down cell production in the bone marrow, which makes it useful for conditions where the body produces too many blood cells or where changing the type of hemoglobin in red blood cells can prevent serious complications. The FDA has approved it for sickle cell disease in both adults and children aged 2 and older, as well as for several types of cancer affecting the blood and bone marrow.
Sickle Cell Disease
Sickle cell disease is the most well-known use for hydroxyurea, and it’s been transformative for people living with this condition. The drug reduces the frequency of pain crises, those episodes of intense pain caused by sickle-shaped red blood cells blocking small blood vessels. In the landmark Multicenter Study of Hydroxyurea, patients taking the drug experienced roughly half the number of pain crises compared to those on a placebo. Hospitalizations due to sickle cell crises dropped by more than half as well.
The way hydroxyurea helps in sickle cell disease is different from its role in cancer. It boosts the production of fetal hemoglobin, a type of hemoglobin that babies produce before birth but that normally drops to very low levels in the first year of life. Fetal hemoglobin prevents red blood cells from sickling. With optimized dosing, fetal hemoglobin levels typically reach 20 to 30 percent of total hemoglobin, and in some patients, particularly young children on well-managed doses, levels above 30 percent are regularly achieved. At those levels, 80 to 90 percent of red blood cells carry enough fetal hemoglobin to resist sickling.
The FDA first approved hydroxyurea for pediatric sickle cell patients (ages 2 and up) in December 2017, making it the first drug specifically approved for children with sickle cell anemia. It had already been in widespread use for adults with the disease for years before that.
Polycythemia Vera and Essential Thrombocythemia
Hydroxyurea is a standard treatment for myeloproliferative neoplasms, a group of conditions where the bone marrow overproduces blood cells. The two most common are polycythemia vera, where the body makes too many red blood cells, and essential thrombocythemia, where platelet counts climb dangerously high. Both conditions raise the risk of blood clots, strokes, and heart attacks.
In polycythemia vera, the goal is to keep the hematocrit (the percentage of blood volume made up of red blood cells) below 45 percent. Hydroxyurea suppresses the bone marrow’s overproduction to bring that number down and keep it stable. Beyond simply lowering cell counts, the drug appears to reduce clotting risk through additional mechanisms: it changes how white blood cells behave, reduces the stickiness of blood vessel walls, and increases nitric oxide, a molecule that helps keep blood vessels relaxed and open. For essential thrombocythemia, the same basic approach applies, with the drug bringing elevated platelet counts into a safer range.
Chronic Myeloid Leukemia
In chronic myeloid leukemia (CML), hydroxyurea plays a more limited but sometimes critical role. It is not the primary long-term treatment for CML, as targeted therapies have largely taken over that role. However, hydroxyurea is used to quickly bring down dangerously high white blood cell counts, a situation called hyperleukocytosis that can cause organ damage if not addressed rapidly. It’s also used as palliative therapy for patients who haven’t responded to other treatments. In the chronic phase of CML, it has been shown to provide significantly longer survival and fewer severe side effects compared to older chemotherapy options.
How Hydroxyurea Works
Hydroxyurea slows cell production by interfering with DNA replication. Its primary target is an enzyme called ribonucleotide reductase, which cells need to build the raw materials for new DNA. By disabling this enzyme, the drug starves dividing cells of the building blocks they need to copy their genetic material.
Research published in PNAS has identified a second mechanism: the drug also generates reactive oxygen species inside the cell nucleus. These molecules damage the machinery that copies DNA (called polymerases), causing it to fall apart and lose its ability to attach to DNA strands. This dual action helps explain why hydroxyurea is effective at slowing down rapidly dividing cells in the bone marrow.
Dosing and How It’s Taken
Hydroxyurea is taken as an oral tablet or capsule, once daily. For sickle cell disease, the starting dose is typically 15 mg/kg per day for adults and 20 mg/kg per day for children. The dose is gradually increased every eight weeks (or sooner if a severe pain crisis occurs) by 5 mg/kg per day, up to a maximum of 35 mg/kg per day. The target is to find the dose that produces mild suppression of certain white blood cell counts without dropping them too low. For patients with kidney disease, the starting dose is lower.
In polycythemia vera and CML, dosing follows a similar weight-based approach but is adjusted based on different blood count targets. In CML, higher initial doses are sometimes used to rapidly reduce white blood cell counts, then tapered once levels stabilize.
Side Effects and Monitoring
Because hydroxyurea suppresses the bone marrow, the most important side effect to watch for is a drop in blood cell counts. White blood cells, red blood cells, and platelets can all decrease, which raises the risk of infection, anemia, and bleeding. Regular blood count monitoring is essential throughout treatment, with adjustments made if counts fall below safe thresholds.
Other common side effects include skin darkening (especially on the nails and skin folds), mouth sores, nausea, and hair thinning. Some people develop leg ulcers with long-term use. Most of these effects are reversible once the dose is adjusted or the drug is stopped.
Hydroxyurea can harm a developing fetus. Women of reproductive age should use effective contraception during treatment and for at least six months after stopping the drug. Men with partners who could become pregnant should use contraception during treatment and for at least one year afterward.
Less Common Uses
Hydroxyurea is occasionally used off-label for conditions beyond its FDA-approved indications. One example is severe psoriasis in people living with HIV, where standard immune-suppressing psoriasis treatments may be too risky. In these cases, hydroxyurea can be considered for treatment-resistant skin disease. These uses are less well-studied and are typically reserved for situations where other options have failed.