Hydroxyurea (HU) is an oral antimetabolite medication, often classified as a chemotherapy agent. It is primarily used to treat myeloproliferative disorders, such as polycythemia vera and chronic myelogenous leukemia. The drug works by inhibiting the enzyme ribonucleotide reductase, which slows DNA synthesis and cell growth. For patients with Sickle Cell Disease (SCD), hydroxyurea is a standard treatment that helps reduce painful crises and the need for blood transfusions by increasing fetal hemoglobin production.
The Most Common Side Effect: Bone Marrow Suppression
The most frequent and dose-limiting side effect of hydroxyurea is myelosuppression, also known as bone marrow suppression. This is a direct consequence of the drug’s mechanism, as it temporarily reduces the bone marrow’s ability to produce new blood cells, including red blood cells, white blood cells, and platelets. This effect is common and significant enough to be cited as the drug’s most serious warning.
Myelosuppression manifests in three distinct ways. A decrease in red blood cell production causes anemia, resulting in symptoms like paleness, fatigue, and weakness. A reduction in white blood cells leads to neutropenia, which impairs the immune system and raises the risk of severe bacterial and fungal infections. Neutropenia is often considered the most common hematologic toxicity and poses the greatest immediate risk.
The third component is thrombocytopenia, a drop in platelets, which are responsible for blood clotting. Low platelet counts can cause easy bruising, unusual bleeding, nosebleeds, and pinpoint red spots on the skin. These toxic effects are generally reversible; blood counts usually recover after the medication is temporarily stopped or the dosage is reduced.
Other Frequently Observed Side Effects
Beyond the effects on blood cell production, patients frequently experience non-hematologic side effects, often involving the digestive system. Gastrointestinal issues are commonly reported, including nausea, vomiting, diarrhea, or constipation. Some individuals may also experience a loss of appetite.
Other common effects are noticeable on the skin and hair. Patients may develop changes in skin pigmentation, such as darkening, and alterations to the fingernails and toenails. Hair thinning or hair loss is also a reported side effect. Headaches and general fatigue, distinct from the fatigue caused by anemia, are commonly noted during treatment.
Severe or Urgent Adverse Reactions
While myelosuppression is the most common severe side effect, other adverse reactions require immediate attention. Severe fever and chills can signal an overwhelming infection, often resulting from neutropenia, which necessitates urgent medical evaluation. Patients should be aware that painful and persistent skin ulcers, especially on the legs, are a serious, though uncommon, form of vasculitic toxicity associated with long-term use.
A serious long-term concern is the rare risk of secondary malignancies, including skin cancer. Patients taking the medication for many years should be vigilant for any new or changing skin lesions. Pulmonary toxicity, such as interstitial lung disease or pneumonitis, is an uncommon but life-threatening complication. This toxicity can present with symptoms like a new or worsening cough, fever, and shortness of breath.
Monitoring and Mitigation Strategies
Careful monitoring is built into the treatment plan because bone marrow suppression is the most common serious side effect. Patients taking hydroxyurea must undergo regular blood tests, specifically a Complete Blood Count (CBC), to track all blood cell types. These tests, typically performed every one to three months, allow the healthcare team to detect low counts before severe complications arise.
If blood counts fall below target ranges, the dosage will be adjusted or the medication may be temporarily stopped for recovery. To mitigate the risk of skin cancer and severe skin reactions, patients must limit sun exposure and consistently use protective clothing and sunscreen. Maintaining excellent hygiene and avoiding sick individuals is also recommended to lower the risk of infection when white blood cell counts are low.