What is the incidence of adverse effects and leukemia development in patients treated with hydroxyurea (Hydrea)?

From the Guidelines

Hydroxyurea is associated with a low incidence of adverse effects, and the risk of leukemia development is considered acceptable given the benefits of the medication, with regular blood monitoring essential to detect any concerning changes early. The incidence of adverse effects in patients treated with hydroxyurea is not explicitly stated in the provided evidence, but it is mentioned that myelosuppression is a potential adverse effect, and a CBC and reticulocyte count is monitored every 1 to 3 months depending on how long the child has been taking the medication and whether the child has attained a stable dose 1. Some key points to consider when prescribing hydroxyurea include:

• The medication is taken once a day orally and is supplied as a capsule, fast-dissolving tablet, or compounded liquid 1
• Hydroxyurea increases total and fetal hemoglobin and decreases vaso-occlusive complications including episodes of painful events and acute chest syndrome, hospitalizations, and need for transfusion 1
• The National Heart, Lung, and Blood Institute-funded Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) demonstrated that hydroxyurea is of significant benefit presymptomatically to infants with HbSS or Sb0-thalassemia and has no unique adverse effects, even if initiated in early infancy and continued for more than a decade 1
• The 2014 National Heart, Lung, and Blood Institute guidelines for SCD recommend offering hydroxyurea to every child with HbSS or Sb0-thalassemia at 9 months of age even without clinical symptoms 1. Given the benefits of hydroxyurea in reducing the incidence of vaso-occlusive complications and improving health-related quality of life, the risk of adverse effects and leukemia development is considered acceptable, and regular blood monitoring is essential to detect any concerning changes early.

From the FDA Drug Label

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in detail in other labeling sections: Myelosuppression [see Warnings and Precautions (5.1)] Hemolytic anemia [see Warnings and Precautions (5.2)] Malignancies [see Warnings and Precautions (5.3)] Vasculitic toxicities [see Warnings and Precautions (5. 5)] Risks with concomitant use of antiretroviral drugs [see Warnings and Precautions (5.7)] Radiation recall [see Warnings and Precautions (5.8)] Macrocytosis [see Warnings and Precautions (5.9)] Pulmonary Toxicity [see Warnings and Precautions (5.10)] 6. 1 Postmarketing Experience The following adverse reactions have been identified during post-approval use of hydroxyurea capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency isorders: dysuria, elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels Nervous system disorders: headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions General Disorders: fever, chills, malaise, edema, and asthenia Hepatobiliary disorders: elevation of hepatic enzymes, cholestasis, and hepatitis Respiratory disorders: diffuse pulmonary infiltrates, dyspnea, and pulmonary fibrosis, interstitial lung disease, pneumonitis, alveolitis, allergic alveolitis and cough Immune disorders: systemic lupus erythematosus Hypersensitivity: Drug-induced fever (pyrexia) (>39°C, >102°F) requiring hospitalization has been reported concurrently with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological or cardiovascular manifestations Onset typically occurred within 6 weeks of initiation and resolved upon discontinuation of hydroxyurea. Upon re-administration fever re-occurred typically within 24 hours. Blood and lymphatic system disorders: hemolytic anemia Adverse reactions observed with combined hydroxyurea and irradiation therapy are similar to those reported with the use of hydroxyurea or radiation treatment alone These effects primarily include bone marrow depression (anemia and leukopenia), gastric irritation, and mucositis. Almost all patients receiving an adequate course of combined hydroxyurea and irradiation therapy will demonstrate concurrent leukopenia. Platelet depression (<100,000 cells/mm3) has occurred in the presence of marked leukopenia

The incidence of adverse effects in patients treated with hydroxyurea (Hydrea) includes:

• Myelosuppression
• Hemolytic anemia
• Malignancies
• Vasculitic toxicities
• Pulmonary toxicity
• Macrocytosis
• Blood and lymphatic system disorders, such as hemolytic anemia and leukopenia
• Other adverse reactions, including elevations in serum uric acid, headache, dizziness, fever, and hepatobiliary disorders The development of leukemia is not directly stated in the label as an adverse effect of hydroxyurea, but malignancies are mentioned as a possible adverse reaction 2.

From the Research

Incidence of Adverse Effects

• The incidence of adverse effects in patients treated with hydroxyurea (Hydrea) varies across different studies, with reports ranging from 16% to 65.5% of patients experiencing unwanted side effects 3, 4.
• Common adverse effects include dermatologic side effects, such as pigmentation of nails, skin, or mucosa, as well as neurological and gastrointestinal adverse effects 4, 5.
• Hematologic toxicity, including hemolytic anemia, has also been reported in some cases 6.

Leukemia Development

• The risk of leukemia development in patients treated with hydroxyurea is a concern, with some studies reporting an incidence of acute myeloid leukemia of 0.4% persons/year 7.
• Other studies have reported cases of acute leukemia or myelodysplasia in patients treated with hydroxyurea, although the overall incidence is relatively low 3.
• The risk of leukemic transformation may be dependent on factors such as age and follow-up duration 7.

Patient-Specific Factors

• Advancing age has been shown to be positively correlated with the presence of adverse effects during hydroxyurea treatment 5.
• Splenectomized patients may be more likely to experience adverse effects of hydroxyurea 5.
• Previous cardiovascular complications may increase the risk of arterial events in patients treated with hydroxyurea 7.