From the Guidelines
Hydroxyurea is associated with several side effects, including bone marrow suppression, gastrointestinal issues, skin problems, and fatigue, as reported in the most recent study 1.
Common Side Effects
The most frequent side effects of hydroxyurea include:
- Bone marrow suppression (resulting in low blood counts)
- Gastrointestinal issues (nausea, vomiting, diarrhea, and loss of appetite)
- Skin problems (rash, hyperpigmentation, and nail changes)
- Fatigue These side effects are well-documented in the literature, with studies such as 1 and 1 providing evidence of their occurrence.
Serious Side Effects
More serious but less common side effects of hydroxyurea include:
- Severe anemia
- Increased risk of infections due to neutropenia
- Bleeding from thrombocytopenia
- Mouth sores
- Skin ulcers
- Hair loss Long-term use of hydroxyurea may also potentially increase the risk of skin cancers and secondary leukemias, as noted in 1.
Monitoring and Management
Patients taking hydroxyurea require regular blood count monitoring, typically every 2-4 weeks initially and then every 2-3 months once on a stable dose, as recommended in 1 and 1. Hydroxyurea works by inhibiting DNA synthesis, which explains why rapidly dividing cells like blood cells, skin cells, and gastrointestinal mucosa are most affected. Patients should report unusual bleeding, signs of infection, skin changes, or severe gastrointestinal symptoms to their healthcare provider immediately. Adequate hydration and avoiding sun exposure can help manage some side effects, as suggested in 1.
From the FDA Drug Label
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 Hydroxyurea capsules may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.
Common side effects of hydroxyurea include:
- Myelosuppression
- Hemolytic anemia
- Malignancies
- Vasculitic toxicities
- Macrocytosis
- Pulmonary toxicity
- 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 reactions (drug-induced fever) 2 2 2
From the Research
Hydroxyurea Side Effects
- The side effects of hydroxyurea have been reported in several studies, including a retrospective cohort study of 152 patients with myeloproliferative disorders, where 16 patients had to withdraw from therapy due to unwanted side effects 3.
- Common side effects of hydroxyurea include myelosuppression, skin toxicities, mild gastrointestinal toxicity, and abnormalities of renal and liver functions 4.
- In patients with sickle cell anemia, hydroxyurea has been shown to be generally well-tolerated, with no instances of alarming toxicity reported in a clinical trial of 299 patients 5.
- However, some patients may experience leg painful ulcers, fever reactions, allergic reactions, or nail pigmentation while taking hydroxyurea 3.
- The risk of acute leukemia or myelodysplasia has also been reported in some patients taking hydroxyurea, although this is rare 3.
- In patients with HIV infection, hydroxyurea has been shown to be effective in combination with other antiretroviral agents, but may increase the risk of pancreatitis and neuropathy when combined with certain nucleoside analogues 4.
- A low dose of hydroxyurea (600 mg daily) has been shown to be well-tolerated and effective in achieving antiretroviral activity, with fewer adverse effects than higher doses 4.
Management of Side Effects
- Prompt recognition of side effects is crucial to avoid more severe complications, and patients should be monitored closely while taking hydroxyurea 3.
- Dose adjustments or withdrawal of therapy may be necessary in some cases to manage side effects 3.
- The use of hydroxyurea in combination with other agents, such as didanosine, should be carefully monitored to minimize the risk of adverse effects 4.