From the Guidelines
Hydroxyurea is associated with several side effects, most notably bone marrow suppression, which can lead to low blood counts, and this is a critical consideration for patients starting treatment. The most frequent side effects of hydroxyurea include bone marrow suppression, gastrointestinal issues, skin problems, and fatigue 1. More serious but less common side effects include severe anemia, increased risk of infections due to low white blood cell counts, bleeding from low platelets, skin ulcers, and secondary malignancies with long-term use. Patients may also experience headaches, dizziness, and hair loss.
Key Side Effects
- 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
Management of Side Effects
Regular blood tests are essential during treatment to monitor blood counts, and patients should report any unusual symptoms to their healthcare provider immediately 1. Staying well-hydrated and taking the medication at the same time each day can help manage some side effects.
Monitoring and Dose Adjustment
A CBC and reticulocyte count should be 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. If side effects occur, the dose of hydroxyurea may need to be adjusted to minimize adverse effects while still achieving therapeutic benefits.
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.
The side effects of hydroxyurea include:
- Myelosuppression
- Hemolytic anemia
- Malignancies
- Vasculitic toxicities
- Risks with concomitant use of antiretroviral drugs
- Radiation recall
- Macrocytosis
- Pulmonary Toxicity
- Dysuria
- Elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels
- Headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions
- Fever, chills, malaise, edema, and asthenia
- Elevation of hepatic enzymes, cholestasis, and hepatitis
- Diffuse pulmonary infiltrates, dyspnea, and pulmonary fibrosis, interstitial lung disease, pneumonitis, alveolitis, allergic alveolitis and cough
- Systemic lupus erythematosus
- Drug-induced fever (pyrexia)
- Hemolytic anemia
- Bone marrow depression (anemia and leukopenia)
- Gastric irritation, and mucositis
- Platelet depression 2
From the Research
Hydroxyurea Side Effects
- Neutropenia, bone marrow suppression, elevation of hepatic enzymes, anorexia, nausea, vomiting, and infertility are common side effects of hydroxyurea 3
- Hydroxyurea can cause pancytopaenia secondary to bone marrow suppression, which is reversible with short-term discontinuation of the therapy 4
- In patients with sickle cell anaemia complicated by chronic kidney disease (CKD), the bone marrow suppressive effects caused by hydroxyurea could be easily potentiated 4
- Other side effects of hydroxyurea include symptomatic macrocytic anemia, fever reactions, allergic reactions, leg painful ulcers, acute leukemia or myelodysplasia, and nail pigmentation 5
- The optimal induction of HbF depends upon selection and maintenance of the proper dose that maximizes benefits and minimizes toxicity, and individualized dosing models can help optimize the hydroxyurea dose and clinical response 6
Specific Side Effects
- Neutropenia: hydroxyurea probably decreases neutrophil counts 7
- Bone marrow suppression: hydroxyurea can cause pancytopaenia secondary to bone marrow suppression 4
- Elevation of hepatic enzymes: one of the common side effects of hydroxyurea 3
- Anorexia, nausea, vomiting: common side effects of hydroxyurea 3
- Infertility: one of the common side effects of hydroxyurea 3
Patient-Specific Side Effects
- Patients with sickle cell anaemia complicated by chronic kidney disease (CKD) may experience potentiated bone marrow suppressive effects caused by hydroxyurea 4
- Patients with myeloproliferative disorders (MPD) may experience side effects such as symptomatic macrocytic anemia, fever reactions, allergic reactions, leg painful ulcers, acute leukemia or myelodysplasia, and nail pigmentation 5