Hydroxyurea

# Hydroxyurea ## Overview - **Classification**: Antineoplastic agent, Antimetabolite - **Mechanism**: Inhibits ribonucleotide reductase, preventing DNA synthesis and causing cell cycle arrest in S phase, leading to cell death. ## Primary Indications 1. **Sickle Cell Disease (SCD)** - To reduce frequency of painful crises and need for blood transfusions in adults and pediatric patients. 2. **Chronic Myelogenous Leukemia (CML)** - For treatment of resistant, recurrent, or advanced CML. 3. **Essential Thrombocythemia (ET)** - To reduce platelet counts and risk of thrombotic events. 4. **Polycythemia Vera (PV)** - To reduce red blood cell mass and platelet counts. ## Adult Dosing ### Standard Dosing **Sickle Cell Disease** - **Dose**: Initial **15 mg/kg** - **Frequency**: Once daily - **Route**: Oral - **Duration**: Chronic. Titrate by **5 mg/kg/day** every 8-12 weeks to desired effect (e.g., increase in fetal hemoglobin, reduction in crises) or myelotoxicity. - **Maximum Dose**: Typically **35 mg/kg/day** or up to **2500 mg/day**. **Chronic Myelogenous Leukemia (CML)** - **Dose**: Initial **15-20 mg/kg** - **Frequency**: Once daily - **Route**: Oral - **Special considerations**: Adjust dose based on WBC count. Usually aim for WBC 2,000-5,000/mm³. **Essential Thrombocythemia (ET) / Polycythemia Vera (PV)** - **Dose**: Initial **15 mg/kg** - **Frequency**: Once daily - **Route**: Oral - **Special considerations**: Adjust dose to maintain platelet count < 600 x 10⁹/L (ET) or HCT < 45% (PV). ### Dose Adjustments - **Renal Impairment**: - CrCl 30-60 mL/min: Reduce dose by **50%**. - CrCl < 30 mL/min or ESRD: Reduce dose by **50-75%**. - Administer after hemodialysis. - **Hepatic Impairment**: No specific dose adjustments recommended; use with caution. - **Elderly Patients**: Start at the lower end of the dosing range due to potential decreased renal function. ## Pediatric Dosing (for Sickle Cell Disease) ### Neonates (0-28 days) - Hydroxyurea is generally **not used** in neonates due to limited data and potential myelotoxicity. ### Infants (1-12 months) - **Dose**: Initial **20 mg/kg** - **Frequency**: Once daily - **Route**: Oral (capsules can be opened and mixed with water/food) - **Maximum**: Titrate by **5 mg/kg/day** every 8-12 weeks up to **35 mg/kg/day** or myelotoxicity. - **Special Notes**: Dosing based on ideal body weight for patients with obesity. ### Children (1-12 years) - **Dose**: Initial **20 mg/kg** - **Frequency**: Once daily - **Route**: Oral (capsules can be opened and mixed with water/food) - **Maximum**: Titrate by **5 mg/kg/day** every 8-12 weeks up to **35 mg/kg/day** or myelotoxicity. Maximum **2500 mg/day**. ### Adolescents (13-18 years) - **Dose**: Follow **adult dosing guidelines** for SCD. Initial **15 mg/kg/day**. - **Maximum**: Up to **35 mg/kg/day** or **2500 mg/day**. ## Safety Information ### Contraindications - **Absolute**: Severe bone marrow depression (leukopenia <2,500 cells/mm³ or platelets <100,000 cells/mm³). - **Absolute**: Pregnancy and breastfeeding. - **Absolute**: Hypersensitivity to hydroxyurea. ### Common Adverse Effects - **Very Common (>10%)**: Myelosuppression (neutropenia, anemia, thrombocytopenia), GI upset (nausea, vomiting, diarrhea, constipation). - **Common (1-10%)**: Skin hyperpigmentation, nail changes, mucositis, alopecia, headache, dizziness, fever. - **Serious but Rare**: Secondary malignancies (leukemia, skin cancer), leg ulcers, pancreatitis, severe hepatotoxicity, peripheral neuropathy. ### Key Drug Interactions - **Live Vaccines**: Increased risk of infection due to immunosuppression; avoid concurrent use. - **Didanosine/Stavudine**: Increased risk of pancreatitis, hepatotoxicity, and peripheral neuropathy. Avoid concomitant use. - **Uricosuric Agents**: May reduce effect of allopurinol by increasing serum uric acid. - **Pimecrolimus/Tacrolimus (topical)**: Increased risk of skin cancer. ## Monitoring & Follow-up - **Before Treatment**: Baseline CBC with differential, renal and hepatic function tests. - **During Treatment**: - CBC with differential and platelet count: **Every 1-2 weeks** until stable dose, then monthly. - Renal and hepatic function: Periodically (e.g., every 3-6 months). - Fetal hemoglobin (HbF) and reticulocyte count: Periodically for SCD. - **Clinical Signs**: Monitor for signs of infection (fever), bleeding, leg ulcers, and skin changes. ## Clinical Pearls - 💡 **Myelosuppression is dose-limiting**: Hold or reduce dose if ANC < 2,000/mm³ or platelets < 80,000/mm³. Restart at reduced dose. - 💡 **Teratogenic**: Counsel patients of reproductive potential on contraception during and after treatment (6 months for females, 1 year for males). - 💡 **Sun Protection**: Advise patients on sun protection (sunscreen, protective clothing) due to increased risk of skin cancer. - 💡 **Hydration**: Encourage adequate fluid intake to prevent hyperuricemia. - 💡 **Capsule Handling**: Hydroxyurea is a cytotoxic agent. Advise caregivers to wear gloves when handling and avoid direct contact with powder. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.