Usage
Hydroxyurea is prescribed for the treatment of certain types of cancer (e.g., chronic myeloid leukemia, head and neck cancers, ovarian cancer), sickle cell anemia, essential thrombocythemia (high platelet count), and other conditions. It is classified as an antineoplastic antimetabolite. Hydroxyurea’s mechanism of action involves inhibiting ribonucleotide reductase, an enzyme crucial for DNA synthesis. This action slows down the production of cancer cells and other rapidly dividing cells. In sickle cell anemia, it promotes the production of fetal hemoglobin, which helps reduce the formation of abnormal sickle-shaped red blood cells.
Alternate Names
Hydroxyurea is also known as hydroxycarbamide. Brand names include Droxia, Hydrea, and Siklos.
How It Works
Pharmacodynamics: Hydroxyurea primarily inhibits ribonucleotide reductase, leading to a decrease in deoxynucleotide triphosphates (dNTPs) needed for DNA synthesis. This cytostatic effect impacts rapidly proliferating cells, including cancerous cells, and in sickle cell disease, it increases the production of fetal hemoglobin (HbF), reducing sickling.
Pharmacokinetics:
- Absorption: Hydroxyurea is well-absorbed orally.
- Metabolism: It is minimally metabolized in the liver.
- Elimination: Primarily excreted via the kidneys.
Mode of action: Hydroxyurea acts by inactivating the ribonucleotide reductase enzyme, thus depleting the dNTP pool and ultimately inhibiting DNA synthesis.
Receptor binding, enzyme inhibition, or neurotransmitter modulation: The primary mechanism is the inhibition of ribonucleotide reductase. There is no known significant receptor binding or neurotransmitter modulation.
Elimination pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
The initial dose is typically 15 mg/kg of body weight administered orally once daily. The dose can be titrated upwards based on blood counts and clinical response, not to exceed 35 mg/kg/day. For other conditions like chronic myeloid leukemia, the dose may vary between 20-30 mg/kg/day.
Children:
For sickle cell anemia, the initial dose is typically 20 mg/kg/day orally, with adjustments based on blood counts and clinical response, not exceeding 35 mg/kg/day. The dose is often calculated using the child’s ideal body weight, or actual body weight if lower. For other conditions, dosing should be determined by the physician. Pediatric safety requires careful monitoring of blood counts.
Special Cases:
- Elderly Patients: May require lower initial doses and closer monitoring due to age-related decline in renal function.
- Patients with Renal Impairment: Dosage adjustments are necessary depending on the degree of impairment. A 50% reduction in the initial dose is often recommended.
- Patients with Hepatic Dysfunction: While hydroxyurea is minimally metabolized in the liver, caution is advised in patients with significant hepatic dysfunction.
- Patients with Comorbid Conditions: Dosage adjustments may be necessary in patients with other conditions, such as HIV or those receiving concomitant myelosuppressive medications.
Clinical Use Cases
Dosing for intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not specifically defined for hydroxyurea, as its primary use is in chronic conditions. Dosages should be adjusted based on the patient’s underlying condition and monitored during these situations.
Dosage Adjustments
Dose modifications are needed in renal or hepatic impairment, based on the severity of organ dysfunction. Genetic polymorphisms affecting drug metabolism may also require individualization of dosage.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, constipation, loss of appetite, mouth sores, skin rash, headache, dizziness, hair loss, nail changes.
Rare but Serious Side Effects
Severe myelosuppression (low blood counts), including leukopenia, neutropenia, thrombocytopenia, and anemia; pulmonary toxicity; secondary malignancies (e.g., leukemia, skin cancer).
Long-Term Effects
Chronic myelosuppression, increased risk of infections, increased risk of secondary malignancies, skin changes.
Adverse Drug Reactions (ADR)
Severe myelosuppression, pulmonary toxicity, allergic reactions.
Contraindications
Absolute contraindications include hypersensitivity to hydroxyurea, severe myelosuppression (e.g., severe anemia, leukopenia, thrombocytopenia). Relative contraindications include renal or hepatic impairment, pregnancy, and breastfeeding.
Drug Interactions
Hydroxyurea interacts with other myelosuppressive agents (e.g., didanosine, stavudine, zidovudine), antiviral agents (e.g., interferon), and live vaccines. It can also affect the results of certain laboratory tests (e.g., blood glucose, uric acid).
Pregnancy and Breastfeeding
Hydroxyurea is contraindicated in pregnancy and breastfeeding due to potential teratogenic effects and excretion in breast milk. Women of childbearing potential and their male partners should use effective contraception during and after treatment.
Drug Profile Summary
- Mechanism of Action: Inhibits ribonucleotide reductase, leading to decreased DNA synthesis.
- Side Effects: Myelosuppression, gastrointestinal effects, skin reactions, secondary malignancies.
- Contraindications: Hypersensitivity, severe myelosuppression, pregnancy, breastfeeding.
- Drug Interactions: Myelosuppressive agents, antiviral agents, live vaccines.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies depending on condition and patient factors. Generally, 15-35 mg/kg/day.
- Monitoring Parameters: Complete blood count (CBC) with differential, renal function tests, liver function tests.
Popular Combinations
Hydroxyurea is frequently used in combination with other chemotherapeutic agents in the treatment of certain cancers. In sickle cell disease, it may be used with other therapies aimed at managing symptoms and complications.
Precautions
General precautions involve monitoring blood counts, renal and hepatic function. Specific precautions include avoidance in pregnancy and breastfeeding. Caution is needed in elderly patients and those with renal or hepatic dysfunction.
FAQs
Q1: What is the recommended dosage for Hydroxyurea?
A: The starting dose for adults is typically 15 mg/kg/day, titrated based on blood counts and clinical response, not to exceed 35mg/kg/day. For children with sickle cell disease, the initial dose is 20 mg/kg/day, with similar titration and maximum limits. Dosages for other conditions vary. Special adjustments are required for patients with renal or hepatic impairment, elderly patients, and those with comorbid conditions.
Q2: What are the most serious side effects of Hydroxyurea?
A: Severe myelosuppression (low blood counts), which increases the risk of infections and bleeding, and the development of secondary malignancies (leukemia and skin cancers).
Q3: Can Hydroxyurea be used during pregnancy?
A: No, Hydroxyurea is contraindicated during pregnancy due to its potential teratogenic effects. Effective contraception is essential.
Q4: How does Hydroxyurea work in sickle cell anemia?
A: It increases the production of fetal hemoglobin (HbF), which reduces the formation of abnormal sickle-shaped red blood cells, thereby decreasing the frequency of painful crises and other complications.
Q5: What are the common side effects of Hydroxyurea?
A: Nausea, vomiting, diarrhea, constipation, loss of appetite, mouth sores, skin rash, headache, dizziness, hair loss, and changes in skin and nails are common side effects.
Q6: Does Hydroxyurea interact with other medications?
A: Yes, it can interact with other myelosuppressive agents, antiviral medications, and certain live vaccines. Concomitant use should be carefully considered.
Q7: How is Hydroxyurea administered?
A: It is administered orally, usually as a single daily dose, with or without food. Capsules should be swallowed whole, or the contents can be dissolved in water for patients with difficulty swallowing.
Q8: What monitoring is required for patients taking Hydroxyurea?
A: Regular monitoring of complete blood counts (CBC), renal function tests, and liver function tests are essential to assess efficacy and detect potential adverse effects.
Q9: Can Hydroxyurea be used in children?
A: Yes, Hydroxyurea is used in children, especially for the treatment of sickle cell disease. However, careful dosing and close monitoring of blood counts are crucial.
Q10: How long does it take for Hydroxyurea to start working?
A: The time to clinical response varies depending on the condition being treated. In sickle cell anemia, benefits may be seen within a few months, while in other conditions it might take longer.
