Drug converted into free radical nitroxide invivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, is inactivated. This cause DNA synthesis inhibition selectively and producing cell death in S phase. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea.This produces synergistic effect with radiation or alkylating agent.Hydroxyurea also increase the level of fetal Hb, leading to a reduction in the incidence of vasooclussive crisis in sickle cell anaemia.The drug selectively reduces the level of episomal DNA and thus potentially reduces drug resistance associated with duplicated genes retained as episomes.
Pharmacokinetics
Absorption- Readily absorbed after oral administration
Distribution- Widely distributed in the body. It crosses the blood brain barrier
Metabolism- Metabolized in the liver to its active and inactive metabolites
Excretion- 50% excreted through urine and others through lungs
On Set of Action
2 hrs
Half Life
Its plasma half life is 2-4 hrs
Adverse Effects
1. Nausea
2. Vomiting
3. Lowered resistance to infection
4. Bruising or unusual bleeding
5. Anemia
6. Weakness
7. Sore in mouth
8. Taste changes
9. Diarrhea
10. Loss of appetite
11. Visual changes
12. Black, tarry stools
13. Blood in urine or in stool
14. Cough or hoarseness
15. Fever
16. Chills
17. Lower back or side pain
18. Painful or difficult urination
19. Pinpoint red spot on skin
20. Slurred speech
21. Swelling on leg or lower leg
22. Hallucinations
23. Dizziness
24. Seizures
25. Fatal Pancreatitis
26. Leucopenia
27. Thrombocytopenia
28. Bone marrow suppression
29. Alopecia
30. Erythema
ContraIndications
1. Hypersensitivity to the drug
2. Bone marrow depression
3. Severe anemia
Special Precautions
1. Patients with recent radiation or chemotherapy.
2. Premenopausal woman.
3. Monitor haematological and renal functions regularly.
Pregnancy
Contraindicated
Breast Feeding
Contraindicated
Elderly
Use with caution
Children
Use with caution
Interactions
Lab tests: May cause increase in serum uric acid, creatinine and BUN levels.
Indications
1. Solid tumors
2. Squamous cell carcinoma
3. Myelocytic leukemia
4. Polycythemia rubra Vera
5. Thrombocytosis
6. Sickle cell disease
7. AIDS (as an adjunct)
8. Ovarian cancer
Dosage
Oral-
Adult-
Chronic myeloid leukemia: 20-30mg/kg/day in single doses
Solid tumors: 80mg/kg as a single dose every 3rd day
Storage
Stored at room temperature. Protect from light and moisture.
Missed Dose
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Over Dose
Give supportive and symptomatic treatment. Transfuse the blood components to avoid drug toxicity.
