Dosing and uses of Droxia, Hydrea (hydroxyurea)
Adult dosage forms and strengths
capsules
- 200mg
- 300mg
- 400mg
- 500mg
Solid Tumors
Intermittent Therapy: 80 mg/kg PO q3day, Or
Continuous Therapy: 20-30 mg/kg PO qDay
Head & Neck Tumors
Concomitant therapy with irradiation
- 80 mg/kg PO q3days
- Begin 7 days prior to initiation of irradiation
Chronic Myelocytic Leukemia, Resistant
Continuous Therapy: 20-30 mg/kg PO qDay
Sickle Cell Disease
Start: 15 mg/kg/day as single dose; monitor patient’s blood count every two weeks
Titrate by 5 mg/kg/day q12wk
Dose is not increased if blood counts are between acceptable range and toxic
Not to exceed 35 mg/kg/day
Discontinue therapy until hematologic recovery if blood counts are considered toxic; may resume treatment after reducing dose by 2.5 mg/kg/day from dose associated with hematological toxicity
Thrombocythemia, Essential
15 mg/kg PO qDay
Titrate to control platelets & maintain WBC count
HIV, Adjunct Treatment (Off-label)
500 mg PO BId
Use with antiretrovirals
Psoriasis (Off-label)
1000-1500 mg/day PO qDay-BId
Other Information
Monitor: CBC
Pediatric dosage forms and strengths
Sickle Cell Disease (Orphan)
Siklos: Orphan designation for treatment of sickle cell disease in patients aged <18 yr
Pedroxa: Treatment of symptomatic sickle cell disease in children aged <17 yr
Sponsors
- Siklos: addmedica Laboratories; 101 rue Saint Lazare; Paris75009 France
- Pedroxa: Ebelle D'Ebelle Pharmaceuticals LLC; 5 Witherwood Drive; Hamburg, NJ 07419
Droxia, Hydrea (hydroxyurea) adverse (side) effects
Frequency not defined
Nausea
Vomiting
Constipation
Diarrhea
Mucositis
Acute pulmonary reactions (rare)
Genetic mutation (long-term use)
Myelosuppression
Secondary leukemia (long-term use)
Elevated BUN, Cr
Hyperuricemia
Renal failure
Rash
Hyperpigmentation
Skin ulcer
Gangrenous disorder
Postmarketing Reports
Tumor lysis syndrome
Anemia
Gastric irritation
Platelet depression
Warnings
Black box warnings
Hydroxyurea therapy may be complicated by severe, sometimes life-threatening, adverse effects; because of this, it should be administered under the supervision of a physician experienced in the use of this medication
Hydroxyurea is mutagenic and clastogenic, and causes cellular transformation to a tumorigenic phenotype, and is thus unequivocally genotoxic and a presumed transspecies carcinogen that implies a carcinogenic risk to humans; advise sun protection and monitor patients for malignancies
Hydroxyurea may cause severe myelosuppression; do not administer if bone marrow function is markedly depressed; monitor blood counts at baseline and throughout treatment; interrupt treatment and reduce dose as necessary
In patients receiving long-term hydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemias have been reported
It is unknown whether this leukemogenic effect is secondary to hydroxyurea or is associated with the patients' underlying disease
The physician and patient must very carefully consider the potential benefits relative to the undefined risk of developing secondary malignancies
Contraindications
Hypersensitivity
Severe anemia, bone marrow depression
WBC <2500/mm³, platelets <100,000/mm³
Pregnancy, lactation
Cautions
Caution in renal impairment, coadministration with myelosuppressive agents
Leukopenia and neutropenia commonly occur; thrombocytopenia and anemia are less common; hematologic toxicity is reversible
Do not change dose too frequently
Not recommended in sickle cell anemia if neutrophils <2,000/mm³, platelets <80,000/mm³, hemoglobin <4 g/dL, or reticulocytes <80,000/mm³ when hemoglobin <9 g/dL
Increased risk of hepatotoxicity, which may be fatal, may occur, particularly in combination with didanosine and stavudine
Risk of cutaneous vasculitic toxicities in patients with myeloproliferative disorders, especially with history of or concurrent interferon therapy
Discontinue if WBC <2500/mm³ and/or plateletes<100,000/mm³
Erythrocyte abnormalities reported; self-limiting megaloblastic erythropoiesis reported early in treatment, unrelated to vitamin B12 or folic acid deficiency
Hyperuricemia may occur; adequate hydration, dosage adjustment, or initiation of uricosuric agents may be necessary
Interferes with analytical analyses of the enzymes (urease, uricase, and lactate dehydrogenase) used in the determination of urea, uric acid and lactic acid, rendering falsely elevated results
Advise females of reproductive potential to use effective contraception during and after treatment for at least 6 months after therapy; advise males of reproductive potential to use effective contraception during and after treatment for at least 1 year after therapy
Avoid use of live vaccine; concomitant use with a live virus vaccine may potentiate replication of virus and/or may increase adverse reaction of vaccine because normal defense mechanisms may be suppressed; may result in severe infection; antibody response to vaccine may be decreased
Pregnancy and lactation
Pregnancy category: d
Lactation: excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Droxia, Hydrea (hydroxyurea)
Mechanism of action
The precise mechanism by which hydroxyurea produces its cytotoxic and cytoreductive effects is not known. However, various studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein.
The mechanisms by which hydroxyurea produces its beneficial effects in patients with sickle cell anemia (SCA) are uncertain. Known pharmacologic effects of hydroxyurea that may contribute to its beneficial effects include increasing hemoglobin F levels in red blood cells (RBCs), decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.
Absorption
Duration: up to 24 hr
Peak Plasma Time: 1-4 hr
Distribution
Vd: 0.5 L/kg
Protein binding: 75-80%
Metabolism
Metabolized (60%) by liver and GI tract
Metabolites: CO2, urea
Elimination
Half-Life: 2-4 hr
Excretion: Urine (40% of administered dose in sickle cell anemia patients)
