hydroxyurea (Rx)

Brand and Other Names:Droxia, Hydrea, more...Siklos, hydroxycarbamide
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Dosing & Uses


Dosage Forms & Strengths


  • 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 (Off-label)

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

Dosage Forms & Strengths


  • Siklos
    • 100mg
    • 1000mg (tripled-scored)

Sickle Cell Disease

Indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in children aged ≥2 years with sickle cell anemia with recurrent moderate-to-severe painful crises

<2 years: Safety and efficacy not established

2-18 years

  • Initial dose
    • 20 mg/kg PO qDay
    • Monitor blood counts q2weeks
  • Dose adjustment based on blood counts
    • Increase dose 5 mg/kg/day q8Weeks or if a painful crisis occurs Give until mild myelosuppression (absolute neutrophil count [ANC] 2,000/mcL to 4,000/mcL) is achieved, not to exceed 35 mg/kg/day
    • Increase dosing only if blood counts are in an acceptable range (see Dosage Modifications) or if a painful crisis occurs
    • Do not increase if myelosuppression occurs

Dosage Modifications

Hepatic impairment: Closely monitor hematologic parameters

Renal Impairment

  • CrCl ≥60 mL/min: No dosage adjustment necessary
  • CrCl <60 mL/min or end-stage renal disease (ESRD): Reduce dose to 10 mg/kg/day and closely monitor the hematologic parameters

Hematologic toxicities

  • Blood counts acceptable range
    • Neutrophils ≥2,000 cells/mm³
    • Platelets ≥80,000/mm³
    • Hemoglobin >5.3 g/dL
    • Reticulocytes ≥80,000/mm³ if hemoglobin <9 g/dL
  • Blood counts toxic range
    • Neutrophils <2,000 cells/mm³
    • Platelets <80,000/mm³ if hemoglobin <4.5 g/dL
    • Reticulocytes <80,000/mm³ if hemoglobin <9 g/dL
    • Younger patients with lower baseline counts may safely tolerate ANC down to 1,250/mm³
    • Discontinue treatment until hematologic recovery
  • Dosing after hematologic recovery
    • Reduce dose by 5 mg/kg/day from the dose associated with hematologic toxicity
    • May titrate up or down q8Weeks in 5 mg/kg/day increments
    • Patient should be at a stable dose with no hematologic toxicity for 24 weeks
    • Permanently discontinue treatment if a patient develops hematologic toxicity twice


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            Adverse Effects


            Infections (39.8%)

            Other infections (22.7%)

            Bacterial infections (16%)

            Gastrointestinal disorders (13.1%)

            Neutropenia (12.6%)


            Viral infections (9.9%)

            Fever (7.7%)

            Thrombocytopenia (7.4%)

            Other gastrointestinal disorders (7.4%)

            Headache (7.4%)

            Vitamin D deficiency (6.2%)

            Other not SCD-related reactions (5.7%)

            Anemia (4.2%) Skin reactions (3.7%)

            Parvovirus B19 infections (3.7%)

            Other skin and subcutaneous tissue disorders (3.2%)

            Other nervous system disorders (2.7%)

            Respiratory thoracic and mediastinal disorders (2.7%)

            Constipation (2.5%)

            Nausea (2.5%)

            Other metabolic and nutrition disorders (2%)

            Weight gain (2%)

            Renal and urinary disorders (2%)

            Frequency Not Defined






            Acute pulmonary reactions (rare)

            Genetic mutation (long-term use)


            Secondary leukemia (long-term use)

            Elevated BUN, Cr


            Renal failure



            Skin ulcer

            Gangrenous disorder

            Postmarketing Reports

            Infections and infestations: Parvovirus B19 infection

            Blood and lymphatic system disorders: bone marrow depression including neutropenia (<2 X 10^9/L), reticulocytopenia (<80 X 10Postmarketing Reports^9/L), macrocytosis, thrombocytopenia (<80 X 10^9/L), anemia (hemoglobin <4.5 g/dL)

            Gastrointestinal disorders: Nausea, gastrointestinal disturbances, vomiting, gastrointestinal ulcer, severe hypomagnesemia, stomatitis

            Hepatobiliary disorders: Elevation of hepatic enzymes

            Skin and subcutaneous tissue disorders: Skin reactions (oral, ungula and cutaneous pigmentation), oral mucositis, rash, melanonychia, alopecia, leg ulcers, cutaneous dryness, nail hyperpigmentation, atrophy of skin and nails, scaling, violet papules, cutaneous lupus erythematosus

            Renal and urinary disorders: Dysuria, elevations in blood urea nitrogen

            Immune disorders: Systemic lupus erythematosus

            Metabolism and nutrition disorders: Anorexia

            Nervous system disorders: Dizziness, drowsiness, disorientation, hallucinations, and convulsions

            Respiratory disorders: Diffuse pulmonary infiltrates, dyspnea, and pulmonary fibrosis, interstitial lung disease, pneumonitis, alveolitis, allergic alveolitis and cough

            Reproductive system and breast disorders: Oligospermia, azoospermia, amenorrhea

            General disorders: Fever, chills, malaise, edema, and asthenia

            Investigations: Weight gain

            Hypersensitivity: Drug-induced fever (pyrexia) (>39°C, >102°F) requiring hospitalization 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



            Black Box Warnings


            • Severe myelosuppression may occur
            • Do not give if bone marrow function is markedly depressed
            • Monitor blood counts at baseline and throughout treatment
            • Interrupt treatment and reduce dose as necessary


            • 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
            • 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
            • Advise sun protection and monitor patients for malignancies



            Severe anemia, bone marrow depression

            WBC <2500/mm³, platelets <100,000/mm³

            Pregnancy, lactation


            Risk of cutaneous vasculitic toxicities in patients with myeloproliferative disorders, especially with history of or concurrent interferon therapy; avoid use in patients with wounds on the legs (leg ulcers)

            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

            Macrocytosis is often seen early in the course of treatment; morphologic change resembles pernicious anemia, but is not related to vitamin B12 or folic acid deficiency; prophylactic folic acid is recommended

            Skin cancer reported in patients receiving long-term therapy; advise protection from sun exposure and monitor for development of secondary malignancies

            Fetal harm may occur when hydroxyurea is administered to a pregnant woman (see Pregnancy)

            Pulmonary toxicity

            • Interstitial lung disease including pulmonary fibrosis, lung infiltration, pneumonitis, and alveolitis/allergic alveolitis (including fatal cases) reported in patients treated for myeloproliferative neoplasm
            • Safety and effectiveness not established for use in treatment of myeloproliferative neoplasms and use not approved by the FDA
            • Monitor patients developing pyrexia, cough, dyspnea, or other respiratory symptoms frequently, investigate and treat promptly; discontinue therapy and manage with corticosteroids


            • Evaluate hematologic status prior to and every two weeks during treatment
            • Provide supportive care and modify dose or discontinue therapy as needed
            • Recovery from myelosuppression is usually observed within 15 days when therapy is interrupted; resume therapy after interruption at a lower dose
            • Monitor hematologic parameters more frequently in patients with hepatic impairment receiving therapy


            • Secondary leukemia reported in patients treated long-term for sickle cell disease; leukemia also reported in patients with sickle cell disease and no prior history of treatment with drug
            • All patients should be followed up on long-term basis with regular blood counts to detect development of leukemia

            Drug interactions overview

            • Pancreatitis, hepatotoxicity, and peripheral neuropathy have occurred when hydroxyurea was administered concomitantly with antiretroviral drugs, including didanosine and stavudine
            • Concomitant use with a live virus vaccine may potentiate the replication of the vaccine virus and/or may increase the adverse reactions of the vaccine virus and result in severe infections
            • Interference with uric acid, urea, or lactic acid assays may falsely elevate results in patients treated with hydroxyurea

            Pregnancy & Lactation


            No data are available with the use of hydroxyurea in pregnant women Limited available data on hydroxyurea use during pregnancy are insufficient to inform drug-associated risks

            In case of an exposure to hydroxyurea of pregnant female patients or pregnant partners of male patients, treated by hydroxyurea, a careful follow-up with adequate clinical, biological and ultrasonographic examinations should be considered

            Based on findings in animals and humans, male fertility may be compromised by treatment; azoospermia or oligospermia has been observed in men; before initiating therapy, inform male patients about the possibility of sperm conservation

            Advise pregnant women of the potential risk to a fetus; verify the pregnancy status of females of reproductive potential prior to initiating therapy

            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

            Animal data

            • In animal reproduction studies, hydroxyurea administration to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m² basis In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae


            Unknown whether hydroxyurea is excreted in human milk, the effects of hydroxyurea on the breastfed child, or the effects of hydroxyurea on milk production

            Because of the potential for serious adverse reactions in a breastfed child from hydroxyurea, including carcinogenicity, advise patients not to breastfeed during treatment

            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.



            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.


            Duration: up to 24 hr

            Peak Plasma Time: 1-4 hr


            Vd: 0.5 L/kg

            Protein binding: 75-80%


            Metabolized (60%) by liver and GI tract

            Metabolites: CO2, urea


            Half-Life: 2-4 hr

            Excretion: Urine (40% of administered dose in sickle cell anemia patients)



            Oral administration

            Administer dose qDay, with a glass of water

            Do not split the Siklos 100 mg tablets into smaller parts

            Patients unable to swallow tablets: Disperse tablets immediately before use in a small quantity of water in a teaspoon

            Hydroxyurea is a cytotoxic drug

            Follow applicable special handling and disposal procedures


            Store at room temperature, 20-25°C (68-77°F); excursions permitted between 15- 30°C (59-86°F)

            Keep tightly closed

            Broken 1000 mg tablets must be stored in the bottle and must be used within 3 months





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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
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