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Hydroxyurea (hydroxycarbamide): Pediatric drug information

Hydroxyurea (hydroxycarbamide): Pediatric drug information
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For additional information see "Hydroxyurea (hydroxycarbamide): Drug information" and "Hydroxyurea (hydroxycarbamide): Patient drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Bone marrow suppression (Droxia, Siklos, Xromi):

Hydroxyurea may cause severe myelosuppression. 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.

Secondary malignancy (Droxia, Siklos, Xromi):

Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies.

Brand Names: US
  • Droxia;
  • Hydrea;
  • Siklos;
  • Xromi
Brand Names: Canada
  • APO-Hydroxyurea;
  • Hydrea;
  • MYLAN-Hydroxyurea;
  • RIVA-Hydroxyurea
Therapeutic Category
  • Antineoplastic Agent, Miscellaneous
Dosing: Pediatric
Sickle cell anemia

Sickle cell anemia: Note: A clinical response to treatment may take 3 to 6 months; a 6-month trial of the maximum tolerated dose is recommended prior to considering discontinuation due to treatment failure; effectiveness of hydroxyurea depends upon daily dosing adherence. For patients who have a clinical response, long-term hydroxyurea therapy is indicated (Ref).

Infants ≥6 months and Children <2 years: Note: Doses should be based on actual body weight. Round calculated dose to the nearest 10 mg.

Initial: Oral: 15 to 20 mg/kg/dose once daily; monitor for myelosuppression closely if using initial doses >15 mg/kg/day (Ref).

Dosage adjustment: Monitor CBC with differential and reticulocyte count every 2 weeks when adjusting dosage; monitor for myelosuppression closely (particularly if initial dose is >15 mg/kg/day) (Ref).

• If blood count in target range (see below): Increase dose by 5 mg/kg/day every 8 to 12 weeks; maximum daily dose: 35 mg/kg/day; Note: The maximum dose for the patient is the highest dose that does not produce toxic blood counts over 24 consecutive weeks not to exceed 35 mg/kg/day (Ref).

Target hematologic ranges: ANC 1,000 to 3,000/mm3 and platelets ≥80,000/mm3.

• If blood count in toxic hematologic range (see below): Hold hydroxyurea until hematologic recovery. If counts recover within 1 week, restart at previous dose. If hematologic toxicity persists >1 week or occurs twice within a 3-month period, restart at a dose reduced by 5 mg/kg/day after count recovery (Ref); however, in clinical trials, reinitiating at a dose reduced by 2.5 mg/kg/day has been reported (Ref).

Toxic hematologic ranges: ANC <1,000/mm3, platelets <80,000/mm3, hemoglobin <4.5 g/dL or 20% decrease from baseline, and reticulocytes <80,000/mm3 if hemoglobin is <9 g/dL.

Children ≥2 years and Adolescents: Note: Doses should be based on ideal or actual body weight, whichever is less. For solid dosage forms, round calculated dose to the nearest 50 mg or 100 mg strengths; for oral solution (ie, Xromi), round calculated dose to nearest 10 mg.

Initial: Oral: 15 to 20 mg/kg/dose once daily (Ref).

Dosage adjustment: Monitor CBC with differential and including reticulocyte count every 2 weeks when adjusting dosage as appropriate; monitor for myelosuppression closely.

• If blood counts in target range (see below): Increase dose by 5 mg/kg/day every 8 weeks or sooner if painful crisis occurs; continue therapy until mild myelosuppression (ANC 2,000 to 4,000/mm3) is achieved (as long as myelosuppression acceptable); maximum daily dose: 35 mg/kg/day; suggested maximum fixed dose of 2,500 mg/day; monitor closely for myelosuppression and adherence (Ref).

Target hematologic ranges: ANC ≥2,000/mm3 (younger patients with lower baseline counts may safely tolerate ANC down to 1,250/mm3), platelets ≥80,000/mm3, hemoglobin >5.3 g/dL, and reticulocytes ≥80,000/mm3 if hemoglobin is <9 g/dL.

• If blood count in toxic hematologic range (see below): Hold hydroxyurea until hematologic recovery (monitor counts weekly). Restart at a dose reduced by 5 mg/kg/day (Ref); some have recommended reinitiating at a dose reduced by 2.5 mg/kg/day (Ref). Titrate dose up or down every 8 weeks in 5 mg/kg/day increments until a stable dose achieved that does not result in hematologic toxicity for 24 weeks (eg, patient's lowest tolerable dose without myelosuppression). If hematologic toxicity recurs, permanently discontinue therapy.

Toxic hematologic ranges: Neutrophils <2,000/mm3, platelets <80,000/mm3, hemoglobin <4.5 g/dL, and reticulocytes <80,000/mm3 if hemoglobin is <9 g/dL.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Note: In trials, a 24-hour urine collection was used for CrCl calculation.

Infants ≥6 months, Children, and Adolescents: Xromi, Siklos:

CrCl ≥60 mL/minute: Oral: No dosage adjustment required.

CrCl <60 mL/minute: Oral: Reduce dose by 50%; monitor hematologic parameters closely.

End-stage kidney disease: Oral: Reduce dose by 50%; on dialysis days, administer after hemodialysis; if initiating, titrate to response/avoidance of toxicity; monitor hematologic parameters closely.

Dosing: Liver Impairment: Pediatric

Infants ≥6 months, Children, and Adolescents: Oral: There are no dosage adjustments provided in the manufacturer's labeling; closely monitor for hematologic toxicity.

Dosing: Adult

(For additional information see "Hydroxyurea (hydroxycarbamide): Drug information")

Note: Doses should be based on ideal or actual body weight, whichever is less (per manufacturer). Prophylactic administration of folic acid is recommended. Per the manufacturer's labeling, do not initiate therapy if bone marrow function is markedly reduced; for oncologic indications, correct severe anemia prior to initiating treatment. Due to potential cutaneous vasculitic toxicity, avoid use in patients with leg ulcer wounds. If at risk for tumor lysis syndrome, hydrate adequately and initiate antihyperuricemic agents as clinically necessary.

Acute myeloid leukemia, cytoreduction

Acute myeloid leukemia, cytoreduction (off-label use): Oral: 50 to 100 mg/kg/day until WBC <100,000/mm3 (Ref) or 50 to 60 mg/kg/day until WBC <10,000 to 20,000/mm3 (Ref).

Chronic myeloid leukemia

Chronic myeloid leukemia (alternative agent) (Hydrea): Note: Hydroxyurea may be used in symptomatic patients for short-term therapy of elevated WBC or platelet counts while awaiting cytogenetics prior to initiating a tyrosine kinase inhibitor (TKI) (Ref)

Initial: Oral: 40 mg/kg/day (reduce initial dose for thrombocytopenia); reduce dose to 20 mg/kg/day if WBC count <2,000/mm3. Further individualize dose based on WBC counts (Ref).

Chronic myelomonocytic leukemia, advanced, proliferative

Chronic myelomonocytic leukemia, advanced, proliferative (off-label use): Initial: Oral: 1 g once daily; adjust dose (up to a maximum of 4 g/day) to maintain WBC between 5,000 and 10,000/mm3 (Ref) or 500 mg twice daily (1 g twice daily if visceral involvement) (Ref). Refer to protocols for dosage titration/adjustment details.

Differentiation syndrome, cytoreduction

Differentiation syndrome, cytoreduction (off-label use): Oral:

Acute promyelocytic leukemia (APL) differentiation syndrome:

WBC 10,000 to 50,000/mm3: Oral: 500 mg four times a day; discontinue when WBC <10,000/mm3 (Ref).

WBC >50,000/mm3: Oral: 1 g four times a day; discontinue when WBC <10,000/mm3 (Ref).

I socitrate dehydrogenase (IDH) differentiation syndrome:

WBC 25,000 to 50,000/mm3 and absolute increase from baseline of 15,000 to 29,000/mm3: Oral: 1 g once daily (Ref).

WBC 51,000 to 75,000/mm3 and absolute increase from baseline of 30,000 to 49,000/mm3: Oral: 2 g twice daily (Ref).

WBC ≥76,000/mm3 and absolute increase from baseline of ≥50,000/mm3: Oral: 3 g twice daily (Ref).

Essential thrombocythemia, high risk

Essential thrombocythemia, high risk (off-label use): Initial: Oral: 500 mg to 1 g daily; adjust dose to maintain platelets <400,000/mm3 (Ref) or 1.5 g once daily; adjust dose to maintain platelets ≤450,000/mm3 (Ref).

Head and neck carcinoma, advanced

Head and neck carcinoma, advanced (excluding lip cancer) (Hydrea): Individualize treatment/regimen based on tumor type, response, and current clinical practice standards. Oral: 1 g every 12 hours for 11 doses per cycle, in combination with continuous infusion fluorouracil and radiation therapy (Ref).

Hypereosinophilic syndrome, refractory

Hypereosinophilic syndrome, refractory (off-label use): Oral: 1 g/day (range: 500 mg to 2 g/day) (Ref) or 1 to 3 g/day (Ref).

Meningioma, recurrent, high risk, or unresectable

Meningioma, recurrent, high risk, or unresectable (off-label use): Oral: 20 mg/kg once daily (Ref).

Myelofibrosis, primary, symptomatic

Myelofibrosis, primary, symptomatic (alternative agent) (off-label use): Note: Use should be limited to patients with intermediate-1 or low-risk primary myelofibrosis with splenomegaly (Ref).

Initial: Oral: 500 mg/day; adjust dose based on efficacy and tolerability (Ref).

Polycythemia vera, high risk

Polycythemia vera, high risk (off-label use): Patients <65 years of age: Oral: 15 to 20 mg/kg/day (Ref) or 500 mg twice daily initially, titrated based on target hematocrit and hematologic toxicity (Ref) or 25 mg/kg/day as induction therapy, followed (after remission achieved) by maintenance dosing of 10 to 15 mg/kg/day (Ref).

Sickle cell anemia

Sickle cell anemia:

Droxia: Initial: Oral: 15 mg/kg once daily. Monitor blood counts every 2 weeks; if blood counts are in an acceptable range, may increase by 5 mg/kg/day every 12 weeks until the maximum tolerated dose of 35 mg/kg/day is achieved or the dose that does not produce toxic effects over 24 consecutive weeks (do not increase dose if blood counts are between acceptable and toxic ranges).

Acceptable hematologic ranges: Neutrophils ≥2,500/mm3; platelets ≥95,000/mm3; hemoglobin >5.3 g/dL; and reticulocytes ≥95,000/mm3 if hemoglobin is <9 g/dL.

Toxic hematologic ranges: Neutrophils <2,000/mm3; platelets <80,000/mm3; hemoglobin <4.5 g/dL; and reticulocytes <80,000/mm3 if hemoglobin is <9 g/dL.

Siklos: Initial: Oral: 15 mg/kg once daily. Calculate rounded doses to the nearest 50 mg or 100 mg strength. Monitor blood counts every 2 weeks; if blood counts are in an acceptable range, may increase by 5 mg/kg/day every 8 weeks or if a painful crisis occurs until mild myelosuppression (ANC 2,000 to 4,000/mm3) is achieved, or up to a maximum dose of 35 mg/kg/day.

Acceptable hematologic ranges: Neutrophils ≥2,000/mm3; platelets ≥80,000/mm3; hemoglobin >5.3 g/dL; and reticulocytes ≥80,000/mm3 if hemoglobin is <9 g/dL.

Toxic hematologic ranges: Neutrophils <2,000/mm3 (neutrophil limit of 1,250/mm3 may be acceptable in younger patients with lower baseline counts); platelets <80,000/mm3; hemoglobin <4.5 g/dL; and reticulocytes <80,000/mm3 if hemoglobin is <9 g/dL.

Note: A clinical response to treatment may take 3 to 6 months; a 6-month trial of the maximum tolerated dose is recommended prior to considering discontinuation due to treatment failure. Effectiveness of hydroxyurea depends upon daily dosing adherence. For patients who have a clinical response, long-term hydroxyurea therapy is indicated (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: For indications in which the anticipated use is short term (eg, cytoreduction for acute myeloid leukemia), the risks versus benefits may not favor empiric dose reduction as described below for patients with altered kidney function or on renal replacement therapies; instead, consider initiating on the low end of the normal range and adjust dose based on targeted hematologic response (eg, WBC reduction) (Ref).

Altered kidney function:

CrCl ≥60 mL/minute: No dosage adjustment necessary (Ref).

CrCl <60 mL/minute: Initial: Administer 50% of the usual indication-specific dose; titrate based on tolerance and response (Ref).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):

Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).

Initial: No dosage adjustment necessary; titrate based on tolerability and response (expert opinion). Note: Since hydroxyurea clearance is dependent on kidney function, titration to doses that may exceed the usual recommended dose may be required in patients with ARC (Ref).

Hemodialysis, intermittent (thrice weekly): There are no data on the extent of removal by hemodialysis (has not been studied); however, based on protein binding (75% to 80%) and Vd (approximates total body water), it is likely somewhat dialyzed, although the full extent is unknown (Ref):

Initial: Administer 50% of the usual indication-specific dose; titrate based on tolerability and response. When scheduled dose falls on hemodialysis days, administer after hemodialysis (Ref).

Peritoneal dialysis: There are no data on the extent of removal by peritoneal dialysis (has not been studied); the following recommendations are empirically derived from hemodialysis patients:

Initial: Administer 50% of the usual indication-specific dose; titrate based on tolerability and response (Ref).

CRRT:

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions (eg, myelosuppression) due to drug accumulation is important. Although there are no data for patients on CRRT (has not been studied), some removal of hydroxyurea may be expected.

Initial: Administer 50% of the usual indication-specific dose; titrate based on tolerability and response (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration):

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, myelosuppression) due to drug accumulation is important. Although there are no data for patients on PIRRT (has not been studied), some removal of hydroxyurea may be expected.

Initial: Administer 50% of the usual indication-specific dose; titrate based on tolerability and response; when scheduled dose falls on PIRRT days, administer after PIRRT (Ref).

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; closely monitor for bone marrow toxicity; however, no need for dosage adjustment is expected; monitor closely for hematologic toxicities (Ref).

Adverse Reactions (Significant): Considerations
Bone marrow suppression

Hydroxyurea may cause severe or life-threatening bone marrow depression at the recommended initial dose. Leukopenia, neutropenia, anemia, and thrombocytopenia may occur; leukopenia/neutropenia occur first. Hematologic toxicity is usually rapidly reversible with treatment interruption.

Mechanism: Related to mechanism of action; as a derivative of urea, hydroxyurea directly inhibits DNA synthesis by inactivating ribonucleotide diphosphate reductase (Ref).

Onset: Intermediate; neutrophil nadir occurred around weeks 2 to 4 after initiation (Ref).

Risk factors:

• Previous cytotoxic chemotherapy or radiation therapy

• Pediatric patients (timing of dose adjustments due to changes in body weight)

Cutaneous vasculitic toxicities

Vasculitic skin ulceration has been reported in patients with myeloproliferative disorders (eg, polycythemia vera, thrombocythemia) during hydroxyurea treatment, most often in patients with a history of or concurrent treatment with interferon. Most common location reported in the literature is leg ulcer, especially in the malleolar area; ulcers are usually painful (Ref). Ulcers may rarely be caused by hypersensitivity angiitis (Ref). Cutaneous lesions may require therapy interruption, dose reduction, discontinuation and/or treatment, depending on severity. Upon discontinuation and appropriate treatment, complete resolution of cutaneous lesions occurred in a median of 5 months (range: 1 to 28); however, some lesions persisted or worsened with continued hydroxyurea therapy (including at reduced doses) or recurred with reintroduction of therapy (Ref).

Mechanism: Not clearly established; direct inhibition of DNA synthesis, macrocytosis, and platelet dysregulation may cause direct tissue damage, including death of keratinocytes, microthrombus formation, and impaired tissue repair (Ref). Biopsies of ulcerations have shown hypersensitivity angiitis, perivascular lymphocytic infiltration, formation of thrombus, swelling of endothelial cells, and thickening of vascular walls (Ref).

Onset: Delayed; mucocutaneous lesions occurred in a mean of 38 months (range: 10 to 74 months) after initiation (Ref).

Risk factors:

• History of or current treatment with interferon therapy

• History of arterial hypertension, diabetes mellitus, peripheral vascular disease (Ref)

• Older females (Ref)

Second primary malignancies

Hydroxyurea is carcinogenic in animal studies, but has not been well defined in the human population. Treatment of myeloproliferative disorders (eg, polycythemia vera, thrombocythemia) and sickle cell disease with long-term hydroxyurea is associated with secondary leukemia; it is unknown if this is drug-related or disease-related. Skin carcinoma has been reported with long-term hydroxyurea use.

Mechanism: Dose- and time-related, related to mechanism of action; DNA inhibition, through targeting of ribonucleotide reductase, can lead to DNA damage and impedance of TP53 gene activation (and by extension DNA repair), which creates a favorable environment for the development of gene mutations, especially involving chromosome 17. For skin cancers, hydroxyurea potentiates the effect of UV radiation and solar hypersensitivity, coupled with the inhibition of DNA repair, leading to development of skin cancer (Ref).

Onset: Delayed; ranges from 6 months to 15 years (Ref).

Risk factors:

• Higher cumulative dose (Ref)

• Longer duration of therapy (Ref)

• Excess sun exposure (Ref)

• Sequential use of busulfan therapy (Ref)

• Older age (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults unless otherwise indicated.

>10%:

Dermatologic: Xeroderma (adults: 12%)

Hematologic & oncologic: Macrocytosis (mean corpuscular volume >97 fL: 42%), neutropenia (5% to 13%)

Infection: Bacterial infection (children, adolescents: 16%; adults: 4%), infection (40% to 43%; serious infection: 4% to 18%)

Nervous system: Headache (children, adolescents: 7%; adults: 20%)

1% to 10%:

Cardiovascular: Peripheral edema (adults: 3%)

Dermatologic: Alopecia (adults: 5%), dermatological reaction (children, adolescents: 4%)

Endocrine & metabolic: Vitamin D deficiency (children, adolescents: 6%), weight gain (2% to 4%)

Gastrointestinal: Constipation (children, adolescents: 3%), diarrhea (adults: 3%), nausea (3% to 6%), upper abdominal pain (adults: 5%)

Genitourinary: Disorder of urinary system (children, adolescents: ≤2%), urinary tract infection (adults: 4%)

Hematologic & oncologic: Anemia (4% to 10%), thrombocytopenia (7%)

Infection: Erythema infectiosum (children, adolescents: 4%), influenza (adults: 4%), viral infection (4% to 10%)

Nervous system: Asthenia (adults: 9%), dizziness (adults: 9%), fatigue (adults: 5%)

Neuromuscular & skeletal: Arthralgia (adults: 9%), back pain (adults: 5%), limb pain (adults: 3%)

Renal: Kidney disease (≤2%)

Respiratory: Bronchitis (adults: 4%), cough (adults: 6%), dyspnea (adults: 4%), nasopharyngitis (adults: 4%), pulmonary disease (adults: 5%)

Miscellaneous: Fever (8%)

Frequency not defined (any population):

Dermatologic: Papular rash, skin depigmentation

Hematologic & oncologic: Bone marrow depression (can be severe bone marrow depression), hemorrhage, leukopenia

Hepatic: Increased gamma-glutamyl transferase

Postmarketing (any population):

Cardiovascular: Edema, vasculitic skin ulceration (patients with myeloproliferative disorders) (Ref)

Dermatologic: Actinic keratosis (Ref), acute mucocutaneous toxicity (Ref), atrophy of nail, basal cell carcinoma of skin (Ref), cutaneous lupus erythematosus (Ref), dermal ulcer (Ref), dermatitis (Ref), dermatomyositis-like skin changes (Ref), desquamation, dyschromia (Ref), eczema (Ref), facial erythema, gangrene of skin and/or subcutaneous tissues (patients with myeloproliferative disorders) (Ref), hyperkeratosis (eg, acral) (Ref), hyperpigmentation (Ref), leg ulcer (Ref), maculopapular rash, nail discoloration (melanonychia) (Ref), nail hyperpigmentation (Ref), papule of skin, photodermatitis (Ref), psoriasiform eruption (plaques) (Ref), skin atrophy (Ref), skin carcinoma (Ref), skin rash

Endocrine & metabolic: Amenorrhea, hypomagnesemia (severe), increased uric acid

Gastrointestinal: Acute pancreatitis (Ref), anorexia, cholestasis, gastric distress (Ref), gastrointestinal ulcer, mucous membrane lesion (Ref), oral mucosa ulcer (Ref), staining of tooth (Ref), stomatitis, tongue discoloration (Ref), vomiting

Genitourinary: Azoospermia, dysuria, oligospermia

Hematologic & oncologic: Hemolytic anemia (Ref), leukemia (secondary) (Ref), malignant neoplasm (Ref), reticulocytopenia (Ref), squamous cell carcinoma (Ref), tumor lysis syndrome

Hepatic: Hepatitis (Ref), increased liver enzymes

Hypersensitivity: Hypersensitivity angiitis (Ref)

Local: Localized erythema (extremities)

Nervous system: Chills, disorientation, drowsiness, hallucination, malaise, seizure

Neuromuscular & skeletal: Panniculitis (Ref), systemic lupus erythematosus (including lupus-like syndrome (Ref)

Renal: Increased blood urea nitrogen, increased serum creatinine

Respiratory: Asthma (Ref), interstitial lung disease, pneumonitis (Ref), pulmonary alveolitis (including allergic, hypersensitivity pneumonitis) (Ref), pulmonary fibrosis (Ref), pulmonary infiltrates (Ref)

Miscellaneous: Drug fever (Ref)

Contraindications

US labeling: Hypersensitivity to hydroxyurea or any component of the formulation.

Canadian labeling: Additional contraindications (not in the US labeling): Severe bone marrow depression (eg, leukopenia [<2,500/mm3], thrombocytopenia [<100,000/mm3], or severe anemia).

Warnings/Precautions

Disease-related issues:

• HIV-infected patients: Pancreatitis, hepatotoxicity, and peripheral neuropathy have occurred when hydroxyurea was administered with antiretroviral medications, including didanosine and stavudine.

Special populations:

• Radiation therapy recipients: Patients with a history of radiation therapy are at risk for exacerbation of post irradiation erythema.

Other warnings/precautions:

• Immunizations: Avoid use of live vaccines during hydroxyurea therapy. Concomitant use may potentiate viral replication and may possibly increase vaccine adverse reactions due to suppression of normal defense mechanisms by hydroxyurea and result in severe infections. The antibody response to vaccines may be decreased. Consider consultation with a specialist if immunization with a live vaccine is necessary.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Droxia: 200 mg, 300 mg [contains fd&c blue #1 (brilliant blue)]

Droxia: 400 mg [contains quinoline yellow (d&c yellow #10)]

Hydrea: 500 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]

Generic: 500 mg

Solution, Oral:

Xromi: 100 mg/mL (148 mL) [contains methylparaben]

Tablet, Oral:

Siklos: 100 mg [scored]

Siklos: 1000 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Capsules (Droxia Oral)

200 mg (per each): $0.91

300 mg (per each): $0.91

400 mg (per each): $0.97

Capsules (Hydrea Oral)

500 mg (per each): $1.64

Capsules (Hydroxyurea Oral)

500 mg (per each): $0.50 - $1.47

Solution (Xromi Oral)

100 mg/mL (per mL): $6.16

Tablets (Siklos Oral)

100 mg (per each): $7.54

1000 mg (per each): $75.35

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Hydrea: 500 mg

Generic: 500 mg

Extemporaneous Preparations

Note: A hydroxyurea oral solution (100 mg/mL) is commercially available.

100 mg/mL Oral Solution (ASHP Standard Concentration) (ASHP 2017)

A 100 mg/mL oral solution may be prepared with capsules. Mix the contents of twenty 500 mg capsules with enough room temperature sterile water (~50 mL) to initially result in a 200 mg/mL concentration. Stir vigorously using a magnetic stirrer for several hours, then filter to remove insoluble contents. Add 50 mL Syrpalta (flavored syrup without color, HUMCO) to filtered solution, resulting in 100 mL of a 100 mg/mL hydroxyurea solution. Stable for 1 month at room temperature in amber plastic bottle (Heeney 2004).

Heeney MM, Whorton MR, Howard TA, et al. Chemical and functional analysis of hydroxyurea oral solutions. J Pediatr Hematol Oncol. 2004;26(3):179-184.15125610
Administration: Pediatric

Note: Impervious, disposable gloves should be worn when handling bottles containing hydroxyurea or when handling/administering hydroxyurea. Wash hands with soap and water before and after contact with hydroxyurea. Avoid exposure to crushed tablets, open capsules. If skin contact occurs, immediately wash the affected area thoroughly with soap and water. If eye(s) contact occurs, the affected area should be flushed thoroughly with water or isotonic eyewash designated for that purpose for at least 15 minutes. If oral solution or powder from the capsules or tablets is spilled, immediately wipe it up with a damp disposable towel and discard (along with the empty capsules) in a closed container, such as a plastic bag. The spill areas should then be cleaned using a detergent solution followed by clean water.

Oral: Administered at the same time each day.

Capsules: Droxia, Hydrea: Swallow whole; the manufacturer does not recommend opening the capsules. Doses rounded to the nearest 100 mg when using capsules allows for dosing accuracy within ~2 mg/kg/day (Ref). For patients unable to swallow capsules, an oral solution may be prepared.

Oral solution: Xromi: Administer with or after meals at the same time each day. Do not shake. Put on disposable gloves. With first use, insert bottle adapter and keep in place; use provided reusable syringes to measure dose: For doses ≤3 mL, use the 3 mL syringe; for doses >3 mL, use the 10 mL syringe. Doses >10 mL will need to be divided into smaller increments. Draw up the correct dose of medication, then insert tip of the syringe into patient's mouth against cheek, depress plunger, and administer dose. After administration while continuing to wear gloves, clean oral syringe(s) with cold or warm soapy water, rinse well; hold syringe under water and move the plunger up and down several times to ensure inside clean; let air dry. Ensure the provided child-resistant cap is secured tightly on the bottle for storage.

Tablets: Siklos: Administer with a glass of water. The 100 mg tablets are scored with 1 line to enable splitting into 2 parts and the 1,000 mg tablets are scored with 3 lines to enable splitting into 4 parts; wear gloves and use a damp paper towel surface to break scored tablets (properly dispose of used gloves and paper towel). Film-coated tablets that are not scored should not be split.

If unable to swallow tablets whole: Disperse immediately before use in a small amount of water in a teaspoon (add tablet to spoon, add water; tablet dissolves in ~1 minute; administer immediately); drink an additional glass of water after administering the dose.

Missed doses: If a dose is missed, it should be taken as soon as remembered if on the same day as scheduled; if not possible, skip dose and continue with next scheduled dose.

Administration: Adult

Oral: Administer at the same time each day.

Capsules (Droxia, Hydrea): Swallow whole; the manufacturer does not recommend opening, breaking, or chewing the capsules. For patients unable to swallow capsules, an oral solution may be prepared.

Tablets (Siklos): Administer with water. If unable to swallow tablets whole, may disperse immediately before use in a small amount of water in a teaspoon (add tablet to spoon, add water; tablet dissolves in ~1 minute; administer immediately); drink an additional glass of water after administering the dose. The 100 mg tablets are scored with 1 line to enable splitting into 2 parts and the 1,000 mg tablets are scored with 3 lines to enable splitting into 4 parts; wear gloves and use a damp paper towel surface to break scored tablets (properly dispose of used gloves and paper towel). Note: Prior to October 2020, the 100 mg tablets were available as a film-coated (not scored) tablet; do not split the 100 mg film-coated (not scored) tablet into smaller parts.

Impervious gloves should be worn when handling bottles containing hydroxyurea or when handling/administering intact capsules/tablets. Wash hands with soap and water before and after contact with hydroxyurea. Avoid exposure to crushed capsules/tablets or open capsules. If skin contact occurs, immediately wash the affected area thoroughly with soap and water. If eye(s) contact occurs, the affected area should be flushed thoroughly with water or isotonic eyewash designated for that purpose for at least 15 minutes. If powder from the capsules or tablets is spilled, immediately wipe it up with a damp disposable towel and discard (along with the empty capsules) in a closed container, such as a plastic bag. The spill areas should then be cleaned using a detergent solution followed by clean water.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Storage/Stability

Droxia, Hydrea: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Keep bottle tightly closed.

Siklos: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Keep bottle tightly closed; use split tablets within 3 months.

Xromi: Store at 2°C to 8°C (35°F to 46°F); excursions permitted to 25°C (77°F) for up to 72 hours; do not freeze. Keep bottle tightly closed. Use within 12 weeks after initially opening the bottle; discard any unused solution remaining after 12 weeks.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product and as follows, must be dispensed with this medication:

Droxia: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/016295s058lbl.pdf#page=16

Siklos: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208843s004lbl.pdf#page=18

Xromi: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216593Orig2s000lbl.pdf#page=12

Use

Management of sickle cell anemia to reduce frequency of painful crises and the need for blood transfusions in patients with moderate to severe painful crises (Xromi: FDA approved in pediatric patients ≥6 months of age; Siklos: FDA approved in ages ≥2 years and adults; Droxia: FDA approved in adults); treatment of resistant chronic myeloid leukemia (CML) (Hydrea: FDA approved in adults); treatment of locally advanced squamous cell carcinomas of the head and neck (excluding lip cancer) in combination with concurrent chemoradiation (Hydrea: FDA approved in adults).

Medication Safety Issues
Sound-alike/look-alike issues:

Hydrea may be confused with Lyrica

Hydroxyurea may be confused with hydroxychloroquine, hydrOXYzine, Ure-Na, Urea (systemic)

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

International issues:

Hydrea [US, Canada, and multiple international markets] may be confused with Hydra brand name for isoniazid [Japan]

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Betibeglogene Autotemcel: Hydroxyurea may decrease therapeutic effects of Betibeglogene Autotemcel. Risk X: Avoid

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

BUPivacaine: Hydroxyurea may increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification

Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Didanosine: Hydroxyurea may increase adverse/toxic effects of Didanosine. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Didanosine may increase adverse/toxic effects of Hydroxyurea. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Risk X: Avoid

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Exagamglogene Autotemcel: Hydroxyurea may decrease therapeutic effects of Exagamglogene Autotemcel. Risk X: Avoid

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor

Lovotibeglogene Autotemcel: Hydroxyurea may decrease therapeutic effects of Lovotibeglogene Autotemcel. Risk X: Avoid

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Nitric Oxide: May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification

Prilocaine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor

Primaquine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Primaquine. Specifically, the risk for methemoglobinemia may be increased. Management: Avoid concomitant use of primaquine and other drugs that are associated with methemoglobinemia when possible. If combined, monitor methemoglobin levels closely. Risk D: Consider Therapy Modification

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification

Sodium Nitrite: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor

Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor

Stavudine: Hydroxyurea may increase adverse/toxic effects of Stavudine. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Stavudine may increase adverse/toxic effects of Hydroxyurea. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Risk X: Avoid

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Dietary Considerations

Supplemental administration of folic acid is recommended; hydroxyurea may mask development of folic acid deficiency.

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who could become pregnant.

It is recommended to discontinue hydroxyurea at least 3 months prior to conception in patients treated for sickle cell disease (SCD) (Jain 2019). Patients diagnosed with myeloproliferative neoplasms should also discontinue hydroxyurea prior to conception (with an adequate wash-out period) (Lishner 2016). According to the manufacturer, patients who could become pregnant should use effective contraception during treatment and for at least 6 months after completion of hydroxyurea therapy (regardless of indication).

Patients with partners who could become pregnant should also use effective contraception during and for at least 6 months (Siklos) or 1 year (Droxia, Hydrea, Xromi) after therapy. Hydroxyurea may damage spermatozoa and testicular tissue, resulting in potential genetic abnormalities.

Patients diagnosed with SCD have impaired semen quality. This may not be further impaired by hydroxyurea (Gille 2021; Joseph 2021). Oligo or azoospermia was reversed in most patients 3 months after hydroxyurea was discontinued in one study (Sahoo 2017). Because long-term use of hydroxyurea may cause damage to spermatogonia and germinal epithelium, the European Society for Medical Oncology recommends referral to a fertility specialist for patients requiring hydroxyurea treatment who wish to preserve fertility (ESMO [Lambertini 2020]).

The effect of hydroxyurea on ovarian reserve is not well studied in patients diagnosed with SCD (Pecker 2018; Pecker 2020). SCD itself may impair fertility by various mechanisms, including effects on the ovaries (Jain 2019).

Pregnancy Considerations

Based on its mechanism of action and data from animal reproduction studies, in utero exposure to hydroxyurea may cause fetal harm.

Treatment of chronic myelogenous leukemia (CML) during pregnancy should be individualized (ELN [Hochhaus 2020]). Pregnancy outcomes have been described in patients treated with hydroxyurea for cancer (NTP 2013). Although use of hydroxyurea for the treatment of CML during pregnancy has been reported (Assi 2021; Madabhavi 2019), use during pregnancy is not recommended (Berman 2018).

Patients with sickle cell disease (SCD) are at an increased risk of adverse pregnancy outcomes (ACOG 2007; Jain 2019). Although available data related to use of hydroxyurea for the treatment of SCD during pregnancy are reassuring (Ballas 2009; de Montalembert 2021; Montironi 2020), due to the potential risk of teratogenic effects, use of hydroxyurea should be discontinued prior to pregnancy (ACOG 2007; Jain 2019; Montironi 2020). Use of hydroxyurea during the second and third trimesters may be considered in select patients (Montironi 2020).

Monitoring Parameters

General: CBC with differential, LFTs and renal function should be checked at baseline and then periodically throughout therapy; serum uric acid; pregnancy status prior to therapy initiation in individuals of reproductive potential; monitor for cutaneous toxicities; signs and symptoms of pancreatitis.

Sickle cell anemia: CBC with differential, reticulocyte count, platelet count, and RBC mean corpuscular volume (MCV) at baseline (NHLBI 2014). Monitor hemoglobin F levels (every 3 to 4 months). During dose escalation, monitor for toxicity every 2 weeks (neutrophils, platelets, hemoglobin, reticulocytes) (manufacturer's labeling) or at least every 4 weeks when adjusting the dose (CBC with WBC differential, reticulocytes) (NHLBI 2014). Once on a stable dose, monitor CBC with differential, reticulocyte count, and platelets every 4 to 12 weeks (NHLBI 2014; Sanchez 2024; manufacturer's labeling).

Mechanism of Action

Hydroxyurea is an antimetabolite that selectively inhibits ribonucleoside diphosphate reductase, preventing the conversion of ribonucleotides to deoxyribonucleotides, halting the cell cycle at the G1/S phase and therefore has radiation sensitizing activity by maintaining cells in the G1 phase and interfering with DNA repair. In sickle cell anemia, hydroxyurea increases red blood cell (RBC) hemoglobin F levels, RBC water content, deformability of sickled cells, and alters adhesion of RBCs to endothelium.

Pharmacokinetics (Adult Data Unless Noted)

Note: In pediatric patients, large interpatient variability and phenotypic differences have been reported (Ware 2011). In children aged 6 months to <2 years and 2 to <6 years receiving a dose of 15 mg/kg/day, the AUC is 40% and 28% lower respectively compared to adults receiving the same dose.

Onset: Sickle cell anemia: Fetal hemoglobin increase: 4 to 12 weeks.

Absorption: Readily absorbed (≥80%); relatively rapid (Rodriguez 1998).

Distribution: Distributes widely into tissues (including into the brain); estimated volume of distribution approximates total body water (Gwilt 1998); concentrates in leukocytes and erythrocytes.

Vd: Pediatric patients: 12.09 ± 7.59 L (range: 2.5 to 52.44 L) (Ware 2011); Adults: ~20 L/m2 (Rodriguez 1998).

Metabolism: Up to 60% via saturable hepatic metabolism and degradation by urease found in intestinal bacteria.

Bioavailability: ~100% (Rodriguez 1998); Siklos: 85% to 100%.

Protein binding: 75% to 80% bound to serum proteins (Gwilt 1998).

Half-life elimination: Pediatric patients: Sickle cell anemia: 1.7 ± 0.53 hours (range: 0.65 to 3.05 hours) (Ware 2011); Adults: 1.9 to 3.9 hours (Gwilt 1998).

Time to peak: Pediatric patients: "Fast" phenotype: 15 to 30 minutes; "Slow" phenotype: 60 to 120 minutes (Ware 2011); Adults: 1 to 4 hours.

Excretion: Urine (sickle cell anemia: pediatric patients: ~40% of administered dose).

Clearance: Pediatric patients: 6.92 ± 3.17 L/hour (range: 1.57 to 21.59) (Ware 2011); Adults: ~7.5 L/hour (Rodriguez 1998).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Exposure is higher in patients with CrCl <60 mL/minute or end-stage renal disease.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Cureaml | Hydrea;
  • (AR) Argentina: Droxiurea | Hidroxiurea delta farma | Hidroxiurea eczane | Hidroxiurea filaxis | Hidroxiurea gobbi | Hidroxiurea gp pharm | Hidroxiurea kemex | Hidroxiurea lkm | Hidroxiurea martian | Hidroxiurea microsules | Hidroxiurea rontag | Hidroxiurea Varifa | Hydrea | Plariv;
  • (AT) Austria: Hydroxyurea | Hydroxyurea medac | Litalir | Siklos;
  • (AU) Australia: Hydrea;
  • (BD) Bangladesh: Hydronix | Mylostat;
  • (BE) Belgium: Hydrea | Siklos;
  • (BG) Bulgaria: Hydrea | Hydroxycarbamid;
  • (BR) Brazil: Hidroxiureia | Hydrea | Tepev | Ureax;
  • (CH) Switzerland: Hydroxycarbamid devatis | Hydroxycarbamid labatec | Litalir;
  • (CL) Chile: Hidroxicarbamida | Hydrea;
  • (CN) China: Hydrea;
  • (CO) Colombia: Hidroxyurea | Hydrea | Hydroxyurea | Oxiria | Syrea;
  • (CZ) Czech Republic: Biosupressin | Litalir;
  • (DE) Germany: Hydrea | Hydroxycarbamid | Hydroxycarbamid devatis | Hydroxycarbamid Hexal | Hydroxycarbamid ribosepharm | Litalir | Siklos | Syrea;
  • (DO) Dominican Republic: Durea | Hidroxiurea varifarma;
  • (EC) Ecuador: Hidroxiurea | Hidroxiurea kemex | Hydrea;
  • (EE) Estonia: Hydrea | Hydroxycarbamid teva;
  • (EG) Egypt: Cytodrox | Hydrea | Hydroxyurea | Syrea;
  • (ES) Spain: Hydrea | Siklos;
  • (ET) Ethiopia: Riborea;
  • (FI) Finland: Hydrea | Hydroxyurea medac | Oribamide | Siklos;
  • (FR) France: Hydrea | Siklos;
  • (GB) United Kingdom: Hydrea | Hydroxycarbam | Siklos;
  • (GR) Greece: Hydrea | Hydreasyn | Hydroxyurea | Siklos;
  • (HK) Hong Kong: Apo hydroxyurea | Hydrea | Hydroxyurea;
  • (HR) Croatia: Litalir | Xybaid;
  • (HU) Hungary: Biosupressin | Hydroxycarbamide pharmacenter | Litalir;
  • (ID) Indonesia: Cytodrox | Hydrea | Hydroxyurea medac;
  • (IE) Ireland: Hydrea;
  • (IL) Israel: Hydrea;
  • (IN) India: Cytodrox | Durea | Hondrea | Hydab | Hydran | Hydrea | Hydroford | Hydrosar | Hydrozest | Hytas | Leukocel | Myelostat | Neodrea | Oxyrea | Riborea | Unidrea;
  • (IT) Italy: Onco carbide | Siklos;
  • (JO) Jordan: Cureaml | Cytodrox | Hydab | Hydrea;
  • (JP) Japan: Hydrea;
  • (KR) Korea, Republic of: Hydrea | Hydrine | Jeil hydroxyurea | Union hydroxyurea;
  • (KW) Kuwait: Hydrea;
  • (LB) Lebanon: Cureaml | Hydrea | Unidrea;
  • (LT) Lithuania: Biosupressin | Hydrea | Zydrox 500;
  • (LU) Luxembourg: Hydrea | Siklos;
  • (LV) Latvia: Biosupressin | Hydrea | Hydroxycarbamid | Hydroxyurea | Litalir;
  • (MA) Morocco: Hydrea;
  • (MX) Mexico: Hydrea;
  • (MY) Malaysia: Dhnp | Hydrea | Hydroxyurea medac;
  • (NG) Nigeria: Hydrine | Oxyurea;
  • (NL) Netherlands: Hydrea | Hydroxycarbamide bmodesto | Hydroxyurea eureco pharma | Hydroxyurea medac | Hydroxyurea orifarm | Siklos;
  • (NO) Norway: Hydrea | Hydroxyurea | Siklos;
  • (NZ) New Zealand: Hydrea;
  • (PE) Peru: Droxamida | Durea | Hidroxicarbamida | Hidroxiurea | Hydrine;
  • (PH) Philippines: Hydab | Litalir | Mpl hi oxy;
  • (PK) Pakistan: Hdx | Hydrea | Hydrine | Hydrourea | Hydroxa;
  • (PL) Poland: Biosupressin | Hydroxycarbamid | Hydroxyurea medac;
  • (PR) Puerto Rico: Droxia | Hydrea | Hydroxyurea | Siklos;
  • (PT) Portugal: Hidroxicarbamida Hikma | Hydrea | Hydroxyurea medac | Siklos;
  • (PY) Paraguay: Hidroxiurea df | Hidroxiurea difucap eurand | Hidroxiurea farmaceutica paraguaya | Hidroxiurea libra | Hidroxiurea lkm | Hidroxiurea varifarma;
  • (QA) Qatar: Cureaml | Hydrea;
  • (RO) Romania: Hydrea;
  • (RU) Russian Federation: Hydrea | Hydroxycarbamide lens | Hydroxycarbamide medac | Hydroxycarbamide nativ | Hydroxyurea;
  • (SA) Saudi Arabia: Cureaml | Hydrea | Hydroxycarbamide medac | Siklos;
  • (SE) Sweden: Hydrea | Hydroxikarbamid orifarm | Hydroxyurea medac | Oribamide | Siklos;
  • (SG) Singapore: Hydrea | Hydrine;
  • (SI) Slovenia: Hydroxyurea medac | Litalir;
  • (SK) Slovakia: Litalir | Xybaid;
  • (SR) Suriname: Cytodrox | Hydroxyurea medac;
  • (TH) Thailand: Hydrea;
  • (TN) Tunisia: Cureaml | Hydrea;
  • (TR) Turkey: Hydmoxia | Hydrea;
  • (TW) Taiwan: Hydrea;
  • (UA) Ukraine: Apo hydroxyurea | Hydrea | Hydroxycarbamid | Hydroxycarbamide vista | Hydroxyurea;
  • (UG) Uganda: Hydroxyurea | Riborea;
  • (UY) Uruguay: Hidroxiurea delta farma | Hidroxiurea filaxis | Hidroxiurea libra | Hidroxiurea lkm | Hidroxiurea martian | Hydrea;
  • (VE) Venezuela, Bolivarian Republic of: Hidrea;
  • (VN) Viet Nam: Hytoxa | Hyxure;
  • (ZA) South Africa: Hydrea
  1. American College of Obstetricians and Gynecologists (ACOG) Committee on Obstetrics. ACOG Practice Bulletin No. 78: Hemoglobinopathies in pregnancy. Obstet Gynecol. 2007;109(1):229-237. doi:10.1097/00006250-200701000-00055 [PubMed 17197616]
  2. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. doi:10.1002/cpt.377 [PubMed 27060684]
  3. Antonioli E, Guglielmelli P, Pieri L, et al. Hydroxyurea-related toxicity in 3,411 patients with Ph'-negative MPN. Am J Hematol. 2012;87(5):552-554. [PubMed 22473827]
  4. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007:100.
  5. ASHP. Standardize 4 Safety Initiative Compounded Oral Liquid Version 1.01. July 2017. https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-ashp-oral-compound-liquids.ashx?la=en&hash=4C2E4F370B665C028981B61F6210335AD5D0D1D6.
  6. Assi R, Kantarjian H, Keating M, et al. Management of chronic myeloid leukemia during pregnancy among patients treated with a tyrosine kinase inhibitor: a single-center experience. Leuk Lymphoma. 2021;62(4):909-917. doi:10.1080/10428194.2020.1849672 [PubMed 33283580]
  7. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872-884. [PubMed 23803709]
  8. Ballas SK, McCarthy WF, Guo N, et al; Multicenter study of hydroxyurea in sickle cell anemia. Exposure to hydroxyurea and pregnancy outcomes in patients with sickle cell anemia. J Natl Med Assoc. 2009;101(10):1046-1051. doi:10.1016/s0027-9684(15)31072-5 [PubMed 19860305]
  9. Barbui T, Tefferi A, Vannucchi AM, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32(5):1057-1069. doi:10.1038/s41375-018-0077-1 [PubMed 29515238]
  10. Bath H, Jawandha K, Elhassan MG. Hydroxyurea-induced acute pancreatitis. Cureus. 2022;14(6):e26132. doi:10.7759/cureus.26132 [PubMed 35891817]
  11. Berman E, Druker BJ, Burwick R. Chronic myelogenous leukemia: pregnancy in the era of stopping tyrosine kinase inhibitor therapy. J Clin Oncol. 2018;36(12):1250-1256. doi:10.1200/JCO.2017.77.2574 [PubMed 29447062]
  12. Bilbao-Meseguer I, Rodríguez-Gascón A, Barrasa H, Isla A, Solinís MÁ. Augmented renal clearance in critically ill patients: a systematic review. Clin Pharmacokinet. 2018;57(9):1107-1121. doi:10.1007/s40262-018-0636-7 [PubMed 29441476]
  13. Brawley OW, Cornelius LJ, Edwards LR, et al. National Institutes of Health Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell Disease. Ann Intern Med. 2008;148(12):932-938. [PubMed 18458271]
  14. Burnett AK, Milligan D, Prentice AG, et al. A Comparison of Low-Dose Cytarabine and Hydroxyurea With or Without All-Trans Retinoic Acid for Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome in Patients Not Considered Fit for Intensive Treatment. Cancer. 2007;109(6):1114-1124. [PubMed 17315155]
  15. Cortes J, Kantarjian H. How I treat newly diagnosed chronic phase CML. Blood. 2012;120(7):1390-1397. [PubMed 22613793]
  16. DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020;4(8):1554-1588. doi:10.1182/bloodadvances.2019001142 [PubMed 32298430]
  17. de Montalembert M, Voskaridou E, Oevermann L, et al; All ESCORT HU Investigators. Real-life experience with hydroxyurea in patients with sickle cell disease: results from the prospective ESCORT-HU cohort study. Am J Hematol. 2021;96(10):1223-1231. doi:10.1002/ajh.26286 [PubMed 34224583]
  18. DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386-2398. [PubMed 29860938]
  19. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-474. doi:10.1182/blood-2009-07-235358 [PubMed 19880497]
  20. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867 [PubMed 35797463]
  21. Droxia (hydroxyurea) [prescribing information]. Montgomery, AL: H2-Pharma LLC; December 2023.
  22. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  23. Fathi AT, DiNardo CD, Kline I, et al; AG221-C-001 Study Investigators. Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2: analysis of a phase 1/2 study. JAMA Oncol. 2018;4(8):1106-1110. doi:10.1001/jamaoncol.2017.4695 [PubMed 29346478]
  24. Finazzi G, Barbui T. How I Treat Patients With Polycythemia Vera. Blood. 2007;109(12):5104-5111. [PubMed 17264301]
  25. Garden AS, Harris J, Vokes EE, et al. Preliminary Results of Radiation Therapy Oncology Group 97-03: A Randomized Phase II Trial of Concurrent Radiation and Chemotherapy for Advanced Squamous Cell Carcinomas of the Head and Neck. J Clin Oncol. 2004;22(14):2856-2864. [PubMed 15254053]
  26. Gavini DR, Salvi DJ, Shah PH, Uma D, Lee JH, Hamid P. Non-melanoma skin cancers in patients on hydroxyurea for Philadelphia chromosome-negative myeloproliferative neoplasms: a systematic review. Cureus. 2021;13(8):e16978. doi:10.7759/cureus.16978 [PubMed 34527458]
  27. Gille AS, Pondarré C, Dalle JH, et al. Hydroxyurea does not affect the spermatogonial pool in prepubertal patients with sickle cell disease. Blood. 2021;137(6):856-859. doi:10.1182/blood.2020008146 [PubMed 33259585]
  28. Gisslinger H, Gotic M, Holowiecki J, et al. Anagrelide Compared With Hydroxyurea in WHO-Classified Essential Thrombocythemia: The ANAHYDRET Study, A Randomized Controlled Trial. Blood. 2013;121(10):1720-1728. [PubMed 23315161]
  29. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi: 10.1200/JCO.21.00471 [PubMed 33939491]
  30. Grund FM, Armitage JO, Burns P. Hydroxyurea in the prevention of the effects of leukostasis in acute leukemia. Arch Intern Med. 1977;137(9):1246-1247. [PubMed 268956]
  31. Gwilt PR, Tracewell WG. Pharmacokinetics and Pharmacodynamics of Hydroxyurea. Clin Pharmacokinet. 1998;34(5):347-358. [PubMed 9592619]
  32. Hankins JS, Ware RE, Rogers ZR, et al. Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. Blood. 2005;106(7):2269-2275. doi:10.1182/Blood-2004-12-4973 [PubMed 16172253]
  33. Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea Compared With Anagrelide in High-Risk Essential Thrombocythemia. N Engl J Med. 2005;353(1):33-45. [PubMed 16000354]
  34. Heeney MM, Ware RE. Hydroxyurea for children with sickle cell disease. Pediatr Clin North Am. 2008;55(2):483-501. [PubMed 18381097]
  35. Heeney MM, Whorton MR, Howard TA, Johnson CA, Ware RE. Chemical and functional analysis of hydroxyurea oral solutions. J Pediatr Hematol Oncol. 2004;26(3):179-184. doi:10.1097/00043426-200403000-00007 [PubMed 15125610]
  36. Hehlmann R, Heimpel H, Hasford J, et al. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group. Blood. 1993;82(2):398-407. [PubMed 8329700]
  37. Hernández-Boluda JC1, Alvarez-Larrán A, Gómez M, et al. Clinical evaluation of the European LeukaemiaNet criteria for clinicohaematological response and resistance/intolerance to hydroxycarbamide in essential thrombocythaemia. Br J Haematol. 2011;152(1):81-88. [PubMed 21083657]
  38. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-984. doi:10.1038/s41375-020-0776-2 [PubMed 32127639]
  39. Hodson L, Ovesen J, Couch J, et al; US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Managing hazardous drug exposures: information for healthcare settings, 2023. https://doi.org/10.26616/NIOSHPUB2023130. Updated April 2023. Accessed December 27, 2024.
  40. Howard LW, Kennedy LD. Hydroxyurea in the Treatment of Sickle-Cell Anemia. Ann Pharmacother. 1997;31(11):1393-1396. [PubMed 9391697]
  41. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  42. Hydrea (hydroxyurea) [prescribing information]. Montgomery, AL: H2-Pharma LLC; December 2023.
  43. Hydrea (hydroxyurea) [prescribing information]. Montgomery, AL: H2-Pharma LLC; November 2023.
  44. Hydrea (hydroxyurea) [product monograph]. Montreal, Canada: Bristol-Myers Squibb Canada; August 2021.
  45. Hydrea (hydroxyurea) [product monograph]. Oakville, Ontario, Canada: Xediton Pharmaceuticals Inc; September 2024.
  46. Issaivanan M, Mitu PS, Manisha C, Praveen K. Cutaneous manifestations of hydroxyurea therapy in childhood: case report and review. Pediatr Dermatol. 2004;21(2):124-127. doi:10.1111/j.0736-8046.2004.21207.x [PubMed 15078351]
  47. Ito S. Drug therapy for breast-feeding women. NEJM. 2000;343(2):118-126. doi:10.1056/NEJM200007133430208 [PubMed 10891521]
  48. Itzykson R, Santini V, Thepot S, et al. Decitabine versus hydroxyurea for advanced proliferative chronic myelomonocytic leukemia: results of a randomized phase III trial within the EMSCO network. J Clin Oncol. 2023;41(10):1888-1897. doi:10.1200/JCO.22.00437 [PubMed 36455187]
  49. Jabr FI, Shamseddine A, Taher A. Hydroxyurea-induced hemolytic anemia in a patient with essential thrombocythemia. Am J Hematol. 2004;77(4):374-376. doi:10.1002/ajh.20222 [PubMed 15558807]
  50. Jain D, Atmapoojya P, Colah R, Lodha P. Sickle cell disease and pregnancy. Mediterr J Hematol Infect Dis. 2019;11(1):e2019040. doi:10.4084/MJHID.2019.040 [PubMed 31308916]
  51. Joseph L, Jean C, Manceau S, et al. Effect of hydroxyurea exposure before puberty on sperm parameters in males with sickle cell disease. Blood. 2021;137(6):826-829. doi:10.1182/blood.2020006270 [PubMed 32976551]
  52. Kato N, Kimura K, Yasukawa K, Yoshida K. Hydroxyurea-related leg ulcers in a patient with chronic myelogenous leukemia: a case report and review of the literature. J Dermatol. 1999;26(1):56-62. doi:10.1111/j.1346-8138.1999.tb03510.x [PubMed 10063214]
  53. Kavanagh PL, Fasipe TA, Wun T. Sickle cell disease: a review. JAMA. 2022;328(1):57-68. doi:10.1001/jama.2022.10233 [PubMed 35788790]
  54. Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011;29(29):3907-3913. doi:10.1200/JCO.2011.36.0792 [PubMed 21911721]
  55. Kinney TR, Helms RW, O’Branski EE, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Blood. 1999;94(5):1550-1554. [PubMed 10477679]
  56. Kintzel PE, Dorr RT. Anticancer Drug Renal Toxicity and Elimination: Dosing Guidelines for Altered Renal Function. Cancer Treat Rev. 1995;21(1):33-64. [PubMed 7859226]
  57. Kissova J, Ovesna P, Penka M, Bulikova A, Kiss I. Second malignancies in Philadelphia-negative myeloproliferative neoplasms-single-center experience. Anticancer Res. 2014;34(5):2489-2496. [PubMed 24778065]
  58. Klion AD, Bochner BS, Gleich GJ, et al. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol. 2006;117(6):1292-1302. doi:10.1016/j.jaci.2006.02.042 [PubMed 16750989]
  59. Krens SD, Lassche G, Jansman FGA, et al. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol. 2019;20(4):e200-e207. doi:10.1016/S1470-2045(19)30145-7 [PubMed 30942181]
  60. Kumar B, Saraswat A, Kaur I. Rediscovering Hydroxyurea: Its Role in Recalcitrant Psoriasis. Int J Dermatol. 2001;40(8):530-534. [PubMed 11703528]
  61. Kutlu Ö, Kutlu FN, Tekin Y. Hydroxyurea-associated multiple squamous cell carcinoma developed on the dermatomyositis-like eruption. Indian J Dermatol. 2023;68(5):588. doi:10.4103/ijd.ijd_242_23 [PubMed 38099103]
  62. Lambertini M, Peccatori FA, Demeestere I, et al; ESMO Guidelines Committee. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO clinical practice guidelines. Ann Oncol. 2020;31(12):1664-1678. doi:10.1016/j.annonc.2020.09.006 [PubMed 32976936]
  63. Layton AM, Cotterill JA, Tomlinson IW. Hydroxyurea-induced lupus erythematosus. Br J Dermatol. 1994;130(5):687-688. doi:10.1111/j.1365-2133.1994.tb13129.x [PubMed 8204488]
  64. Lishner M, Avivi I, Apperley JF, et al. Hematologic malignancies in pregnancy: management guidelines from an international consensus meeting. J Clin Oncol. 2016;34(5):501-508. doi:10.1200/JCO.2015.62.4445 [PubMed 26628463]
  65. Lo-Coco F, Avvisati G, Vignetti M, et al; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111-121. doi:10.1056/NEJMoa1300874 [PubMed 23841729]
  66. Longhurst HJ, Pinching AJ. Pancreatitis Associated With Hydroxyurea in Combination With Didanosine. Br Med J. 2001;322(7278):81.
  67. Madabhavi I, Sarkar M, Modi M, Kadakol N. Pregnancy outcomes in chronic myeloid leukemia: a single center experience. J Glob Oncol. 2019;5:1-11. doi:10.1200/JGO.18.00211 [PubMed 31584851]
  68. Martínez-Trillos A, Gaya A, Maffioli M, et al. Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. Ann Hematol. 2010;89(12):1233-1237. doi:10.1007/s00277-010-1019-9 [PubMed 20567824]
  69. Mattessich S, Ferenczi K, Lu J. Successful treatment of hydroxyurea-associated panniculitis and vasculitis with low-dose methotrexate. JAAD Case Rep. 2017;3(5):422-424. doi:10.1016/j.jdcr.2017.06.009 [PubMed 28932785]
  70. McMullin MF, Harrison CN, Ali S, et al; BSH Committee. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology Guideline. Br J Haematol. 2019;184(2):176-191. doi:10.1111/bjh.15648 [PubMed 30478826]
  71. Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519-1531. doi:10.1056/NEJMoa2117344 [PubMed 35443108]
  72. Montironi R, Cupaiolo R, Kadji C, et al. Management of sickle cell disease during pregnancy: experience in a third-level hospital and future recommendations. J Matern Fetal Neonatal Med. 2020:1-9. doi:10.1080/14767058.2020.1786054 [PubMed 32627603]
  73. Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997;90(9):3370-3377. [PubMed 9345019]
  74. National Heart, Lung, and Blood Institute (NHLBI). Evidence-based management of sickle cell disease: expert panel report, 2014. Bethesda, MD: National Institutes of Health; 2014. http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines. Accessed March 19, 2015.
  75. National Toxicology Program. NTP monograph: developmental effects and pregnancy outcomes associated with cancer chemotherapy use during pregnancy. NTP Monogr. 2013;(2):i-214. [PubMed 24736875]
  76. Newton HB, Scott SR, Volpi C. Hydroxyurea chemotherapy for meningiomas: enlarged cohort with extended follow-up. Br J Neurosurg. 2004;18(5):495-499. doi:10.1080/02688690400012392 [PubMed 15799152]
  77. Newton HB, Slivka MA, Stevens C. Hydroxyurea Chemotherapy for Unresectable or Residual Meningioma. J Neurooncol. 2000;49(2):165-170. [PubMed 11206012]
  78. Ogbogu PU, Bochner BS, Butterfield JH, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009;124(6):1319-1325. doi:10.1016/j.jaci.2009.09.022 [PubMed 19910029]
  79. Okuyucu M, Atay MH. Hydroxyurea-induced tooth discoloration. Turk J Haematol. 2020;37(1):74-75. doi:10.4274/tjh.galenos.2019.2019.0275 [PubMed 31711282]
  80. Ovesen JL, Sam­mons D, Connor TH, et al; US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NIOSH list of hazardous drugs in healthcare settings, 2024. https://doi.org/10.26616/NIOSHPUB2025103. Updated December 18, 2024. Accessed December 20, 2024.
  81. Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med. 1978;89(2):167-172. [PubMed 677578]
  82. Pecker LH, Hussain S, Christianson MS, Lanzkron S. Hydroxycarbamide exposure and ovarian reserve in women with sickle cell disease in the multicenter study of hydroxycarbamide. Br J Haematol. 2020;191(5):880-887. doi:10.1111/bjh.16976 [PubMed 32712966]
  83. Pecker LH, Maher JY, Law JY, Beach MC, Lanzkron S, Christianson MS. Risks associated with fertility preservation for women with sickle cell anemia. Fertil Steril. 2018;110(4):720-731. doi:10.1016/j.fertnstert.2018.05.016 [PubMed 30196969]
  84. Pressiat C, Rakotoson MG, Habibi A, et al. Impact of renal function on hydroxyurea exposure in sickle-cell disease patients. Br J Clin Pharmacol. 2021;87(5):2274-2285. doi:10.1111/bcp.14653 [PubMed 33217005]
  85. Randi ML, Ruzzon E, Luzzatto G, Tezza F, Girolami A, Fabris F. Safety profile of hydroxyurea in the treatment of patients with Philadelphia-negative chronic myeloproliferative disorders. Haematologica. 2005;90(2):261-262. [PubMed 15710584]
  86. Refer to manufacturer's labeling.
  87. Restituto P, Mugueta C, Alegre E, et al. Analytical Interference of Hydroxyurea in the Determination of Urea, Uric Acid, and Lactic Acid. Anal Biochem. 2006;357(1):147-149. [PubMed 16843426]
  88. Rodgers GP, Dover GJ, Noguchi CT, et al. Hematologic Responses of Patients With Sickle Cell Disease to Treatment With Hydroxyurea. N Engl J Med. 1990;322(15):1037-1045. [PubMed 1690857]
  89. Rodgers GP, Dover GJ, Uyesaka N, et al. Augmentation by Erythropoietin of the Fetal-Hemoglobin Response to Hydroxyurea in Sickle Cell Disease. N Engl J Med. 1993;328(2):73-80. [PubMed 7677965]
  90. Rodriguez GI, Kuhn JG, Weiss GR, et al. A bioavailability and pharmacokinetic study of oral and intravenous hydroxyurea. Blood. 1998;91(5):1533-1541. [PubMed 9473217]
  91. Rose PG, Ali S, Watkins E, et al. Long-Term Follow-Up of a Randomized Trial Comparing Concurrent Single Agent Cisplatin, Cisplatin-Based Combination Chemotherapy, or Hydroxyurea During Pelvic Irradiation for Locally Advanced Cervical Cancer: A Gynecologic Oncology Group Study. J Clin Oncol. 2007;25(19):2804-2810. [PubMed 17502627]
  92. Rosenthal MA, Ashley DL, Cher L. Treatment of High Risk or Recurrent Meningiomas With Hydroxyurea. J Clin Neurosci. 2002;9(2):156-158. [PubMed 11922703]
  93. Sahoo LK, Kullu BK, Patel S, et al. Study of seminal fluid parameters and fertility of male sickle cell disease patients and potential impact of hydroxyurea treatment. J Assoc Physicians India. 2017;65(6):22-25. [PubMed 28782309]
  94. Sánchez LM, Morrone K, Frei-Jones M, Fasipe TA. Clinical practice patterns in sickle cell disease treatment: disease-modifying and potentially curative therapies. J Pediatr Hematol Oncol. 2024;46(5):e277-e283. doi:10.1097/MPH.0000000000002869 [PubMed 38718300]
  95. Sandhu HS, Barnes PJ, Hernandez P. Hydroxyurea-induced hypersensitivity pneumonitis: a case report and literature review. Can Respir J. 2000;7(6):491-495. doi:10.1155/2000/297045 [PubMed 11121094]
  96. Sanz MA, Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood. 2014;123(18):2777-2782. doi:10.1182/blood-2013-10-512640 [PubMed 24627526]
  97. Siklos (hydroxyurea) [prescribing information]. Rosemont, PA: Medunik USA Inc; November 2023.
  98. Strouse JJ, Heeney MM. Hydroxyrea for the treatment of sickle cell disease: efficacy, barriers, toxicity, and management in children. Pediatr Blood Cancer. 2012;59(2):365-371. [PubMed 22517797]
  99. Sylvester RK, Lobell M, Teresi ME, Brundage D, Dubowy R. Excretion of hydroxyurea into milk. Cancer. 1987;60(9):2177-2178. doi:10.1002/1097-0142(19871101)60:9<2177::aid-cncr2820600911>3.0.co;2-p [PubMed 3481556]
  100. Tefferi A, Pardanani A. Essential thrombocythemia. N Engl J Med. 2019;381(22):2135-2144. doi:10.1056/NEJMcp1816082 [PubMed 31774958]
  101. Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874-1881. doi:10.1038/leu.2013.163 [PubMed 23739289]
  102. Thornburg CD, Files BA, Luo Z, et al. Impact of Hydroxyurea on Clinical Events in the BABY HUG Trial. Blood. 2012;120(22):4304-4310. [PubMed 22915643]
  103. Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi:10.2165/11318140-000000000-00000 [PubMed 20000886]
  104. United States Pharmacopeia. <800> Hazardous Drugs—Handling in Healthcare Settings. In: USP-NF. United States Pharmacopeia; July 1, 2020. Accessed January 16, 2025. doi:10.31003/USPNF_M7808_07_01
  105. Vannucchi AM, Barbui T, Cervantes F, et al; ESMO Guidelines Committee. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(suppl 5):v85-v99. doi:10.1093/annonc/mdv203 [PubMed 26242182]
  106. Vannucchi AM. How I treat polycythemia vera. Blood. 2014;124(22):3212-3220. doi:10.1182/blood-2014-07-551929 [PubMed 25278584]
  107. Veillet-Lemay G, Haber RM. Hydroxyurea-induced oral hyperpigmentation: a case report and review of the literature. J Cutan Med Surg. 2019;23(1):111-113. doi:10.1177/1203475418803074 [PubMed 30232899]
  108. Wang WC, Ware RE, Miller ST, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011;377(9778):1663-1672. doi:10.1016/S0140-6736(11)60355-3 [PubMed 21571150]
  109. Wang WC, Wynn LW, Rogers ZR, Scott JP, Lane PA, Ware RE. A two-year pilot trial of hydroxyurea in very young children with sickle-cell anemia. J Pediatr. 2001;139(6):790-796. doi:10.1067/mpd.2001.119590 [PubMed 11743503]
  110. Ware RE, Despotovic JM, Mortier NA, et al. Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia. Blood. 2011;118(18):4985-4991. doi:10.1182/blood-2011-07-364190 [PubMed 21876119]
  111. Ware RE, Marahatta A, Ware JL, McElhinney K, Dong M, Vinks AA. Hydroxyurea exposure in lactation: a pharmacokinetics study (HELPS). J Pediatr. 2020;222:236-239. doi:10.1016/j.jpeds.2020.02.002 [PubMed 32171562]
  112. Wattel E, Guerci A, Hecquet B, et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Français des Myélodysplasies and European CMML Group. Blood. 1996;88(7):2480-2487. [PubMed 8839839]
  113. Westerman DA, Schwarer A, Grigg AP. Hydroxyurea-induced fever and hepatitis. Aust N Z J Med. 1998;28(5):657-659. doi:10.1111/j.1445-5994.1998.tb00664.x [PubMed 9847957]
  114. Wong TE, Brandow AM, Lim W, Lottenberg R. Update on the use of hydroxyurea therapy in sickle cell disease. Blood. 2014;124(26):3850-3857. [PubMed 25287707]
  115. Worley B, Glassman SJ. Acral keratoses and leucocytoclastic vasculitis occurring during treatment of essential thrombocythaemia with hydroxyurea. Clin Exp Dermatol. 2016;41(2):166-169. doi:10.1111/ced.12708 [PubMed 26269121]
  116. Xromi (hydroxyurea) [prescribing information]. Franklin, TN: Rare Disease Therapeutics Inc; December 2024.
  117. Xromi (hydroxyurea) [summary of product characteristics]. Dublin, Ireland: Nova Laboratories Ireland Limited.
  118. Yan JH, Ataga K, Kaul S, et al. The influence of renal function on hydroxyurea pharmacokinetics in adults with sickle cell disease. J Clin Pharmacol. 2005;45(4):434-445. doi:10.1177/0091270004273526 [PubMed 15778424]
  119. Yanamandra U, Sahu KK, Malhotra P, Varma S. Photodermatosis secondary to hydroxyurea. BMJ Case Rep. 2014;2014:bcr2014205974. doi:10.1136/bcr-2014-205974 [PubMed 25270158]
  120. Yanes DA, Mosser-Goldfarb JL. A cutaneous lupus erythematosus-like eruption induced by hydroxyurea. Pediatr Dermatol. 2017;34(1):e30-e31. doi:10.1111/pde.13018 [PubMed 27813209]
  121. Zimmerman SA, Schultz WH, Davis JS, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood. 2004;103(6):2039-2045. doi:10.1182/blood-2003-07-2475 [PubMed 14630791]
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