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.
Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies.
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.
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.
Infants ≥6 months, Children, and Adolescents: Oral: There are no dosage adjustments provided in the manufacturer's labeling; closely monitor for hematologic toxicity.
(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.
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 (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 (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).
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).
Meningioma, recurrent, high risk, or unresectable (off-label use): Oral: 20 mg/kg once daily (Ref).
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:
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.
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).
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).
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)
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)
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)
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)
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).
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.
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
May be product dependent
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Hydrea: 500 mg
Generic: 500 mg
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).
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.
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 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).
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.
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
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).
Hydrea may be confused with Lyrica
Hydroxyurea may be confused with hydroxychloroquine, hydrOXYzine, Ure-Na, Urea (systemic)
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).
Hydrea [US, Canada, and multiple international markets] may be confused with Hydra brand name for isoniazid [Japan]
None known.
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
Supplemental administration of folic acid is recommended; hydroxyurea may mask development of folic acid deficiency.
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).
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).
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).
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.
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).
Altered kidney function: Exposure is higher in patients with CrCl <60 mL/minute or end-stage renal disease.