Advanced Breast Cancer: Learn about treatment options.

Hydroxyurea (Systemic)


VA CLASSIFICATION
Primary: AN300
Secondary: BL400

Commonly used brand name(s): Droxia; Hydrea.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

Antianemic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Carcinoma, ovarian (treatment)1 or
[Carcinoma, cervical (treatment)]1—Hydroxyurea is indicated for treatment of recurrent, metastatic, or inoperable carcinoma of the ovary{01}{09}{11}{12} and for treatment of cervical carcinoma{06}.

Carcinoma, head and neck (treatment adjunct)—Used with irradiation therapy for local control of primary squamous cell (epidermoid) carcinomas of the head and neck, excluding the lip.{09}{10}{11}{12}

Leukemia, chronic myelocytic (treatment)—Hydroxyurea is indicated for treatment of resistant chronic myelocytic leukemia {01}{09}{10}{11}{12}.

Melanoma (treatment)—Hydroxyurea is indicated for the treatment of melanoma.{09}{10}{11}{12}

[Thrombocytosis, essential (treatment) ]1 or
[Polycythemia vera (treatment)]1—Hydroxyurea is indicated for treatment of essential thrombocytosis{07} and polycythemia vera{02}{03}.

Sickle cell anemia, painful crises (prophylaxis) 1—Hydroxyurea is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises (generally at least 3 during the preceding 12 months){08}.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    76.05

Mechanism of action/Effect:

Hydroxyurea is classified as an antimetabolite. Hydroxyurea is thought to be cell cycle–specific for the S phase of cell division. The exact mechanism of antineoplastic activity is unknown but is thought to involve interference with synthesis of DNA, with no effect on synthesis of RNA or protein.

Pharmacologic effects of hydroxyurea that may contribute to its beneficial effects in sickle cell anemia include increasing hemoglobin F levels in red blood cells (RBCs), decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to the endothelium{08}.

Absorption:

Well absorbed from the gastrointestinal tract{08}.

Distribution:

Crosses the blood-brain barrier.

Volume of distribution (VD)—Equal to total body water.

Concentrates in leukocytes (white blood cells) (WBCs) and erythrocytes (red blood cells) (RBCs).

Biotransformation:

Hepatic.

Half-life:

3 to 4 hours.

Time to peak concentration:

1 to 4 hours.{08}

Elimination:
    Renal—80% within 12 hours {01} (50% unchanged). In adults with sickle cell anemia, the mean cumulative urinary excretion was 62% of the administered dose at 8 hours{08}.
    Hepatic—Saturable.{08}
    Respiratory—As carbon dioxide.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to tartrazine may be sensitive to the capsule dosage form available in Canada also, since the capsules may contain tartrazine.

Carcinogenicity

Secondary malignancies are potential delayed effects of many antineoplastic agents, although it is not clear whether the effect is related to their mutagenic or immunosuppressive action. The effect of dose and duration of therapy is also unknown, although risk seems to increase with long-term use. Although information is limited, available data seem to indicate that the carcinogenic risk is greatest with the alkylating agents.

Antimetabolites have been shown to be carcinogenic in animals and may be associated with an increased risk of development of secondary carcinomas in humans, although the risk appears to be less than with alkylating agents.

Tumorigenicity

An increased incidence of mammary tumors has been reported for female rats administered intraperitoneal hydroxyurea at 125 to 250 mg per kilogram (mg/kg) of body weight (about 0.6 to 1.2 times the maximum recommended human oral daily dose on a mg per square meter [mg/m 2] basis) three times a week for six months{08}.

Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype{08}.

Mutagenicity

Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells{08}.

Hydroxyurea is clastogenic in vitro (in hamster cells and human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay){08}.

Pregnancy/Reproduction
Fertility—
Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking antineoplastic therapy, especially with the alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian function impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents. Hydroxyurea causes reversible germ cell toxicity.

Pregnancy—
No adequate and well controlled studies have been done in pregnant women.

First trimester: It is usually recommended that use of antineoplastics, especially combination chemotherapy, be avoided whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered.

Other hazards to the fetus include adverse reactions seen in adults.

In general, use of a contraceptive is recommended during cytotoxic drug therapy.

Hydroxyurea is teratogenic in animals. It is also embryotoxic, causing decreased fetal viability, decreased litter size, developmental delays, growth retardation, impaired learning ability, and malformations (partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, missing lumbar vertebrae) at 180 mg/kg per day (about 0.8 times the maximum recommended human daily dose on a mg per square meter of body surface area basis) in rats and at 30 mg/kg per day (about 0.3 times the maximum recommended human daily dose on a mg per square meter of body surface area basis) in rabbits.

FDA Pregnancy Category D{08}.

Breast-feeding

Hydroxyurea is excreted in human breast milk. {08} Because of the potential for serious adverse effects, a decision should be made to discontinue nursing or discontinue the medication, taking into consideration the importance of the medication to the mother.

Pediatrics

Although appropriate studies on the relationship of age to the effects of hydroxyurea have not been performed in the pediatric population, children may be more sensitive to the effects of hydroxyurea.


Geriatrics


Although appropriate studies on the relationship of age to the effects of hydroxyurea have not been performed in the geriatric population, the elderly may be more sensitive to effects of hydroxyurea {01}. In addition, elderly patients are more likely to have age-related renal function impairment, which may require reduction of dosage in patients receiving hydroxyurea.


Dental

The bone marrow depressant effects of hydroxyurea may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene during treatment, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Hydroxyurea may also cause stomatitis associated with considerable discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Allopurinol or
Colchicine or
» Probenecid or
» Sulfinpyrazone    (hydroxyurea may raise the concentration of blood uric acid; dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse hydroxyurea-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents)


Blood dyscrasia–causing medications (see Appendix II)    (leukopenic and/or thrombocytopenic effects of hydroxyurea may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of hydroxyurea, if necessary, should be based on blood counts )


» Bone marrow depressants, other (see Appendix II) or
Radiation therapy    (additive bone marrow depression may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


» Didanosine or
» Stavudine or
» Antiretroviral agents, other    (in HIV-infected patients, fatal and nonfatal pancreatitis, hepatotoxicity, hepatic failure, and peripheral neuropathy have been reported with concurrent treatment with other antiretroviral agents, especially didanosine with or without stavudine{09})


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by hydroxyurea therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medications used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by hydroxyurea therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the hydroxyurea therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medications used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. Immunization with oral poliovirus vaccine should also be postponed in persons in close contact with the patient, especially family members)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Blood urea nitrogen (BUN) and
Creatinine, serum and
Uric acid, serum    (concentrations may occasionally be temporarily increased as a result of impairment of renal tubular function{01}{08})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Anemia or
» Leukopenia or
» Neutropenia or
» Thrombocytopenia{08}    (if severe, must be corrected with whole blood replacement before initiation of hydroxyurea therapy{01})


» Bone marrow depression
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)


Gout, history of or
Urate renal stones, history of    (risk of hyperuricemia)


» HIV infection, especially concurrent treatment with antiretroviral agents    (fatal and nonfatal pancreatitis, hepatotoxicity, hepatic failure, and peripheral neuropathy reported with concurrent treatment with other antiretroviral agents, especially didanosine with or without stavudine{09})


» Infection
» Renal function impairment    (reduced elimination; lower dosage is recommended)


» Hypersensitivity to hydroxyurea {01}
» Caution should be used in patients who have had previous cytotoxic drug therapy and radiation therapy.

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood urea nitrogen (BUN) concentrations and
Creatinine concentrations, serum    (recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


» Hematocrit or hemoglobin and
» Leukocyte count, total and, if appropriate, differential and
» Platelet count    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


Uric acid concentrations, serum    (recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)




Side/Adverse Effects

Note: Many “side effects” of antineoplastic therapy are unavoidable and represent the medication's pharmacologic action. Some of these (for example, leukopenia and thrombocytopenia) are actually used as parameters to aid in individual dosage titration.
Administration of hydroxyurea to patients with severe renal function impairment may produce visual and auditory hallucinations and pronounced hematologic toxicity.
Skin changes resembling atrophic lichen planus, including atrophy, brittle nails, darkening or redness of skin, and skin ulcers, have been reported rarely in patients receiving prolonged (over several years) daily treatment with hydroxyurea {04} {05}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Anemia {01} or erythrocytic or platelet abnormalities
    
leukopenia
    
neutropenia (cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination)— usually asymptomatic

Note: Self-limiting megaloblastic erythropoiesis occurs commonly early in the course of therapy; morphologic changes resemble pernicious anemia, but are not related to vitamin B 12 or folic acid deficiency {01}. Plasma iron clearance may be delayed and rate of iron utilization by erythrocytes reduced, but hydroxyurea does not appear to alter red blood cell survival time {01}.
Onset of leukopenia occurs about 10 days after initiation of therapy.
Hematologic abnormalities usually recover 2 weeks after cessation of therapy.{08}


Incidence less frequent
    
Melanonychia (blackening of fingernails and toenails)
    
stomatitis (sores in mouth and on lips)
    
thrombocytopenia (unusual bleeding or bruising; black, tarry stools ; blood in urine or stools; pinpoint red spots on skin)—usually asymptomatic

Incidence rare
    
Hyperuricemia or uric acid nephropathy (joint pain; lower back or side pain; swelling of feet or lower legs)
    
neurotoxicity or cerebral metastatic disease (confusion; convulsions; dizziness; hallucinations; headache)
    
renal function impairment {01} (difficulty in urination)

Note: Hyperuricemia or uric acid nephropathy occurs most commonly during initial treatment of patients with leukemia, as a result of rapid cell breakdown, which leads to elevated serum uric acid concentrations.




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
—dose-related     
Diarrhea
    
drowsiness —large doses
    
loss of appetite
    
nausea or vomiting

Incidence less frequent
    
Constipation
    
exacerbation of postirradiation erythema ( redness of skin at place of irradiation)
    
skin rash and itching



Those not indicating need for medical attention
Incidence less frequent
    
Loss of hair

Note: Normal hair growth usually returns after treatment has ended, although it may be slightly different in color or texture




Those indicating the need for medical attention if they occur after medication is discontinued
    
Bone marrow depression (black, tarry stools; blood in urine; cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination; pinpoint red spots on skin; unusual bleeding or bruising)




Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Edema of palms and soles (swelling of palms and soles of feet)

scaling of hands and feet

severe generalized hyperpigmentation of the skin (darkening of skin color)

soreness

stomatitis (sores in mouth and on lips)

violet erythema (violet flushing of the skin)
{08}

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Hydroxyurea (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to hydroxyurea

Pregnancy—Use not recommended because of mutagenic, teratogenic, and carcinogenic potential; advisability of using contraception; telling physician immediately if pregnancy is suspected





Breast-feeding—Hydroxyurea is excreted in human breast milk; not recommended because of risk of serious side effects




Use in children—Children may be more sensitive to effects






Use in the elderly—Elderly patients may be more sensitive to effects
Other medications, especially probenecid, sulfinpyrazone, other bone marrow depressants, didanosine, stavudine, other antiretroviral agents, or previous cytotoxic drug or radiation therapy
Other medical problems, especially anemia, chickenpox, herpes zoster, infection (especially HIV treated with antiretroviral drugs), leukopenia, neutropenia, renal function impairment, or thrombocytopenia

Proper use of this medication
» Importance of not taking more or less medication than the amount prescribed

For patients who cannot swallow capsules: Contents of capsules may be emptied into glass of water and taken immediately; some inert material may not dissolve and may float on surface {01}

Caution in taking combination chemotherapy; taking each medication at the right time

Importance of ample fluid intake and subsequent increase in urine output to aid in excretion of uric acid

» Frequency of nausea, vomiting, and diarrhea; importance of continuing medication despite stomach upset

Checking with physician if vomiting occurs shortly after dose is taken

» Proper dosing
Not taking at all; not doubling doses

» Proper storage

Precautions while using this medication
» Importance of close monitoring by the physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding other persons who have taken oral poliovirus vaccine or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during period of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury could occur


Side/adverse effects
Signs of potential side effects, especially anemia, erythrocytic or platelet abnormalities, leukopenia, neutropenia, melanonychia, stomatitis, thrombocytopenia, hyperuricemia or uric acid nephropathy, neurotoxicity, cerebral metastatic disease, or renal function impairment

Physician or nurse can help in dealing with side effects


General Dosing Information
Patients receiving hydroxyurea should be under supervision of a physician experienced in antimetabolite chemotherapy.

Dosage must be adjusted to meet the individual requirements of each patient, based on clinical response and appearance or severity of toxicity.

Dosage reduction may be necessary in children and in the elderly, who may be more sensitive to effects of the drug.

If the patient is unable to swallow capsules, the contents of the capsule may be emptied into a glass of water (some inert material may float on the surface) and taken immediately.

Development of uric acid nephropathy in patients with leukemia or lymphoma may be prevented by adequate oral hydration and, in some cases, administration of allopurinol. Alkalinization of urine may be necessary if serum uric acid concentrations are elevated.

If there is no clinical response after 6 weeks of therapy, the medication should be discontinued; if a response occurs, the medication may be continued indefinitely.

Combination therapy with radiation may be associated with more frequent and severe side effects of the radiation, including gastric distress and inflammation of mucous membranes at the irradiated site. Severe reactions may require temporary withdrawal of hydroxyurea therapy.

It is recommended that hydroxyurea therapy be temporarily withdrawn if marked leukopenia (particularly granulocytopenia) or thrombocytopenia occurs. Therapy may be resumed if, after 3 days, the counts rise significantly towards normal values; counts usually return to normal within 10 to 30 days after discontinuation of hydroxyurea. If anemia occurs, it may be corrected with whole blood replacement, without interruption of hydroxyurea therapy.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of hydroxyurea. These may include extreme care in performing invasive procedures; regular inspection of intravenous sites, skin (including perirectal area), and mucous membrane surfaces for signs of bleeding or bruising; limiting frequency of venipuncture and avoiding intramuscular injections; testing urine, emesis, stool, and secretions for occult blood; care in use of regular toothbrushes, dental floss, toothpicks, safety razors, and fingernail and toenail cutters; avoiding constipation; and using caution to prevent falls and other injuries. Such patients should avoid alcohol and any aspirin intake because of the risk of gastrointestinal bleeding. Platelet transfusions may be required.

Patients who develop leukopenia should be observed carefully for signs of infection. Antibiotic support may be required. In neutropenic patients who develop fever, broad-spectrum antibiotic coverage should be initiated empirically, pending bacterial cultures and appropriate diagnostic tests.

When hydroxyurea is used in sickle cell anemia, the prophylactic administration of folic acid is recommended as hydroxyurea may mask the incidental development of folic acid deficiency.


Oral Dosage Forms

HYDROXYUREA CAPSULES USP

Usual adult dose
Carcinoma, ovarian1
Oral, 80 mg per kg of body weight in a single dose every third day, or 20 to 30 mg per kg of body weight per day in a single dose.{09}

Carcinoma, head and neck, epidermoid
Oral, 80 mg per kg of body weight in a single dose every third day, in combination with radiation therapy.{09}{10}

Note: Administration of hydroxyurea should begin at least seven days prior to initiation of radiation therapy, and should be continued under adequate observation during radiation therapy and indefinitely afterwards.{09}{10}


Leukemia, chronic myelocytic, resistant
Oral, 20 to 30 mg per kg of body weight a day in a single dose{01}{09}{10} or two divided daily doses.

Melanoma
Oral, 80 mg per kg of body weight in a single dose every third day{09}{10}, or 20 to 30 mg per kg of body weight per day in a single dose{09}.


Note: Although dosages are based on the patient's actual weight, use of estimated lean body mass (dry weight) is recommended in obese patients or those with abnormal fluid retention.
In general, use of intermittent dosage is associated with less risk of serious toxicity than continuous daily dosage.

Sickle cell anemia, painful crises
Oral, 15 mg per kg of body weight per day as a single dose. If blood counts are within “acceptable” range, the dose may be increased by 5 mg/kg per day every 12 weeks until a maximum tolerated dose (the highest dose that does not produce “toxic” blood counts over 24 consecutive weeks), or 35 mg/kg per day, is reached{08}.

Note: The dosage should be based on the patient's actual or ideal body weight, whichever is lower.
Blood counts in the “acceptable” range are defined as neutrophils ³ 2500 cells/mm3, platelets ³ 95,000/mm3, hemoglobin > 5.3 g/dL, and reticulocytes ³ 95,000/mm3 if the hemoglobin concentration is < 9 g/dL. Blood counts in the “toxic” range are defined as neutrophils < 2000 cells/mm3, platelets < 80,000/mm3, hemoglobin < 4.5 g/dL, and reticulocytes < 80,000/mm3 if the hemoglobin concentration is < 9 g/dL{08}.



Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


200 mg (Rx) [Droxia]


300 mg (Rx) [Droxia]


400 mg (Rx) [Droxia]


500 mg (Rx) [Hydrea (lactose)][Generic]

Canada—


500 mg (Rx) [Hydrea (tartrazine 3 mg)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Keep container tightly closed.



Revised: 07/09/2002



References

Note: References used in the development and subsequent revisions of this monograph have not been incorporated into the database and therefore are not listed below.

  1. Hydrea package insert, Squibb (U.S.), 2/87.
  1. Per Hematology-Oncology Advisory Panel (1985-1990).
  1. Silverstein MN, Tefferi A. Erythrocytosis and polycythemia vera. In: Bennett JC, Plum F, editors. Cecil textbook of medicine. Philadelphia: W. B. Saunders Co; 1996. p. 920-22.
  1. Kennedy BJ, Smith R, Goltz RW. Skin changes secondary to hydroxyurea therapy. Arch Dermatol 1975; 111: 183-7.
  1. Renfro L, Raphael B, Sanchez M. Ulcerative lichen planus–like dermatitis associated with hydroxyurea. J Am Acad Dermatol 1991; 24: 143-4.
  1. Reviewers' responses to Hematologic-Oncologic Disease Advisory Panel Memo #9 of 1/30/97.
  1. Tefferi A, Silverstein MN. Chronic myeloproliferative diseases. In: Bennett JC, Plum F, editors. Cecil textbook of medicine. Philadelphia: W. B. Saunders Co; 1996. p. 922-5.
  1. Product Information: Droxia®, hydroxyurea. Bristol Laboratories, Princeton, NJ, USA, Rev 3/98, Rec 9/99.
  1. Product Information: Hydrea®, hydroxyurea. Bristol-Myers Squibb Oncology, Princeton, NJ, (PI revised 03/2001) reviewed 04/2001.
  1. Product Information: Hydrea®, hydroxyurea. Bristol-Myers Squibb Canada, Inc. In: Welbanks L (ed): Compendium of Pharmaceuticals and Specialties, 35th ed. Canadian Pharmaceutical Association, Ottawa, Ontario, Canada, 2000; p. 703–704.
  1. Manufacturer comment, FDA-approved uses, Bristol-Myers Squibb, 4/25/2001.
Pat Welborn, Medical Information
  1. Manufacturer comment, FDA-approved uses, Bristol-Myers Squibb, 4/25/2001.
Mary Atwell, Reimbursement

Advanced Breast Cancer: Learn about treatments to improve quality of life. Click Here

Close
Hide
(web2)