- Hydroxyurea Side Effects
- For the Consumer
- For Healthcare Professionals
- Further information
- More about hydroxyurea
The following adverse reactions are described in detail in other labeling sections:
- Embryo-fetal toxicity
- Vasculitic toxicities
- Risks with concomitant use of antiretroviral drugs
- Radiation recall
The following adverse reactions have been identified during postapproval use of HYDREA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.
- Reproductive System and Breast disorders: azoospermia, and oligospermia
- Gastrointestinal disorders: stomatitis, nausea, vomiting, diarrhea, and constipation
- Metabolism and Nutrition disorders: anorexia, tumor lysis syndrome
- Skin and subcutaneous tissue disorders: maculopapular rash, skin ulceration, dermatomyositis-like skin changes, peripheral and facial erythema, hyperpigmentation, atrophy of skin and nails, scaling, violet papules, and alopecia
- Renal and urinary disorders: dysuria, elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels
- Nervous system disorders: headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions
- General Disorders: fever, chills, malaise, edema, and asthenia
- Hepatobiliary disorders: elevation of hepatic enzymes, cholestasis, and hepatitis
- Respiratory disorders: diffuse pulmonary infiltrates, dyspnea, and pulmonary fibrosis
Adverse reactions observed with combined hydroxyurea and irradiation therapy are similar to those reported with the use of hydroxyurea or radiation treatment alone. These effects primarily include bone ÃÂ marrow depression (anemia and leukopenia), gastric irritation, and mucositis. Almost all patients receiving an adequate course of combined hydroxyurea and irradiation therapy will demonstrate concurrent leukopenia. Platelet depression ( < 100,000 cells/mm³) has occurred in the presence of marked leukopenia. HYDREA may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.
Read the entire FDA prescribing information for Hydrea (Hydroxyurea)
Hydroxyurea Side Effects
Medically reviewed by Drugs.com. Last updated on Dec 23, 2018.
- Side Effects
For the Consumer
Applies to hydroxyurea: oral capsule, oral tablet
Oral route (Tablet)
Myelosuppression and MalignanciesMyelosuppression: Hydroxyurea oral tablets may cause severe myelosuppression. Monitor blood counts at baseline and throughout treatment. Interrupt treatment and reduce dose as necessary.Malignancies: Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies.
Oral route (Capsule)
Hydroxyurea may cause severe myelosuppression. 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 malignancy.
Along with its needed effects, hydroxyurea may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking hydroxyurea:
- lower back or side pain
- painful or difficult urination
- Black, tarry stools
- blackening of the fingernails and toenails
- blood in the urine or stools
- pinpoint red spots on the skin
- sores in the mouth and on the lips
- unusual bleeding or bruising
- joint pain
- seeing, hearing, or feeling things that are not there
- swelling of the feet or lower legs
Incidence not known
- Bleeding under the skin
- blisters on the skin
- bluish or pale color on the skin of the fingers or toes
- coldness of the fingers or toes
- crater-like lesions on the skin
- fast heartbeat
- hives, itching, skin rash
- joint pain, stiffness, or swelling
- numbness or tingling of the fingers or toes
- pain in the fingers or toes
- swelling of the eyelids, face, lips, hands, or feet
- tightness in the chest
- troubled breathing or swallowing
- unusual tiredness or weakness
- weight loss
Some side effects of hydroxyurea may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
- loss of appetite
- redness of skin at the place of radiation
- skin rash and itching
Incidence not known
- Bluish-brownish bands on the nails
For Healthcare Professionals
Applies to hydroxyurea: compounding powder, oral capsule, oral tablet
Very common (10% or more): Bone marrow failure, CD4 lymphocytes decreased, leukopenia, thrombocytopenia, platelet count decreased, anemia
Common (1% to 10%): Neutropenia
Very common (10% or more): Pyrexia, asthenia, chills, malaise, fever, edema
Very common (10% or more): Cutaneous vasculitis, dermatomyositis, alopecia, maculopapular rash, papular rash, skin exfoliation, skin atrophy, skin ulcer, erythema, skin hyperpigmentation, nail disorder
Very rare (less than 0.01%): Transverse melanonychia
Frequency not reported: Squamous dysplasia, facial erythema
Common (1% to 10%): Skin cancers, neoplasms benign and malignant )
Frequency not reported: This drug has been shown to be mutagenic, clastogenic, and cause cellular transformation to a tumorigenic phenotype. This drug has been reported to be unequivocally genotoxic and a presumed transspecies carcinogen, which implies a carcinogenic risk to humans.
Very common (10% or more): Azoospermia, oligospermia
Very rare (less than 0.01%): Dysuria
Common (1% to 10%): Convulsion, dizziness, peripheral neuropathy, drowsiness
Frequency not reported: Severe peripheral neuropathy has been reported in HIV-infected patients who received this drug in combination with antiretroviral drugs
Common (1% to 10%): Hepatotoxicity, hepatic enzyme increased, cholestasis, hepatitis
Frequency not reported: Both fatal and nonfatal hepatotoxicity have been reported in HIV-infected patients who received this drug in combination with antiretroviral agents
Common (1% to 10%): Pulmonary fibrosis, pulmonary edema, lung infiltration, dyspnea
Very rare (less than 0.01%): Tumor lysis syndrome
Common (1% to 10%): Hallucination, disorientation
Very common (10% or more): Dysuria, blood creatinine increased, blood urea increased, blood uric acid increased
2. “Product Information. Droxia (hydroxyurea).” Bristol-Myers Squibb, Princeton, NJ.
3. “Product Information. Hydroxyurea (hydroxyurea (hydroxyUREA)).” Par Pharmaceutical Inc, Chestnut Ridge, NY.
4. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Some side effects may not be reported. You may report them to the FDA.
More about hydroxyurea
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- Drug class: antimetabolites
- Hydroxyurea Tablets
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Other brands: Hydrea, Droxia, Siklos, Mylocel
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Hydroxyurea is a prescription drug sold under the brand name Hydrea.
It’s used to treat psoriasis, chronic myelogenous leukemia (a cancer of the white blood cells), ovarian cancer, melanoma (a form of skin cancer), and certain head and neck cancers.
The medicine also helps people with sickle cell anemia (an inherited blood disorder) by reducing the frequency of painful sickle cell crisis episodes and the need for blood transfusions.
Additionally, hydroxyurea is sometimes used to treat polycythemia vera (a disorder of the bone marrow) by reducing the red blood cell mass.
Hydroxyurea belongs to a class of drugs called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body, and by helping to prevent the formation of abnormal red blood cells.
The Food and Drug Administration (FDA) approved hydroxyurea in 1967. It’s marketed by Bristol-Myers Squibb Company.
Hydroxyurea contains a black-box warning because it can cause a severe drop in the number of blood cells in your bone marrow. This can increase your risk of a serious infection or bleeding.
Tell your doctor right away if you experience any of the following symptoms while taking hydroxyurea:
- Fever, sore throat, cough, congestion, or other signs of infection
- Unusual bruising or bleeding
- Vomit that’s bloody or looks like coffee grounds
- Bloody or black, tarry stools
Try to avoid contact with people who have infections or colds while taking this drug.
Don’t receive any vaccinations while taking hydroxyurea without first talking to your doctor.
Hydroxyurea also contains a black-box warning because the medicine may increase your chance of developing other cancers.
Some people have reported skin cancer or secondary leukemia after taking hydroxyurea.
Call your healthcare provider right away if you notice any of the following symptoms:
- Change in the appearance of a mole
- A new growth on the skin
- Any unusual skin changes
Before taking hydroxyurea, tell your doctor if you have, or have had:
- Severe bone marrow depression
- Low white blood cell counts
- Low blood platelet levels
- Severe anemia or another blood disorder
- Kidney disease
- Liver disease
- Allergies to medicines
Also, let your healthcare provider know if you’ve ever been treated with chemotherapy or radiation.
Tell your doctor you take hydroxyurea before having any type of surgery, including a dental procedure.
Hydroxyurea may interfere with certain medical tests. Tell all health professionals who treat you that you’re taking this medicine.
Elderly people may be more sensitive to certain side effects of hydroxyurea. Talk to your doctor if this is a concern.
The safety and effectiveness of hydroxyurea in children haven’t been confirmed. Don’t give this medicine to a child unless a doctor tells you otherwise.
People who aren’t taking hydroxyurea shouldn’t come in contact with the medicine. Caregivers should wear disposable gloves when handling this drug.
Your doctor will want to perform important tests to monitor your body’s response to hydroxyurea. Keep all appointments with your doctor and laboratory.
Pregnancy and Hydroxyurea
Hydroxyurea can harm an unborn baby. Don’t become pregnant while taking this medicine.
Both men and women should use an effective form of birth control while taking hydroxyurea.
The drug may also affect a woman’s ability to become pregnant and a man’s ability to father a child. Talk to your doctor if this is a concern.
Since hydroxyurea can be absorbed through the skin and lungs, pregnant women, and those who may become pregnant, shouldn’t handle the drug or breathe in the dust from the capsules.
Hydroxyurea is passed into breast milk. Don’t breastfeed while taking this medicine.
After the drug was suspended, the ulcerous lesions and melanonychia regressed (Figures 4, 5 and 6). The patient later died of acute myocardial infarction.
Hydroxyurea is an hydroxylated urea derivative that has been used in the treatment of many hematological disorders such as Chronic Myeloid Leukemia, Polycythemia Vera, Essential Thrombocytemia, Thalassemia and Sickle-cell Disease.3,6 More recently, it has been used as alternative in severe cases of refractory Psoriasis and as an adjuvant in HIV infection. 7,9,10
This chemotherapeutic agent blocks the conversion of ribonucleotides into desoxyribonucleotides when it inhibits M2 subunit of ribonucleotide reductase. Consequently, it interferes in DNA synthesis of proliferative cells, leading them to death in the S phase of cell cycle. 6
It is normally a well-tolerated drug in usual doses, with rare serious side effects. Among the possible mucocutaneous complications are: xerosis, diffuse hyperpigmentation of the skin and oropharyngeal mucosa, alopecia, erythema, nail alterations (melanonychia, onycholysis, blue lunula), palmoplantar keratodermia, dermatomyositis-like lesions, stomatitis and aphthoid ulcers. More severe adverse effects include leg ulcers and skin carcinomas (basal and squamous cells). 3,5,7,11-13
The pathogenesis of skin alterations induced by hydroxyurea is still not well understood. It is believed that leg ulcers develop as a consequence of the decrease of blood flow in microcirculation and anoxia secondary to macrocytosis induced by the drug.There seems to be a platelet deregulation associated with these factors, with microthrombos formation and loss of tissue repair by direct toxic action of the drug. 4
The basic disease seems to influence the risk for ulcer development, which may be evident in around 9% of patients undergoing treatment for Myelodysplastic Diseases and in 29% of Sickle-Cell Disease carriers.4,12 The ulcers are located almost exclusively in areas of leg trauma and affect more frequently elderly women (65% of cases), who have been using the drug for at least one year.12 Studies reveal that spontaneous healing of ulcerated lesions occur during the period from eight weeks to nine months after suspension of the drug.1,2,12 Haniffa et al.1 and Neynaber et al.5 advocate topical care and dose reduction, preferring to withdraw hydroxyurea administration only in refractory cases. In the reported case, contrary to the described, the patient is male and presented ulcer of atypical localization (forearm). We believe there is a connection between the onset of the ulcerated lesion and administration of the drug, since after it was suspended the lesion regressed.
Several hypotheses have been suggested for the pathogenesis of hyperpigmentation of skin, mucosa and nails induced by hydroxyurea. It is believed that genetic predisposition, photosensitization, focal stimulation of melanocytes and the toxic effect on ungueal bed and matrix are involved.12,14 The more probable hypothesis seems to be the increase in melanin production by direct activation of melanocytes by the drug. A review of English literature revealed that cutaneous hyperpigmentation without ungueal infection is more common, and the isolated presence of melanonychia is rare12. Adult and black patients, as well as those with basic sickle-cell disease are more predisposed to pigmentary alterations caused by hydroxyurea. 14
The most usually found ungual findings are longitudinal bands of variable pigment intensity, normally on just a few nails, mainly fingernails. The literature reports only four cases where 20 nails were involved in the same patient, which was also observed in the present reported case.5 Other patterns have already been described, such as transverse bands and their diffuse pigmentation, which may occur simultaneously in the same patient. In a previous study, it was observed that the risk for melanonychia in patients receiving hydroxyurea therapy was 4%, most of them women and after a long period of treatment. 5 A few months after suspension of the drug, the pigmentary alterations tend to resolve.
After 10 years of hydroxyurea treatment, the patient developed an histologically well-differentiated spinocellular carcinoma on the helix of the right outer ear. Among the most severe adverse effects of hydroxyurea is the development of skin carcinomas, usually after a long period of treatment with the drug. 8,1 3 A theory is posed that there is mutagenic potential of the chemotherapeutic agent for carcinogenesis and action as inhibitor of DNA repair mechanisms after damage caused by external factors (i.e. ultraviolet radiation). 5, 7
A direct cumulative damage, as well as a cytotoxic effect of hydroxyurea on basal keratinocytes, resulting in atrophic skin lesion has also been proposed . 3 In the case of our patient it became evident that, with the passing of time, numerous atrophic lesions appeared, more pronounced on the forearms and back of hands. Other cutaneous adverse reactions reported in the literature as secondary to the prolonged use of the drug, such as cutaneous xerosis and ichthyosiform lesions were also observed in this case.
1. Friedrich S, Raff K, Landthaler M, Karrer S. Cutaneous ulcerations on hands and heels secondary to long-term hydroxyurea treatment. Eur J Dermatol. 2004;14:343-6.
2. Haniffa MA, Speight EL. Painful leg ulcers and a rash in a patient with polycythaemia rubra vera. Diagnoses: hydroxyurea-induced leg ulceration and dermatomyositis-like skin changes. Clin Exp Dermatol. 2006;31:733-4.
3. Zargari O, Kimyai-Asadi A, Jafroodi M. Cutaneous adverse reactions to hydroxyurea in patients with intermediate thalassemia. Pediatr Dermatol. 2004;21:633-5.
6. Zaccaria E, Cozzani E, Parodi A. Secondary cutaneous effects of hydroxyurea: possible pathogenetic mechanisms. J Dermatolog Treat. 2006;17:176-8.
7. Jeevankumar B, Thappa DM. Blue lunula due to hydroxyurea. J Dermatol. 2003;30:628-30.
9. Menon K, Van Voorhees AS, Bebo BF Jr, Gladman DD, Hsu S, Kalb RE, et al. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62:291-9.
13. Saraceno R, Teoli M, Chimenti S. Hydroxyurea associated with concomitant occurrence of diffuse longitudinal melanonychia and multiple squamous cell carcinomas in an elderly subject. Clin Ther. 2008;30:1324-9.
Received on 21.05.2010.
Approved by the Advisory Board and accepted for publication on 07.07.2010.
Conflict of interest: None
Financial funding: None
Study carried out at the University of Pernambuco (Universidade de Pernambuco – UPE) – Recife (PE), Brazil.