SIKLOS (hydroxyurea)

There are 1 contraindications. Absolute contraindication.

Contraindication List
Lactation

There are 9 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Hypoplastic anemia
Interstitial lung disease
Neutropenic disorder
Pregnancy
Thrombocytopenic disorder

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Disease of liver
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Postirradiation erythema

There are 36 severe adverse reactions.

More Frequent	Less Frequent
Infection Leukopenia Neutropenic disorder	Anemia Pulmonary infiltrates Thrombocytopenic disorder

Rare/Very Rare

Abnormal hepatic function tests Alveolitis Basal cell carcinoma of skin Cholestasis CNS toxicity Cutaneous vasculitis Dermatomyositis Gangrene Hallucinations Hemolytic anemia Hemorrhage Hepatic failure Hepatitis Hypersensitivity pneumonitis Interstitial pneumonitis Kidney disease with reduction in glomerular filtration rate (GFr) Macrocytosis Maculopapular rash Malignant neoplasm of skin Pancreatitis Pulmonary fibrosis Radiation recall syndrome Secondary acute myeloid leukemia Seizure disorder Skin ulcer Squamous cell carcinoma of skin Systemic lupus erythematosus Tonic clonic seizure Tumor lysis syndrome Uric acid nephropathy

There are 33 less severe adverse reactions.

More Frequent	Less Frequent
Anorexia Diarrhea Headache disorder Nausea Vomiting	Alopecia Constipation Dry skin Erythema Pruritus of skin Skin rash Stomatitis

Rare/Very Rare
Acute cognitive impairment Amenorrhea Azoospermia Chills Cough Cutaneous lupus erythematosus Dizziness Drowsy Dyspnea Dysuria Edema Fever Gastritis General weakness Malaise Nail disorders Oligospermia Skin atrophy Skin pigmentation enhancement Skin scaling Weight gain

Hydroxyurea can cause fetal toxicity when administered to pregnant women, but potential benefits from use of the drug may be acceptable in certain conditions despite the possible risks to the fetus. Hydroxyurea crosses the placenta and has been shown to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys, when administered in doses within onefold of the human dose based on body surface area. Administration of 180 mg/kg daily (about 0.8 times the maximum recommended human daily dose on a mg/m2 basis) or 30 mg/kg daily (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) of the drug resulted in fetal malformations (including partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae) in rats or rabbits, respectively.

Embryotoxicity, manifested as decreased fetal viability, reduced live litter sizes, and developmental delays, also was observed. Single doses of 375 mg/kg (approximately 1.7 times the maximum recommended human daily dose on a mg/m2 basis) in rats resulted in growth retardation and impaired learning ability. In other studies in rats, the teratogenic properties of hydroxyurea were demonstrated at dosages 10- to 20-fold greater than those administered in patients with sickle cell disease, and aspirin was equally teratogenic at comparable dosages.

There are no adequate and well-controlled studies to date using hydroxyurea in pregnant women. Hydroxyurea should be used during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. When the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.

Women of childbearing potential should be advised to avoid becoming pregnant during therapy with hydroxyurea. Children born to patients entered in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia and treated with hydroxyurea have shown no evidence of birth defects or developmental abnormalities to date. Women with chronic myelogenous leukemia receiving hydroxyurea therapy have also borne normal children, and there currently are no reports of hydroxyurea-treated males with chronic myelogenous leukemia having fathered a child with genetic abnormalities, but it has not been established whether risks exist to a fetus whose father was being treated with the drug at the time of conception.

There currently are no reports establishing hydroxyurea as causing any teratogenic or mutagenic effects in humans; however, because hydroxyurea affects DNA synthesis, its potential as a mutagenic agent should be considered in male or female patients who may contemplate conception. In addition, although the long-term risks of hydroxyurea (including teratogenesis, mutagenesis, leukemogenesis/carcinogenesis, and chromosomal abnormalities) are poorly documented, they should not be ignored. Therefore, hydroxyurea should not be administered to pregnant women or to women of childbearing age who may become pregnant unless the potential benefit to the patient outweighs the possible risk to the fetus.

In addition, some clinicians recommend that hydroxyurea not be used for long-term therapy (e.g., sickle cell anemia) in patients likely to become pregnant, and that every effort be made to prevent conception and pregnancy in women who are patients (or partners of patients) receiving the drug chronically.

Hydroxyurea is distributed into milk. Because of the potential for serious adverse reactions to hydroxyurea in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No enhanced Geriatric Use information available for this drug.