Hydroxyurea

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Hydroxyurea capsules are indicated for the treatment of: Resistant chronic myeloid leukemia. Locally advanced squamous cell carcinomas of the head and neck (excluding the lip) in combination with chemoradiation. Hydroxyurea capsules are an antimetabolite indicated for the treatment of: Resistant chronic myeloid leukemia. (1) Locally advanced squamous cell carcinomas of the head and neck, (excluding lip) in combination with concurrent chemoradiation. (1) Dosage and administration 2 DOSAGE AND ADMINISTRATION Individualize treatment based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards. (2.1) Renal impairment: Reduce the dose of hydroxyurea capsules by 50% in patients with creatinine clearance less than 60 mL/min. (2.3 , 8.6 , 12.3) 2.1 Dosing Information Hydroxyurea capsules are used alone or in conjunction with other antitumor agents or radiation therapy to treat neoplastic diseases. Individualize treatment based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards. Base all dosage on the patient’s actual or ideal weight, whichever is less. Hydroxyurea capsules are a cytotoxic drug. Follow applicable special handling and disposal procedures [see References (15) ]. Swallow hydroxyurea capsules whole. Do NOT open, break, or chew capsules because hydroxyurea capsules are a cytotoxic drug. Prophylactic administration of folic acid is recommended [see Warnings and Precautions (5.8) ]. Monitor blood counts at least once a week during hydroxyurea capsules therapy. Severe anemia must be corrected before initiating therapy with hydroxyurea capsules. 2.2 Dose Modifications for Toxicity Monitor for the following and reduce the dose or discontinue hydroxyurea capsules accordingly: Myelosuppression [see Warnings and Precautions (5.1) ] Cutaneous vasculitis [see Warnings and Precautions (5.5) ] Consider dose modifications for other toxicities. 2.3 Dose Modifications for Renal Impairment Reduce the dose of hydroxyurea capsules by 50% in patients with measured creatinine clearance of less than 60 mL/min or with end-stage renal disease (ESRD) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ]. Creatinine Clearance (mL/min) Recommended Hydroxyurea Capsules Initial Dose (mg/kg once daily) ≥60 15 <60 or ESRD On dialysis days, administer hydroxyurea capsules to patients following hemodialysis. 7.5 Close monitoring of hematologic parameters is advised in these patients. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Myelosuppression: Do not give if bone marrow function is markedly depressed. Monitorblood counts at baseline and throughout treatment. Interrupt treatment and reduce doseas necessary. (5.1) Hemolytic anemia: Monitor blood counts throughout treatment. If hemolysis persists, discontinue hydroxyurea capsules. (5.2) Malignancies: Advise protection from sun exposure and monitor for secondary malignancies. (5.3) Embryo-Fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. (5.4 , 8.1 , 8.3) Vasculitic toxicities: Discontinue hydroxyurea capsules and initiate treatment if this occurs. (5.5) Live Vaccinations: Avoid live vaccine use in a patient taking hydroxyurea capsules. (5.6) Risks with concomitant use of antiretroviral drugs: Pancreatitis, hepatotoxicity, and neuropathy have occurred. Monitor for signs and symptoms in patients with HIV infection using antiretroviral drugs; discontinue hydroxyurea capsules and implement treatment. (5.7) Radiation recall: Monitor for skin erythema in patients who previously received radiation and manage symptomatically. (5.8) 5.1 Myelosuppression Hydroxyurea causes severe myelosuppression. Treatment with hydroxyurea should not be initiated if bone marrow function is markedly depressed. Bone marrow suppression may occur, and leukopenia is generally its first and most common manifestation. Thrombocytopenia and anemia occur less often and are seldom seen without a preceding leukopenia. Bone marrow depression is more likely in patients who have previously received radiotherapy or cytotoxic cancer chemotherapeutic agents; use hydroxyurea cautiously in such patients. Evaluate hematologic status prior to and during treatment with hydroxyurea capsules. Provide supportive care and modify dose or discontinue hydroxyurea as needed. Recovery from myelosuppression is usually rapid when therapy is interrupted. 5.2 Hemolytic Anemia Cases of hemolytic anemia in patients treated with hydroxyurea for myeloproliferative diseases have been reported [see Adverse Reactions (6.1) ]. Patients who develop acute jaundice or hematuria in the presence of persistent or worsening of anemia should have laboratory tests evaluated for hemolysis (e.g., measurement of serum lactate dehydrogenase, haptoglobin, reticulocyte, unconjugated bilirubin levels, urinalysis, and di