Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Hydroxyurea Capsules USP 500 mg are available as a two-piece hard gelatin capsule with purple opaque cap and pink opaque body filled with white powder, imprinted in black ink stylized barr 882 and packaged in bottles of 100 capsules (NDC 42291-321-01). 16.2 Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. 16.3 Handling and Disposal Hydroxyurea Capsules USP are a cytotoxic drug. Follow applicable special handling and disposal procedures [see References ( 15 )] . To decrease the risk of contact, advise caregivers to wear disposable gloves when handling Hydroxyurea Capsules USP or bottles containing Hydroxyurea Capsules USP. Wash hands with soap and water before and after contact with the bottle or capsules when handling Hydroxyurea Capsules USP. Do not open Hydroxyurea Capsules USP. Avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs on the skin, wash affected area immediately and thoroughly with soap and water. If contact with crushed or opened capsules occurs on the eye(s), the affected area should be flushed thoroughly with water or isotonic eyewash designated for that purpose for at least 15 minutes. If the powder from the capsule is spilled, immediately wipe it up with a damp disposable towel and discard in a closed container, such as a plastic bag; as should the empty capsules. The spill areas should then be cleaned three times using a detergent solution followed by clean water. Keep the medication away from children and pets. Contact your doctor for instructions on how to dispose of outdated capsules.; Package/Label Display Panel 1
- 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Hydroxyurea Capsules USP 500 mg are available as a two-piece hard gelatin capsule with purple opaque cap and pink opaque body filled with white powder, imprinted in black ink stylized barr 882 and packaged in bottles of 100 capsules (NDC 42291-321-01). 16.2 Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. 16.3 Handling and Disposal Hydroxyurea Capsules USP are a cytotoxic drug. Follow applicable special handling and disposal procedures [see References ( 15 )] . To decrease the risk of contact, advise caregivers to wear disposable gloves when handling Hydroxyurea Capsules USP or bottles containing Hydroxyurea Capsules USP. Wash hands with soap and water before and after contact with the bottle or capsules when handling Hydroxyurea Capsules USP. Do not open Hydroxyurea Capsules USP. Avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs on the skin, wash affected area immediately and thoroughly with soap and water. If contact with crushed or opened capsules occurs on the eye(s), the affected area should be flushed thoroughly with water or isotonic eyewash designated for that purpose for at least 15 minutes. If the powder from the capsule is spilled, immediately wipe it up with a damp disposable towel and discard in a closed container, such as a plastic bag; as should the empty capsules. The spill areas should then be cleaned three times using a detergent solution followed by clean water. Keep the medication away from children and pets. Contact your doctor for instructions on how to dispose of outdated capsules.
- Package/Label Display Panel 1
Overview
Hydroxyurea Capsules USP are an antineoplastic available for oral use as capsules providing 500 mg hydroxyurea, USP. Inactive ingredients: anhydrous citric acid, benzyl alcohol, black iron oxide, butylparaben, carboxymethylcellulose sodium, D&C red no. 28, D&C yellow no. 10 aluminum lake, dibasic sodium phosphate, edetate calcium disodium, FD&C blue no. 1, FD&C blue no. 1 aluminum lake, FD&C blue no. 2 aluminum lake, FD&C red no. 40, FD&C red no. 40 aluminum lake, gelatin, lactose monohydrate, magnesium stearate, methylparaben, pharmaceutical glaze, propylparaben, propylene glycol, red iron oxide, sodium lauryl sulfate, sodium propionate, and titanium dioxide. Hydroxyurea, USP is a white to off-white crystalline powder. It is hygroscopic and freely soluble in water, but practically insoluble in alcohol. Its structural formula is: CH 4 N 2 O 2 M.W. 76.05 chemical structure
Indications & 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 & 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 ) ]. Patients should swallow hydroxyurea capsules whole and not to open, since hydroxyurea is a cytotoxic drug. Prophylactic administration of folic acid is recommended [see Warnings and Precautions ( 5.7 )]. 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 ( 5.4 )] Monitor blood counts at least once a week during hydroxyurea therapy. Severe anemia must be corrected before initiating therapy with hydroxyurea capsules. 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 Initial Dose (mg/kg once daily) ≥60 15 <60 or ESRD* 7.5 * On dialysis days, administer hydroxyurea capsules to patients following hemodialysis. Close monitoring of hematologic parameters is advised in these patients.
Warnings & Precautions
Myelosuppression: Do not give if bone marrow function is markedly depressed. Monitor hematology labs and interrupt, reduce dose as appropriate. ( 5.1 ) Malignancies: Advise protection from sun exposure and monitor for secondary malignancies. ( 5.2 ) Embryo-Fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.3 , 8.1 , 8.3 ) Vasculitic toxicities: Discontinue hydroxyurea and initiate treatment if this occurs. ( 5.4 ) Live Vaccinations: Avoid live vaccine use in a patient taking hydroxyurea capsules. ( 5.5 ) 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. ( 5.6 ) Radiation recall: Monitor for skin erythema in patients who previously received radiation and manage symptomatically. ( 5.7 ) 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 capsules as needed. Recovery from myelosuppression is usually rapid when therapy is interrupted. 5.2 Malignancies Hydroxyurea is a human carcinogen. In patients receiving long-term hydroxyurea for myeloproliferative disorders, secondary leukemia has been reported. Skin cancer has also been reported in patients receiving long-term hydroxyurea. Advise protection from sun exposure and monitor for the development of secondary malignancies. 5.3 Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, hydroxyurea capsules can cause fetal harm when administered to a pregnant woman. Hydroxyurea was embryotoxic and teratogenic in rats and rabbits at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m 2 basis. Advise pregnant women of the potential risk to a fetus [see Use in Specific Populations ( 8.1 )]. Advise females of reproductive potential to use effective contraception during and after treatment with hydroxyurea capsules for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with hydroxyurea capsules for at least 1 year after therapy [see Use in Specific Populations ( 8.1 , 8.3 )]. 5.4 Vasculitic Toxicities Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. These vasculitic toxicities were reported most often in patients with a history of, or currently receiving, interferon therapy. If cutaneous vasculitic ulcers occur, institute treatment and discontinue hydroxyurea capsules. 5.5 Live Vaccinations Avoid use of live vaccine in patients taking hydroxyurea capsules. Concomitant use of hydroxyurea capsules with a live virus vaccine may potentiate the replication of the virus and/or may increase the adverse reaction of the vaccine because normal defense mechanisms may be suppressed by hydroxyurea capsules. Vaccination with live vaccines in a patient receiving hydroxyurea capsules may result in severe infection. Patient’s antibody response to vaccines may be decreased. Consider consultation with a specialist. 5.6 Risks with Concomitant Use of Antiretroviral Drugs Pancreatitis, hepatotoxicity, and peripheral neuropathy have occurred when hydroxyurea was administered concomitantly with antiretroviral drugs, including didanosine and stavudine [see Drug Interactions ( 7.1 )] . 5.7 Radiation Recall Patients who have received irradiation therapy in the past may have an exacerbation of post-irradiation erythema. Monitor for skin erythema in patients who previously received radiation and manage symptomatically. 5.8 Macrocytosis Hydroxyurea may cause macrocytosis, which is self-limiting, and is often seen early in the course of treatment. The morphologic change resembles pernicious anemia, but is not related to vitamin B 12 or folic acid deficiency. This may mask the diagnosis of pernicious anemia. Prophylactic administration of folic acid is recommended. 5.10 Pulmonary Toxicity Interstitial lung disease including pulmonary fibrosis, lung infiltration, pneumonitis, and alveolitis/allergic alveolitis (including fatal cases) have been reported in patients treated for myeloproliferative neoplasm. Monitor patients developing pyrexia, cough, dyspnea, or other respiratory symptoms frequently, investigate and treat promptly. Discontinue hydroxyurea and manage with corticosteroids [see Adverse Reactions (6.1)]. 5.11 Laboratory Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays is possible, rendering falsely elevated results of these in patients treated with hydroxyurea [see Drug Interactions (7.2)]. Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin. If a patient using a CGM is to be prescribed hydroxyurea, consult with the CGM prescriber about alternative glucose monitoring methods [see Drug Interactions (7.2)]. 5.11 Laboratory Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays is possible, rendering falsely elevated results of these in patients treated with hydroxyurea [see Drug Interactions (7.2)]. Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin. If a patient using a CGM is to be prescribed hydroxyurea, consult with the CGM prescriber about alternative glucose monitoring methods [see Drug Interactions (7.2)].
Contraindications
Hydroxyurea is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of the formulation. In patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation. ( 4 )
Adverse Reactions
The following adverse reactions are described in detail in other labeling sections: Myelosuppression [see Warnings and Precautions ( 5.1 )] Malignancies [see Warnings and Precautions ( 5.2 )] Embryo-fetal toxicity [see Warnings and Precautions ( 5.3 )] Vasculitic toxicities [see Warnings and Precautions ( 5.4 )] Risks with concomitant use of antiretroviral drugs [see Warnings and Precautions ( 5.6 )] Radiation recall [see Warnings and Precautions ( 5.7 )] Macrocytosis [see Warnings and Precautions ( 5.8 )] 6.1 Postmarketing Experience The following adverse reactions have been identified during post-approval use of hydroxyurea. 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, nail 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 Hypersensitivity: Drug-induced fever (pyrexia) (>39°C, >102°F) requiring hospitalization has been reported concurrently with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological or cardiovascular manifestations. Onset typically occurred within 6 weeks of initiation and resolved upon discontinuation of hydroxyurea. Upon re-administration fever re-occurred typically within 24 hours. 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 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/mm 3 ) has occurred in the presence of marked leukopenia. Hydroxyurea may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis. To report SUSPECTED ADVERSE REACTIONS contact AvKARE at 1-855-361-3993; email [email protected]; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Most common adverse reactions (≥30%) are hematological, gastrointestinal symptoms, and anorexia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email [email protected]; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions
• Antiretroviral drugs (7.1) • Laboratory Test Interference (7.2) 7.1 Increased Toxicity with Concomitant Use of Antiretroviral Drugs Pancreatitis In patients with HIV infection during therapy with hydroxyurea and didanosine, with or without stavudine, fatal and nonfatal pancreatitis have occurred. Hydroxyurea is not indicated for the treatment of HIV infection; however, if patients with HIV infection are treated with hydroxyurea, and in particular, in combination with didanosine and/or stavudine, close monitoring for signs and symptoms of pancreatitis is recommended. Permanently discontinue therapy with hydroxyurea in patients who develop signs and symptoms of pancreatitis. Hepatotoxicity Hepatotoxicity and hepatic failure resulting in death have been reported during postmarketing surveillance in patients with HIV infection treated with hydroxyurea and other antiretroviral drugs. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. Avoid this combination. Peripheral Neuropathy Peripheral neuropathy, which was severe in some cases, has been reported in patients with HIV infection receiving hydroxyurea in combination with antiretroviral drugs, including didanosine, with or without stavudine. 7.2 Laboratory Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays Studies have shown that there is an analytical interference of hydroxyurea with the enzymes (urease, uricase, and lactate dehydrogenase) used in the determination of urea, uric acid, and lactic acid, rendering falsely elevated results of these in patients treated with hydroxyurea. Interference with Continuous Glucose Monitoring Systems. Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin. If a patient using a CGM is to be prescribed hydroxyurea, consult with the CGM prescriber about alternative glucose monitoring methods.
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