Hydroxyurea Oral Capsules From TAJ PHARMA |

TAJ PHARMA Hydroxyurea

PronunciationBrand Name: TAJ PHARMA Hydroxyurea is used for:
TAJ PHARMA Hydroxyurea is an antineoplastic agent. It works by preventing necessary steps for cancer cell growth and reproduction, resulting in cell death.
·         you are allergic to any ingredient in TAJ PHARMA Hydroxyurea
·         you have severe bone marrow depression, low white blood cell counts, low blood platelet levels, or severe anemia
·         you are taking didanosine or stavudine
Contact your doctor or health care provider right away if any of these apply to you
Some medical conditions may interact with TAJ PHARMA Hydroxyurea. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
·         if you are pregnant, planning to become pregnant, or are breast-feeding
·         if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
·         if you have allergies to medicines, foods, or other substances
·         if you are able to become pregnant or father a child
·         if you have anemia, folic acid deficiency, or kidney or liver problems
·         if you have HIV, especially if you take medicine for HIV
·         if you have previously received or are currently receiving chemotherapy, radiation therapy, or interferon therapy
Some MEDICINES MAY INTERACT with TAJ PHARMA Hydroxyurea. Tell your health care provider if you are taking any other medicines, especially any of the following:
·         Didanosine or stavudine because the risk of side effects, such as inflammation of the pancreas, may be increased
This may not be a complete list of all interactions that may occur. Ask your health care provider if TAJ PHARMA Hydroxyurea may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine. 
  
  
  
  
  
  
  
 
·         Take TAJ PHARMA Hydroxyurea by mouth with or without food.
·         People who are not taking TAJ PHARMA Hydroxyurea should not come into contact with it.
·         Wash your hands before and after handling TAJ PHARMA Hydroxyurea or the bottle it comes in. Wear disposable gloves while you are handling TAJ PHARMA Hydroxyurea or its bottle. Follow your doctor's instructions for disposing of the gloves after you remove them.
·         Do not open the capsules. Avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs, wash immediately and thoroughly. If the powder from the capsule is spilled, it should be wiped up immediately with a damp towel and disposed of in a closed container (eg, plastic bag), as should the empty capsules.
·         Do not use TAJ PHARMA Hydroxyurea if the expiration date has passed. Ask your doctor or pharmacist how to properly dispose of expired medicine.
·         Taking TAJ PHARMA Hydroxyurea at the same time each day will help you remember to take it.
·         If you miss a dose of TAJ PHARMA Hydroxyurea, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.
Ask your health care provider any questions you may have about how to use TAJ PHARMA Hydroxyurea.
·         TAJ PHARMA Hydroxyurea may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use TAJ PHARMA Hydroxyurea with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
·         Your doctor may prescribe a folic acid supplement for you to take while you are taking TAJ PHARMA Hydroxyurea. Be sure to follow your doctor's instructions. Discuss any questions or concerns with your doctor.
·         Do NOT take more than the recommended dose without checking with your doctor.
·         Tell your doctor or dentist that you take TAJ PHARMA Hydroxyurea before you receive any medical or dental care, emergency care, or surgery.
·         TAJ PHARMA Hydroxyurea may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.
·         TAJ PHARMA Hydroxyurea may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.
·         With long-term use in patients with cell development disorders, secondary leukemias have been reported. It is unknown if this is related to TAJ PHARMA Hydroxyurea or to the patient's underlying cell disorder. Talk with your doctor if you have any questions about this information.
·         TAJ PHARMA Hydroxyurea may harm your liver; cause pancreas problems; or cause burning, numbness, or tingling of your arms, hands, legs, or feet if you take it with certain HIV medicines (eg, didanosine, stavudine). Talk to your doctor if you have any questions about this information.
·         Skin cancer has been reported with long-term use of TAJ PHARMA Hydroxyurea. Contact your doctor right away if you notice a change in the appearance of a mole, new growth on the skin, or any unusual skin change.
·         Do not receive a live vaccine (eg, measles, mumps) while you are taking TAJ PHARMA Hydroxyurea. Talk with your doctor before you receive any vaccine.
·         TAJ PHARMA Hydroxyurea may affect your ability to become pregnant or to father a child. Discuss any questions or concerns with your doctor.
·         Women who may become pregnant should use effective birth control while they are taking TAJ PHARMA Hydroxyurea. Check with your doctor if you have questions about effective birth control.
·         TAJ PHARMA Hydroxyurea may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking TAJ PHARMA Hydroxyurea.
·         Lab tests, including complete blood cell counts, kidney function, and liver function, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.
·         Use TAJ PHARMA Hydroxyurea with caution in the ELDERLY; they may be more sensitive to its effects.
·         TAJ PHARMA Hydroxyurea should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.
·         PREGNANCY and BREAST-FEEDING: TAJ PHARMA Hydroxyurea may cause harm to the fetus. Do not become pregnant while you are using it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using TAJ PHARMA Hydroxyurea while you are pregnant. TAJ PHARMA Hydroxyurea is found in breast milk. Do not breast-feed while taking TAJ PHARMA Hydroxyurea.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Constipation; diarrhea; dizziness; hair loss; loss of appetite; nausea; vomiting.
Seek medical attention right away if any of these SEVERE side effects occur:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); change in the amount of urine produced; confusion; difficult or painful urination; fever, chills, or persistent cough or sore throat; hallucinations; headache; seizures; severe or persistent diarrhea, nausea, loss of appetite, or vomiting; shortness of breath; skin sores or ulcers; sudden, unusual weight gain; swelling of the hands, ankles, or feet; swelling or soreness of the mouth, lips, or tongue; symptoms of liver problems (eg, yellowing of the eyes or skin, pale stools, dark urine, persistent loss of appetite, severe stomach pain); unusual bruising or bleeding; unusual tiredness or weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include dark discoloration of the skin; swelling or soreness of the mouth, lips, or tongue; swelling, soreness, or redness of the palms of the hands and soles of the feet, followed by scaling of the skin.
Proper storage of TAJ PHARMA Hydroxyurea:
Store TAJ PHARMA Hydroxyurea at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep TAJ PHARMA Hydroxyurea out of the reach of children and away from pets.
·         If you have any questions about TAJ PHARMA Hydroxyurea, please talk with your doctor, pharmacist, or other health care provider.
·         TAJ PHARMA Hydroxyurea is to be used only by the patient for whom it is prescribed. Do not share it with other people.
·         If your symptoms do not improve or if they become worse, check with your doctor.
·         Check with your pharmacist about how to dispose of unused medicine.
This information should not be used to decide whether or not to take TAJ PHARMA Hydroxyurea or any other medicine. Only your health care provider has the knowledge and training to decide which medicines are right for you. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about TAJ PHARMA Hydroxyurea. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to TAJ PHARMA Hydroxyurea. This information is not specific medical advice and does not replace information you receive from your health care provider. You must talk with your healthcare provider for complete information about the risks and benefits of using TAJ PHARMA Hydroxyurea.
Review Date: January 6, 2017
Applies to TAJ PHARMA Hydroxyurea: oral capsule, oral tablet
In addition to its needed effects, some unwanted effects may be caused by TAJ PHARMA Hydroxyurea. In the event that any of these side effects do occur, they may require medical attention.
Major Side Effects
You should check with your doctor immediately if any of these side effects occur when taking TAJ PHARMA Hydroxyurea:
More common:
·         Cough or hoarseness
·         fever or chills
·         lower back or side pain
·         painful or difficult urination
Less common:
·         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
Rare
·         Confusion
·         convulsions (seizures)
·         difficulty with urination
·         dizziness
·         headache
·         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
·         itching skin
·         numbness or tingling of the fingers or toes
·         pain in the fingers or toes
·         unusual tiredness or weakness
·         weight loss
Minor Side Effects
Some of the side effects that can occur with TAJ PHARMA Hydroxyurea may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:
More common:
·         Diarrhea
·         drowsiness
·         loss of appetite
·         nausea or vomiting
Less common:
·         Constipation
·         redness of skin at the place of radiation
·         skin rash and itching
Applies to TAJ PHARMA Hydroxyurea: compounding powder, oral capsule, oral tablet
Hematologic
Very common (10% or more): Bone marrow failure, CD4 lymphocytes decreased, leukopenia, thrombocytopenia, platelet count decreased, anemia
Common (1% to 10%): Neutropenia^[Ref]
Gastrointestinal
Very common (10% or more): Pancreatitis, nausea, vomiting, diarrhea, stomatitis, constipation, mucositis, stomach discomfort, dyspepsia, abdominal pain, melena^[Ref]
Other
Very common (10% or more): Pyrexia, asthenia, chills, malaise, fever, edema^[Ref]
Dermatologic
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^[Ref]
Oncologic
Common (1% to 10%): Skin cancers, neoplasms benign and malignant [including cysts and polyps])
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.^[Ref]
Genitourinary
Very common (10% or more): Azoospermia, oligospermia
Very rare (less than 0.01%): Dysuria^[Ref]
Nervous system
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^[Ref]
Hepatic
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^[Ref]
Respiratory
Common (1% to 10%): Pulmonary fibrosis, pulmonary edema, lung infiltration, dyspnea^[Ref]
Metabolic
Very rare (less than 0.01%): Tumor lysis syndrome^[Ref]
Psychiatric
Common (1% to 10%): Hallucination, disorientation^[Ref]
Renal
Very common (10% or more): Dysuria, blood creatinine increased, blood urea increased, blood uric acid increased^[Ref]
References
1. Pharmaceutical Society of Australia "APPGuide online. Australian prescription products guide online. Available from: URL: http://www.appco.com.au/appguide/default.asp." ([2006]):
2. "Product Information. Droxia (TAJ PHARMA Hydroxyurea)." Bristol-Myers Squibb, Princeton, NJ.
3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
Applies to the following strength(s): 500 mg ; 200 mg ; 300 mg ; 400 mg ; 1000 mg
The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.
Usual Adult Dose for:
·         Chronic Myelogenous Leukemia
·         Head and Neck Cancer
·         Sickle Cell Anemia
Additional dosage information:
·         Renal Dose Adjustments
·         Liver Dose Adjustments
·         Dose Adjustments
·         Precautions
·         Dialysis
·         Other Comments
NOTE: Different products have different approved indications. Consult the manufacturer product information for approved indications.
15 mg/kg/day orally
Comments:
-Therapy should be individualized based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards.
-All dosages should be based on patient actual or ideal weight, whichever is less.
-Prophylactic administration of folic acid is recommended.
-Blood counts should be monitored at least once a week during therapy.
-Severe anemia should be corrected before initiating therapy.
Uses:
-Resistant chronic myeloid leukemia (CML)
-Locally advanced squamous cell carcinomas of the head and neck, (excluding lip) in combination with concurrent chemoradiation
NOTE: Different products have different approved indications. Consult the manufacturer product information for approved indications.
15 mg/kg/day orally
Comments:
-Therapy should be individualized based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards.
-All dosages should be based on patient actual or ideal weight, whichever is less.
-Prophylactic administration of folic acid is recommended.
-Blood counts should be monitored at least once a week during therapy.
-Severe anemia should be corrected before initiating therapy.
Uses:
-Resistant chronic myeloid leukemia (CML)
-Locally advanced squamous cell carcinomas of the head and neck, (excluding lip) in combination with concurrent chemoradiation
NOTE: Different products have different approved indications. Consult the manufacturer product information for approved indications.
Initial dose: 15 mg/kg orally per day; increase 5 mg/kg/day every 12 weeks
Maximum dose: 35 mg/kg/day
Dosing based on blood counts:
-Counts in acceptable range: Increase dose 5 mg/kg/day every 12 weeks to a maximum dose of 35 mg/kg/day (maximal dose is the highest dose that does not produce toxic blood counts over 24 consecutive weeks); increase dosing only if blood counts are in acceptable range; do not increase if myelosuppression occurs
-Counts between acceptable and toxic range: Do not increase dose; if in toxic range, discontinue therapy until hematologic recovery
-Dosing after hematologic recovery: Reduce dose by 2.5 mg/kg/day. Reduce the dose from the dose associated with hematologic toxicity. May titrate up or down every 12 weeks in 2.5 mg/kg/day increments. The patient should be at a stable dose with no hematologic toxicity for 24 weeks. Discontinue treatment permanently if patient develops hematologic toxicity twice.
-BLOOD COUNTS IN THE ACCEPTABLE RANGE:
Neutrophils greater than or equal to 2500 cells/mm3
Platelets greater than or equal to 95,000/mm3
Hemoglobin greater than 5.3 g/dL
Reticulocytes greater than or equal to 95,000/mm3 if the hemoglobin concentration is less than 9 g/dL
-BLOOD COUNTS IN THE TOXIC RANGE:
Neutrophils less than 2000 cells/mm3
Platelets less than 80,000/mm3
Hemoglobin less than 4.5 g/dL
Reticulocytes less than 80,000/mm3 if the hemoglobin concentration is less than 9 g/dL
Comments:
-Dosage is based on the actual or ideal patient weight, whichever is less.
-The patient blood count should be monitored every 2 weeks.
-Fetal hemoglobin (HbF) levels may be used to evaluate the efficacy of therapy in clinical use. Obtain HbF levels every 3 to 4 months. Monitor for an increase in HbF of at least 2-fold over the baseline value.
-Prophylactic administration of folic acid is recommended.
Use: To reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises.
-CrCl 60 mL/minute or greater: Initial dose: 15 mg/kg/day
-CrCl less than 60 mL/minute or end stage renal disease (ESRD): Initial dose: 7.5 mg/kg/day
Data not available; however, caution is recommended.
-Concurrent use of this drug with other myelosuppressive agents may require adjustment of dosages.
-Although no specific dose adjustment guidelines have been suggested, elderly patients may require a lower dose of this drug.
US BOXED WARNINGS:
-MYELOSUPPRESSION: This drug may cause severe myelosuppression. Blood counts should be monitored at baseline and throughout treatment. Treatment should be interrupted and the dose should be reduced as necessary.
MALIGNANCIES: This drug is carcinogenic. Patients should use sun protection and be monitored for malignancies.
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
-MYELOSUPPRESSION: This drug may cause severe myelosuppression. Blood counts should be monitored at baseline and throughout treatment. Treatment should be interrupted and the dose should be reduced as necessary.
MALIGNANCIES: This drug is carcinogenic. Patients should use sun protection and be monitored for malignancies.
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
Hemodialysis: Administer the dose following hemodialysis.
Administration advice:
-All dosage should be based on the patient's actual or ideal weight, whichever is less.
-The contents of capsules may be emptied into a glass of water and administered immediately. The contents of the capsule should not be inhaled or allowed to come into contact with the skin or mucous membranes.
General:
-Different individual products are used for specific indications. The manufacturer product information should be consulted prior to using a product.
-All dosage should be based on the patient's actual or ideal weight, whichever is less.
-The contents of capsules may be emptied into a glass of water and administered immediately. The contents of the capsule should not be inhaled or allowed to come into contact with the skin or mucous membranes.
General:
-Different individual products are used for specific indications. The manufacturer product information should be consulted prior to using a product.
A total of 178 drugs (490 brand and generic names) are known to interact with TAJ PHARMA Hydroxyurea.
·         33 major drug interactions (84 brand and generic names)
·         145 moderate drug interactions (406 brand and generic names)
Show all medications in the database that may interact with TAJ PHARMA Hydroxyurea.
TAJ PHARMA Hydroxyurea capsules, USP is 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.
2.1 Dosing Information
TAJ PHARMA Hydroxyurea is 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.
TAJ PHARMA Hydroxyurea is a cytotoxic drug. Follow applicable special handling and disposal procedures [see REFERENCES (15)].
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 TAJ PHARMA Hydroxyurea 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 TAJ PHARMA Hydroxyurea therapy. Severe anemia must be corrected before initiating therapy with TAJ PHARMA Hydroxyurea. Consider dose modifications for other toxicities.
2.3 Dose Modifications for Renal Impairment
Reduce the dose of TAJ PHARMA 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 TAJ PHARMA Hydroxyurea Capsules Initial Dose (mg/kg daily)
≥60	15
<60 or ESRD*	7.5
*On dialysis days, administer hyroxyurea capsules to patients following hemodialysis.

Close monitoring of hematologic parameters is advised in these patients.
Capsules:
·         500 mg dark green opaque (cap) printed “724” in white ink/ pink opaque (body) printed “taj” in black ink.
TAJ PHARMA Hydroxyurea capsules are contraindicated in patients who have demonstrated a previous hypersensitivity to TAJ PHARMA Hydroxyurea or any other component of the formulation.
5.1 Myelosuppression
TAJ PHARMA Hydroxyurea causes severe myelosuppression. Treatment with TAJ PHARMA 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 TAJ PHARMA Hydroxyurea cautiously in such patients.
Evaluate hematologic status prior to and during treatment with TAJ PHARMA Hydroxyurea capsules. Provide supportive care and modify dose or discontinue TAJ PHARMA Hydroxyurea as needed. Recovery from myelosuppression is usually rapid when therapy is interrupted.
5.2 Malignancies
TAJ PHARMA Hydroxyurea is a human carcinogen. In patients receiving long-term TAJ PHARMA Hydroxyurea for myeloproliferative disorders, secondary leukemia has been reported. Skin cancer has also been reported in patients receiving long-term TAJ PHARMA 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, TAJ PHARMA Hydroxyurea can cause fetal harm when administered to a pregnant woman. TAJ PHARMA 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/m2 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 TAJ PHARMA Hydroxyurea capsules for at least 6 months after therapy.  Advise males of reproductive potential to use effective contraception during and after treatment with TAJ PHARMA 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 TAJ PHARMA 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 TAJ PHARMA Hydroxyurea capsules.
5.5 Live Vaccinations
Avoid use of live vaccine in patients taking TAJ PHARMA Hydroxyurea capsules. Concomitant use of TAJ PHARMA 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 TAJ PHARMA Hydroxyurea capsules. Vaccination with live vaccines in a patient receiving TAJ PHARMA 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 TAJ PHARMA 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 postirradiation erythema. Monitor for skin erythema in patients who previously received radiation and manage symptomatically.
5.8 Macrocytosis
TAJ PHARMA Hydroxyurea capsules 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 B12 or folic acid deficiency. This may mask the diagnosis of pernicious anemia. Prophylactic administration of folic acid is recommended.
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)]
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of TAJ PHARMA Hydroxyurea capsules.
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 TAJ PHARMA Hydroxyurea and irradiation therapy are similar to those reported with the use of TAJ PHARMA 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 TAJ PHARMA Hydroxyurea and irradiation therapy will demonstrate concurrent leukopenia. Platelet depression (<100,000 cells/mm3) has occurred in the presence of marked leukopenia. TAJ PHARMA Hydroxyurea capsules may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.
7.1 Increased Toxicity with Concomitant Use of Antiretroviral Drugs
Pancreatitis
In patients with HIV infection during therapy with TAJ PHARMA Hydroxyurea and didanosine, with or without stavudine, fatal and nonfatal pancreatitis have occurred. TAJ PHARMA Hydroxyurea is not indicated for the treatment of HIV infection; however, if patients with HIV infection are treated with TAJ PHARMA 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 TAJ PHARMA 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 TAJ PHARMA Hydroxyurea and other antiretroviral drugs. Fatal hepatic events were reported most often in patients treated with the combination of TAJ PHARMA 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 TAJ PHARMA Hydroxyurea in combination with antiretroviral drugs, including didanosine, with or without stavudine.
7.2 Test Interference
Interference with Uric Acid, Urea, or Lactic Acid Assays
Studies have shown that there is an analytical interference of TAJ PHARMA 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 TAJ PHARMA Hydroxyurea.
8.1 Pregnancy
Risk Summary
TAJ PHARMA Hydroxyurea capsules can cause fetal harm based on findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology (12.1)]. There are no data with TAJ PHARMA Hydroxyurea capsules use in pregnant women to inform a drug-associated risk. In animal reproduction studies, administration of TAJ PHARMA Hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m2basis (see Data). Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated with TAJ PHARMA Hydroxyurea capsules.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
TAJ PHARMA Hydroxyurea has been demonstrated to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys at doses within 1-fold of the human dose given on a mg/m2 basis. TAJ PHARMA Hydroxyurea is embryotoxic and causes fetal malformations (partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, missing lumbar vertebrae) at 180 mg/kg/day (about 0.8 times the maximum recommended human daily dose on a mg/m2basis) in rats and at 30 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) in rabbits. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. TAJ PHARMA Hydroxyurea crosses the placenta. Single doses of ≥375 mg/kg (about 1.7 times the maximum recommended human daily dose on a mg/m2 basis) to rats caused growth retardation and impaired learning ability.
8.2 Lactation
Risk Summary
TAJ PHARMA Hydroxyurea is excreted in human milk. Because of the potential for serious adverse reactions in a breastfed infant from TAJ PHARMA Hydroxyurea, including carcinogenicity, discontinue breastfeeding during treatment with TAJ PHARMA Hydroxyurea capsules.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating TAJ PHARMA Hydroxyurea capsules therapy.
Contraception
Females
TAJ PHARMA Hydroxyurea capsules can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during and after treatment with TAJ PHARMA Hydroxyurea capsules for at least 6 months after therapy. Advise females to immediately report pregnancy.
Males
TAJ PHARMA Hydroxyurea capsules may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during and after treatment with TAJ PHARMA Hydroxyurea capsules for at least 1 year after therapy [see Nonclinical Toxicology (13.1)].
Infertility
Males
Based on findings in animals and humans, male fertility may be compromised by treatment with TAJ PHARMA Hydroxyurea capsules. Azoospermia or oligospermia, sometimes reversible, has been observed in men. Inform male patients about the possibility of sperm conservation before the start of therapy [see Adverse Reactions (6) and Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
Elderly patients may be more sensitive to the effects of TAJ PHARMA Hydroxyurea, and may require a lower dose regimen. TAJ PHARMA Hydroxyurea is excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.3)].
​8.6 Renal Impairment
The exposure to TAJ PHARMA Hydroxyurea is higher in patients with creatinine clearance of less than 60 mL/min or in patients with end-stage renal desease (ESRD). Reduce dosage and closely monitor the hematologic parameters when TAJ PHARMA Hydroxyurea capsules is to be administered to these patients [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
There are no data that support specific guidance for dosage adjustment in patients with hepatic impairment. Close monitoring of hematologic parameters is advised in these patients.
Acute mucocutaneous toxicity has been reported in patients receiving TAJ PHARMA Hydroxyurea at dosages several times the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, and stomatitis have also been observed.
TAJ PHARMA Hydroxyurea Capsules, USP are an antineoplastic agent available for oral use as capsules containing 500 mg TAJ PHARMA Hydroxyurea. Inactive ingredients include colloidal silicon dioxide, colorants (D&C Yellow No. 10, FD&C Blue No. 1 and FD&C Red No. 40), gelatin, magnesium stearate and titanium dioxide. Imprinting ink constituents: D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, pharmaceutical glaze, pharmaceutical shellac, propylene glycol, polyvinylpyrrolidone, sodium hydroxide, synthetic black iron oxide and titanium dioxide.
TAJ PHARMA Hydroxyurea is a white to off-white crystalline powder. It is hygroscopic and freely soluble in water, but practically insoluble in alcohol.  The empirical formula is CH4N2O2and it has a molecular weight of 76.05. Its structural formula is:

12.1 Mechanism of Action
The precise mechanism by which TAJ PHARMA Hydroxyurea produces its antineoplastic effects cannot, at present, be described.  However, the reports of various studies in tissue culture in rats and humans lend support to the hypothesis that TAJ PHARMA Hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. This hypothesis explains why, under certain conditions, TAJ PHARMA Hydroxyurea may induce teratogenic effects.
Three mechanisms of action have been postulated for the increased effectiveness of concomitant use of TAJ PHARMA Hydroxyurea therapy with irradiation on squamous cell (epidermoid) carcinomas of the head and neck. In vitro studies utilizing Chinese hamster cells suggest that TAJ PHARMA Hydroxyurea (1) is lethal to normally radioresistant S-stage cells, and (2) holds other cells of the cell cycle in the G1 or pre-DNA synthesis stage where they are most susceptible to the effects of irradiation. The third mechanism of action has been theorized on the basis of in vitro studies of HeLa cells. It appears that TAJ PHARMA Hydroxyurea, by inhibition of DNA synthesis, hinders the normal repair process of cells damaged but not killed by irradiation, thereby decreasing their survival rate; RNA and protein synthesis have shown no alteration.
12.3 Pharmacokinetics
Absorption
Following oral administration of TAJ PHARMA Hydroxyurea capsules, TAJ PHARMA Hydroxyurea reaches peak plasma concentrations in 1 to 4 hours. Mean peak plasma concentrations and AUCs increase more than proportionally with increase of dose.
There are no data on the effect of food on the absorption of TAJ PHARMA Hydroxyurea.
Distribution
TAJ PHARMA Hydroxyurea distributes throughout the body with a volume of distribution approximating total body water.
TAJ PHARMA Hydroxyurea concentrates in leukocytes and erythrocytes.
Metabolism
Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation by urease found in intestinal bacteria.
Excretion
In patients with sickle cell anemia, the mean cumulative urinary recovery of TAJ PHARMA Hydroxyurea was about 40% of the administered dose.
Specific Populations
Renal Impairment
The effect of renal impairment on the pharmacokinetics of TAJ PHARMA Hydroxyurea was assessed in adult patients with sickle cell disease and renal impairment. Patients with normal renal function (creatinine clearance [CrCl] >80 mL/min), mild (CrCl 50 to 80 mL/min), moderate (CrCl =30 to <50 mL/min), or severe (<30 mL/min) renal impairment received a single oral dose of 15 mg/kg TAJ PHARMA Hydroxyurea.  Patients with ESRD received two doses of 15 mg/kg separated by 7 days; the first was given following a 4-hour hemodialysis session, the second prior to hemodialysis. The exposure to TAJ PHARMA Hydroxyurea (mean AUC) in patients with CrCl <60 mL/min and those with ESRD was 64% higher than in patients with normal renal function (CrCl >60 mL/min). Reduce the dose of TAJ PHARMA Hydroxyurea capsules when it is administered to patients with creatinine clearance of <60 mL/min or with ESRD following hemodialysis [see Dosage and Administration (2.3) and Use in Specific Populations (8.6)].
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Conventional long-term studies to evaluate the carcinogenic potential of TAJ PHARMA Hydroxyurea capsules have not been performed. However, intraperitoneal administration of 125 to 250 mg/kg TAJ PHARMA Hydroxyurea (about 0.6 to 1.2 times the maximum recommended human oral daily dose on a mg/m2 basis) thrice weekly for 6 months to female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. TAJ PHARMA Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. TAJ PHARMA Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo(SCE assay in rodents, mouse micronucleus assay). TAJ PHARMA Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype.
TAJ PHARMA Hydroxyurea administered to male rats at 60 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females.
OSHA.http://www.osha.gov/SLTC/hazardousdrugs/index.html.
16.1 How Supplied
TAJ PHARMA Hydroxyurea capsules, USP 500 mg are dark green opaque (cap) printed "724" in white ink/ pink opaque (body) printed "TAJ" in black ink capsules.
They are supplied in bottles of 100 (NDC# 49884-724-01).
Dispense in a tight container as defined in the USP.
16.2 Storage
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep tightly closed.
16.3 Handling and Disposal
TAJ PHARMA Hydroxyurea capsules is 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 TAJ PHARMA Hydroxyurea capsules or bottles containing TAJ PHARMA Hydroxyurea capsules. Wash hands with soap and water before and after contact with the bottle or capsules when handling TAJ PHARMA Hydroxyurea capsules. Do not open TAJ PHARMA Hydroxyurea capsules. 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.
There is a risk of myelosuppression. Monitoring blood counts weekly throughout the duration of therapy should be emphasized to patients taking TAJ PHARMA Hydroxyurea capsules [see Warnings and Precautions (5.1)]. Advise patients to report signs and symptoms of infection or bleeding immediately.
Advise patients that there is a risk of cutaneous vasculitic toxicities and secondary malignancies including leukemia and skin cancers [see Warnings and Precautions (5.2, 5.4)].
Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy. Advise females and males of reproductive potential to use contraception during and after treatment with TAJ PHARMA Hydroxyurea capsules [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1,8.3)].
Advise patients to inform their healthcare provider if they have received or are planning to receive vaccinations while taking TAJ PHARMA Hydroxyurea capsules as this may result in a severe infection [see Warnings and Precautions (5.5)].
Advise females to discontinue breastfeeding during treatment with TAJ PHARMA Hydroxyurea capsules [see Use in Specific Populations (8.3)].
Patients with HIV infection should contact their physician for signs and symptoms of pancreatitis, hepatic events, and peripheral neuropathy [see Warnings and Precautions (5.6)].
Postirradiation erythema can occur in patients who have received previous irradiation therapy [see Warnings and Precautions (5.7)].
Manufactured by:
Taj Pharmaceuticals Ltd., Mumbai India
Revised 05/2016


 

Hydroxyurea Hydroxyurea capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:49884-724 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Hydroxyurea (Hydroxyurea) Hydroxyurea 500 mg

Inactive Ingredients Ingredient Name Strength SILICON DIOXIDE D&C YELLOW NO. 10 FD&C BLUE NO. 1 FD&C RED NO. 40 GELATIN MAGNESIUM STEARATE TITANIUM DIOXIDE

Product Characteristics Color GREEN (Dark Green) , PINK (Pink) Score no score Shape CAPSULE Size 19mm Flavor Imprint Code 724;taj Contains

Packaging # Item Code Package Description 1 NDC:49884-724-01 100 CAPSULE in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075340 02/24/1999

Labeler - TAJ Pharmaceutical, Inc. (09*************)

Registrant - TAJ Pharmaceutical Inc. (092733********)

 

Treating skin cancer, cancer of the ovary, or chronic myelocytic leukemia that is recurrent, has spread, or cannot be helped with surgery. It may also be used with radiation to control skin cancers of the head and neck. It may also be used for other conditions as determined by your doctor.
All the information is for Healthcare professionals.

© 2016 Taj Pharma (India) Ltd. | All Rights Reserved® Taj Pharma Holdings Taj Pharma Group. 
Site Map | Terms and Conditions| Privacy Policy| Legal Notice

This website and its information is intended for use by India residents only. Regulatory requirements, data requirements or medical practices may differ between countries. Therefore, information on this site may be inappropriate for use outside of the India. Site contents are intended for informational purposes only and not intended to replace discussion with a healthcare provider. If you have any questions regarding this site, contact Taj Pharma India. This product information is intended only for residents of India. Taj Pharmaceuticals Limited, medicines help to treat and prevent a range of conditions—from the most common to the most challenging—for people around the world. The Price of the drugs indicated above may not match the actual price at which they are sold. Prices can change depending on many factors, including local taxes. These are only approximate indicative prices of the drug. The products discussed herein may have different product labeling in different countries. The product information provided in this site is intended only for the residents of India. Unless expressly indicated otherwise, Taj Pharma is not the responsible for the graphics presented on this site. Actual product packaging and materials may contain more and different information than what is shown on our website. We recommend that you do not rely solely on the information presented on our website. Please always read labels, warnings, and directions provided with the product before using or consuming the product.