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.
|
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 |
||||||||||||||||||||
|
||||||||||||||||||||
|
||||||||||||||||||||
|
||||||||||||||||||||
|
||||||||||||||||||||
|
||||||||||||||||||||
|
||||||||||||||||||||
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
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.