DRUGS & SUPPLEMENTS
RECENT MAJOR CHANGES
Indications and Usage, melanoma (1) Removed 7/2015
Indications and Usage, carcinoma of the ovary (1) Removed 7/2015
Dosage and Administration (2) 7/2015
Warnings and Precautions, Embryo-Fetal Toxicity (5.3) 3/2016
Warnings and Precautions, Live Vaccinations (5.5) 3/2016
1 INDICATIONS AND USAGE
Urdox capsules, USP is indicated for the treatment of:
Urdox capsules, USP is an antimetabolite indicated for the treatment of:
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Information
Urdox 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.
Urdox 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 Urdox accordingly:
Monitor blood counts at least once a week during Urdox therapy. Severe anemia must be corrected before initiating therapy with Urdox. Consider dose modifications for other toxicities.
2.3 Dose Modifications for Renal Impairment
Reduce the dose of Urdox 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) ].
Close monitoring of hematologic parameters is advised in these patients.
3 DOSAGE FORMS AND STRENGTHS
Urdox capsules are contraindicated in patients who have demonstrated a previous hypersensitivity to Urdox or any other component of the formulation.
5 WARNINGS AND PRECAUTIONS
Urdox causes severe myelosuppression. Treatment with Urdox 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 Urdox cautiously in such patients.
Evaluate hematologic status prior to and during treatment with Urdox capsules. Provide supportive care and modify dose or discontinue hydroxyurea as needed. Recovery from myelosuppression is usually rapid when therapy is interrupted.
Urdox is a human carcinogen. In patients receiving long-term Urdox for myeloproliferative disorders, secondary leukemia has been reported. Skin cancer has also been reported in patients receiving long-term Urdox. Advise protection from sun exposure and monitor for the development of secondary malignancies.
5.3 Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals, hydroxyurea can cause fetal harm when administered to a pregnant woman. Urdox 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 ].
Advise females of reproductive potential to use effective contraception during and after treatment with Urdox capsules for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with Urdox 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 Urdox. 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 Urdox capsules.
5.5 Live Vaccinations
Avoid use of live vaccine in patients taking Urdox capsules. Concomitant use of Urdox 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 Urdox capsules. Vaccination with live vaccines in a patient receiving Urdox 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 Urdox was administered concomitantly with antiretroviral drugs, including didanosine and stavudine [see Drug Interactions ].
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.
Urdox 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.
6 ADVERSE REACTIONS
The following adverse reactions are described in detail in other labeling sections:
The following adverse reactions have been identified during postapproval use of Urdox capsules.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.
Adverse reactions observed with combined Urdox and irradiation therapy are similar to those reported with the use of Urdox 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 Urdox and irradiation therapy will demonstrate concurrent leukopenia. Platelet depression (<100,000 cells/mm3) has occurred in the presence of marked leukopenia. Urdox capsules may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.
Most common adverse reactions (≥30%) are hematological, gastrointestinal symptoms, and anorexia. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
7 DRUG INTERACTIONS
7.1 Increased Toxicity with Concomitant Use of Antiretroviral Drugs
In patients with HIV infection during therapy with Urdox and didanosine, with or without stavudine, fatal and nonfatal pancreatitis have occurred. Urdox is not indicated for the treatment of HIV infection; however, if patients with HIV infection are treated with Urdox, and in particular, in combination with didanosine and/or stavudine, close monitoring for signs and symptoms of pancreatitis is recommended. Permanently discontinue therapy with Urdox in patients who develop signs and symptoms of pancreatitis.
Hepatotoxicity and hepatic failure resulting in death have been reported during postmarketing surveillance in patients with HIV infection treated with Urdox and other antiretroviral drugs. Fatal hepatic events were reported most often in patients treated with the combination of Urdox, didanosine, and stavudine. Avoid this combination.
Peripheral neuropathy, which was severe in some cases, has been reported in patients with HIV infection receiving Urdox 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 Urdox 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 Urdox.
8 USE IN SPECIFIC POPULATIONS
Urdox 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 Urdox capsules use in pregnant women to inform a drug-associated risk. In animal reproduction studies, administration of Urdox 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/m2 basis (see Data). Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated with Urdox 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.
Urdox 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. Urdox 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/m2 basis) 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. Urdox 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.
Urdox is excreted in human milk. Because of the potential for serious adverse reactions in a breastfed infant from Urdox, including carcinogenicity, discontinue breastfeeding during treatment with Urdox capsules.
8.3 Females and Males of Reproductive Potential
Verify the pregnancy status of females of reproductive potential prior to initiating Urdox capsules therapy.
Urdox capsules can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ]. Advise females of reproductive potential to use effective contraception during and after treatment with Urdox capsules for at least 6 months after therapy. Advise females to immediately report pregnancy.
Urdox 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 Urdox capsules for at least 1 year after therapy [see Nonclinical Toxicology (13.1) ].
Based on findings in animals and humans, male fertility may be compromised by treatment with Urdox 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 Urdox, and may require a lower dose regimen. Urdox 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 ].
8.6 Renal Impairment
The exposure to Urdox 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 Urdox 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 Urdox 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.
Urdox Capsules, USP are an antineoplastic agent available for oral use as capsules containing 500 mg Urdox. 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.
Urdox 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 CH4N2O2 and it has a molecular weight of 76.05. Its structural formula is:
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The precise mechanism by which Urdox 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 Urdox 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, Urdox may induce teratogenic effects.
Three mechanisms of action have been postulated for the increased effectiveness of concomitant use of Urdox therapy with irradiation on squamous cell carcinomas of the head and neck. In vitro studies utilizing Chinese hamster cells suggest that Urdox (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 Urdox, 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.
Following oral administration of Urdox capsules, Urdox 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 Urdox.
Urdox distributes throughout the body with a volume of distribution approximating total body water.
Urdox concentrates in leukocytes and erythrocytes.
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.
In patients with sickle cell anemia, the mean cumulative urinary recovery of Urdox was about 40% of the administered dose.
The effect of renal impairment on the pharmacokinetics of Urdox 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 Urdox. 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 Urdox (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 Urdox 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 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Conventional long-term studies to evaluate the carcinogenic potential of Urdox capsules have not been performed. However, intraperitoneal administration of 125 to 250 mg/kg Urdox (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. Urdox is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Urdox is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Urdox causes the transformation of rodent embryo cells to a tumorigenic phenotype.
Urdox 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.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
Urdox capsules, USP 500 mg are dark green opaque printed "724" in white ink/ pink opaque (body) printed "par" 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.
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Keep tightly closed.
16.3 Handling and Disposal
Urdox capsules is a cytotoxic drug. Follow applicable special handling and disposal procedures .
To decrease the risk of contact, advise caregivers to wear disposable gloves when handling Urdox capsules or bottles containing Urdox capsules. Wash hands with soap and water before and after contact with the bottle or capsules when handling Urdox capsules. Do not open Urdox 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.
17 PATIENT COUNSELING INFORMATION
There is a risk of myelosuppression. Monitoring blood counts weekly throughout the duration of therapy should be emphasized to patients taking Urdox 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 Urdox 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 Urdox capsules as this may result in a severe infection [see Warnings and Precautions (5.5) ].
Advise females to discontinue breastfeeding during treatment with Urdox 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 ) ].
Chestnut Ridge, NY 10977
For more information, go to www.parpharm.com or call 1-800-828-9393.
Urdox pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Urdox available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Urdox destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Urdox Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Urdox pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Urdox?
Depending on the reaction of the Urdox after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Urdox not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Urdox addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on Urdox, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Urdox consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
One visitor reported side effectsDid you get side effects while taking the Urdox drug, or were there no side effects?
According to the survey conducted by website sdrugs.com users, the below-mentioned percentages indicate the number of people experiencing the side effects and the number of people not experiencing the side effects when taking Urdox medicine. Every drug produces minimal side effects, and they are negligible most times, when compared to the desired effect [use] of the medicine. Side effects depend on the dose you are taking, any drug interactions that happen when you are on other medications, if the patient is sensitive, and other associated conditions. If you cannot tolerate the side effects, consult your doctor immediately, so he can either adjust the dose or change the medication.
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
One visitor reported dosesWhat is the dose of Urdox drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 201-500mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitor reported time for resultsNo survey data has been collected yet
Visitor reported administrationNo survey data has been collected yet
Visitor reported ageNo survey data has been collected yet
The information was verified by Dr. Arunabha Ray, MD Pharmacology