DRUGS & SUPPLEMENTS

Uroprot

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Uroprot uses


1 INDICATIONS AND USAGE

Uroprot is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis.

Limitation of Use: 

Uroprot is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia. 

Uroprot is a cytoprotective agent indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis. (1)

Limitation of Use:

Uroprot is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia. (1)

2 DOSAGE AND ADMINISTRATION

Uroprot may be given on a fractionated dosing schedule of three bolus intravenous injections or a single bolus injection followed by two oral administrations of Uroprot Tablets as outlined below. The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is adjusted, the ratio of Uroprot to ifosfamide should be maintained.


0 Hours


4 Hours


8 Hours


Ifosfamide


1.2 g/m2


--


--


Uroprot Injection


240 mg/m2


240 mg/m2


240 mg/m2


0 Hours


2 Hours


6 Hours


Ifosfamide


1.2 g/m2


--


--


Uroprot Injection


240 mg/m2


--


--


Uroprot Tablets


--


480 mg/m2


480 mg/m2


Maintain sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. (2.3)

2.1 Intravenous Dosing

Uroprot may be given on a fractionated dosing schedule of three bolus intravenous injections as outlined below.

Uroprot injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage weight by weight (w/w) at the time of ifosfamide administration and 4 and 8 hours after each dose of ifosfamide. The total daily dose of Uroprot is 60% of the ifosfamide dose. The recommended dosing schedule is outlined below in Table 1.


 


0 Hours


4 Hours


8 Hours


Ifosfamide


1.2 g/m2






Uroprot Injection The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of Uroprot to ifosfamide should be maintained.


240 mg/m2


240 mg/m2


240 mg/m2

2.2 Intravenous and Oral Dosing

Uroprot may be given on a fractionated dosing schedule of a single bolus injection followed by two oral administrations of Uroprot tablets as outlined below.

Uroprot injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage at the time of ifosfamide administration. Uroprot tablets are given orally in a dosage equal to 40% of the ifosfamide dose 2 and 6 hours after each dose of ifosfamide. The total daily dose of Uroprot is 100% of the ifosfamide dose. The recommended dosing schedule is outlined in Table 2.


 


0 Hours


2 Hours


6 Hours


Ifosfamide


1.2 g/m2






Uroprot injection The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of Uroprot to ifosfamide should be maintained.


240 mg/m2






Uroprot tablets




480 mg/m2


480 mg/m2


The efficacy and safety of this ratio of intravenous and oral Uroprot has not been established as being effective for daily doses of ifosfamide higher than 2 g/m2.

Patients who vomit within two hours of taking oral Uroprot should repeat the dose or receive intravenous Uroprot.

2.3 Monitoring for Hematuria

Maintain adequate hydration and sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. If severe hematuria develops when Uroprot is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.

2.4 Preparation for Intravenous Administration and Stability

Preparation

Determine the volume of Uroprot injection for the intended dose.

Dilute the volume of Uroprot injection for the dose in any of the following fluids to obtain a final concentration of 20 mg/mL:

  • 5% Dextrose Injection, USP
  • 5% Dextrose and 0.2% Sodium Chloride Injection, USP
  • 5% Dextrose and 0.33% Sodium Chloride Injection, USP
  • 5% Dextrose and 0.45% Sodium Chloride Injection, USP
  • 0.9% Sodium Chloride Injection, USP
  • Lactated Ringer’s Injection, USP

Stability

The Uroprot injection multidose vials may be stored and used for up to 8 days after initial puncture.

Store diluted solutions at 25°C (77°F). Use diluted solutions within 24 hours.

Do not mix Uroprot injection with epirubicin, cyclophosphamide, cisplatin, carboplatin, and nitrogen mustard.

The benzyl alcohol contained in Uroprot injection vials can reduce the stability of ifosfamide. Ifosfamide and Uroprot may be mixed in the same bag provided the final concentration of ifosfamide does not exceed 50 mg/mL. Higher concentrations of ifosfamide may not be compatible with Uroprot and may reduce the stability of ifosfamide.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any solutions which are discolored, hazy, or contain visible particulate matter should not be used.

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3 DOSAGE FORMS AND STRENGTHS

  • Uroprot injection: 1 g Multidose Vial, 100 mg/mL
  • Uroprot tablets: 400 mg film-coated tablets with functional score
  • Injection: 1g (100 mg/mL) Multidose vials (3)
  • Tablets: 400 mg with functional score (3)

4 CONTRAINDICATIONS

Uroprot is contraindicated in patients known to be hypersensitive to Uroprot or to any of the excipients.

  • Known hypersensitivity to Uroprot or to any of the excipients, including benzyl alcohol. (4)

5 WARNINGS AND PRECAUTIONS

  • Hypersensitivity reactions: Anaphylactic reactions have been reported. Less severe hypersensitivity reactions may also occur. Monitor patients. If a reaction occurs, discontinue Uroprot and provide supportive care.
  • Dermatologic toxicity: Skin rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis have occurred. Skin rash, urticaria, and angioedema have also been seen. Monitor patients. If a reaction occurs, discontinue Uroprot and provide supportive care. (5.2)
  • Benzyl alcohol toxicity: The preservative benzyl alcohol has been associated with serious adverse reactions and death in neonates and premature infants. Avoid use in neonates, premature, and low-birth weight infants. (5.3)
  • Laboratory test alterations: False positive tests for urinary ketones and interference with enzymatic CPK activity tests have been seen. (5.4)

5.1 Hypersensitivity Reactions

Uroprot may cause systemic hypersensitivity reactions, including anaphylaxis. These reactions may include fever, cardiovascular symptoms (hypotension, tachycardia), acute renal impairment, hypoxia, respiratory distress, urticaria, angioedema, laboratory signs of disseminated intravascular coagulation, hematological abnormalities, increased liver enzymes, nausea, vomiting, arthralgia, and myalgia. These reactions may occur with the first exposure or after several months of exposure. Monitor for signs or symptoms. Discontinue Uroprot and provide supportive care.

5.2 Dermatologic Toxicity

Drug rash with eosinophilia and systemic symptoms and bullous and ulcerative skin and mucosal reactions, consistent with Stevens-Johnson syndrome or toxic epidermal necrolysis have occurred. Uroprot may cause skin and mucosal reactions characterized by urticaria, rash, erythema, pruritus, burning sensation, angioedema, periorbital edema, flushing and stomatitis. These reactions may occur with the first exposure or after several months of exposure. Discontinue Uroprot and provide supportive care.

5.3 Benzyl Alcohol Toxicity

Benzyl alcohol, a preservative in Uroprot, has been associated with serious adverse reactions and death in neonates, premature, and low-birth weight infants. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Consider the combined daily metabolic load of benzyl alcohol from all sources when prescribing Uroprot (10.4 mg benzyl alcohol per mL). Neonates, premature, and low-birth weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Monitor patients for signs or symptoms of toxicity. Avoid use in neonates, premature, and low-birth weight infants..

5.4 Laboratory Test Interferences

False-Positive Urine Tests for Ketone Bodies

A false positive test for urinary ketones may arise in patients treated with Uroprot when using nitroprusside sodium-based urine tests (including dipstick tests). The addition of glacial acetic acid can be used to differentiate between a false positive result (cherry-red color that fades) and a true positive result (red-violet color that intensifies).

False-Negative Tests for Enzymatic CPK Activity

Uroprot may interfere with enzymatic creatinine phosphokinase (CPK) activity tests that use a thiol compound (e.g., N-acetylcysteine) for CPK reactiviation. This may result in a falsely low CPK level.

False-Positive Tests for Ascorbic Acid

Uroprot may cause false-positive reactions in Tillman’s reagent-based urine screening tests for ascorbic acid.

5.5 Use in Patients with a History of Adverse Reactions to Thiol Compounds

Uroprot is a thiol compound, i.e., a sulfhydryl (SH) group-containing organic compound. Hypersensitivity reactions to Uroprot and to amifostine, another thiol compound, have been reported. It is not clear whether patients who experienced an adverse reaction to a thiol compound are at increased risk for a hypersensitivity reaction to Uroprot.

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6 ADVERSE REACTIONS

The following are discussed in more detail in other sections of the labeling.

  • Hypersensitivity Reactions
  • Dermatological Toxicity
  • Benzyl Alcohol Toxicity
  • Laboratory Test Interferences
  • Use in Patients with a History of Adverse Reactions to Thiol Compounds.

The most common adverse reactions (> 10%) when Uroprot is given with ifosfamide are nausea, vomiting, constipation, leukopenia, fatigue, fever, anorexia, thrombocytopenia, anemia, granulocytopenia, diarrhea, asthenia, abdominal pain, headache, alopecia, and somnolence. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Uroprot adverse reaction data are available from four Phase 1 studies in which single intravenous doses of 600-1200 mg Uroprot Injection without concurrent chemotherapy were administered to a total of 53 healthy volunteers and single oral doses of 600-2400 mg of Uroprot Tablets were administered to a total of 82 healthy volunteers. The most frequently reported side effects (observed in two or more healthy volunteers) for healthy volunteers receiving single doses of Uroprot Injection alone were headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperesthesia, influenza-like symptoms, and coughing. In two Phase 1 multiple-dose studies where healthy volunteers received Uroprot Tablets alone or intravenous Uroprot followed by repeated doses of Uroprot Tablets, flatulence and rhinitis were reported. In addition, constipation was reported by healthy volunteers who had received repeated doses of intravenous Uroprot.

Additional adverse reactions in healthy volunteers receiving Uroprot alone included injection site reactions, abdominal pain/colic, epigastric pain/burning, mucosal irritation, lightheadedness, back pain, arthralgia, myalgia, conjunctivitis, nasal congestion, rigors, paresthesia, photophobia, fatigue, lymphadenopathy, extremity pain, malaise, chest pain, dysuria, pleuritic pain, dry mouth, dyspnea, and hyperhidrosis. In healthy volunteers, Uroprot was commonly associated with a rapid (within 24 hours) decrease in lymphocyte count, which was generally reversible within one week of administration.

Because Uroprot is used in combination with ifosfamide or ifosfamide-containing chemotherapy regimens, it is difficult to distinguish the adverse reactions which may be due to Uroprot from those caused by the concomitantly administered cytotoxic agents.

Adverse reactions reasonably associated with Uroprot administered intravenously and orally in four controlled studies in which patients received ifosfamide or ifosfamide-containing regimens are presented in Table 3.


Uroprot Regimen


Intravenous-Intravenous-IntravenousIntravenous dosing of ifosfamide and Uroprot followed by either intravenous or oral doses of Uroprot according to the applicable dosage schedule..


Intravenous-Oral-Oral


N exposed


119 (100.0%)


119 (100%)


Incidence of AEs


101 (84.9%)


106 (89.1%)


Nausea


65 (54.6)


64 (53.8)


Vomiting


35 (29.4)


45 (37.8)


Constipation


28 (23.5)


21 (17.6)


Leukopenia


25 (21.0)


21 (17.6)


Fatigue


24 (20.2)


24 (20.2)


Fever


24 (20.2)


18 (15.1)


Anorexia


21 (17.6)


19 (16.0)


Thrombocytopenia


21 (17.6)


16 (13.4)


Anemia


20 (16.8)


21 (17.6)


Granulocytopenia


16 (13.4)


15 (12.6)


Asthenia


15 (12.6)


21 (17.6)


Abdominal Pain


14 (11.8)


18 (15.1)


Alopecia


12 (10.1)


13 (10.9)


Dyspnea


11 (9.2)


11 (9.2)


Chest Pain


10 (8.4)


11 (9.2)


Hypokalemia


10 (8.4)


11 (9.2)


Diarrhea


9 (7.6)


17 (14.3)


Dizziness


9 (7.6)


5 (4.2)


Headache


9 (7.6)


13 (10.9)


Pain


9 (7.6)


10 (8.4)


Sweating Increased


9 (7.6)


2 (1.7)


Back Pain


8 (6.7)


6 (5.0)


Hematuria


8 (6.7)


7 (5.9)


Injection Site Reaction


8 (6.7)


10 (8.4)


Edema


8 (6.7)


9 (7.6)


Edema Peripheral


8 (6.7)


8 (6.7)


Somnolence


8 (6.7)


12 (10.1)


Anxiety


7 (5.9)


4 (3.4)


Confusion


7 (5.9)


6 (5.0)


Face Edema


6 (5.0)


5 (4.2)


Insomnia


6 (5.0)


11 (9.2)


Coughing


5 (4.2)


10 (8.4)


Dyspepsia


4 (3.4)


6 (5.0)


Hypotension


4 (3.4)


6 (5.0)


Pallor


4 (3.4)


6 (5.0)


Dehydration


3 (2.5)


7 (5.9)


Pneumonia


2 (1.7)


8 (6.7)


Tachycardia


1 (0.8)


7 (5.9)


Flushing


1 (0.8)


6 (5.0)

6.2 Postmarketing Experience

The following adverse reactions have been reported in the postmarketing experience of patients receiving Uroprot in combination with ifosfamide or similar drugs, making it difficult to distinguish the adverse reactions which may be due to Uroprot from those caused by the concomitantly administered cytotoxic agents. Because these reactions are reported from a population of unknown size, precise estimates of frequency cannot be made.

Cardiovascular: Hypertension

Gastrointestinal: Dysgeusia

Hepatobiliary: Hepatitis

Nervous System: Convulsion

Respiratory: Hemoptysis

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7 DRUG INTERACTIONS

No clinical drug interaction studies have been conducted with Uroprot.

8 USE IN SPECIFIC POPULATIONS

  • Pregnancy: Use only if clearly needed.
  • Nursing mothers: Women should not breastfeed during therapy. (8.3)
  • Geriatric use: Dose selection should be cautious. (8.5)

8.1 Pregnancy

Pregnancy Category B.

Risk Summary

There are no studies of Uroprot in pregnant women. Reproduction studies performed in rats and rabbits at oral doses approximately 10 times the maximum recommended total daily intravenous-oral-oral human dose on a body surface area basis revealed no evidence of harm to the fetus due to Uroprot. The incidence of malformations in human pregnancies has not been established for Uroprot. All pregnancies, regardless of drug exposure, have a background rate of 2 to 4% for major malformations and 15 to 20% for pregnancy loss. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Uroprot or dimesna is excreted in human milk. Benzyl alcohol present in maternal serum is likely to cross into human milk and may be orally absorbed by a nursing infant. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from Uroprot, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness of Uroprot in pediatric patients have not been established. Uroprot contains benzyl alcohol which has been associated with serious adverse reactions and death in pediatric patients. The "gasping syndrome," (characterized by central nervous system depression, metabolic acidosis and gasping respirations) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates, premature, and low-birth weight infants. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Neonates, premature, and low-birth weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

8.5 Geriatric Use

Clinical studies of Uroprot did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The ratio of ifosfamide to Uroprot should remain unchanged.

8.6 Use in Patients with Renal Impairment

No clinical studies were conducted to evaluate the effect of renal impairment on the pharmacokinetics of Uroprot.

8.7 Use in Patients with Hepatic Impairment

No clinical studies were conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of Uroprot.

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10 OVERDOSAGE

There is no known antidote for Uroprot.

In a clinical trial, 11 patients received intravenous Uroprot 10 mg/kg to 66 mg/kg per day for 3 to 5 days. Patients also received ifosfamide or cyclophosphamide. Adverse reactions included nausea, vomiting, diarrhea and fever. An increased rate of these adverse reactions has also been found in oxazaphosphorine-treated patients receiving ≥80 mg Uroprot per kg per day intravenously compared with patients receiving lower doses or hydration treatment only.

Postmarketing, administration of 4.5 g to 6.9 g of Uroprot resulted in hypersensitivity reactions including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing.

11 DESCRIPTION

Uroprot is a detoxifying agent to inhibit the hemorrhagic cystitis induced by ifosfamide. The active ingredient, Uroprot, is a synthetic sulfhydryl compound designated as sodium-2-mercaptoethane sulfonate with a molecular formula of C2H5NaO3S2 and a molecular weight of 164.18. Its structural formula is as follows:

HS–CH2–CH2SO3–Na+

Uroprot (mesna) injection is a sterile, nonpyrogenic, aqueous solution of clear and colorless appearance in clear glass multidose vials for intravenous administration. Uroprot injection contains 100 mg/mL Uroprot, 0.25 mg/mL edetate disodium and sodium hydroxide for pH adjustment. Uroprot Injection multidose vials also contain 10.4 mg/mL of benzyl alcohol as a preservative. The solution has a pH range of 7.5-8.5.

Uroprot (mesna) tablets are white, oblong, scored biconvex film-coated tablets with the imprint M4. They contain 400 mg Uroprot. The excipients are calcium phosphate, cornstarch, hydroxypropylmethylcellulose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, simethicone, and titanium dioxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Uroprot reacts chemically with the urotoxic ifosfamide metabolites, acrolein and 4-hydroxy-ifosfamide, resulting in their detoxification. The first step in the detoxification process is the binding of Uroprot to 4-hydroxy-ifosfamide forming a non-urotoxic 4-sulfoethylthioifosfamide. Uroprot also binds to the double bonds of acrolein and to other urotoxic metabolites and inhibits their effects on the bladder.

12.3 Pharmacokinetics

Absorption

Following oral administration, peak plasma concentrations were reached within 1.5 to 4 hours and 3 to 7 hours for free Uroprot and total Uroprot (mesna plus dimesna and mixed disulfides), respectively. Oral bioavailability averaged 58% (range 45 to 71%) for free Uroprot and 89% (range 74 to 104%) for total Uroprot based on plasma AUC data from 8 healthy volunteers who received 1200 mg oral or intravenous doses.

Food does not affect the urinary availability of orally administered Uroprot.

Distribution

Mean apparent volume of distribution (Vd) for Uroprot is 0.652 ± 0.242 L/kg after intravenous administration which suggests distribution to total body water (plasma, extracellular fluid, and intracellular water).

Metabolism

Analogous to the physiological cysteine-cystine system, Uroprot is rapidly oxidized to its major metabolite, Uroprot disulfide (dimesna). Plasma concentrations of Uroprot exceed those of dimesna after oral or intravenous administration.

Excretion

Following intravenous administration of a single 800 mg dose, approximately 32% and 33% of the administered dose was eliminated in the urine in 24 hours as Uroprot and dimesna, respectively. Mean plasma elimination half-lives of Uroprot and dimesna are 0.36 hours and 1.17 hours, respectively. Uroprot has a plasma clearance of 1.23 L/h/kg.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of Uroprot.

Uroprot was not genotoxic in the in vitro Ames bacterial mutagenicity assay, the in vitro mammalian lymphocyte chromosomal aberration assay or the in vivo mouse micronucleus assay.

No studies on male or female fertility were conducted. No signs of male or female reproductive organ toxicity were seen in 6-month oral rat studies (≤ 2000 mg/kg/day) or 29-week oral dog studies (520 mg/kg/day) at doses approximately 10-fold higher than the maximum recommended human dose on a body surface area basis.

14 CLINICAL STUDIES

14.1 Intravenous Uroprot

Hemorrhagic cystitis produced by ifosfamide is dose dependent. At a dose of 1.2 g/m2 ifosfamide administered daily for 5 days, 16 to 26% of the patients who received conventional uroprophylaxis (high fluid intake, alkalinization of the urine, and the administration of diuretics) developed hematuria (>50 RBC per hpf or macrohematuria) (Studies 1, 2, and 3). In contrast, none of the patients who received Uroprot injection together with this dose of ifosfamide developed hematuria (Studies 3 and 4). In two randomized studies, (Studies 5 and 6), higher doses of ifosfamide, from 2 g/m2 to 4 g/m2 administered for 3 to 5 days, produced hematuria in 31 to 100% of the patients. When Uroprot was administered together with these doses of ifosfamide, the incidence of hematuria was less than 7%.


Study


Conventional

Uroprophylaxis

(number of patients)


Standard Uroprot

Intravenous Regimen

(number of patients)


Uncontrolled Studies Ifosfamide dose 1.2 g/m2 d x 5


Study 1


16% (7/44)


-


Study 2


26% (11/43)


-


Study 3


18% (7/38)


0% (0/21)


Study 4


-


0% (0/32)


Controlled Studies Ifosfamide dose 2 g/m2 to 4 g/m2 d x 3 to 5


Study 5


31% (14/46)


6% (3/46)


Study 6


100% (7/7)


0% (0/8)

14.2 Oral Uroprot

Clinical studies comparing recommended intravenous and oral Uroprot dosing regimens demonstrated incidences of grade 3 to 4 hematuria of <5%. Study 7 was an open label, randomized, two-way crossover study comparing three intravenous doses with an initial intravenous dose followed by two oral doses of Uroprot in patients with cancer treated with ifosfamide at a dose of 1.2 g/m2 to 2.0 g/m2 for 3 to 5 days. Study 8 was a randomized, multicenter study in cancer patients receiving ifosfamide at 2.0 g/m2 for 5 days. In both studies, development of grade 3 or 4 hematuria was the primary efficacy endpoint. The percent of patients developing hematuria in each of these studies is presented in Table 5.


Uroprot Dosing Regimen


Study


Standard Intravenous

Regimen

(number of patients)


Intravenous +

Oral Regimen

(number of patients)


Study 7


0% (0/30)


3.6% (1/28)


Study 8


3.7% (1/27)


4.3% (1/23)

16 HOW SUPPLIED/STORAGE AND HANDLING

Uroprot (mesna) injection 100 mg/mL

  • NDC 0338-1305-01

    1 g Multidose Vial, Box of 1 vial of 10 mL

  • NDC 0338-1305-03

    1 g Multidose Vial, Box of 10 vials of 10 mL


Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F)

Uroprot (mesna) tablets

  • NDC 67108-3565-9

    400 mg scored tablets packaged in box of 10 tablets


Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F)

17 PATIENT COUNSELING INFORMATION

  • Advise the patient to discontinue Uroprot and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction, including systemic anaphylactic reactions occur.
  • Advise the patient to take Uroprot at the exact time and in the exact amount as prescribed. Advise the patient to contact their healthcare provider if they vomit within 2 hours of taking oral Uroprot, or if they miss a dose of oral Uroprot.
  • Uroprot does not prevent hemorrhagic cystitis in all patients nor does it prevent or alleviate any of the other adverse reactions or toxicities associated with ifosfamide. Advise the patient to report to their healthcare provider if his/her urine has turned a pink or red color.
  • Advise the patient to drink 1 to 2 liters of fluid each day during Uroprot therapy.
  • Advise the patient that Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms and bullous and ulcerative skin and mucosal reactions have occurred with Uroprot. Advise the patient to report to their healthcare provider if signs and symptoms of these syndromes occur.

Baxter Logo

Uroprot (mesna) injection manufactured by:

Uroprot (mesna) tablets manufactured for:

Baxter Healthcare Corporation

Deerfield, IL 60015 USA

For Product Inquiry 1800 ANA DRUG (1-800-262-3784)

Made in Germany

Baxter, Uroprot, and IFEX are trademarks of Baxter International Inc.

Material No. HA-30-01-447

Patient Information

Uroprot (MES-nex)

(mesna)

tablets

Uroprot (MES-nex)

(mesna)

injection

What is the most important information I should know about Uroprot?

Uroprot can cause serious allergic reactions and skin reactions. These side effects can happen the first time you are treated with Uroprot, or after several months of treatment with Uroprot. Stop treatment with Uroprot and call your doctor or go to the nearest hospital emergency room right away if you develop any of the symptoms listed below:

  • fever
  • swelling of your face, lips, mouth, or tongue
  • trouble breathing or wheezing
  • itching
  • burning
  • skin rash or hives
  • skin redness or swelling
  • skin blisters or peeling
  • feel lightheaded or faint
  • feel like your heart is racing
  • nausea or vomiting
  • joint or muscle aches
  • mouth sores

See “What are the possible side effects of Uroprot?” for more information about side effects.

What is Uroprot?

Uroprot is a prescription medicine used to reduce the risk of inflammation and bleeding of the bladder (hemorrhagic cystitis) in people who receive ifosfamide (a medicine used to treat cancer).

Uroprot is not for use to reduce the risk of blood in the urine (hematuria) due to other medical conditions.

It is not known if Uroprot is safe and effective in children.

Who should not receive Uroprot?

Do not take Uroprot if you are allergic to Uroprot or any of the ingredients in Uroprot. See the end of this leaflet for a complete list of ingredients in Uroprot.

What should I tell my doctor before receiving Uroprot?

Before you receive Uroprot, tell your doctor if you:

  • have any other medical conditions
  • are pregnant or plan to become pregnant. It is not known if Uroprot will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Uroprot passes into your breast milk. You and your doctor should decide if you will receive Uroprot or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive Uroprot?

  • Uroprot is given on the same day that you receive ifosfamide.
  • Uroprot can be given by an intravenous (IV) infusion into a vein or tablets taken by mouth.
  • You will receive Uroprot in one of two ways:
    • Uroprot intravenous (IV) infusion into a vein at the time you receive ifosfamide and 4 and 8 hours after you receive ifosfamide.
    • Uroprot intravenous (IV) infusion into a vein at the time you receive ifosfamide and Uroprot tablets taken by mouth 2 and 6 hours after you receive ifosfamide.
  • Take Uroprot tablets at the exact times and the exact dose your doctor tells you to take it.
  • You may need to take half of a Uroprot tablet for your complete dose. Each tablet has a groove in the middle that will make it easier to break the tablet in half.
  • During treatment with Uroprot,you should drink 4 to 8 cups of liquid (1 to 2 liters) each day, whether you receive Uroprot by intravenous infusion or take Uroprot tablets by mouth.
  • Tell your doctor if you:
    • vomit within 2 hours of taking Uroprot tablets by mouth
    • miss a dose of Uroprot tablets
    • have pink or red colored urine

What are the possible side effects of Uroprot?

Uroprot may cause serious side effects, including:

See “What is the most important information I should know about Uroprot?”

  • Uroprot that is given by intravenous infusion contains the preservative benzyl alcohol. Benzyl alcohol has been shown to cause serious side effects and death in newborn, premature, and low-birth weight babies. Uroprot tablets do not contain benzyl alcohol.

The most common side effects of Uroprot when given with ifosfamide include:

  • nausea
  • vomiting
  • constipation
  • decreased white blood cell count
  • tiredness
  • fever
  • decreased appetite
  • decreased platelet count
  • decreased red blood cell count
  • diarrhea
  • weakness
  • stomach (abdomen) pain
  • headache
  • hair loss
  • sleepiness

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Uroprot. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Uroprot tablets?

  • Store Uroprot tablets at room temperature between 68°F to 77°F (20°C to 25°C).

Keep Uroprot and all medicines out of the reach of children.

General information about the safe and effective use of Uroprot

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Uroprot for a condition for which it was not prescribed. Do not give Uroprot to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Uroprot that is written for health professionals.

For more information, call 1-800-262-3784.

What are the ingredients in Uroprot?

Active ingredient: Uroprot

Inactive ingredients:

Uroprot injection: edetate disodium, sodium hydroxide, and benzyl alcohol as a preservative.

Uroprot tablets: calcium phosphate, cornstarch, hydroxypropylmethylcellulose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, simethicone, and titanium dioxide.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Baxter Healthcare Corporation

Deerfield, IL 60015 USA

Baxter and Uroprot are trademarks of Baxter International Inc.

Revised: January 2015

Container Label 400 mg Tablets

List 3565-9

Rx only

400 mg

Mesnex®

(mesna) Tablets

Baxter Healthcare

Corporation

460-656-00

Lot-number/Expires:

JMXXX MM.JJJJ

Carton Label 400 mg Tablets

10 400 mg Tablets

NDC 67108-3565-9

400 mg

Uroprot

(mesna) Tablets

10 400 mg Tablets

NDC 67108-3565-9

400 mg

Uroprot

(mesna) Tablets

Rx only

Each tablet contains 400 mg Uroprot.

Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F)

.

For ORAL ADMINISTRATION

Dosage: See package insert for directions for use. Should not be prescribed without thorough

knowledge of dose, indications, and toxicology as contained in accompanying literature.

Manufactured for:

Baxter Logo

Baxter Healthcare Corporation

Deerfield, IL 60015 USA

10 400 mg Tablets

NDC 67108-3565-9

400 mg

Uroprot

(mesna) Tablets

10 400 mg Tablets

NDC 67108-3565-9

400 mg

Uroprot

(mesna) Tablets

Rx only

Each tablet contains 400 mg Uroprot.

Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F)

.

For ORAL ADMINISTRATION

Dosage: See package insert for directions for use. Should not be prescribed without thorough

knowledge of dose, indications, and toxicology as contained in accompanying literature.

Manufactured for:

Baxter Logo

Baxter Healthcare Corporation

Deerfield, IL 60015 USA

460-657-00

Bar Code

N3 6710835659 1

70010157-

1714/943

10 400 mg Tablets

NDC 67108-3565-9

400 mg

Uroprot

(mesna) Tablets

C

943

HA-80-01-785

USA

Lot Number/Expires:

2640B4050

JMXXXA MM.JJJJ

Bar Code

Uroprot pharmaceutical active ingredients containing related brand and generic drugs:

infoActive 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.


Uroprot available forms, composition, doses:

infoForm 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.


Uroprot destination | category:

infoDestination 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.


Uroprot Anatomical Therapeutic Chemical codes:

infoA 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.


Uroprot pharmaceutical companies:

infoPharmaceutical 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.


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References

  1. Dailymed."MESNEX (MESNA) TABLET, FILM COATED [BAXTER HEALTHCARE CORPORATION]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Uroprot?

Depending on the reaction of the Uroprot after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Uroprot 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 Uroprot 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.

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Review

sDrugs.com conducted a study on Uroprot, 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 Uroprot 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.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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