Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1120
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Mesnex (Tablet)
|
| dailymed-instance:dosage |
For the prophylaxis
of ifosfamide induced hemorrhagic cystitis, mesna may be given on a
fractionated dosing schedule of three bolus intravenous injections or a
single bolus injection followed by two oral administrations of Mesnex
Tablets as outlined below.<br/>Intravenous
Schedule: Mesna is
given as intravenous bolus injections in a dosage equal to 20%
of the ifosfamide dosage (w/w) at the time of ifosfamide
administration and 4 and 8 hours after each dose of ifosfamide.
The total daily dose of mesna is 60% of the ifosfamide dose. The
recommended dosing schedule is outlined below:<br/>Intravenous and
Oral Dosing: Mesna
Injection is given as intravenous bolus injections in a dosage
equal to 20% of the ifosfamide dosage (w/w) at the time of
ifosfamide administration. Mesnex 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 mesna is 100%
of the ifosfamide dose. The
recommended dosing schedule is outlined below: Patients
who vomit within two hours of taking oral mesna should repeat
the dose or receive intravenous mesna. The efficacy and safety
of this ratio of IV and PO mesna has not been established as
being effective for daily doses of IFEX higher than
2.0 g/m. The dosing
schedule should be repeated on each day that ifosfamide is
administered. When the dosage of ifosfamide is adjusted (either
increased or decreased), the ratio of Mesna to IFEX should be
maintained.<br/>Preparation of
Intravenous Solutions/Stability: The Mesna
multidose vials may be stored and used for up to 8 days. For IV
administration the drug can be diluted by adding the Mesna
Injection solution to any of the following fluids obtaining
final concentrations of 20 mg mesna/mL: For
example: One mL of
Mesna Injection multidose vial 100 mg/mL may be added to 4 mL of
any of the solutions listed above to create a final
concentration of 20 mg mesna/mL. Diluted
solutions are chemically and physically stable for 24 hours at
25��C (77��F). Mesna is
not compatible with cisplatin or carboplatin. Parenteral
drug products should be inspected visually for particulate
matter and discoloration prior to administration.
|
| dailymed-instance:descripti... |
Mesna is a
detoxifying agent to inhibit the hemorrhagic cystitis induced by
ifosfamide (IFEX). The active ingredient mesna is a synthetic
sulfhydryl compound designated as sodium-2-mercaptoethane sulfonate with
a molecular formula of
CHNaOSand a molecular
weight of 164.18. Its structural formula is as follows: HS���CH���CHSO���Na Mesna Injection is
a sterile, nonpyrogenic, aqueous solution of clear and colorless
appearance in clear glass multidose vials for intravenous
administration. Mesna Injection contains 100 mg/mL mesna, 0.25 mg/mL
edetate disodium and sodium hydroxide for pH adjustment. Mesna Injection
multidose vials also contain 10.4 mg of benzyl alcohol as a
preservative. The solution has a pH range of 7.5-8.5. Mesnex Tablets are
white, oblong, scored biconvex film-coated tablets with the imprint M4.
They contain 400 mg mesna. Excipients include lactose, microcrystalline
cellulose, calcium phosphate, cornstarch, povidone, magnesium stearate,
hydroxypropylmethylcellulose, polyethylene glycol, titanium dioxide, and
simethicone.
|
| dailymed-instance:clinicalP... |
Mechanism of Action: Mesna was
developed as a prophylactic agent to reduce the risk of
hemorrhagic cystitis induced by ifosfamide. Analogous
to the physiological cysteine-cystine system, mesna is rapidly
oxidized to its major metabolite, mesna disulfide (dimesna).
Mesna disulfide remains in the intravascular compartment and is
rapidly eliminated by the kidneys. In the
kidney, the mesna disulfide is reduced to the free thiol
compound, mesna, which 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 mesna to
4-hydroxy-ifosfamide forming a nonurotoxic
4-sulfoethylthioifosfamide. Mesna also binds to the double bonds
of acrolein and to other urotoxic metabolites. In multiple
human xenograft or rodent tumor model studies of limited scope,
using IV or IP routes of administration, mesna in combination
with ifosfamide (at dose ratios of up to 20-fold as single or
multiple courses) failed to demonstrate interference with
antitumor efficacy.<br/>Pharmacokinetics: At doses of
2-4 g/m, the terminal elimination half-life of
ifosfamide is about 4-8 hours. As a result, in order to maintain
adequate levels of mesna in the urinary bladder during the
course of elimination of the urotoxic ifosfamide metabolites,
repeated doses of Mesna are required.<br/>IV-IV-IV
Regimen: After intravenous administration of an 800-mg dose, the
half-lives of mesna and dimesna in the blood are 0.36
hours and 1.17 hours, respectively. Approximately 32%
and 33% of the administered dose was eliminated in the
urine in 24 hours as mesna and dimesna, respectively.
The majority of the dose recovered was eliminated within
4 hours. Mesna has a plasma clearance of 1.23
L/h/kg.<br/>IV-Oral-Oral Regimen: The
half-life of mesna ranged from 1.2-8.3 hours after
administration of intravenous plus oral doses of Mesna,
as recommended in the DOSAGE AND ADMINISTRATION section. The
urinary bioavailability of oral mesna ranged from 45-79%
of intravenously administered mesna. Food does not
affect the urinary availability of orally administered mesna. Approximately 18-26% of the combined intravenous
and oral mesna dose appears as free mesna in the urine.
When compared to intravenously administered mesna, the
intravenous plus oral dosing regimen increases systemic
exposures (150%) and provides more sustained excretion
of mesna in the urine over a 24-hour period.
Approximately 5% of the mesna dose is excreted during
the 12-24 hour interval, as compared to negligible
amounts in patients given the IV regimen. The fraction
of the administered dose of mesna excreted in the urine
is independent of dose. Protein binding of mesna is in a
moderate range (69-75%).<br/>Special
Populations:<br/>Clinical Studies:<br/>IV Mesna: Hemorrhagic cystitis produced by ifosfamide is dose
dependent (Table 1). At a dose of 1.2 g/mifosfamide administered daily for 5 days, 16-26% of the
patients who received conventional uroprophylaxis (high
fluid intake, alkalinization of the urine, and the
administration of diuretics) developed hematuria
(>50 RBC/hpf or macrohematuria) (Morgan,
Einhorna, Costanzi). In contrast, none of the patients
who received Mesna Injection together with this dose of
ifosfamide developed hematuria (Einhorn).
In two randomized studies, (Fukuoka, Scheef), higher
doses of ifosfamide, from 2 to 4 g/madministered for 3-5 days, produced hematuria in 31-100%
of the patients. When mesna was administered together
with these doses of ifosfamide, the incidence of
hematuria was less than 7%.<br/>Oral Mesna: Clinical studies comparing recommended intravenous and
oral mesna dosing regimens demonstrated incidences of
grade 3-4 hematuria of<5%. Study D07093-0018 was
an open label, randomized, two-way crossover study
comparing three IV doses with an initial IV dose
followed by two oral doses of mesna in patients with
cancer treated with ifosfamide at a dose of 1.2-2.0
g/mfor 3-5 days. Study MED504 was a
randomized, multicenter study in cancer patients
receiving ifosfamide at 2.0 g/mfor 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 2. A
crossover pharmacokinetic study supports the low
incidence of grade 3 or 4 hematuria with the recommended
intravenous and oral mesna dosing regimens used in the
two controlled studies.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Mesna is
contraindicated in patients known to be hypersensitive to mesna or other
thiol compounds.
|
| dailymed-instance:supply |
Mesna Injection 100
mg/mL Mesnex
(mesna) Tablets Store at 20��-25��C (68��-77��F), excursions
permitted to 15��-30��C (59��-86��F) [see USP Controlled Room
Temperature]. U.S. Patent Nos.:
5,262,169, 5,252,341, and 5,696,172 Mesnex
(mesna) Tablets manufactured for: Mesna Injection
manufactured by: Baxter Healthcare Corporation Deerfield, IL 60015
USA For Product Inquiry
1 800 ANA DRUG (1-800-262-3784) USA 5663 9331 C66 Issued August 2004
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... |
dailymed-ingredient:Corn_Starch,
dailymed-ingredient:Dibasic_Calcium_Phosphate,
dailymed-ingredient:Hydroxypropyl_Methylcellulose,
dailymed-ingredient:Lactose,
dailymed-ingredient:Magnesium_Stearate,
dailymed-ingredient:Microcrystalline_Cellulose,
dailymed-ingredient:Polyethylene_Glycol_6000,
dailymed-ingredient:Povidone,
dailymed-ingredient:Simethicone,
dailymed-ingredient:Titanium_Dioxide
|
| dailymed-instance:precautio... |
Information for
Patients: Healthcare
providers should advise patients taking Mesna to drink at least
a quart of liquid a day. Patients should be informed to report if their urine has turned a pink or red color, if they vomit
within 2 hours of taking oral Mesna, or if they miss a dose of
oral Mesna. See Patient
Information Leaflet for Mesnex
Tablets.<br/>Laboratory Tests: A false
positive test for urinary ketones may arise in patients treated
with Mesna. In this test, a red-violet color develops which,
with the addition of glacial acetic acid, will return to
violet.<br/>Drug Interactions: No clinical
drug studies have been conducted.<br/>Carcinogenesis,
Mutagenesis, and Impairment of Fertility:<br/>Carcinogenesis: No
long-term studies in animals have been performed to
evaluate the carcinogenic potential of
Mesna.<br/>Mutagenesis: Mesna 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.<br/>Impairment
of Fertility: 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 (at doses up to 2000
mg/kg/day) or 29-week oral dog studies (520 mg/kg/day;
both studies approximately 10-fold higher than the
maximum recommended human dose on a body surface area basis).<br/>Pregnancy:<br/>Pregnancy
Category B: Reproduction studies have been performed in rats and
rabbits at oral doses of 1000 mg/kg in rabbits and 2000 mg/kg in rats (approximately 10 times the maximum
recommended total daily IV-oral-oral human dose on a
body surface area basis) and have revealed no evidence
of harm to the fetus due to mesna. There are however, no
adequate and well-controlled studies in pregnant women.
Because animal reproductive studies are not always
predictive of human response, this drug should be used
during pregnancy only if clearly needed.<br/>Nursing Mothers: It is not
known whether mesna or dimesna is excreted in human milk.
Because many drugs are excreted in human milk and because of the
potential for adverse reactions in nursing infants from mesna, a
decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the
drug to the mother.<br/>Pediatric Use: Safety and
effectiveness of Mesnex Tablets in pediatric patients have not
been established. Because of
the benzyl alcohol content in Mesna Injection, the multidose
vial should not be used in neonates or infants and should be
used with caution in older pediatric patients.<br/>Geriatric Use: Clinical
studies of mesna 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. However, the ratio of
ifosfamide to mesna should remain unchanged.
|
| dailymed-instance:overdosag... |
There is no known
antidote for mesna. Oral doses of 6.1 and 4.3 g/kg were lethal to mice
and rats, respectively. These doses are approximately 15 and 22 times
the maximum recommended human dose on a body surface area basis. Death
was preceded by diarrhea, tremor, convulsions, dyspnea, and
cyanosis.
|
| dailymed-instance:genericMe... |
mesna
|
| dailymed-instance:fullName |
Mesnex (Tablet)
|
| dailymed-instance:adverseRe... |
Mesna adverse
reaction data are available from four phase I studies in which single IV
bolus doses of 600-1200 mg Mesna Injection without concurrent
chemotherapy were administered to a total of 53 subjects and single oral
doses of 600-2400 mg of Mesnex Tablets were administered to a total of 82 subjects. The most frequently reported side effects (observed in two or more patients) for patients
receiving single doses of Mesna IV were headache, injection site
reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea,
anorexia, fever, pharyngitis, hyperaesthesia, influenza-like symptoms,
and coughing. Among patients who received a single 1200-mg dose as an
oral solution, rigors, back pain, rash, conjunctivitis, and arthralgia
were also reported. In two phase I multiple-dose studies where patients
received Mesnex Tablets alone or IV Mesna followed by repeated doses of
Mesnex Tablets, flatulence and rhinitis were reported. In addition,
constipation wasreported by patients who had received repeated doses of
IV Mesna. Because mesna is
used in combination with ifosfamide or ifosfamide-containing
chemotherapy regimens, it is difficult to distinguish the adverse
reactions which may be due to Mesna from those caused by the
concomitantly administered cytotoxic agents. Adverse reactions
reasonably associated with mesna administered IV and orally in four
controlled studies in which patients received ifosfamide or
ifosfamide-containing regimens are presented in Table 3.<br/>Postmarketing
Surveillance: Allergic
reactions, decreased platelet counts associated with allergic
reactions, hypertension, hypotension, increased heart rate,
increased liver enzymes, injection site reactions (including
pain and erythema), limb pain, malaise, myalgia, ST-segment elevation, tachycardia, and tachypnea have been reported as part
of postmarketing surveillance.
|
| dailymed-instance:warning |
Allergic reactions
to mesna ranging from mild hypersensitivity to systemic anaphylactic
reactions have been reported. Patients with autoimmune disorders who
were treated with cyclophosphamide and mesna appeared to have a higher
incidence of allergic reactions. The majority of these patients received
mesna orally. Mesna has been
developed as an agent to reduce the risk of ifosfamide-induced
hemorrhagic cystitis. It will not prevent or alleviate any of the other
adverse reactions or toxicities associated with ifosfamide therapy. Mesna does not
prevent hemorrhagic cystitis in all patients. Up to 6% of patients
treated with mesna have developed hematuria (��50 RBC/hpf or WHO grade 2
and above). As a result, a morning specimen of urine should be examined
for the presence of hematuria (microscopic evidence of red blood cells)
each day prior to ifosfamide therapy. If hematuria develops when Mesna
is given with ifosfamide according to the recommended dosage schedule,
depending on the severity of the hematuria, dosage reductions or
discontinuation of ifosfamide therapy may be initiated. In order to reduce
the risk of hematuria, Mesna must be administered with each dose of
ifosfamide as outlined in the DOSAGE AND ADMINISTRATION section. Mesna is not effective in
reducing the risk of hematuria due to other pathological conditions such
as thrombocytopenia. Because of the
benzyl alcohol content, the multidose vial should not be used in
neonates or infants and should be used with caution in older pediatric
patients.
|
| dailymed-instance:indicatio... |
Mesna is indicated
as a prophylactic agent in reducing the incidence of ifosfamide-induced
hemorrhagic cystitis.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Mesnex
|