Mesnex Information
Mesnex (Mesna) Description
Mesnex (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 CHNaOS and a molecular weight of 164.18. Its structural formula is as follows:
HS—CH—CHSO—Na
Mesnex (Mesna) Injection is a sterile, nonpyrogenic, aqueous solution of clear and colorless appearance in clear glass multidose vials for intravenous administration. Mesnex (Mesna) Injection contains 100 mg/mL mesna, 0.25 mg/mL edetate disodium and sodium hydroxide for pH adjustment. Mesnex (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 (Mesna) 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.
Mesnex (Mesna) Clinical Pharmacology
Mesnex (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.
Mesnex (Mesna) Indications And Usage
Mesnex (Mesna) is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis.
Mesnex (Mesna) Contraindications
Mesnex (Mesna) is contraindicated in patients known to be hypersensitive to mesna or other thiol compounds.
Mesnex (Mesna) Warnings
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.
Mesnex (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.
Mesnex (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 Mesnex (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, Mesnex (Mesna) must be administered with each dose of ifosfamide as outlined in the section. Mesnex (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.
Mesnex (Mesna) Precautions
Safety and effectiveness of Mesnex (Mesna) Tablets in pediatric patients have not been established.
Because of the benzyl alcohol content in Mesnex (Mesna) Injection, the multidose vial should not be used in neonates or infants and should be used with caution in older pediatric patients.
Mesnex (Mesna) Adverse Reactions
Mesnex (Mesna) adverse reaction data are available from four phase I studies in which single IV bolus doses of 600-1200 mg Mesnex (Mesna) Injection without concurrent chemotherapy were administered to a total of 53 subjects and single oral doses of 600-2400 mg of Mesnex (Mesna) 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 Mesnex (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 (Mesna) Tablets alone or IV Mesnex (Mesna) followed by repeated doses of Mesnex (Mesna) Tablets, flatulence and rhinitis were reported. In addition, constipation was reported by patients who had received repeated doses of IV Mesnex (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 Mesnex (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.
Mesnex (Mesna) Overdosage
There is no known antidote for Mesnex (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.
Mesnex (Mesna) Dosage And Administration
For the prophylaxis of ifosfamide induced hemorrhagic cystitis, Mesnex (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 (Mesna) Tablets as outlined below.
Mesnex (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:
Mesnex (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 (Mesna) 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 Mesnex (Mesna) to IFEX should be maintained.
The Mesnex (Mesna) multidose vials may be stored and used for up to 8 days.
For IV administration the drug can be diluted by adding the Mesnex (Mesna) Injection solution to any of the following fluids obtaining final concentrations of 20 mg mesna/mL:
For example:
One mL of Mesnex (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.
Mesnex (Mesna) How Supplied
Mesnex (Mesna) Injection 100 mg/mL
Mesnex (Mesna) (mesna) Tablets
Mesnex (Mesna) (mesna) Injection manufactured by:
Mesnex (Mesna) Tablets manufactured for:
Baxter, Mesnex (Mesna) and Ifex are trademarks of Baxter International Inc.
U.S. Patent Nos.:5,262,169, 5,252,341 and 5,696,172
Mesnex (Mesna)
Mesnex (Mesna) Package Label - Principal Display Panel
1 Multidose Vial
NDC 0338-1305-01
Mesnex (Mesna) Injection
FOR INTRAVENOUS USE
1g
Rx only
1 Multidose Vial
NDC 0338-1305-01
Mesnex (Mesna) Injection
1g
FOR INTRAVENOUS USE
Rx only
Manufactured byBaxter Healthcare CorporationDeerfield, IL 60015 USA
List 3565-9
Rx only
400 mg
Mesnex (Mesna) (mesna) Tablets
Baxter Healthcare Corporation460-656-00USA 5363 9222
(01)00067108356590Lot-number:/Expires:
JMXXX
MM.JJJJ
10 400 mg Tablets
NDC 67108-3565-9
400 mg
Mesnex (Mesna) (mesna) Tablets
Rx only
Each tablet contains 400 mg mesna.Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F)[see USP Controlled Room Temperature].
For ORAL ADMINISTRATION
Dosage:
Manufactured for: Deerfield, IL 60015 USA
