Uromes

Mesna.

Each mL contains: Mesna, KP 100 mg.

Pharmacology: Pharmacodynamics: Mesna is an antidote, and offers the possibility of reliably preventing urotoxic side-effects associated with aggressive cancer chemotherapy using oxazaphosphorine cytostatics. Extensive and wide-ranging pharmacological and toxicological investigations have shown that mesna has no intrinsic pharmacodynamics and low toxicity. The pharmacological and toxicological inertness of mesna administered systemically and its excellent detoxifying effect in the efferent urinary tract and bladder, are due to the nature of its pharmacokinetics.
Pharmacokinetics: Following IV or oral administration, Mesna is rapidly and almost completely oxidized in systemic circulation to dimesna (mesna disulfide). In a limited number of healthy adults who received a single 800-mg IV dose of Mesna, peak plasma concentrations of Mesna and dimesna averaged 18.2 and 59.7 μg/mL, respectively. The volume of distribution for Mesna has been reported to be approximately 0.65 L/kg in healthy adults. The drug does not cross the blood-brain barrier.
Mesna and dimesna are eliminated principally in urine. Following IV administration of a single 800-mg Mesna dose, peak urine concentrations are achieved within 4 hours and average 1.57 and 1.4 mg/mL for Mesna and dimesna, respectively. A urine Mesna concentration of 0.1 mg/mL has been proposed as the minimum effective uroprotective concentration.

Prevention of urothelial toxicity of oxazaphosphorines, Ifosfamide and Cyclophosphamide.

For IV administration, the contents of an ampule should be diluted with an appropriate volume of a compatible IV solution (i.e., 5% dextrose; 5% dextrose and 0.2, 0.33, or 0.45% sodium chloride; 0.9% sodium chloride; lactated Ringer's) to obtain a solution containing 20 mg/mL. The diluted solution may then be given by direct IV injection or infused IV over a period of 15-30 minutes.
IV administration with Oxazaphosphorine injection: If ifosfamide or cyclophosphamide is given as an intravenous bolus, Mesna as 20% of the dose of the antineoplastic on a weight for weight basis is given intravenously on 3 occasions over 15 to 30 minutes at 4-hourly intervals beginning at the same time as the antineoplastic injection.
This regimen is repeated for each dose of the antineoplastic. The dose of Mesna may be increased to 40% of the dose of the antineoplastic and given 4 times at 3-hourly intervals for patients at high risk of urotoxicity.
IV administration with Oxazaphosphorine infusion: If the antineoplastic is given as by intravenous infusion over 24 hours, Mesna as 20% of the total antineoplastic dose is given by intravenous injection, followed by 100% of the total dose by intravenous infusion over 24 hours, then followed by 60% by infusion over a further 12 hours.
The final 12-hour infusion may be replaced by 3 injections each of 20% of the antineoplastic dose at 4-hourly intervals. Urinary output should be maintained and the urine monitored for haematuria and proteinuria throughout the treatment period. However, frequent emptying of the bladder should be avoided.
When Mesna is exposed to oxygen, it is oxidized. Therefore, unused portions of the injection should be discarded.
Diluted solutions for drip infusion should be used within 24 hours after preparation.

There is no known antidote for Mesna. The 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.

It is contraindicated in patients known to be hypersensitive to Mesna or other thiol compounds.

The elderly.
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.
Mesna has been developed as an agent to prevent ifosfamide-induced urinary toxicity. 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 (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.
Use in Children: Safety and effectiveness in pediatric patients have not been established.
Use in Elderly: 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. According to decrease administration of ifosfamide, Mesna administration decreases in quantity (A dosage; 20% of ifosfamide in 1 day).

Reproduction studies in rats and rabbits with oral doses up to 1000 mg/kg have revealed no harm to the fetus due to Mesna. Mesna should be given to pregnant woman or nursing mother only if the benefits clearly outweigh any possible risk. 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.

Gastrointestinal system: Hydrodipsomania, vomiting, diarrhea, anorexia, dysgeusia.
Circulatory system: Hypotension, tachycardia.
Neurologic: Cephalalgia.
Musculoskeletal system: Melalgia.
Liver: Increase in AST, Increase in ALT.
Hematologic: Leukocytopenia.
Hypersensitivity: Pruritus, erythema, bleb, exanthem.
Others: Pain of injection site, malaise, edema, fever.
Because Mesna is used in combination with ifosfamide and other chemotherapeutic agents with documented toxicities, it is difficult to distinguish the adverse reactions which may be due to Mesna from those caused by the concomitantly administered cytostatic agents.
In phase I studies in which IV bolus doses of 0.8 to 1.6 g/m² Mesna were administered as single or three repeated doses to a total of 10 patients, a bad taste in the mouth (100%) and soft stools (70%) were reported. After intravenous and oral bolus doses of 2.4 g/m² which are approximately 10 times the recommended clinical doses (0.24 g/m²) headache (50%), fatigue (33%), diarrhea (83%), limb pain (50%), hypotension (17%), and allergy (17%) have also been reported in the 6 patients who participated in this study.

Drug-Drug Interactions: The route of administration of cisplatin should be different with one of Mesna if cisplatin is taken in conjunction with Mesna.
Mesna is not compatible with erythromycin, oxytetracyclin, aminophylline, lipiodol, epirubicin, nitrogen mustard.
Drug-Laboratory Test Interactions: 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.

Special Precautions for Handling: Do not preserve in other containers in order to maintain quality of the drug and avoid misuse.

Store at temperatures not exceeding 30ºC.

Antidotes & Detoxifying Agents / Supportive Care Therapy

V03AF01 - mesna ; Belongs to the class of detoxifying agents used in antineoplastic treatment.

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