Composition, form of production and packaging
The solution for intravenous administration is clear, colorless.
mesna 400 mg
Excipients: disodium edetate, sodium hydroxide, water d / u.
4 ml - glass ampoules (5) - packings, cell planimetric (3) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
Mesna is an antidote of acrolein, a metabolite of antitumor agents from the group of oxazaphosphorines (ifosfamide, cyclophosphamide), which irritates the mucosa of the bladder. The protective properties of mesna are due to the interaction with the double bond of the molecule of acrolein, which leads to the formation of a stable non-toxic thioester. By reducing the urotoxic effects of oxazaphosphorines, mesna does not weaken their antitumor effect.
With IV introduction, the active substance is rapidly oxidized to disulfide (dimenes). In the epithelium of the renal tubules, the dimene is reduced to a free thiol compound, which irreversibly binds to the metabolites of oxazaphosphorines, forming nontoxic stable thioethers.
Binding to plasma proteins is 69-75%. Systemic clearance -1.23 l / h / kg.
After intravenous administration in a dose of 800 mg T 1/2, the mesnes and dimes in the blood make up 0.36 h and 1.17 h, respectively. About 32% and 33% of the administered dose were excreted in the urine within 24 hours, respectively, in the form of mesna and dimesna. Most of the reconstituted dose was excreted in the urine for 4 hours.
Local detoxification of urotoxic effects of cytostatics - derivatives of oxazaphosphorines, incl. in the following cases:
- with the administration of ifosfamide;
- with the introduction of oxazaphosphorines in high doses (more than 10 mg / kg);
- in patients at risk - previous radiation therapy on the pelvic area, development of cystitis during previous therapy with oxazaphosphorines, and a history of urinary system diseases.
Uromitexan В® is usually injected / injected (slowly). A single dose for adults is 20% of a single dose of oxazaphosphorin. The first administration is carried out simultaneously with the first administration of oxazaphosphorin, the second and third injections are administered 4 hours and 8 hours after the administration of the oxazaphosphorin.
In children, a single dose of Uromitexan is 60% of the dose of cytostatic, the administration of the drug is continued every 3 hours.
If continuous infusion (24 hours) ifosfamide or cyclophosphamide Uromitexan В® should be administered at a dose of 20% of the dose of the cytostatic at the beginning of the infusion, then at a dose of 100% of the dose of the cytotoxic as a 24-hour infusion and after the cytostatic injection, -12 h in the same dose.
In the case of the use of oxazaphosphorines in very high doses, for example, before bone marrow transplantation, the total dose of Uromixane can be increased to 120-160% of the dose of oxazaphosphorin. After the administration of 20% of Uromitexan at the start of the administration of the cytotoxic, the remaining calculated dose is recommended to be injected iv for a long time, for 24 hours with the help of a perfusor. Alternatively, a fractional bolus injection is possible: for adults 3? 40% (time 0, 4, 8 hours) or 4? 40% (time 0, 3, 6, 9 hours). Instead of bolus injections, short infusions with a duration of 15 minutes are possible.
Adverse reactions occurring more often than in single cases are listed according to the following gradation: very often (> 10%); often (> 1%, <10%); sometimes (> 0.1%, <1%); rarely (> 0.01%, <0.1%); very rarely (<0.01%).
From the digestive system: often - nausea, vomiting, diarrhea, constipation, abdominal pain, flatulence, anorexia.
From the hemopoietic system: very rarely - thrombocytopenia. Also observed were granulocytopenia, leukopenia, anemia. The causal relationship of these phenomena with Uromitexane has not been established, this could be due to concomitant cytotoxic therapy.
From the side of the central nervous system: often - dizziness, drowsiness, headache, irritability, depression.
From the cardiovascular system: often - tides of blood to the face.
On the part of the immune system: very rarely - hypersensitivity reactions (skin rash, itching, Lyell's syndrome, Stevens-Johnson syndrome, urticaria, conjunctivitis, lowering blood pressure, tachycardia, tachypnea, anaphylactoid reactions, increased blood pressure, ST segment elevation, myalgia, and also increased activity of a number of functional liver samples).
From the respiratory system: often - cough.
Local reactions: rarely - phlebitis at the injection site, pain and redness.
Other: often - arthralgia, back pain, fever, chills, flu-like syndrome, pharyngitis; very rarely - pain in the extremities, increased fatigue, weakness. Also often observed pneumonia, alopecia. The causal relationship of these phenomena with Uromitexane has not been established, this could be due to concomitant cytotoxic therapy.
- hypersensitivity to mesna, any component of the drug or other thiol compounds.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
APPLICATION FOR CHILDREN
The application is possible according to the dosing regimen.
Mesna exerts a protective effect only on the urinary system and does not eliminate other side effects of cytostatics, therefore, when treating patients with oxazaphosphorin, a full range of maintenance and symptomatic therapy is necessary.
Uromitexan В® does not prevent hemorrhagic cystitis in all patients. Therefore, every morning urine sample must be analyzed for hematuria. In the case of hematuria, when Uromitexan is used with oxazaphosphorines according to the recommended dosing regimen, it may be necessary to reduce doses or discontinue oxazaphosphorin therapy.
Because of the possibility of anaphylactic reactions, it is necessary to guarantee the availability of suitable medications for emergency care.
In patients with autoimmune diseases treated with cyclophosphamide and Uromixane, hypersensitivity reactions are detected at a higher frequency. In such patients, the protection of the urinary tract with Uromixan should only be carried out after careful analysis of the risk / benefit and under close medical supervision.
During treatment, false positive reactions to the presence of ketone bodies in the urine are noted (when carrying out a color reaction to ketones, a reddish-violet staining of urine is possible, which is unstable and immediately disappears when glacial acetic acid is added to the urine).
The specific antidote for Uromitexan is unknown.
Symptoms: nausea, flatulence, diarrhea, headache , fatigue, pain in the limbs and joints, malaise, weakness, depression, irritability, rash, lowering blood pressure, tachycardia.
Mesna is compatible with cyclophosphamide and ifosfamide, so it can be administered with them in the same solution, while the antitumor activity of the latter does not change.
The drug is not compatible with cisplatin (binding and inactivation of the latter), so mesna should not be mixed in one solution with cisplatin.
Mesna has no effect on the therapeutic efficacy of doxorubicin. carmustine, cisplatin, methotrexate, vincristine, as well as the activity of cardiac glycosides.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. Store at temperatures below 30 В° C. Keep out of the reach of children. Shelf life - 5 years.