Mesna-lance - instructions for use. Mesna - instructions for use, pharmacological action, indications for use, dosage and method of administration, contraindications, side effects Side effects of Mesna

R No. 001945 / 01-221209

Tradename: Mesna-LENS ®

International non-proprietary name:

mesna

Dosage form:

solution for intravenous administration

Composition
1 ml of solution contains:
active substance: mesna - 100 mg;
excipients: sodium benzoate, disodium edetate (Trilon B), sodium hydroxide (caustic soda), water for injection.

Description
Transparent with light opalescence, colorless or slightly colored liquid.

Pharmacotherapeutic group:

antidote

ATX code: V03AF01

Pharmacological properties
Pharmacodynamics
Mesna is an antidote to acrolein, a metabolite of anticancer drugs from the oxazaphosphorin group (ifosfamide, cyclophosphamide), which irritates the bladder mucosa. The protective properties of mesna are due to the interaction with the double bond of the acrolein molecule, which leads to the formation of a stable thioester. By reducing the urotoxic effects of oxazaphosphorins, mesna does not weaken their antitumor effect.
Pharmacokinetics
When administered intravenously (iv), the active substance is rapidly oxidized to disulfide (dimesna). In the epithelium of the renal tubules, dimesna is reduced to a free thiol compound, which irreversibly binds to metabolites of oxazaphosphorins, forming non-toxic stable thioesters. The connection with blood plasma proteins is 69-75%. Systemic clearance is 1.23 l / h / kg /. After i.v. use at a dose of 800 mg, the half-lives of mesna and dimesna in the blood are 0.36 hours and 1.17 hours, respectively. About 32% and 33% of the administered dose was excreted by the kidneys within 24 hours, respectively, in the form of mesna and dimesna. Most of the restored dose was excreted by the kidneys within 4 hours.

Indications for use
Local detoxification of the urotoxic effects of cytostatics - oxazaphosphorin derivatives, incl. in the following cases:

• with the introduction of ifosfamide;
• with the introduction of oxazaphosphorins in high doses (more than 10 mg / kg);
• in patients at risk - previous radiation therapy to the pelvic area, the development of cystitis during previous therapy with oxazaphosphorines, a history of urinary tract diseases.

Contraindications
Increased sensitivity to mesna, any other component of the drug or thiol compounds.
Pregnancy and lactation.

Method of administration and dosage
The drug Mesna-LENS ® is usually injected intravenously (slowly). A single dose for adults is 20% of a single dose of oxazaphosphorine. The first administration is carried out simultaneously with the first administration of oxazaphosphorine, the second and third injections - 4 hours and 8 hours after the administration of oxazaphosphorine.
In children, a single dose of Mesna-LENS ® is 60% of the cytostatic dose, the drug is administered every 3 hours.
With continuous infusion (24 hours) of ifosfamide or cyclophosphamide, Mesna-LENS® should be administered at a dose of 20% of the cytostatic dose at the beginning of the infusion, then at a dose of 100% of the cytostatic dose as a 24-hour infusion and at the end of the cytostatic administration. Mesna-LENS ® is continued for another 6-12 hours at the same dose. In the case of very high doses of oxazaphosphorines, for example, before bone marrow transplantation, the total dose of Mesna-LENS ® can be increased to 120-160% of the oxazaphosphorine dose. After the injection of 20% Mesna-LENS ® at the beginning of the cytostatic injection, the remaining calculated dose is recommended to be administered intravenously for a long time within 24 hours. 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 of 15 minutes each are possible.

Side effect
Adverse Reactions, which occurred more often than in isolated cases, are listed in accordance with the following gradation: very often (\u003e 10%); often (\u003e 1%, 0.1%, 0.01%, From the digestive system: often - nausea, vomiting, diarrhea, constipation, abdominal pain, flatulence, anorexia;
From the side of the hematopoietic organs: very rarely - thrombocytopenia. Granulocytopenia, leukopenia, anemia were also observed. The causal relationship of these phenomena with the use of mesna has not been established, this could be due to concomitant cytotoxic therapy.
From the central nervous system: often - dizziness, drowsiness, headache, irritability, depression.
From the side of cardio-vascular system: often - "rush" of blood to the face.
From the side immune system: very rarely - hypersensitivity reactions (skin rash, itching, Lyell's syndrome, Stevens-Johnson syndrome, urticaria, conjunctivitis, anaphylactoid reactions, decreased blood pressure, increased blood pressure, tachycardia, tachypnea, myalgia, as well as an increase in the activity of a number of functional liver tests (for example, transaminases).
From the respiratory system: often - cough.
Local reactions: rarely - phlebitis at the injection site, pain and redness.
Others: often - arthralgia, back pain, fever, chills, flu-like syndrome, pharyngitis; very rarely - pain in the extremities, increased fatigue, weakness, pneumonia, alopecia were also often observed. The causal relationship of these phenomena with the use of mesna has not been established, this could be due to concomitant cytotoxic therapy.

Interacting with others medicines
Mesna is compatible with cyclophosphamide and ifosfamide, therefore it can be administered with them in the same solution, while the antitumor activity of the latter does not change.
Pharmaceutically, the drug is incompatible with cisplatin (binding and inactivation of the latter), and therefore mesna should not be mixed in the same solution with cisplatin.
Mesna does not affect the therapeutic efficacy of doxorubicin, carmustine, cisplatin, methotrexate, vincristine, as well as the activity of cardiac glycosides.

Overdose
The specific antidote for mesna is not known. Possible overdose symptoms: nausea, flatulence, diarrhea, headache, fatigue, pain in the limbs and joints, malaise, weakness, depression, irritability, skin rash, decreased blood pressure, tachycardia. Treatment is symptomatic.

special instructions
Mesna has a protective effect only on the urinary system and does not eliminate other side effects of cytostatics, therefore, when treating with drugs of the oxazaphosphorin group, it is necessary to use a full range of supportive and symptomatic therapy.
Mesna does not prevent the development of hemorrhagic cystitis in all patients. Therefore, it is necessary to analyze the morning portion of urine daily for hematuria. In the case of hematuria on the background of the use of mesna with oxazaphosphorines according to the recommended dosing regimen, it may be necessary to reduce doses or discontinue therapy with oxazaphosphorines. Due to the potential for anaphylactic reactions, it is necessary to ensure the availability of suitable drugs for emergency care... In patients with autoimmune diseases who were treated with cyclophosphamide and local, hypersensitivity reactions are detected with a higher frequency. In these patients, urinary tract protection with mass should be performed only after careful risk-benefit analysis and under close medical supervision. During the treatment period, false positive reactions for the presence of ketone bodies in urine (when carrying out a color reaction to ketones, a reddish-purple coloration of urine is possible, which is unstable and immediately disappears when glacial acetic acid is added to the urine).

Release form
Solution for intravenous administration 200mg / 2ml and 400mg / 4ml (100 mg / ml) in vials. Each bottle with instructions for use in a pack of cardboard, or 3, 5 or 10 bottles together with instructions for use in a pack with partitions or special cardboard slots. 50, 85, 100 vials with instructions for use, based on one instruction for ten vials, in a cardboard box (for hospitals).

Storage conditions
List B.
In a dry, dark place at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life
2 years.
Do not use after the expiration date printed on the package.

Conditions of dispensing from pharmacies
On prescription.

Manufacturer:

LLC "LENS-Pharm", a subsidiary of OJSC "Veropharm"
Legal address: 143033, Moscow region, Odintsovo district, pos. Gorki-X, d.ZOA
Address of production and acceptance of claims: 601125, Vladimir region, Petushinsky district, pos. Volginsky, building 95, building 67

Mesna (Mesna)
Synonyms
Mesna-LENS (Russia), Uromitexan (Germany)

Mucolytics
Release form of the drug
Solution for inhalation 200 mg; 400 mg Solution for inhalations in / in 200 mg Film-coated tablets, 400 mg; 0.6 g
Feature of the chemical structure
Acrolein antidote, sodium salt of 2-mercaptoethane sulfonic acid.
Mechanism of action
Free sulfhydryl groups are capable of breaking disulfide bonds, as a result of which the viscosity of the secretion of the upper respiratory tractseparated paranasal sinuses nose, external auditory canal. Mucolytic action is close to acetylcysteine.
It is an antidote to acrolein (a metabolite of antitumor agents from the oxazaphosphorin group), which irritates the mucous membrane of the bladder. The protective properties of mesna are due to the interaction with the double bond of the acrolein molecule, which leads to the formation of a stable non-toxic thioester.
The main effects of Mesna
Has a mucolytic effect.
It has a uroprotective effect. By reducing the urotoxic effects of oxazaphosphorins, it does not weaken their antitumor effect.
Pharmacokinetics
Binds to plasma proteins by 69-75%. When administered intravenously, it is rapidly oxidized to disulfide, in the kidneys it is reduced to a free thiol compound, which irreversibly binds to alkylating derivatives, forming non-toxic stable thioesters. The maximum excretion is 2-3 hours after intravenous injection. T1 / 2 after intravenous administration at a dose of 60 mg / kg in the fast phase - 0.17 hours, in the slow phase - 1.08 hours.Fully excreted by the kidneys within 8 hours, and in the first 4 hours excretion occurs in the form of SH -mesny, 32% of the dose - in the form of thiol and 33% - disulfide. The elimination rate is the same for oral and parenteral administration.
When taken orally, the absorption of the mesna occurs in small intestine... Food intake does not interfere with its absorption. Cmax of free thiol compounds in urine on average is achieved after 2-4 hours. About 25% of the dose taken is found in urine as free mesna in the first 4 hours. Bioavailability (based on the concentration created in urine) during oral administration makes up 45-79% of bioavailability with intravenous administration. Compared to IV administration, the regimen combined use leads to an increase in systemic exposure up to 150% and provides a more constant level of excretion of the mass in the urine throughout the day.
When administered by inhalation, it is rapidly absorbed from the respiratory tract and excreted unchanged.

Indications for use.
Solution for inhalation and intracavitary administration - asthmatic bronchitis, emphysema and pulmonary atelectasis, bronchiectasis, sinusitis, otitis media (serous), bronchoalveolar lavage.
Solution for inhalation and intracavitary administration - aspiration (prophylaxis in postoperative period during neurosurgical operations, operations on chest), sinusitis.
Nasal aerosol - rhinitis (with hard-to-separate secretions).
Other indications:
solution for injection and tablets - local protection against urotoxic effects in the treatment of oxazaphosphorines (ifosfamide, cyclophosphamide) in high doses (more than 10 mg / kg) and in patients at risk (previous radiation therapy in the pelvic area, diseases urinary tract history, hemorrhagic during previous therapy with oxazaphosphorines).
Method of administration and dosage
Inhalation is used at a dose of 0.6-1.2 g (without dilution or at a 1: 1 dilution in distilled water or in 0.9% sodium chloride solution) 2-3 r / day. The course of treatment is 2-24 days.
For intratracheal infusion, it is used in the same dose and in the same dilution. Injected using a tracheostomy tube or intratracheal probe every hour until liquefaction and excretion.
In case of sinusitis, 2-3 ml of undiluted drug is administered after preliminary washing of the sinus (if necessary, every 2-3 days).
Intranasally 1 dose (one injection) of aerosol into both nasal passages 4 r / day.
IV stream (slowly): the first injection is performed simultaneously with the first administration of oxazaphosphorine, the second and third - 4 and 8 hours after administration of oxazaphosphorine at a dose of 20% of the oxazaphosphorine dose or 240 mg / m2. With continuous infusion (24 hours), the cytostatic is administered mesna at a dose of 20% of the cytostatic dose, then at a dose of 100% of the cytostatic dose in the form of 24 hours of infusion, after the end of the cytostatic administration, the mesna is continued for another 6-12 hours at the same dose.
Combined intravenous and oral therapy - injected in / in a stream (slowly) simultaneously with the first administration of oxazaphosforin, a single dose is 20% of a single dose of oxazaphosphorin. After 2 and 6 hours after intravenous administration, tablets are taken orally at a dose of 40% of the oxazaphosphorine dose.
The experience of treating children with the use of oral forms of mesna shows that more frequent (for example, every 3 hours) and longer (for example, up to 6 times) administration of the drug is advisable.
Contraindications
Hypersensitivity.
Pregnancy.
Lactation period.
For use as a mucolytic (optional) - general weakness, causing the ineffectiveness of the cough, without thickening of mucus in the bronchial tree.
Precautions, control of therapy
During the treatment period, there are false positive reactions to the presence of ketone bodies in the urine.
A reddish-purple coloration of urine is possible, which is unstable and immediately disappears when glacial acetic acid is added to the urine.
Mesna has a protective effect only on the urinary system, so its use does not cancel additional preventive measures and symptomatic therapy.
It is not recommended to prescribe inside when possible vomiting or vomiting.
Given the presence of benzyl alcohol impurities in the vials, they should not be used in newborns and infants, but they can be used with caution in the treatment of elderly patients.
Sick, suffering bronchial asthma, the drug is administered only in the presence of a doctor.
Side effects
From the side digestive system:
nausea;
vomiting;
increased activity of "hepatic" transaminases;
diarrhea (with a single dose of more than 60 mg / kg). From the side of the central nervous system:
headache;
weakness. Other effects:
rarely - phlebitis at the injection site, hematuria;
allergic reactions on the skin and mucous membranes;
with intranasal use - irritation of the mucous membrane of the nasal cavity;
with the on / in the introduction - a decrease in blood pressure;
for inhalation use - cough, bronchospasm.
Interaction

Gross formula

C 2 H 6 O 3 S 2

Pharmacological group of Mesna substance

Nosological classification (ICD-10)

CAS code

3375-50-6

Pharmacology

pharmachologic effect - mucolytic, which reduces the cytotoxicity of oxazaphosphorins.

Inactivates in the kidneys and bladder some derivatives of oxazaphosphorins (endoxan, ifosfamide, etc.), depriving them of their alkylating properties.

Reduces the viscosity of phlegm, discharge of the paranasal sinuses and external auditory canal.

After intravenous injection, it is rapidly oxidized to disulfide, in the kidneys it is reduced to a free thiol compound, which irreversibly binds to alkylating derivatives, forming non-toxic stable thioesters. Reduces cyst and urotoxicity of alkylating agents.

After i.v. administration of 800 mg T 1/2 in the blood is 0.36 for mesna, for disulfide - 1.17 hours. 32% of the dose is excreted in the urine in the form of thiol and 33% as disulfide.

Application of the substance Mesna

Injection: prevention of urotoxicity of cytostatics - oxazaphosphorin derivatives, hemorrhagic cystitis caused by alkylating agents.

Solution for inhalation: bronchial asthma, chronic and obstructive bronchitis, emphysema and pulmonary atelectasis, bronchiectasis, postoperative aspiration pneumonia in neurosurgical and thoracic operations, in intensive care units (prevention and treatment).

Nasal aerosol: rhinitis, accompanied by difficulty in separating secretions ( symptomatic treatment).

Contraindications

Hypersensitivity (including to other thiol compounds). Solution for inhalation: general weakness, causing ineffectiveness of cough, bronchial asthma without thickening of mucus in the bronchial tree.

Side effects of Mesna substance

Dyspeptic symptoms (nausea, vomiting, diarrhea), hematuria, allergic manifestations on the skin and mucous membranes. Solution for inhalation: cough, burning sensation and pain behind the breastbone, bronchospasm.

Interaction

Incompatible in the same infusion solution with cisplatin (binds and inactivates it).

Route of administration

IV jet (slow), inhalation, endotracheal, instillation in maxillary sinuses, intranasally.

Mesna Precautions

Due to the presence of benzyl alcohol impurities in the vials, they should not be used in newborns and infants, but they can be used with caution in the treatment of elderly patients.

Mesna

Composition and release form of the drug

4 ml - bottles (1) - cardboard packs.
4 ml - bottles (3) - cardboard packs.
4 ml - bottles (5) - cardboard packs.
4 ml - bottles - cardboard packs.

pharmachologic effect

Mucolytic agent. An agent for correcting the urotoxic effects of antineoplastic agents from the oxazaphosphorin group.

Mucolytic action is due to the presence of a sulfhydryl group in the molecule active substance, which contributes to the rupture of disulfide bonds. Reduces the viscosity of the secretions of the upper respiratory tract, discharge of the paranasal sinuses, external auditory canal.

Eliminates the toxic effect of acrolein, a metabolite of anticancer drugs from the oxazaphosphorin group, which irritates the bladder mucosa.

At the first stage of detoxification, mesna interacts with the double bond of the acrolein molecule, which leads to the formation of a stable thioester. At the second stage, under the influence of mesna, the rate of cleavage of 4-hydroxy metabolites of cyclophosphamide or in urine decreases. A relatively stable neurotoxic condensation product is formed from mesna and 4-hydroxycyclophosphamide or 4-hydroxyiphosphamide. As a result of this chemical integration, mesna inhibits the degradation of 4-hydroxycyclophosphamide or 4-hydroxyphosphamide and hence the formation of acrolein.

By reducing the urotoxic effects of oxazaphosphorins, mesna does not weaken their antitumor effect.

Pharmacokinetics

The blood protein binding is 10%. T 1/2 - 1 hour. Excreted by the kidneys. It is completely excreted after 8 hours, and in the first 4 hours - in the form of SH-mesna. The elimination rate is the same for oral administration and for parenteral administration.

Indications

For inhalation or topical application: cystic fibrosis, asthmatic bronchitis, chronical bronchitis, emphysema of the lungs, bronchiectasis, atelectasis of the lung, proceeding with thickening of sputum and mucus and blockage of the bronchi; symptomatic treatment of rhinitis with difficult secretion, sinusitis, serous inflammation of the mucous membrane of the middle ear, bronchoalveolar lavage; prevention and treatment of aspiration in the postoperative period during neurosurgical operations, operations on the chest, as well as in intensive care units.

For parenteral use: prevention and local detoxification of the urotoxic effect of antineoplastic agents from the oxazaphosphorin group.

Contraindications

Hypersensitivity to mesna.

Dosage

Individual, depending on the indications used dosage form and treatment regimens.

Side effects

With inadequate dosage, a burning sensation and pain behind the breastbone, nausea, vomiting, diarrhea are possible; rarely - hematuria, allergic reactions to the skin and mucous membranes, irritation of the nasal mucosa (with intranasal administration).

From the digestive system: possible nausea, vomiting, diarrhea, increased activity of transaminases.

From the side of the central nervous system: possible weakness.

On the part of the cardiovascular system: possible arterial hypotension; with the introduction of mesna in the form of monotherapy or in combination with ifosfamide.

Allergic reactions: possible urticaria, angioedema.

Dermatological reactions: exanthema, enanthema are possible.

Others: possible pain in the limbs; after inhalation use, bronchospasm is possible.

Drug interactions

In experimental studies on animals in vitro and in vivo, it was shown that the simultaneous use of mesna does not affect the effectiveness of cytotoxic agents.

special instructions

Patients suffering from bronchial asthma, the introduction is carried out only in the presence of a doctor.

There is a message about pronounced against the background of the use of mesna.

When using mesna, it is possible false positive results diagnostic tests for the presence of ketones in the urine and false positive or false negative results for the presence of red blood cells in the urine.

Pregnancy and lactation

Adequate and strictly controlled clinical research the safety of mesna during pregnancy has not been carried out. Use is possible only in cases where the potential benefit of therapy for the mother outweighs possible risk for the fetus.