Uromitexan

A specific agent for antidote therapy, Uromitexan, is used to reduce or eliminate intoxication caused by antitumor drugs.

Indications of the uromiteksana

Uromitexane is used to prevent the toxic effects of antitumor agents such as Ifosfamide, Cyclophosphamide, Trophosphamide on the urinary system. Especially often, Uromitexan is used in patients belonging to a particular risk group - for example, after irradiation of the pelvic area, with inflammation of the bladder after antitumor therapy, with a history of urinary function disorder.

[1], [2], [3]

Release form

Antidote Uromitexan is a liquid without a certain color and odor, sealed in ampoules of 0.4 g (4 ml).

The cardboard box contains 15 ampoules.

Uromitexan can be produced in tableted form - 10 white convex tablets 0.4 g or 0.6 g in a blister plate made of aluminum.

The active ingredient of Uromitexan is mesna - the substance-antidote of acrolein (a metabolite of antitumor drugs of a number of oxazaphosphorines).

Pharmacodynamics

Uromitexan serves as an antidote to the substance of acrolein, which in turn is a product of the metabolism of antitumor drugs of a number of oxazaphosphorines damaging the mucosal tissues of the urinary system.

The protective abilities of Uromitexane are explained by the connection of mesna to the molecule of acrolein: this process provokes the formation of a stable non-toxic thioester.

By reducing the urotoxic effect of antitumor drugs, Uromitexan does not have a negative effect directly on their antitumor abilities.

Pharmacokinetics

After intravenous injection, the active ingredient, Uromitexan, is soon transformed into a disulfide, and in the renal filtration system is again resumed. As a result, a free thiol compound is formed, which is in contact with the alkylating derivative, to form a non-toxic stable ester.

The limiting half-life is 2-3 hours after intravenous injection.

The half-life of 60 mg per kg in the accelerated phase is 0.17 hours, and in the slowed-down phase, 1.08 hours.

Uromitexane is fully excreted through the kidneys for eight hours.

After oral intake of the tablets, the absorption of Uromitexan begins in the small intestine. The average peak content of metabolites in the urinary fluid is found after 2-4 hours. About 25-35% of the amount used Uromitexan is in the urinary fluid as a free substance for the initial four hours. The amount of 2-4 g per m ² duration half-toxicant is 5-7 hours.

To keep the required amount of Uromitexan in the urinary system, it is required to observe the appropriate multiplicity of the drug's intake into the body. Biological availability in urinary fluid with internal use of Uromitexan may range from 45 to 79%, relative to availability after intravenous injection.

The presence of dietary masses in the digestive tract does not affect the quality of accessibility of the drug in the urine after ingestion.

After combined intravenous and oral administration of Uromitexan, systemic exposure is increased to 150%, which allows to maintain a constant excretion of the active ingredient within 24 hours.

Approximately 5% of the active ingredient is excreted in the 12-24 hour interval, relative to the intravenous injection. The degree of binding to plasma proteins is from 69 to 75%.

[4], [5], [6], [7], [8]

Dosing and administration

Most often, Uromitexan is used as a jet intravenous infusion (slowed down). A single dosage should be 20% of a single amount of an antitumor agent.

The first injection of Uromitexan is performed in conjunction with the first infusion of the antitumor drug, and the second and third injection is administered four and eight hours after the infusion of the antitumor drug.

With the continuous daily infusion of oxazaphosphorin preparations, Uromitexan is administered in an amount of 20% of the volume of the antitumor agent at the beginning of the infusion, after that - in the amount of 100% of the volume of the antitumor agent infused over the day, and upon completion of infusion of the cytotoxic agent, Uromitexan injection is administered over a 6- 12 hours in the same amount.

In a combined treatment, Uromitexan should be administered as an intravenous, slow, slow injection at the same time as the first infusion of the antitumor agent: a single amount of the drug should be 20% of a single dose of the cytostatic. Two and six hours after intravenous injection, oral Uromitexan should be taken in an amount of 40% of the volume of the cytostatic.

When treating Uromitexan in pediatric patients, it is appropriate to use frequent and prolonged infusion of the solution (eg, every three hours, up to six times).

Uromitexan has a protective effect only on the urinary tract, but does not relieve other adverse effects when using cytotoxic drugs. Therefore, along with Uromiteksan, other supporting and symptomatic agents should be prescribed.

[11], [12], [13]

Use of the uromiteksana during pregnancy

A solution or Uromitexan tablets can not be used by pregnant and nursing patients, nor can they be performed directly with cytostatic treatment.

If the doctor still resorts to the appointment of Uromitexan, then he must carefully weigh the possible risks and benefits of such treatment for each patient individually.

Contraindications

A solution or Uromitexan tablets are usually not prescribed:

• with a tendency to an allergic reaction to the drug;
• women with nursing or breastfeeding baby.

[9], [10]

Side effects of the uromiteksana

Given that Uromitexan is always prescribed against the backdrop of antitumor treatment, it is often difficult to determine which particular drug leads to the development of adverse events. Nevertheless, it is commonly believed that the negative consequences of Uromiteksan treatment can be:

• nausea, diarrhea, abdominal pain;
• feverish states, tides;
• dizziness, sleep disturbance, lethargy, headaches;
• rash and local reactions.

During the course of Uromitexan therapy, false positive reactions can occur with the detection of ketone bodies in urine analysis. Urinary fluid can acquire a reddish purple color that disappears after adding to the urine of cold acetic acid.

Overdose

It is proved that single amounts of Uromitexan from 4 to 7 g can lead to the development of signs of overdose:

• nausea and abdominal pain, diarrhea;
• pain in the head, fatigue;
• joint pain;
• skin rash;
• increased body temperature;
• lowering of blood pressure;
• a change in the rhythm of the heart;
• numbness of limbs;
• phenomena of bronchospasm.

If these signs appear, it is necessary to urgently provide the patient with emergency medical care according to the detected symptoms.

Antidote to the drug Uromiteksan does not exist.

[14], [15]

Interactions with other drugs

Uromitexane can be freely combined with any antitumor drugs from a number of oxazaphosphorines: the antidote can be administered in one infusion, without any drug interaction.

Pharmacologically, Uromitexane does not combine with Cisplatin because of its binding and deactivation, so this combination is considered not pharmaceutically recommended.

Uromitexane can not affect the medicinal effects of cardiac glycosides, as well as drugs such as Adriamycin, Vincristine, Methotrexate, Carmustine.

[16], [17]

Storage conditions

Uromiteksan in the form of a medicinal liquid is kept in temperature ranges from +15 to +30 ° C, and tablets - up to + 25 ° C.

It is important not to allow children to the storage of medications.

[18]

Shelf life

Uromiteksan solution is stored in intact ampoules up to 5 years.

The tablet drug Uromitexan can be stored for up to 3 years.