Uromitexan

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

Indications Uromitexana

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

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Release form

The antidote Uromitexan is a liquid without a specific color or odor, sealed in ampoules of 0.4 g (4 ml).

The cardboard box contains 15 ampoules.

Uromitexan can also be produced in tablet form - 10 white convex tablets of 0.4 g or 0.6 g in an aluminum blister plate.

The active ingredient of Uromitexan is mesna, a substance that is an antidote to acrolein (a metabolite of antitumor drugs of the oxazaphosphorine series).

Pharmacodynamics

Uromitexan serves as an antidote to the substance acrolein, which, in turn, is a product of the metabolism of antitumor drugs of the oxazaphosphorine series, which damage the mucous tissues of the urinary system.

The protective properties of Uromitexan are explained by the bond between mesna and the acrolein molecule: this process provokes the formation of a stable non-toxic thioether.

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

Pharmacokinetics

After intravenous injection, the active ingredient Uromitexan is quickly transformed into a disulfide and is again regenerated in the renal filtration system. As a result, a free thiol compound is formed, which enters into a bond with an alkylating derivative, forming a non-toxic stable ester.

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

The half-life of 60 mg/kg in the accelerated phase is 0.17 hours, and in the slow phase it is 1.08 hours.

Uromitexan is completely excreted through the kidneys within eight hours.

After oral administration of tablets, absorption of Uromitexan begins in the small intestine. The average peak content of metabolites in the urine is detected after 2-4 hours. Approximately 25-35% of the consumed amount of Uromitexan is in the urine as a free substance during the initial four hours. In an amount of 2-4 g per m2, ^the half-life of the toxic substance is 5-7 hours.

To maintain the required amount of Uromitexan in the urinary system, it is necessary to maintain the appropriate frequency of drug intake into the body. Biological availability in urine fluid when taken orally, Uromitexan can be from 45 to 79%, relative to availability after intravenous injection.

The presence of food masses in the digestive tract does not affect the quality of drug availability in urine after oral administration.

After combined intravenous and oral administration of Uromitexan, systemic exposure increases to 150%, which allows for constant excretion of the active ingredient over 24 hours.

Approximately 5% of the active ingredient is eliminated within 12-24 hours, relative to intravenous injection. The degree of binding to plasma proteins is from 69 to 75%.

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Dosing and administration

Most often, Uromitexan is used in the form of jet intravenous infusions (slow). A single dosage should be 20% of a single amount of the antitumor agent.

The first injection of Uromitexan is given in combination with the first infusion of the antitumor drug, and the second and third injections are given four and eight hours after the infusion of the antitumor drug.

With continuous daily infusion of oxazaphosphorine preparations, Uromitexan is administered in an amount of 20% of the volume of the antitumor agent at the beginning of the infusion, then in an amount of 100% of the volume of the antitumor agent infused per day, and upon completion of the infusion of the cytostatic agent, Uromitexan is injected over the course of 6-12 hours in the same amount.

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

When treating pediatric patients with Uromitexan, it is appropriate to use frequent and prolonged infusions of the solution (for example, every three hours, up to six times).

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

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Use Uromitexana during pregnancy

The solution or tablets of Uromitexan cannot be used by pregnant and lactating patients, as well as direct cytostatic treatment.

If the doctor does resort to prescribing Uromitexan, he must carefully weigh the possible risks and benefits of such treatment for each patient individually.

Contraindications

Uromitexan solution or tablets are usually not prescribed:

• if you are prone to allergic reactions to the drug;
• women during pregnancy or breastfeeding.

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Side effects Uromitexana

Considering that Uromitexan is always prescribed against the background of antitumor treatment, it is often difficult to determine which drug exactly leads to the development of side effects. However, it is generally accepted that the negative consequences of Uromitexan treatment may be:

• nausea, diarrhea, abdominal pain;
• feverish conditions, hot flashes;
• dizziness, sleep disturbances, lethargy, headaches;
• rash and local reactions.

During the course of therapy with Uromitexan, false-positive reactions with detection of ketone bodies in urine analysis may be observed. Urine fluid may acquire a reddish-purple color, which disappears after adding cold acetic acid to the urine.

Overdose

It has been proven that single doses of Uromitexan from 4 to 7 g can lead to the development of overdose symptoms:

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

If the above symptoms appear, it is necessary to immediately provide the patient with emergency medical care according to the symptoms detected.

There is no antidote to the drug Uromitexan.

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Interactions with other drugs

Uromitexan can be freely combined with any antitumor drugs from the oxazaphosphorine series: the antidote can be administered in one infusion, without any drug interaction.

Pharmacologically, Uromitexan is not compatible with Cisplatin due to its binding and inactivation, therefore such a combination is considered pharmaceutically not recommended.

Uromitexan cannot affect the medicinal effect of cardiac glycosides, as well as such drugs as Adriamycin, Vincristine, Methotrexate, Carmustine.

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Storage conditions

Uromitexan in the form of a medicinal liquid is stored at temperatures ranging from +15 to +30°C, and tablets – up to +25°C.

It is important to keep children away from places where medications are stored.

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Shelf life

Uromitexan solution is stored in intact ampoules for up to 5 years.

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