Choloxane

Holoxan has antitumor properties.

Indications Choloxane

It is used in the treatment of malignant neoplasms that are inoperable. These include bronchogenic carcinoma, ovarian carcinoma, testicular cancer, breast cancer, cervical cancer, soft tissue tumors, and neoplasms in children (such as nephroblastoma, sarcomas, neuroblastoma, germ cell tumors, and malignant lymphomas).

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Release form

The drug is released in the form of an injection lyophilisate, inside vials, the volume of which is 0.5, 1 or 2 g.

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Pharmacodynamics

The drug has a cytostatic effect, and at the same time alkylates nucleophilic cellular centers. This is due to the activation and hydroxylation of the C4 type atom under the action of the oxazaphosphorine ring and is manifested by blocking the late stages of mitosis (S-, as well as G2).

Being an alkylant, the drug falls into the category of genotoxic substances.

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Pharmacokinetics

Ifosfamide does not demonstrate activity in vitro, but in vivo, on the contrary, it shows high efficiency. Activation occurs mainly inside the liver, with the participation of microsomal oxidases, which have a mixed-functional nature.

Excretion of ifosfamide with its metabolic products is mostly carried out with urine. The half-life from blood serum (with the introduction of a portion of 1-2 g / m ²; three times 1.6-2.4 g / m ² ) is on average about 4-7 hours.

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Dosing and administration

The drug must be administered intravenously. Unless otherwise prescribed, 80 mg/kg of the substance (maximum 2.4 g/m2 of body area) must be administered daily for 5 days ^. The procedure is carried out in the form of a fractionated application (for example, a short infusion lasting approximately half an hour). It is necessary to monitor that in the case of peripheral administration of the drug, the 4% concentration of the liquid is not exceeded. There are no reports of hypersensitivity to more highly concentrated substances for intravenous infusions (for example, using pumping systems).

If it is necessary to use a lower daily dose, or to distribute the total dosage over a longer period, the medication is administered every other day (on the 1st, 3rd, as well as the 5th, 7th and 9th days) or daily for 10 days in small doses (20-30 mg/kg; 2 g/m2 ⁾.

For intermittent treatment, Holoxan is administered at a dose of 80 mg/kg (or 3.2 g/m2 ⁾ daily for 2-3 days.

A prolonged infusion lasting 24 hours is administered in portions of 125-200 mg/kg (or 5-8 g/m2 ⁾. After this, Uromitexan must be administered for the next 12 hours. For prolonged infusion, the medication should first be dissolved in a 5% glucose solution or 0.9% NaCl solution (volume - 3 liters).

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Use Choloxane during pregnancy

It is prohibited to prescribe to pregnant women. Breastfeeding should also be avoided during the therapy period.

If clinical indications require the use of Holoxan in the 1st trimester, it is necessary to resolve the issue of abortion. At later stages of pregnancy, if it is not possible to postpone treatment and the patient refuses to terminate the pregnancy, the use of chemotherapy is allowed after warning about the risk of developing teratogenic effects of the drug.

Contraindications

Among the contraindications:

• the presence of hypersensitivity to medicinal elements;
• suppression of bone marrow activity (especially in people who have previously taken cytostatic drugs or undergone radiotherapy procedures);
• renal failure;
• obstruction in the urinary tract, as well as cystitis.

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Side effects Choloxane

Systemic and local tolerance of the drug is quite good. Among the possible side effects, the development of which depends on the dosage size:

• the appearance of cystitis, nausea, alopecia or vomiting, and in addition to this, suppression of bone marrow activity of varying degrees (anemia, thrombocytopenia or leukopenia). Disorders in the functioning of the sex glands and weakening of the immune system may also be noted. Sometimes a disorder of renal function develops;
• During and after therapy, creatinine or urea levels may increase, and creatinine clearance may decrease. Increased secretion of glucose and protein, as well as phosphates in the urine, is also possible;
• Undiagnosed or untreated kidney problems can (especially in children) develop into glucose-phosphate-amine diabetes. Liver dysfunction is occasionally observed;
• Encephalopathies (usually treatable) may develop, which manifest as a feeling of confusion or disorientation.

The drug is prescribed with extreme caution to people with low serum albumin levels or with weakened renal function.

Administration of the drug may result in the appearance of hypersensitivity symptoms.

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Interactions with other drugs

The drug potentiates the antidiabetic effect of sulfonylurea derivatives, and in addition, the skin reaction to radiation.

The effectiveness of the vaccination is weakened when it is carried out against the background of the use of immunosuppressants and ifosfamide.

Combination with allopurinol increases the myelosuppressant activity of ifosfamide.

With previous or combined use of cisplatin, an increase in the hemato- or nephrotoxicity of the drug, as well as its toxic effect on the central nervous system, may be observed.

In case of previous therapy with phenytoin, phenobarbital or chloral hydrate, there is a possibility of enzymatic induction, due to which there is an increased biotransformation of the element ifosfamide.

Combination with warfarin can cause a significant deterioration in blood clotting and increase the likelihood of bleeding.

Storage conditions

Holoxan must be kept in a place inaccessible to children. Temperature conditions – maximum 25°C.

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Shelf life

Holoxan can be used within 5 years from the date of release of the drug.

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Analogues

Analogues of the drug are Alkeran, Alfalan, Bentero, Ifolem, Ifomid, Ifos, Ifosfamide, Klokeran, Leukeran, Cel, Cyclophosphamide Sandoz, Cyclophosphamide, Endoxan.

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