Holoksan

Holoxane has antitumor properties.

Indications Holoxan

It is used in the treatment of neoplasms of malignant nature, which have an inoperable form. Among these, bronchogenic carcinoma, ovarian carcinoma, testicular cancer, breast cancer, uterine neck cancer, soft tissue tumors and neoplasms in children (such as nephroblastoma, sarcomas, neuroblastoma, germ-type neoplasms, and malignant type lymphomas).

[1]

Release form

Release of the medication is carried out as an injection lyophilizate, inside the vials, the volume of which is 0.5, 1 or 2 g.

[2], [3], [4], [5], [6],

Pharmacodynamics

The drug has a cytostatic effect, and along with this alkylates nucleophilic cell centers. This is due to the activation and hydroxylation of the C4 type atom under the action of the oxazaphosphoric ring and is manifested by blocking the late stages of mitosis (S-, as well as G2).

Being an alkylant, the drug is included in the category of genotoxic substances.

[7], [8], [9]

Pharmacokinetics

Ifosfamide during in vitro tests does not show activity, and when in vivo - on the contrary, it shows high efficiency. Activation mainly occurs inside the liver, with the participation of microsomal oxidases, which have a mixed-functional character.

The excretion of ifosfamide with its metabolic products is mostly done with urine. The half-life of blood serum (when a portion of 1-2 g / m ^{2 is} introduced , three times by 1.6-2.4 g / m ² ) is about 4-7 hours on average.

[10], [11], [12], [13]

Dosing and administration

The medication must be administered intravenously. In the absence of other prescriptions, it is required to inject 80 mg / kg of substance daily (maximum 2.4 g / m ²  of body area) during 5 days . The procedure is carried out in the form of a fractionated application (eg, a short infusion lasting about half an hour). It is required to monitor that in the case of peripheral drug administration, a 4% concentration of liquid is not exceeded. There was no evidence of hypersensitivity to higher concentrations of substances for intravenous infusion (for example, using pumping systems).

If you want to use a lower daily dose, or distribute the total dosage for a longer period, the medication is administered through the day (on the 1st, 3rd, and the 5th, 7th and 9th days) or daily for 10 days in small portions (20-30 mg / kg, 2 g / m ² ).

With intermittent treatment, Holoxane is administered at a rate of 80 mg / kg (or 3.2 g / m ² ) daily, for 2-3 days.

Continuous infusion, which lasts 24 hours, is administered in portions of 125-200 mg / kg (or 5-8 g / m ² ). After this, during the next 12 hours, the management of Uromitexan is necessary. For prolonged infusion, the medication should be previously dissolved in a 5% glucose solution or 0.9% NaCl solution (volume - 3 liters).

[18], [19], [20], [21]

Use Holoxan during pregnancy

Prescribe to pregnant is prohibited. Also, you need to give up breastfeeding for the period of therapy.

If the clinical indications require the use of Holoxan in the 1st trimester, it is necessary to decide the issue of abortion. In later stages of pregnancy, if there is no possibility to postpone treatment, and the patient refuses to terminate pregnancy, the use of chemotherapy is allowed after warning of the existence of a risk of development of teratogenic effects of drugs.

Contraindications

Among the contraindications:

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

[14], [15]

Side effects Holoxan

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

• the appearance of cystitis, nausea, alopecia or vomiting, and in addition suppression of bone marrow activity of various degrees (anemia, thrombocyto- or leukopenia). Also, there may be a breakdown in the functioning of the sex glands and a weakening of immunity. Sometimes a disorder of kidney function develops;
• In the course of therapy and after its termination, the creatinine or urea ratio may increase, and in addition the level of creatinine clearance decreases. It is also possible to increase the secretion of glucose and protein, and besides this, phosphate together with urine;
• not identified or not healed in time problems with the work of the kidneys can (especially in the child) develop into glucose-phosphate-amine diabetes. Occasionally, a disorder of the hepatic activity is noted;
• can develop encephalopathies (usually curable) that manifest themselves as a feeling of confusion or disorientation.

Extremely cautious medicine is prescribed for people with a low serum albumin index or with impaired renal activity.

The introduction of the drug may lead to the appearance of symptoms of hypersensitivity.

[16], [17],

Interactions with other drugs

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

The effectiveness of vaccination is weakened when it is performed against the background of the use of immunosuppressors and ifosfamide.

Combination with allopurinol increases myelodepressive activity of ifosfamide.

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

In the case of previous therapy using phenytoin, phenobarbital or chloral hydrate, there is a possibility of enzyme induction, which causes the enhanced biotransformation of the ifosfamide element.

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

Storage conditions

Holoksan is required to be kept in a place that is closed from children's access. The temperature conditions are a maximum of 25 ° C.

[22],

Shelf life

Holoksan is allowed to be used within 5 years from the date of release of the drug.

[23]

Analogues

The analogues of the medication are Alkeran, Alfalan, Bentero, Ipholem, Ifomide, Ifos, Ifosfamide, Clokeran, Leukeran, Cel, Cyclophosphamide sandoz, Cyclophosphamide, Endoxane.

[24], [25], [26], [27]