Ifosfamid

General characteristics. Structure:

Active ingredient: 1 g of an ifosfamid.

Pharmacological properties:

Pharmacodynamics. The antineoplastic means alkylating the connection derivative of oksazafosforin. Antineoplastic activity is caused by alkylation of the nucleophilic centers, disturbance of synthesis of DNA and blockade of mitotic division of tumor cells. DNA damages most often happen in the phases G1 and G2 of a cellular cycle.

Pharmacokinetics. Later in/in introductions the medicinal substance which is pro-medicine (an inactive transport form) is metabolized in pharmacological active metabolite 4-gidroksiifosfamid. Becomes more active enzymes (phosphoamidase) of a liver and tumoral fabric. At patients with abnormal liver functions activation is slowed down and is even reduced.

In insignificant quantities gets through GEB. After single in/in introductions of 5 g/sq.m plasma concentration decreases bieksponentsialno, T of ½ final phases are 15 h, is allocated with kidneys (61% of a dose in not changed look); at purpose of smaller doses (1,6-2,4 g/sq.m.). removal proceeds monoeksponentsialno with   T ½ about 7 h, at the same time the share of not changed drug in urine decreases by 4-5 times (12-18% of a dose)

Indications to use:

Nonresectable malignant tumors: lung cancer, ovarian cancer, small egg cancer, sarcoma of soft tissues, breast cancer, pancreatic cancer, kidney cancer, bladder cancer, cancer of a neck of uterus, endometrial cancer, malignant lymphoma (lymphogranulomatosis, nekhodzhkinsky lymphoma), Ewing's sarcoma; tumors at children - sarcoma, Vilms's tumor, a neuroblastoma, germinogenny tumors, malignant lymphoma

Route of administration and doses:

In/in kapelno (use solution with concentration not higher than 4%), daily in the morning (or every other day), on 50-60 mg/kg within 5 days; or on 80 mg/kg within 2-3 days. An average dose on a course - 250-300 mg/kg. The course can be repeated in 4 weeks.

For preparation of solution of 200 mg part in 5 ml of water for injections, 500 mg - in 13 ml of water for injections, the solution prepared thus is diluted by 500 ml of solution of Ringer. Duration of infusions - 0.5-2 h.

For continuous infusion (within a day) appoint in a daily dose 125-250 mg/kg with the subsequent break not less than 3-4 weeks. For this purpose solution of an ifosfamid dissolve 5% of solution of a dextrose or 0,9% of NaCI solution in 3 l.

Features of use:

In case of need uses in the period of a lactation it is necessary to stop breastfeeding. Women of reproductive age need to apply reliable methods of contraception during all course of treatment and for 3 months after its end.

It is not necessary to carry out chemotherapy before 3 months after a nephrectomy. Before an initiation of treatment sanitation of the centers of persistent infection and correction of possible disturbances of electrolytic balance is necessary. During therapy it is regularly necessary to control a pattern of peripheral blood, laboratory indicators of function of a liver, kidneys, to carry out the general analysis of urine.

During administration of drug increase in concentration of urea and creatinine in plasma, increase in removal with urine of glucose, protein, phosphates is possible. Therapy ifosfamidy should be combined with reception of a mesna for the prevention of urotoksichesky effects. The refusal of immunization both the live, and inactivated virus vaccines is necessary (if it is not approved by the doctor during treatment or in the range from 3 months till 1 year after administration of drug).

Other family members living with the patient should refuse immunization by a peroral vaccine against poliomyelitis, and also to avoid contacts with the people receiving a vaccine against poliomyelitis or to wear the protective mask closing a nose and a mouth. At patients of advanced age the frequency of developing of a renal failure increases.

Side effects:

From the alimentary system: nausea, vomiting, stomatitis, abnormal liver functions, hepatotoxic. 

From a nervous system: agitation, confusion of consciousness, hallucination, unusual fatigue, dizziness, encephalopathy, spasms; seldom - epileptic seizures, a coma, peripheral polyneuropathy.

From bodies of a hemopoiesis: leukopenia, thrombocytopenia.

From an urinogenital and urinary system: hemorrhagic cystitis, dysuria, frequent urination, renal failure, nephropathy, dysfunction of gonads (azoospermism, amenorrhea).

Others: hair loss, cardiotoxic action, photosensitization, immunosuppression, infectious complications, delay of speed of healing of wounds, allergic reactions

Interaction with other medicines:

Uromiteksan reduces nephrotoxicity. Cisplatinum increases expressiveness of side effects from TsNS.

Let's combine with other antineoplastic drugs. At simultaneous use with the medicines causing myelotoxic and nephrotoxic effects strengthening of side effect is possible.

At combined use with inductors of microsomal enzymes of a liver increase in formation of the alkylating metabolites is possible.

At simultaneous use strengthens hypoglycemic effect of antidiabetic drugs.

Allopyrinolum strengthens a miyelosupressiya.

Contraindications:

Hypersensitivity, heavy oppression of function of marrow, pregnancy, the lactation period, earlier than in 3 months after a nephrectomy.

With care. Oppression of a marrowy hemopoiesis (including against the background of sopustvuyushchy beam or chemotherapy, infiltration of marrow tumor cells), a hypoproteinemia (hypoalbuminemia), a renal and/or liver failure, impassability of urinary tract, a tumor of a kidney (especially only), acute infectious diseases of the virus, fungal or bacterial nature (including chicken pox, shingles), advanced age

Overdose:

Symptoms: more bystry development and sharp expressiveness of the main side effects.

Treatment: symptomatic with obligatory use of an uromiteksan.

Storage conditions:

List B. To store in dry, protected from light and the place, unavailable to children, at   a temperature not above 25 °C. Period of validity 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for infusions on 1,0 g in bottles of colourless glass with a capacity of 25 ml. On 1 bottle with drug together with the application instruction place in a pack from a cardboard.