Ifosfamide refers to cytostatic drugs, which are characterized by an alkylating type of action. The active substance is closely structured with cyclophosphamide and is used in the chemotherapy of many inoperable tumors.
Ifosfamide was used as a prototype for the creation of a new drug, Gliufosfamide.
Composition, form and packaging
The cytostatic is produced in the form of a fine crystalline powder of almost white color, which is used to prepare a solution for parenteral administration. The drug is highly soluble in water and has a weak specific odor.
The powder consists only of the active substance, the auxiliary components are not used during production.
Manufacturer
Issued by Ifosfamide by the Russian pharmaceutical company JSC "Biokhimik"( the city of Saransk).
Indications for use
Ifosfamide is used to treat inoperable neoplasms that can not be removed with surgical procedures:
- Lung cancer;
- Cervical cancer;
- Testicular tumors;
- Sarcoma( a malignant tumor that originates from cells of connective, fat and vascular tissue);
- Pancreatic cancer;
- Breast Cancer;
- Germogenic tumors;
- Ovarian cancer;
- Bladder cancer;
- Endometrial cancer;
- Lymphomas( malignant formations from cells of lymphoid tissue).
With a different tumor location, monotherapy with Ifosfamide is not effective.
Contraindications
Use of the drug is not possible in the following cases:
- Hypersensitivity to ifosfamide;
- Hypoplastic phenomena in the bone marrow;
- Cystitis;
- Pregnancy and lactation;
- Obstruction of the urinary tract;
- Severe disturbances in kidney and liver function.
Caution is necessary to use cytostatics in the following pathologies:
- Impaired balance of electrolytes in the blood;
- Older patients;
- Hypoproteinemia;
- Immunosuppressive states;
- Diabetes mellitus;
- Chronic form of renal or hepatic insufficiency;
- The appearance of metastases in the brain tissues;
- Acute infectious diseases caused by viruses, bacteria or fungi;
- Presence of cerebral symptoms.
Pharmacological action of
Ifosfamide has antitumor, cytostatic effect, which is based on the alkylation of nucleophilic centers in polymer biomolecules. This leads to a violation of their synthesis.
Ifosfamide is a prodrug that is activated by microsomal enzymes of the liver through the hydroxylation of the carbon atom in the ring. As a result, an unstable active metabolite is formed. The substance can rapidly transform into stable inactive metabolites, which are excreted together with urine( 4-keto-phosphoside and β-carboxyophosphamide).
The drug is able to pass through the BBB in a small amount. In patients who have a history of impaired liver function, there may be a decrease in activity of Ifosfamide.
Cytostatic has a carcinogenic effect - in the experiments on rats, an increase in the incidence of leiomyosarcomas, breast tumors was recorded. Numerous tests confirm the mutagenic effect of Ifosfamide, so the drug is prohibited from use in pregnant women.
Instructions for use Ifosfamide: dosage
Cytostatic is administered intravenously( each infusion is continued for 30 minutes) for several days.
The course dosage should not exceed 300 mg / kg. The next course is allowed only 3-4 weeks after the normalization of the peripheral blood composition, elimination of side effects.
With a brief infusion over 30 minutes - 2 hours, the powder is dissolved first in water for injection to achieve a concentration of 40 mg Ifosfamide per 1 ml water( 0.2 g in 5 ml water, 0.5 g - 13 ml).The resulting solution is diluted with 500 ml of Ringer's solution.
The drug is administered for 6-7 days at 50-60 mg / kg per day. If the infusion is used for 5 days, the dose is increased to 80 mg / kg.
With continuous infusion over the course of the day, 125-250 mg / kg of Ifosfamide per day is used. After this, a break for 3-4 weeks is necessary.
Solution Ifosfamide is dissolved in 3 liters of isotonic sodium chloride solution or glucose. The solution should be used within 24 hours after preparation, stored in the refrigerator. This will preserve the sterility of the drug. To reduce the nephrotoxic effect of Ifosfamide, Mesna can be added to the solution for intravenous infusion.
Side effects of
Ifosfamide is usually well tolerated by patients, however, depending on the dosage used, these side effects may occur:
- From the nervous system: fatigue, confusion, agitation( strong fear and emotional arousal), hallucinations, dizziness, convulsions, encephalopathy. In rare cases, epileptic seizures, coma, polyneuropathy develop;
- Myelosuppression - development of thrombocytopenia, leukopenia;
- On the part of the digestive system: stomatitis, vomiting and nausea, liver disorders;
- From the part of the reproductive organs - development of azoospermia, amenorrhea;
- From the part of the urinary organs: , renal dysfunction, frequent urination, hemorrhagic cystitis, development of nephropathy;
- Among other side effects are: cardiotoxic action, alopecia( full or partial), increased sensitivity to ultraviolet radiation, development of immunosuppressive states, decreased rate of reparative processes, allergy development of secondary tumors.
Overdose of
As side effects increase, side effects will be more pronounced. A specific antidote is not developed, symptomatic therapy is required, which presupposes mandatory administration of umiteksan.
Special instructions
During therapy, the status of peripheral blood should be monitored regularly, and the biochemical performance of the liver and kidneys monitored. Receipt of Ifosfamide can cause an increase in creatinine and urea in the plasma, excretion of urine protein, glucose and phosphate.
If chemotherapy is performed against a background of breastfeeding, then it is necessary to stop lactation. Women and men of reproductive age should use reliable contraceptives within 3-4 months after completion of the course. This is due to the mutagenic action of Ifosfamide.
Chemotherapy is contraindicated for 3 months after an operation to remove the kidney. In this case, the dosage should be selected individually. Before therapy, a complete recovery of urine outflow is required, sanitation of foci of chronic infection.
Patients should not use live and inactivated vaccines unless approved by a physician.
People who live with the oncobacillus should stop using the oral polio vaccine and contact people who have been immunized.
The drug is able to cause phenomena of encephalopathy, so you need to abandon the control of the machine and work with other mechanisms.
Drug Interaction
- Simultaneous reception of mesna promotes decrease in nephrotoxicity of Ifosfamide.
- Cytostatic promotes increased hypoglycemic activity of antidiabetics.
- The combination of Ifosfamide with Allopurinol leads to an increase in myelosuppression.
- If a course of cytostatic therapy is performed after chemotherapy with Cisplatinum, then side effects of Ifosfamide may be increased. But the drug is compatible with other cytotoxic drugs.
- Simultaneous reception with inductors of microsomal liver enzymes leads to increased formation of alkylating metabolites.
- The introduction of vaccines against cytostatic infusion leads to a decrease in the effectiveness of the vaccine.
- Joint reception with warfarin leads to a disruption of blood clotting, increasing the risk of bleeding.
Reviews
Vasily, 34 years, Moscow:
Seven months ago, I was diagnosed with testicular cancer. The doctor appointed Iphosphamide for 5 days. After 3 infusions, unpleasant symptoms appeared: dizziness, severe nausea, hair began to fall out. I needed 2 courses of therapy to achieve positive dynamics.
Antonina, 47, Moscow:
The oncologist has appointed Ifosfamid as part of breast cancer therapy. We administered 50 mg / kg daily for 6 days. After the course, the number of leukocytes and platelets in the blood decreased, which required additional treatment.
Prices of Ifosfamide
In pharmacies you can buy 1 g of cytostatics for 890-1000 rubles per bottle.
Analogues
These cytotoxic drugs are distinguished which have a similar effect:
- Phosphamide;
- Prodimin;
- Fotrin;
- Benoat;
- Fluorobenzotate.
Synonyms for
Synonyms are the following:
- Ifosfamide is sterile;
- Vero-Ifosfamide;
- Holoksan;
- Ifosfamide-LENS.
Conditions for dispensing from pharmacies
Ifosfamide belongs to the list B preparations, so it is prescription-dispensed.
Storage conditions and shelf life
The cytostatic should be used within 2 years from the date of manufacture, provided that the storage standards are observed: the temperature regime is not more than 25 ° C, stored in a place where direct sunlight does not penetrate.