Cyclophosphamide

When ATH:
L01AA01

Characteristic.

The white crystalline powder. Soluble in water: 40 g / l, slightly soluble in alcohol, benzene, ethylene glycol, carbon tetrachloride, dioksane; difficult to dissolve in ether and acetone. Molecular weight - 279,10.

Pharmacological action.
Antitumor, cytostatic, alkylating, immunosuppressive.

Application.

Small cell lung cancer, ovarian cancer, cervix and uterus, Breast, Bladder, prostate, testicular seminoma; sympathicoblastoma, retinoblastoma, angiosarkoma, retikulosarkoma, lymphosarcoma, chronic lymphatic- and myeloid leukemia, acute lymphoblastic, myelogenous, monoblastnыy leukemia, limfogranulematoz, non-Hodgkin's lymphoma, multiple myeloma, Wilms' tumor, Ewing's tumor, soft tissue sarcoma, osteosarcoma, germ cell tumors, granulosarcoid; autoimmune diseases, including systemic connective tissue disease, incl. rheumatoid arthritis, psoriaticheskiy arthritis, autoimmunnaya gemoliticheskaya anemia, nephrotic syndrome, suppression of graft rejection.

Contraindications.

Hypersensitivity, severe renal dysfunction, bone marrow hypoplasia, leukopenia (число лейкоцитов менее 3,5·10⁹/l) and / or thrombocytopenia (число тромбоцитов менее 120·10⁹/l), severe anemia, severe cachexia, terminal stage of cancer, pregnancy, lactation.

Restrictions apply.

Assessment of the risk-benefit ratio is needed, if necessary purpose in the following cases: enable vetryanaya, herpes zoster and other systemic infections, impairment of renal function (urolithiasis disease, gout, and the like.), liver, severe heart disease, suppression of bone marrow function, bone marrow infiltration of tumor cells, hyperuricemia, cystitis, adrenalэktomiya, prior cytotoxic or radiation therapy, the elderly and children's age.

Pregnancy and breast-feeding.

Contraindicated in pregnancy.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

At the time of treatment should stop breastfeeding.

Side effects.

From the digestive tract: anorexia, stomatitis, dry mouth, nausea, vomiting, diarrhea, stomach ache, gastrointestinal bleeding, gemorragicheskiy colitis, toxic hepatitis, jaundice.

From the nervous system and sensory organs: asthenia, dizziness, headache, confusion, blurred vision.

Cardio-vascular system and blood (hematopoiesis, hemostasis): mielodeprescia, leukopenia, agranulocytosis, thrombocytopenia, anemia, bleeding and hemorrhage, flushing, cardiotoxicity, heart failure, heartbeat, hemorrhagic mioperikardit, perikardit.

From the respiratory system: breathlessness, pneumonitis, interstitial pulmonary fibrosis.

With the genitourinary system: hemorrhagic cystitis, uretrit, fibrosis bladder, atypia of cells of the bladder, hematuria, palpitations, painful or difficult urination, hyperuricemia, nephropathy, edema of the lower extremities, giperurikozurija, renal tubular necrosis, amenorrhea, inhibition of ovarian function, azoospermia.

For the skin: alopecia, giperpigmentatsiya (fingernails, palms), w / hemorrhage, redness of the face, rash, hives, itch, hyperemia, puffiness, pain at the injection site.

Other: anaphylactoid reactions, pain syndrome (backache, by, bones, joints), feverish syndrome, chills, the development of infections, syndrome of inappropriate secretion of ADH, myxedema (swelling of the lips), giperglikemiâ, increased activity of transaminases in the blood.

Cooperation.

Effect increase chlorpromazine, tricyclic antidepressants, barbiturates, theophylline, thyroid hormones, Inductors of microsomal liver enzymes (improve education alkylating metabolites), weaken (incl. toxic effect) - Glyukokortikoidы and chloramphenicol. Other myelotoxicity drugs, radiation therapy, allopurinol may potentiate the inhibition of bone marrow function. Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, enhances viral replication and side effects of vaccination. Can improve (resulting in inhibition of synthesis of clotting factors in the liver and platelet disorders) or decrease the activity of indirect anticoagulants. Weakens effect (increases the concentration of uric acid) protivopodagricakih drugs (allopurinola, colchicine, probenecid or sulfinpirazona) in the treatment of hyperuricemia and gout (last dose adjustment is necessary). Increases cardiotoxicity cytarabine, doxorubicin, It strengthens the blockade of neuromuscular transmission, caused by succinylcholine. Uricosuric agents increase the risk of nephropathy, immunosuppressants (azathioprine, khlorambutsil, glucocorticoids, cyclosporine, merkaptopurin) - The risk of secondary tumors and infections. On the background of lovastatin in patients after heart transplantation increased risk rhabdomyolysis and acute renal failure.

Overdose.

Symptoms: nausea, vomiting, severe bone marrow depression, fever, syndrome, dilated cardiomyopathy, multiple organ failure, hemorrhagic cystitis, etc..

Treatment: hospitalization, monitoring vital functions; simptomaticheskaya therapy, incl. appointment of antiemetics; if necessary - transfusion of blood components; administering stimulants hematopoiesis, broad-spectrum antibiotics, vitamin (pyridoxine / w 0,05 r et al.).

Dosing and Administration.

Inside, I /, / m, in cavity (intraperitoneally or intrapleurally). Choosing the route of administration, dosing regimen is carried out in accordance with the indications and chemotherapy regimen. Dose picked individually, is corrected on the basis of clinical effect, the severity of the toxic effect. Heading dose of 8-14 g, Then go to the supportive care - 0.1-0.2 g 2 times a week. As immunosuppressive agent prescribed rate of 0.05-0.1 g / day (11.5 mg / kg / day), with good endurance - 3-4 mg / kg.

Precautions.

Use only under medical supervision, with experience chemotherapy. Should strictly abide by dose regimen, incl. at a certain time (especially in combination therapy) and do not double post-dose, If you missed the previous. For the preparation of drugs for use in infants is not recommended diluents, containing benzyl alcohol, tk. may develop fatal toxic syndrome: metabolic acidosis, CNS depression, respiratory failure, renal failure, gipotenziya, convulsions, intracranial hemorrhage.

Prior to and during treatment (at short intervals) you must determine the level of hemoglobin, or hematocrit, the number of leukocytes (overall, differential), Platelet, BUN, bilirubin, creatinine, Uric acid, ALT activity, IS, LDH, measurement of diuresis, urine specific gravity, identification microhematuria. Severe leukopenia with the lowest number of white blood cells develop 7-12 days after the injection. The level of formed elements recovered after 17-21 days. При уменьшении числа лейкоцитов менее 2,5·10⁹/л и/или тромбоцитов — менее 100·10⁹/l treatment should be stopped until symptoms resolve gematotoksichnosti. Cardiotoxic effect is most pronounced (at doses of 180-270 mg / kg) for 4-6 days.

During the course of treatment recommended blood transfusion (100-125 Ml 1 once a week). In order to prevent hyperuricemia and nephropathy, due to increased production of uric acid (often occur during the initial period of treatment), before therapy and cyclophosphamide for 72 hours after its application is recommended adequate intake of fluid (to 3 liter per day), use of allopurinol (in some cases) and the use of funds, alkalizing urine. For the prevention of hemorrhagic cystitis (It can develop within a few hours or a few weeks after administration) It should be taken in the morning (the bulk of the metabolites is derived before bedtime), as often as possible to empty the bladder and apply UROMITEKSAN. At the first signs of hemorrhagic cystitis treatment stops to eliminate the symptoms of the disease.

In order to reduce possible dyspepsia receiving cyclophosphamide in small doses for 1 d. Partial or total alopecia, observed during treatment, reversible, and after completion of treatment normal hair growth is restored (structure and color can be changed). If the following symptoms: chills, fever, cough or hoarseness, pain in the lower back or side, painful or difficult urination, bleeding or hemorrhage, black stools, blood in the urine or feces should immediately consult a doctor.

The occurrence of thrombocytopenia necessitates extreme caution when performing invasive procedures and dental procedures, regular inspection of places on / in the, skin and mucous membranes (for signs of bleeding), limit frequency troublesome and the rejection of the / m injection, Control of blood in the urine, vomit, Kale. The patients must be carefully shave, manicure, brush your teeth, dentists use threads and toothpicks, to carry out prevention of constipation, avoid falls and other injuries, as well as the intake of alcohol and acetylsalicylic acid, increase the risk of gastrointestinal bleeding. Should defer vaccination schedule (conduct after 3-12 months after the last cycle of chemotherapy) sick and living with him family members (should abandon immunization oral polio vaccine). It is recommended to avoid contact with infectious patients, or use non-event for the prevention of infection (face mask, etc.). During treatment should use appropriate contraceptive measures. In case of contact with skin or mucous membranes must be thorough washing with water (mucosa) or soap and water (skin). Dissolution, dilution and administration of the preparation is carried out by trained medical staff with the protection (gloves, masks, clothing and other.).

Cautions.

When you run diagnostic tests (each sample candidiasis, эpidemicheskiy mumps, trihofitii, tuberkulinovaya sample) perhaps: suppression of a positive reaction, and during Papanicolaou method - getting false positives. A solution for injection using neliofiolizirovannogo or lyophilized powder is prepared by adding water for injection (sterile or bacteriostatic, using as the only preservative paraben) vials (the concentration of cyclophosphamide 20 mg / ml). The prepared solution is stable at room temperature for 24 no, in the fridge - 6 days. For administration by i / v infusion added to solutions for parenteral administration. If the solution is not prepared bacteriostatic water, it should be used within 6 no. Chemotherapy in neonates as diluent exclude the use of benzyl alcohol.

Cooperation