Cyclophosphane

Cyclophosphamide is a cytostatic that belongs to the chemical category of oxazaphosphorines. The process of cyclophosphamide activation is carried out by microsomal enzymes inside liver cells, where it is converted into the metabolic element 4-hydroxy-cyclophosphamide.

The cytotoxic effect of the drug is largely based on the interaction of deoxyribonucleic acid with its alkylating metabolic components. As a result, the chemical cross-links between DNA strands are disrupted. This leads to a slowdown in the G2 stage of the cell cycle. [ 1 ]

Indications Cyclophosphane

It is used in case of the following disorders and pathologies:

• lung, ovarian or breast carcinoma, lymphosarcoma, NHL and Hodgkin's lymphoma, osteogenic sarcoma, reticulosarcoma, multiple myeloma, ALL, chronic lymphocytic leukemia, endothelial myeloma, nephroblastoma and testicular seminoma;
• prevention of the development of rejection in relation to the transplant;
• SLE, rheumatoid arthritis, multiple sclerosis and nephrotic syndrome (as an immunosuppressant).

Release form

The medicinal substance is released in the form of a lyophilisate for injections - inside 0.2 g vials. The box contains 1 such vial.

Pharmacokinetics

Cyclophosphamide is almost completely absorbed in the intestine. With a single use of the drug, during the period of 24 hours, a significant decrease in its indicators and the values of its derivatives in the blood occurs. [ 2 ]

The average half-life is 7 hours (in adults) and 4 hours (in children). Excretion of cyclophosphamide with its metabolic elements is realized mainly through the kidneys.

Dosing and administration

Cyclophosphamide therapy can only be carried out under the supervision of an experienced oncologist. The dose size is selected individually, the medicine is administered at a low rate by the attending physician - intravenously through a dropper.

The dosage regimens listed below are used for monotherapy. In case of combination with other cytostatics, a reduction in dosage or prolongation of the interval between treatment procedures is required.

Dosage sizes for monotherapy:

• when performing intermittent therapy, it is necessary to administer 10-15 mg/kg of the drug at 2-5 day intervals;
• in case of continuous treatment, the medication is used daily at a dosage of 3-6 mg/kg;
• In a course of treatment with breaks, when high dosages are used, doses of 20-40 mg/kg are used at 3-4 week intervals.

Use Cyclophosphane during pregnancy

Cyclophosphamide is prohibited during pregnancy. In the presence of strict indications, an abortion may be prescribed in the first trimester.

The medicine is excreted in breast milk, which is why breastfeeding should be avoided during treatment.

Contraindications

Among the contraindications:

• severe intolerance associated with cyclophosphamide;
• severe bone marrow dysfunction (especially in people who have undergone radiation therapy or used cytotoxic drugs);
• cystitis;
• delay in urination;
• infection in an active form.

Side effects Cyclophosphane

Main side effects:

• Infectious infections: often with severe suppression of bone marrow activity, agranulocytic fever develops, and secondary infections similar to pneumonia appear, which then progress to sepsis. Rarely, such lesions lead to death;
• immune disorders: occasionally, symptoms of intolerance occur, which include rash, bronchial spasm, chills, tachycardia, fever, hot flashes, dyspnea, swelling and a sharp decrease in blood pressure. Isolated anaphylactoid manifestations can progress to the development of anaphylaxis;
• Problems with lymph and hematopoiesis: Depending on the portion size, different types of bone marrow suppression may develop: leukopenia, neutro- and thrombocytopenia with an increased likelihood of anemia and bleeding. It should be taken into account that with severe suppression of bone marrow function, secondary infections and agranulocytic fever occur. During the 1st and 2nd weeks of treatment, a minimum platelet count with leukocytes is observed. Bone marrow regeneration occurs quite quickly, and the blood composition usually stabilizes within 20 days. The development of anemia is noted only after several consecutive therapeutic courses. The most severe suppression of bone marrow activity is expected in individuals who have undergone chemotherapy or radiation therapy immediately before using Cyclophosphamide, as well as in people with renal insufficiency;
• disorders in the functioning of the nervous system: neurotoxic symptoms, paresthesia, polyneuropathy, taste disturbances, neuropathic pain and convulsions appear sporadically;
• Gastrointestinal disorders: nausea and vomiting most often occur (these are dose-dependent symptoms). Sometimes diarrhea, anorexia, constipation and inflammation in the mucous membranes (from stomatitis to ulceration) may occur. Active pancreatitis, hemorrhagic colitis and gastrointestinal bleeding may occur. Liver dysfunctions (increased levels of alkaline phosphatase, transaminases, GGT and bilirubin) may occur occasionally. Obliterating endophlebitis of the liver vessels was observed in some patients who took large doses of cyclophosphamide in combination with busulfan or body irradiation during allogeneic bone marrow transplantation. Contributing factors include liver dysfunctions and the use of hepatotoxic substances in combination with chemotherapy courses in large doses. Liver encephalopathy is observed in isolated cases;
• Urogenital disorders: metabolic elements of the drug that enter the urine lead to changes associated with the bladder. Hemorrhagic cystitis and microhematuria depend on the dosage and most often develop when using this drug (in these cases, its use should be discontinued). Cystitis occurs frequently. Sometimes bleeding, sclerosis or swelling of the bladder walls and interstitial inflammation are observed. The introduction of large portions sometimes causes renal dysfunction. The use of uromitexan or drinking large amounts of fluid can significantly reduce the frequency and intensity of urotoxic negative signs. There is information about the occurrence of hemorrhagic cystitis leading to death. Toxic nephropathy and renal failure in an active or chronic form may develop. Spermatogenesis disorders (oligo- and azoospermia) or ovulation, decreased estrogen levels and the development of amenorrhea are rarely observed;
• blood flow-related lesions: cardiotoxicity develops with the following symptoms: the appearance of weak fluctuations in blood pressure, changes in ECG readings, arrhythmia and secondary cardiomyopathy with deterioration of left ventricular function and the development of heart failure. Clinical manifestations of cardiotoxicity include angina attacks or thoracalgia. A single injection of the drug causes atrial fibrillation or ventricular fibrillation, pericarditis, myocarditis, infarction or even cardiac arrest;
• respiratory disorders: cough, bronchial spasm and dyspnea develop most often. Occasionally, pulmonary endophlebitis of the obliterating type, pulmonary embolism, edema or hypertension, pneumonitis or interstitial pneumonia occur. There is evidence of the development of RDS syndrome and severe respiratory failure leading to death;
• benign and malignant tumors: there is an increased probability of secondary neoplasms and their precursors. The risk of developing carcinoma of the urogenital system and myelodysplastic disorders, which sometimes progress to active leukemia, increases. Animal testing has shown that the use of uromitexan significantly reduces the likelihood of developing bladder carcinoma;
• lesions in the epidermis and signs of allergy: focal alopecia (complete baldness may occur) is reversible and occurs quite often. There are reports of dermatitis, epidermal pigmentation disorders on the feet and hands, and erythrodysestia. Rarely, SJS, TEN, shock and fever occur;
• problems affecting metabolic processes and the hormonal system: dehydration, Parhon syndrome, hyponatremia and normotensive hyperaldosteronism are observed occasionally;
• visual disturbances: conjunctivitis, decreased vision and swelling of the eyelids may develop;
• lesions affecting blood vessels: thromboembolism, peripheral ischemia, hemolytic syndrome and DIC syndrome (chemotherapy using drugs increases the incidence of these disorders);
• Systemic manifestations: fever, malaise and asthenia are extremely common in people with oncology. Rarely, erythema, inflammation or phlebitis appear in the injection area.

Administration in combination with other drugs that suppress hematopoiesis processes often requires dosage adjustment. It is necessary to use the corresponding tables for changing the portions of cytotoxic drugs.

Overdose

There are no antidotes for cyclophosphamide, so it should be used with extreme caution. The drug is excreted during dialysis. Intoxication results in dose-dependent bone marrow depression and leukopenia. It is necessary to closely monitor blood test values, as well as the general condition of the patient. If thrombocytopenia develops, it is necessary to replenish the loss of platelets.

Interactions with other drugs

Use in combination with antidiabetic drugs potentiates their therapeutic effect.

Combination with indirect anticoagulants causes a violation of anticoagulant blood activity.

Administration of cyclophosphamide together with allopurinol potentiates myelotoxicity.

Use in combination with cytarabine, daunorubicin and doxorubicin may result in cardiotoxic effects.

Prescribing the drug together with immunosuppressants increases the likelihood of developing secondary tumors and infections.

The combination of the drug with lovastatin increases the risk of muscle necrosis, as well as acute renal failure.

Storage conditions

Cyclophosphamide should be stored in a place closed to children. Temperature indicators - no higher than 10 °C.

Shelf life

Cyclophosphamide can be used for a period of 36 months from the date of manufacture of the therapeutic substance.

Analogues

The analogs of the drug are Ribomustin, Endoxan and Leukeran with Alkeran, as well as Holoxan and Ifosfamide.

Reviews

Cyclophosphamide generally receives positive reviews as a drug that is effective in the treatment of systemic vasculitis.