Cyclophosphamide - instructions for use. Cyclophosphamide-lance instant cyclophosphamide recipe in Latin

Cyclophosphamide is classified as an "alkylating agent".

Active substance: cyclophosphamide.
Pharmacotherapeutic group:antineoplastic agents. Alkylating compounds.
Synonyms of the drug:cyclophosphamide, mitoxan, cytoxan.
Release form:tablets, powder for solution for injection.
Storage conditions:Store at a temperature not exceeding 25°C away from moisture and heat.
Terms of sale: on prescription.
Manufacturer:PAT "Kievmedpreparat", Ukraine.

Indications for use

Cyclophosphamide is used in the treatment of:

chronic lymphocytic;
chronic myelocytic;
neuroblastoma;

Cyclophosphamide is also used in bone marrow transplant regimens and for the treatment of diseases that are not oncological (rheumatoid arthritis, vasculitis, Wegener's granulomatosis, scleroderma, lupus erythematosus, nephrotic syndrome). Cyclophosphamide is more often used simultaneously or sequentially with other anticancer drugs.

Contraindications

Cyclophosphamide is contraindicated in patients with:

active or recent infection;
cystitis;
hypersensitivity to cyclophosphamide;
a weak immune system (caused by illness or using certain medications);
heart, kidney or liver diseases;
myelosuppression.

You should tell your doctor if you are being treated with other chemotherapy drugs or if you have ever had radiation therapy. In such cases, Cyclophosphamide should be taken with caution.

In connection with the listed contraindications, before starting treatment, the patient’s urinary and hematopoietic systems, kidneys, and liver are carefully checked.

Use during pregnancy and lactation

It is dangerous for pregnant women to use Cyclophosphamide as it has been shown to be toxic to the developing baby. During chemotherapy, it is important to carefully protect against pregnancy, and if you do become pregnant, consult your doctor for advice.

Cyclophosphamide passes into breast milk and may harm a nursing baby.

Children

The drug is used in pediatric practice. Doses are calculated according to the appropriate instructions.

pharmachologic effect

Cyclophosphamide has a cytostatic, antitumor, and immunosuppressive effect. It is inactive in vitro and is activated only in the liver, where cyclophosphamide is converted to 4-hydroxyn-cyclophosphamide. It interacts with the DNA of cells and leads to their apoptosis. Alkylating agents, which this drug belongs to, are most active in the cell resting phase. This drug is non-cell cycle specific.

Pharmacokinetics

Approximately 20% of cyclophosphamide is protein bound. After intravenous administration, the half-life ranges from 3 to 12 hours with a total clearance of 4-5.6 l/h. After oral administration, the drug is almost completely absorbed from the digestive tract and reaches its highest concentration after 1 hour.

24 hours after the last administration, the concentration of the drug in the blood plasma decreases significantly, and is completely eliminated within 72 hours.

Cyclofosan is biotransformed to active alkylating metabolites mainly in the liver (75% of the substance). These metabolites inhibit the growth of susceptible, rapidly proliferating malignant cells. From 10 to 20% of Cyclophosphamide is excreted unchanged in the urine, and 4% is excreted into the bile.

Instructions for use

Cyclophosphamide is usually administered in several ways: orally and intravenously by injection or infusion. In addition, the drug is approved for intramuscular, intraperitoneal and intrapleural administration. The method of administration of Cyclophosphamide is selected based on the dose, type of disease and patient's condition.

The tablets should be taken with food or after meals. They should not be cut, chewed or crushed. During treatment, you should drink more fluids and go to the toilet more often to avoid side effects from the kidneys and bladder.

The dosage and schedule of administration depend on a number of individual factors, so they are selected by the oncologist. The standard initial course of Cyclophosphamide when used as monotherapy in patients without hematological deficiency is 40-50 mg/kg when administered intravenously in divided doses over 2-5 days.

Other intravenous regimens include 10–15 mg/kg every 7–10 days or 3–5 mg/kg twice weekly. The oral dose of cyclophosphamide is usually 1 to 5 mg/kg per day. The course of treatment can be repeated several times, with a break of 3-4 weeks between each course. The regimen may be adjusted based on evidence of antitumor activity and the development of myelosuppression.

Before intravenous administration, cyclophosphamide powder is diluted with a 0.9% sodium chloride solution in the following ratio: per 1 g of drug - 50 ml of sodium chloride. The concentration of cyclophosphamide should be 20 mg/ml. The diluted drug can be stored at room temperature for another 24 hours.

Dosage for the treatment of nephrotic syndrome in children: An oral dose of 2 mg/kg body weight per day for 8-12 weeks (maximum cumulative dose 168 mg/kg) is recommended.

Precautionary measures

When using cyclophosphamide, it is necessary to follow safety regulations when working with cytotoxic substances.

The drug can only be used under the supervision of a specialist!

Side effects

Common side effects of Cyclophosphamide that can often be managed are:

nausea;
loss of appetite;
stomach pain or upset, diarrhea;
temporary hair loss;
increased sweating;
menstrual irregularities;
change in skin and nail color.

Also, chemotherapy drugs of this group have a depressing effect on the bone marrow, and therefore a person’s hematopoiesis is impaired. This entails a lack of platelets (thrombocytopenia), erythrocytes (erythropenia), and leukocytes (leukopenia). Cyclophosphamide has the greatest effect on leukocytes, the deficiency of which increases the patient’s risk of infection.

Some unwanted effects (including, for example, dizziness and blurred vision) may affect a person's ability to operate machinery.

Symptoms of serious side effects may include:

blood in urine or stool;
pain or burning when urinating;
pale skin, rapid heartbeat;
increased sweating;
skin rash, hives, or itching;
sudden chest pain;
wheezing, dry cough;
elevated temperature;
ulcers in the oral mucosa;
bleeding from the nose, mouth, vagina, or rectum;
purple or red dotted spots under the skin;
jaundice;
severe allergic reaction.

The listed violations are a reason to consult a doctor. Using cyclophosphamide may increase the risk of developing other types of cancer, such as bladder cancer. This medicine may also affect the ability of men or women to have children.

Overdose

Symptoms of overdose may include severe forms of some of the side effects listed in this leaflet.

Serious signs of overdose are:

blood in urine;
dizziness, confusion, or agitation;
joint pain;
intermittent breathing;
swelling of the legs or arms;
severe weakness.

There are no antidotes for Cyclophosphamide, so it must be taken with caution, not exceeding the prescribed dose. To remove the substance from the body, hemodialysis is performed.

special instructions

Avoid contact with sick people while you are being treated with Cyclophosphamide. Tell your doctor right away if you notice signs of infection. Do not take a live vaccine during chemotherapy, and avoid contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you.

It is important to check with your doctor regularly while you are taking Cyclophosphamide to monitor side effects and check your response to therapy. You will have blood drawn periodically to monitor your blood cell count and the function of other organs (particularly your kidneys and liver).

To reduce the likelihood of side effects, pay sufficient attention to oral hygiene. It is advisable to avoid alcohol during chemotherapy.

Interaction

Before starting treatment with Cyclophosphamide, be sure to tell your doctor about any other medications you are taking. Do not take aspirin or products containing aspirin unless your doctor tells you to do so.

Combined or sequential use of cyclophosphamide and other agents with similar toxicity may increase the negative effects on the body. For example, increased hematotoxicity and immunosuppression may result from the interaction of Cyclophosphamide with:

ACE inhibitor drugs;
Natalizumab;
Paclitaxel;
thiazide diuretics;
Zidovudine.

Cardiotoxicity increases when cyclophosphamide is combined with:

Anthracyclines;
Pentostatin;
Trastuzumab.

Other drugs that can increase the toxicity of Cyclophosphamide:

Amphotericin B;
Indomethacin;
Azathioprine (increased risk of liver necrosis);
Busulfan;
Protease inhibitors;
Metronidazole;
Tamoxifen (increases the risk of thromboembolic complications);
Coumarins;
Cyclosporine;
depolarizing muscle relaxants.

Formula: C7H15Cl2N2O2P, chemical name: N,N-bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorine-2-amine-2-oxide.
Pharmacological group: antitumor agents/alkylating agents.
Pharmachologic effect: alkylating, antitumor, immunosuppressive, cytostatic.

Pharmacological properties

Cyclophosphamide is an alkylating cytostatic drug, chemically close to the nitrogen analogues of mustard gas. Cyclophosphamide is metabolized in the liver to form active metabolites that have an alkylating effect. Alkylating metabolites of cyclophosphamide attack the nucleophilic centers of protein molecules, form cross-links between the strands of ribonucleic and deoxyribonucleic acid and block the mitosis of tumor cells, as well as inhibition of protein synthesis. Cyclophosphamide has a wide spectrum of antitumor activity. The immunosuppressive effect of cyclophosphamide is manifested in the suppression of the proliferation of lymphocytic clones (mainly B lymphocytes) that participate in the immune response. There is evidence of the use of cyclophosphamide in systemic lupus erythematosus, glomerulonephritis, nonspecific aortoarteritis, multiple sclerosis, dermatomyositis, and Wegener's granulomatosis.
With prolonged use of cyclophosphamide (over several years), the development of secondary malignant tumors (long-term effect) is possible: bladder cancer (especially in patients with hemorrhagic cystitis), lymphoproliferative and myeloproliferative diseases, renal pelvis cancer (noted in a patient who was on treatment regarding cerebral vasculitis).
There are many reports of suppression of the function of the gonads in patients who use cyclophosphamide (depending on the dose, duration of use of the drug, joint use of other anticancer drugs); In some patients, infertility may be irreversible. When cyclophosphamide is used in prepubertal age, secondary sexual characteristics in boys and girls usually develop normally; in girls, menstrual cycles occur regularly and pregnancy subsequently occurs, but in boys azoospermia or oligospermia, testicular atrophy, and increased gonadotropin secretion are possible. There are reports that after prolonged therapy in late prepubertal age, girls experienced the development of ovarian fibrosis and the complete disappearance of germ cells. The administration of cyclophosphamide to men before conceiving a child has led to the appearance of malformations of the limbs and heart in children. The use of cyclophosphamide during pregnancy in women led to the birth of both healthy children and children with developmental defects (heart defects, absence of toes and/or hands, hernias), as well as to a decrease in the body weight of newborns.
When administered to experimental animals, cyclophosphamide exhibits carcinogenic properties. The use of cyclophosphamide during pregnancy in animals (rats, mice, monkeys, rabbits) in doses that are respectively 0.08; 0.02; 0.07; 0.5 doses recommended for humans revealed the presence of teratogenic effects.
Cyclophosphamide is well absorbed when taken orally. The bioavailability of cyclophosphamide is 75 - 90%. The maximum concentration of metabolites in plasma is achieved 2 to 3 hours after intravenous administration. After a single intravenous administration, the concentration of cyclophosphamide and its metabolites in plasma decreases rapidly on the first day, but can be determined within 3 days. When administered orally, the concentrations of cyclophosphamide and its metabolites are almost the same as when administered intravenously. The volume of distribution of cyclophosphamide is 0.6 l/kg. Cyclophosphamide binds to plasma proteins to a low degree (12 - 14%), but for some active derivatives the binding to plasma proteins is 60% or more. Cyclophosphamide is biotransformed in the liver (including initial activation and further conversion) to form active metabolites. Cyclophosphamide is metabolized mainly under the action of the microsomal oxidase system (CYP2C19 isoenzyme), forming active alkylating metabolites (4-OH cyclophosphamide and aldophosphamide), some of which undergo further transformation to inactive metabolites, some are transported into cells, where, under the influence of phosphatases, they are converted into metabolites with cytotoxic effect. Cyclophosphamide passes through the placental barrier and is excreted in breast milk. Penetrates through the blood-brain barrier to a limited extent. The half-life of cyclophosphamide is 3 - 12 hours. When administered intravenously, the maximum concentration of cyclophosphamide metabolites in the serum is achieved after 2 to 3 hours. Cyclophosphamide is excreted mainly in the urine in the form of metabolites (acrolein, chloroacetic acid and others) and unchanged (5 - 25%), as well as in bile. Cyclophosphamide is removed during dialysis. In renal failure, no increased severity of the toxic effects of cyclophosphamide was observed.

Indications

Cancer of the lung, bladder, cervix and body of the uterus, ovaries, breast, prostate, testicular seminoma; retinoblastoma, neuroblastoma, angiosarcoma, lymphosarcoma, reticulosarcoma, osteogenic sarcoma; chronic lympho- and myeloid leukemia; acute lymphoblastic, myeloblastic, monoblastic leukemia; non-Hodgkin's lymphoma, lymphogranulomatosis, myeloma, Ewing's tumor, Wilms' tumor, soft tissue sarcoma, germ cell tumors, mycosis fungoides; autoimmune diseases, including systemic connective tissue diseases, including autoimmune hemolytic anemia, psoriatic arthritis, rheumatoid arthritis, collagenosis, systemic lupus erythematosus, nephrotic syndrome, multiple sclerosis; suppression of transplant rejection reaction.

Method of administration of cyclophosphamide and dose

Cyclophosphamide is taken orally, administered intramuscularly, intravenously, or into cavities (intrapleural or intraperitoneal). The choice of dosage regimen and route of administration is carried out in accordance with the indications and chemotherapy regimen. The dose is set individually and adjusted based on the clinical effect and the severity of the toxic effect.
The course dose is 8 - 14 g, then they switch to maintenance therapy - 0.1 - 0.2 g 2 times a week.
As an immunosuppressive agent, it is prescribed at the rate of 0.05 - 0.1 g per day (1 - 1.5 mg/kg per day), with good tolerance - 3 - 4 mg/kg.
The most commonly used doses and regimens: 50 - 100 mg/m2 daily for 2 - 3 weeks; 100 - 200 mg/m2 2 or 3 times a week for 3 - 4 weeks; 600 - 750 mg/m2 once every 2 weeks; 1500 - 2000 mg/m2 1 time every 3-4 weeks up to a total dose of 6 - 14 g.
With an intermittent treatment regimen, treatment cycles can be repeated every 3 to 4 weeks. The duration of treatment and/or intervals depend on the indication, combination treatment regimen, general condition of the patient, laboratory parameters, and restoration of the number of blood cells.
With the development of myelosuppression with the number of leukocytes more than 4000 per μl and platelets more than 100,000 per μl, the full planned dose of cyclophosphamide is used; when the number of leukocytes is 4000 - 2500 per μl, 50% of the planned dose of cyclophosphamide is used; if the number of leukocytes is less than 2500 per µl and platelets less than 100,000 per µl, treatment is postponed until the values are normalized or a decision is made on a separate case.
In severe liver failure, it is necessary to reduce the dose of cyclophosphamide. When plasma bilirubin concentration is from 3.1 to 5 mg/100 ml (0.053 - 0.086 mmol/l or 53 - 86 µmol/l), it is recommended to reduce the dose of cyclophosphamide by 25%.
In patients with severe renal impairment, a dose reduction of 50% is recommended. Cyclophosphamide is eliminated by dialysis. Dosage selection for elderly patients should be made with caution, taking into account the more frequent decline in liver, kidney or cardiac function, as well as concomitant disease and the use of other drugs.
When cyclophosphamide is used together with other anticancer drugs, it may be necessary to reduce the dose of both cyclophosphamide and other drugs.
The use of cyclophosphamide is possible only under the supervision of a physician who has experience in chemotherapy.
It is necessary to strictly adhere to the dosing regimen, including at certain times of the day (especially with combination treatment) and not to double the subsequent dose if the previous dose was missed.
For the preparation of drugs for use in newborns, it is not recommended to use diluents that contain benzyl alcohol, since the development of a lethal toxic syndrome is possible: depression of the central nervous system, metabolic acidosis, renal failure, respiratory failure, hypotension, intracranial hemorrhage, convulsions.
Before and during therapy (at short intervals) with cyclophosphamide, hematocrit, hemoglobin, urea nitrogen, creatinine, bilirubin, uric acid concentrations, alanine aminotransferase activity, aspartate aminotransferase, lactate dehydrogenase, leukocyte count (total and differential), platelets, measure diuresis, specific gravity of urine, detect microhematuria.
Severe leukopenia with the lowest number of leukocytes develops 7 to 12 days after administration of cyclophosphamide. The content of formed elements is restored after 17 - 21 days. If the number of leukocytes decreases to less than 2.5 10^9/l and/or platelets to less than 100 10^9/l, therapy should be stopped until the symptoms of hematotoxicity are eliminated.
The cardiotoxic effect is most pronounced within 4 - 6 days at doses of 180 - 270 mg/kg.
During the entire course of therapy, it is recommended to receive blood transfusions (100 - 125 ml once a week).
To prevent hyperuricemia and nephropathy, which is caused by increased formation of uric acid (often develops during the initial period of therapy), before treatment with cyclophosphamide and for 3 days after its use, adequate fluid intake (up to 3 liters per day) and the administration of allopurinol (in some cases) are recommended. ) and the use of drugs that alkalinize the urine.
To prevent hemorrhagic cystitis, which can develop within a few hours or several weeks after administration of the drug, it is necessary to take cyclophosphamide in the morning (when most of the metabolites are eliminated before bed), empty the bladder as often as possible and use the drug mesna. When the first signs of hemorrhagic cystitis develop, cyclophosphamide therapy is stopped until the symptoms of the disease are eliminated.
Complete or partial alopecia, which is observed during therapy, is reversible and after completion of the course of treatment, normal hair growth is restored, but the color and structure may be changed.
To reduce the symptoms of dyspepsia, it is possible to take cyclophosphamide in small doses for 1 day.
In case of febrile neutropenia and/or leukopenia, antibiotics and/or antifungals should be prescribed for prophylactic purposes.
Careful monitoring of patients with reduced immunity (for example, diabetes mellitus or chronic liver and/or kidney diseases) is necessary.
Before initiating cyclophosphamide therapy, urinary tract obstruction, cystitis or infections should be excluded or corrected.
The cardiotoxic effect of cyclophosphamide may be enhanced in patients with previous radiation therapy to the heart and/or concomitant therapy with pentostatin or anthracyclines. Therefore, regular monitoring of electrolyte levels and caution is necessary, especially in patients with heart disease.
To reduce the severity and frequency of nausea and vomiting, it is necessary to prescribe antiemetic drugs in a timely manner. Alcohol may increase vomiting and nausea induced by cyclophosphamide. To prevent the development of stomatitis, you should carefully maintain oral hygiene.
In patients with diabetes mellitus, it is necessary to regularly check the concentration of glucose in the blood in order to promptly correct hypoglycemic therapy.
If you develop chills, cough, fever, hoarseness, painful or difficult urination, pain in the lower back or side, black stools, bleeding or hemorrhage, or blood in the urine or stool during treatment with cyclophosphamide, you should immediately consult your doctor.
Extreme caution is necessary in case of development of thrombocytopenia when performing dental interventions, invasive procedures, regular inspection of intravenous injection sites, skin and mucous membranes (to identify signs of bleeding), limiting the frequency of intravenous injections, avoiding intramuscular injections, monitoring the blood content in vomit, urine , kale. Such patients need to carefully brush their teeth, do manicures, shave, use toothpicks and dental floss, avoid falls and other injuries, prevent constipation, and also avoid drinking alcohol and taking acetylsalicylic acid, which increase the risk of gastrointestinal bleeding.
During treatment with cyclophosphamide, it is recommended to avoid contact with infectious patients or use nonspecific measures to prevent infections (protective mask, etc.). It is necessary to delay the vaccination schedule (carry out 3 - 12 months after completion of the last course of chemotherapy) for the patient and family members living with him (it is necessary to refuse immunization with oral polio vaccine).
Some patients who were previously treated with cyclophosphamide alone or in combination with other antineoplastic agents and/or other therapies developed secondary malignancies. Most often these were bladder tumors (usually in patients who had previously suffered from hemorrhagic cystitis), lymphoproliferative or myeloproliferative diseases. Secondary tumors most often developed in patients as a result of therapy for primary myeloproliferative malignant tumors or non-malignant diseases with impaired immune processes. In some cases, a secondary tumor developed several years after cessation of cyclophosphamide therapy. When assessing the relationship between the expected positive results and the possible risk of using cyclophosphamide, you must always keep in mind the likelihood of the drug inducing a malignant tumor.
Cyclophosphamide may increase anticoagulant activity as a result of decreased hepatic synthesis of coagulation factors and impaired platelet formation, as well as as a result of an unknown mechanism.
If infections occur during treatment with cyclophosphamide, the dose of the drug should be reduced or treatment interrupted.
According to electrocardiogram and echocardiogram data, in patients who suffered episodes of cardiotoxic effects of high doses of cyclophosphamide, no residual effects on the state of the myocardium were detected.
In girls, as a result of treatment with cyclophosphamide in the prepubertal period, secondary sexual characteristics developed normally and menstruation was normal, and they were subsequently able to conceive. In boys, during treatment with cyclophosphamide in the prepubertal period, secondary sexual characteristics developed normally, but oligospermia or azoospermia and increased secretion of gonadotropins may be observed. Sexual desire and potency in men are not affected during cyclophosphamide therapy.
Adequate contraception must be used during cyclophosphamide therapy.
During the treatment period, you must refrain from drinking alcoholic beverages, as well as from eating grapefruit (including juice).
If during the first ten days after surgery, which was performed under general anesthesia, the patient is prescribed cyclophosphamide, then the anesthesiologist must be notified.
After adrenalectomy, the patient should adjust the doses of glucocorticosteroids used for replacement therapy and cyclophosphamide.
In 15-50% of patients who receive high doses of cyclophosphamide along with busulfan and total irradiation during allogeneic bone marrow transplantation, obliterating endophlebitis of the hepatic veins develops. The same reaction can occur in very rare cases in patients who receive high doses of cyclophosphamide alone in patients with aplastic anemia. This syndrome usually develops 1 to 3 weeks after bone marrow transplantation and is characterized by a sharp increase in body weight, hepatomegaly, ascites, hyperbilirubinemia, and hepatic encephalopathy.
When performing the Papanicolaou test during treatment with cyclophosphamide, false-positive results may be obtained. When performing diagnostic tests (skin test for trichophytosis, mumps, candidiasis, tuberculin test) during treatment with cyclophosphamide, a positive reaction may be suppressed.
Cyclophosphamide injection solution using lyophilized or non-lyophilized powder is prepared by adding water for injection (bacteriostatic or sterile, using only paraben as a preservative) to the vials (cyclophosphamide concentration is 20 mg/ml). The prepared solution is stable at room temperature for 24 hours, in the refrigerator for 6 days. For administration by intravenous infusion, add to solutions for parenteral administration. If the solution is not prepared with bacteriostatic water, then it must be used within 6 hours. During chemotherapy in newborns, the use of benzyl alcohol as a diluent is excluded.
Since the cytostatic effect of cyclophosphamide appears after its activation, which occurs mainly in the liver, there is only a slight risk of tissue damage with accidental paravenous administration of a cyclophosphamide solution. If a cyclophosphamide solution is inadvertently administered as a paravenous injection, the injection should be stopped immediately, the drug administered paravasally should be removed by aspiration using a cannula placed in this area, the area should be rinsed with sodium chloride solution and immediately fixed.
Dissolution, dilution and administration of cyclophosphamide is carried out by trained medical personnel in compliance with protective measures (masks, gloves, clothing, etc.). If cyclophosphamide comes into contact with mucous membranes or skin, wash them thoroughly with soap and water (skin) or water (mucous membranes).
During treatment with cyclophosphamide, care must be taken when engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions (including driving vehicles and machinery).

Contraindications for use

Hypersensitivity, bone marrow hypoplasia, severe impairment of bone marrow function, severe renal and/or liver dysfunction, urinary retention, thrombocytopenia (platelet count less than 120 10^9/l) and/or leukopenia (white blood cell count less than 3.5 10^9 /l), severe anemia, active infections, cystitis, terminal stages of cancer, severe cachexia, breastfeeding, pregnancy.

Restrictions on use

Chickenpox, herpes zoster and other systemic infections, impaired renal function, urolithiasis, nephrourolithiasis, gout, impaired liver function, severe heart disease, infiltration of the bone marrow with tumor cells, suppression of bone marrow function, hyperuricemia, adrenalectomy, previous radiation or cytotoxic therapy, elderly and children.

Use during pregnancy and breastfeeding

The use of cyclophosphamide is contraindicated during pregnancy and breastfeeding. Experimental studies have established the embryotoxic and teratogenic effects of cyclophosphamide. Adequate contraception must be used during cyclophosphamide therapy. Breastfeeding should be stopped during cyclophosphamide therapy.

Side effects of cyclophosphamide

Digestive system: anorexia, dry mouth, stomatitis, nausea, diarrhea, vomiting, stomach pain, hemorrhagic colitis, stomatitis, constipation, gastrointestinal bleeding, toxic hepatitis, jaundice, increased activity of transaminases, alkaline phosphatase in the blood, increased bilirubin in the serum blood, mucositis, dehydration, liver function disorders, ascites, ulceration, acute pancreatitis, activation of viral hepatitis, endophlebitis of the hepatic veins (sharp weight gain, hepatomegaly, ascites, hyperbilirubinemia, hepatic encephalopathy).
Nervous system and sensory organs: asthenia, headache, confusion, dizziness, convulsions, paresthesia, taste disturbance, hepatic encephalopathy, blurred vision, blurred vision, conjunctivitis, ocular edema.
Cardiovascular system and blood (hemostasis, hematopoiesis): flushing, heart failure, cardiotoxicity, hemorrhagic myopericarditis, tachycardia, palpitations, pericarditis, bleeding, thromboembolism, changes in blood pressure, acute myopericarditis, severe heart failure (associated with hemorrhagic myocarditis and myocardial necrosis), myelosuppression, agranulocytosis, leukopenia, thrombocytopenia , bleeding and hemorrhage, anemia, febrile neutropenia, disseminated intravascular coagulation, hemolytic-uremic syndrome.
Respiratory system: pneumonitis, shortness of breath, interstitial pneumosclerosis.
Genitourinary system: urethritis, hemorrhagic cystitis, bladder fibrosis, hemorrhagic urethritis, hematuria, atypia of bladder cells, frequent urination, painful urination, difficulty urinating, nephropathy, hyperuricemia, edema of the lower extremities, necrosis of the renal tubules, hyperuricosuria, suburethral bleeding, swelling of the bladder wall, interstitial inflammation, sclerosis of the bladder, impaired renal function, fluid retention, hyponatremia, amenorrhea, menstrual disorders, azoospermia, impaired oogenesis and spermatogenesis, oligospermia, sterility of men and women (including irreversible), reduced concentrations of female sex hormones, irreversible disorders ovulation, suppression of ovarian function.
Skin: hyperpigmentation (fingernails, palms), nail changes, alopecia, intradermal hemorrhages, rash, increased sweating, facial redness, urticaria, regeneration disorders, Stevens-Johnson syndrome, epidermal necrolysis, severe skin reactions, itchy inflammation, erythema, hyperemia, swelling , itching, pain at the injection site.
Allergic reactions: skin rash, urticaria, anaphylactic reactions, anaphylactoid reactions, cross-sensitivity with other alkylating compounds.
Other: pain syndrome (pain in the side, back, joints, bones, muscles), rhabdomyolysis, spasm, chills, febrile syndrome, development of infections, flushing of the facial skin, facial hyperemia, syndrome of inadequate secretion of antidiuretic hormone, myxedema (swelling of the lips), development secondary malignant tumors, hyperglycemia, fatigue, weakness, malaise, retrospective radiation dermatitis, multiple organ failure, chest pain; pain and reactions in the injection area, phlebitis.

Interaction of cyclophosphamide with other substances

The effect of cyclophosphamide is enhanced by tricyclic antidepressants, chlorpromazine, barbiturates, thyroid hormones, theophylline, inducers of microsomal liver enzymes (increase the formation of alkylating metabolites). Previous or concomitant use of phenobarbital, phenytoin, benzodiazepine or chloral hydrate may lead to the induction of liver microsomal enzymes.
The effect of cyclophosphamide (including toxic effects) is weakened by glucocorticoids and chloramphenicol.
Other myelotoxic drugs, allopurinol, and radiation therapy may enhance the inhibition of bone marrow function by cyclophosphamide.
Cyclophosphamide reduces the effectiveness of immunization with inactivated vaccines. When using vaccines that contain live viruses, cyclophosphamide increases viral replication and adverse reactions to vaccination.
With simultaneous use, cyclophosphamide may enhance the effect of hypoglycemic drugs.
Cyclophosphamide, as a result of impaired platelet formation and inhibition of the synthesis of blood coagulation factors in the liver, can increase or decrease the activity of indirect anticoagulants.
Cyclophosphamide weakens the effect (by increasing the uric acid content) of anti-gout drugs (colchicine, allopurinol, probenecid, sulfinpyrazone) in the treatment of gout and hyperuricemia (dosage adjustment of anti-gout drugs is necessary).
Cyclophosphamide enhances the blockade of neuromuscular transmission caused by succinylcholine.
Cyclophosphamide enhances the cardiotoxicity of doxorubicin and cytarabine.
Uricosuric drugs increase the risk of nephropathy when used together with cyclophosphamide.
Immunosuppressants (chlorambucil, azathioprine, cyclosporine, glucocorticoids, mercaptopurine) increase the risk of developing infections and secondary tumors when used together with cyclophosphamide.
With the combined use of lovastatin and cyclophosphamide in patients after heart transplantation, the risk of developing acute renal failure and acute necrosis of skeletal muscles increases.
Grapefruit juice interferes with the activation and thereby the action of cyclophosphamide.
Fluoroquinolone antimicrobial agents (such as ciprofloxacin) prior to cyclophosphamide (especially before bone marrow transplantation) may reduce the effectiveness of cyclophosphamide and lead to relapse of the underlying disease.
The concomitant use of indomethacin must be carried out with caution, since isolated cases of acute general overhydration are known.
An increased risk of pulmonary toxicity (alveolar fibrosis, pneumonia) has been reported in isolated reports in patients receiving cytotoxic chemotherapy, including cyclophosphamide and granulocyte colony-stimulating growth factor or granulocyte-macrophage colony-stimulating growth factor.
The pharmacokinetic interaction between ondansetron and high doses of cyclophosphamide results in an increase in the area under the concentration-time curve.
A strong inhibition of the bioactivation of cyclophosphamide by thiotepa was detected during high-dose chemotherapy in cases where thiotepa was prescribed 1 hour before taking cyclophosphamide. It is necessary to consider the interaction of these drugs when used together.
Amino acids for parenteral nutrition, a combination of amino acids for parenteral nutrition + other drugs [minerals] are pharmaceutically compatible with cyclophosphamide.
When cyclophosphamide and amphotericin B are used together, the risk of developing kidney damage, bronchospasm and hypotension increases.
Against the background of asparaginase, the effect of cyclophosphamide may be enhanced, which requires a dose reduction.
When cyclophosphamide is used together with the combination of bisoprolol + hydrochlorothiazide, increased myelotoxicity is possible.
When bleomycin and cyclophosphamide are used together, the risk of pulmonary toxicity increases.
Bupropion is metabolized to the main active metabolite (hydroxybupropion), mainly with the participation of the CYP2B6 isoenzyme. Caution is required when using bupropion and cyclophosphamide together, which affects the activity of the CYP2B6 isoenzyme.
Busulfan mutually enhances the effects of cyclophosphamide, including the likelihood and severity of adverse reactions, possible veno-occlusive disease, cardiac tamponade.
Combinations of valsartan + hydrochlorothiazide, hydrochlorothiazide + dihydralazine + reserpine, hydrochlorothiazide + telmisartan reduce the renal excretion of cyclophosphamide and enhance its myelosuppressive effect.
Cyclophosphamide modifies the effect of warfarin; prothrombin time may be shortened or prolonged.
When gemcitabine and cyclophosphamide are used together, the risk of infections increases.
Hydrazine sulfate mutually enhances the effect of cyclophosphamide.
Nevirapine (as part of the combination lamivudine + zidovudine + nevirapine) may help reduce cyclophosphamide concentrations.
Cyclophosphamide enhances the hypoglycemic effect of glibenclamide, gliquidone, insulin and its preparations (biphasic insulin [human genetically engineered], biphasic insulin [human semisynthetic], insulin detemir, soluble insulin [human genetically engineered], soluble insulin [human semisynthetic], insulin- isophane [human genetically engineered], insulin-isophane [human semi-synthetic]), metformin, chlorpropamide, gliclazide + metformin combination.
Daunorubicin and doxorubicin mutually enhance the effects of cyclophosphamide, including side effects (especially cardiotoxic); when used together, the dose of daunorubicin and doxorubicin should not exceed 400 mg/m2.
When cladribine is prescribed in high doses exceeding standard ones, together with cyclophosphamide and radiation therapy, nephrotoxicity (acute renal failure) and neurotoxicity (irreversible paraparesis and tetraparesis) increases.
Cyclophosphamide, by inhibiting the activity of cholinesterase, reduces or slows down hydrolysis, enhances and prolongs the effect of cocaine, and the risk of developing the toxicity of the latter increases.
Colchicine increases the risk of developing nephropathy when used together with cyclophosphamide.
Lovastatin mutually increases the risk of adverse reactions; when used together with cyclophosphamide, an increase in cases of acute skeletal muscle necrosis and acute renal failure may occur.
Cyclophosphamide, by inhibiting cholinesterase activity, reduces the metabolism of mepivacaine, procaine, and tetracaine.
When mercaptopurine and cyclophosphamide are used together, the risk of developing infection and secondary tumors increases (due to increased immunosuppressive effects).
Mesna reduces the risk of urinary tract injury from cyclophosphamide.
Cyclophosphamide displaces methotrexate from its binding to plasma proteins and increases the concentration of the free fraction in the blood, which can lead to increased effects of methotrexate, including toxic ones.
The toxicity of cyclophosphamide increases with morphine (shown in an animal study).
Concomitant use of pyridoxine and cyclophosphamide may cause anemia and neuropathy.
Palonosetron does not reduce the antitumor activity of cyclophosphamide.
Primidone enhances the effect of cyclophosphamide.
Pegaspargase mutually increases the risk of complications when used together with cyclophosphamide.
When cyclophosphamide (metabolized exclusively by the CYP2B6 isoenzyme and has a narrow therapeutic range) and prasugrel (a weak inhibitor of CYP2B6) interacts, the effect can be clinically significant.
The potential of ranolazine to inhibit the CYP2B6 isoenzyme has not been established; Caution is recommended when prescribing ranolazine with cyclophosphamide.
Rituximab did not affect the systemic exposure of cyclophosphamide when used together in patients with chronic lymphocytic leukemia. In clinical studies in patients with rheumatoid arthritis, concomitant use of cyclophosphamide did not affect the pharmacokinetics of rituximab.
Tegafur is compatible with cyclophosphamide.
When cyclophosphamide and tamoxifen are used together, the likelihood of developing thromboembolic complications increases.
Cyclophosphamide, by reducing the activity of pseudocholinesterase (an enzyme that hydrolyzes succinylcholine), deepens and prolongs the blockade of neuromuscular transmission, possibly severe or prolonged respiratory depression or arrest; Caution is necessary when using cyclophosphamide and suxamethonium iodide together or sequentially.
When cyclophosphamide and trastuzumab are used together, the risk of cardiac dysfunction mutually increases.
When cyclophosphamide and fluconazole are used together, plasma concentrations of creatinine and bilirubin increase; this combination is acceptable given the risk of increased creatinine and bilirubin concentrations; Caution and possible dosage adjustment are necessary.
Fluorouracil mutually enhances the effects of cyclophosphamide, including the risk of development and severity of adverse reactions.
Chlorambucil, cyclosporine mutually increases the risk of developing secondary tumors and infections when used together with cyclophosphamide.
Concomitant use of high doses of cytarabine with cyclophosphamide in preparation for bone marrow transplantation led to an increased incidence of cardiomyopathy with subsequent death (cardiotoxicity may depend on the drug regimen).
Concomitant use of etanercept and cyclophosphamide is not recommended.

Overdose

In case of an overdose of cyclophosphamide, nausea, vomiting, fever, severe bone marrow depression, dilated cardiomyopathy, multiple organ failure, hemorrhagic cystitis and other bleeding develop.
hospitalization, monitoring of vital functions; symptomatic and supportive treatment (including treatment of infections, manifestations of myelosuppression and/or cardiotoxicity), including the prescription of antiemetic drugs, if necessary, transfusion of blood components, administration of broad-spectrum antibiotics, hematopoietic stimulants, vitamin therapy (pyridoxine intramuscularly 0.05 g and others ), prevention of cystitis mesnos. A specific antidote for cyclophosphamide overdose is unknown. Cyclophosphamide is eliminated by dialysis, so immediate hemodialysis is indicated for the treatment of overdose or intoxication. The dialysis rate of 78 ml/min was calculated based on the concentration of unmetabolized cyclophosphamide in the dialysate (normal renal clearance is approximately 5 - 11 ml/min). The second working group reported the value to be 194 ml/min. After 6 hours of dialysis, 72% of the administered dose of cyclophosphamide is found in the dialysate.

Cyclophosphamide is an alkylating compound. Antitumor drug.

Release form and composition

The powder for preparing a solution for intravenous and intramuscular administration is crystalline, from almost white to white.

Composition of 1 bottle: cyclophosphamide – 200 mg.

Indications for use

acute lymphoblastic and chronic lymphocytic leukemia;
non-Hodgkin's lymphomas;
lymphogranulomatosis;
multiple myeloma;
breast and ovarian cancer;
neuroblastoma;
retinoblastoma;
mycosis fungoides.

As part of complex therapy for the following diseases:

lung cancer;
germ cell tumors;
cervical cancer;
bladder cancer;
soft tissue sarcoma;
reticulosarcoma;
Ewing's sarcoma;
Wilms tumor;
prostate cancer.

Cyclophosphamide is also used as an immunosuppressive agent for progressive autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis, collagenosis, autoimmune hemolytic anemia, nephrotic syndrome, as well as to suppress transplant rejection.

Contraindications

Absolute contraindications:

increased sensitivity to the components of the drug;
severe dysfunction of the bone marrow;
cystitis;
urinary retention;
active infections;
pregnancy and lactation period.

Relative contraindications:

severe diseases of the heart, kidneys, liver;
adrenalectomy;
history of gout;
nephrourolithiasis;
suppression of bone marrow function;
infiltration of bone marrow by tumor cells;
previous radiation or chemotherapy.

Directions for use and dosage

Cyclophosphamide is included in many chemotherapy treatment regimens. When choosing doses, route and mode of administration in each individual case, one should be guided by data from specialized literature.

The most common regimens and doses for adults and children:

50–100 mg/m2 every day for 2-3 weeks;
100–200 mg/m2 2-3 times a week for 3-4 weeks;
600–750 mg/m2 once every 2 weeks;
1500–2000 mg/m2 1 time every 3-4 weeks up to a total dose of 6000–14,000 mg.

When taking Cyclophosphamide together with other anticancer drugs, it may be necessary to reduce the dose of both Cyclophosphamide and other drugs.

Preparation of the solution

A 0.9% sodium chloride solution should be added to the powder bottle in accordance with the following recommendations:

for 100 mg of Cyclophosphamide – 5 ml of solvent;
for 200 mg of Cyclophosphamide - 10 ml of solvent;
for 500 mg of Cyclophosphamide - 25 ml of solvent;
for 1000 mg of Cyclophosphamide – 50 ml of solvent;
for 2000 mg of Cyclophosphamide - 100 ml of solvent.

To prepare a solution for infusion, add Ringer's solution, 0.9% sodium chloride solution or glucose solution to the contents of the bottle to a total volume of about 500 ml.

Side effects

hematopoietic system: neutropenia, leukopenia, anemia, thrombocytopenia (the greatest decrease in the number of platelets and leukocytes is usually observed on the 7–14th day of taking the drug. For leukopenia, after cessation of therapy, recovery usually begins on the 7–10th day);
digestive system: anorexia, nausea, vomiting, stomatitis, pain or discomfort in the abdominal area, diarrhea, constipation. There are isolated reports of the development of hemorrhagic colitis, jaundice, and liver dysfunction with an increase in the activity of alkaline phosphatase, transaminases and bilirubin content in the blood serum. In 15–50% of patients using high doses of cyclophosphamide in combination with busulfan and total irradiation during allogeneic bone marrow transplantation, obliterating endophlebitis of the hepatic veins develops. It also occurs in very rare cases in patients with aplastic anemia who use cyclophosphamide alone in high doses. This syndrome develops 1–3 weeks after bone marrow transplantation (symptoms: sudden increase in body weight, hepatomegaly, ascites, hyperbilirubinemia). There is also a risk of hepatic encephalopathy;
skin and skin appendages: alopecia (after completion of treatment or during long-term treatment, hair regrowth occurs, differences in hair structure and color are possible), rash, skin pigmentation, nail changes;
urinary system: hemorrhagic urethritis/cystitis, necrosis of the renal tubules (even death), fibrosis of the bladder (including common) with and without cystitis. It is possible to detect atypical bladder epithelial cells in the urine. When using the drug in high doses, renal dysfunction, hyperuricemia, nephropathy (due to increased formation of uric acid) is possible;
cardiovascular system: when high doses of Cyclophosphamide (120–270 mg/kg) were administered for several days, cardiotoxicity was observed with episodes of congestive heart failure caused by hemorrhagic myocarditis, sometimes leading to death;
respiratory system: interstitial pulmonary fibrosis (noted when using the drug for a long time in high doses);
reproductive system: disturbance of spermatogenesis and oogenesis. Both men and women can develop sterility (including irreversible). Amenorrhea often develops in women, and after discontinuation of the drug, regular menstruation is usually restored. In girls undergoing treatment with Cyclophosphamide in the prepubertal period, normal development of secondary sexual characteristics and normal menstruation were noted; the drug did not affect further ability to conceive. The use of the drug in men can cause oligospermia or azoospermia (without impaired sexual desire), associated with an increase in the level of gonadotropins with normal testosterone secretion. In boys undergoing treatment with Cyclophosphamide in the prepubertal period, normal development of secondary sexual characteristics is noted, but oligospermia, azoospermia, and increased secretion of gonadotropins may be noted. Testicular atrophy of varying degrees is possible. Azoospermia is reversible in some cases, but restoration of impaired function may take several years.

When using Cyclophosphamide, allergic reactions such as urticaria, skin rash, itching, and anaphylactic reactions are possible. There is a risk of cross-sensitivity with other alkylating compounds.

Patients with severe immunosuppression may develop serious infections.

The following undesirable effects are also possible: a syndrome similar to the syndrome of inadequate secretion of antidiuretic hormone (ADH), facial flushing or flushing of the face, increased sweating, headache, development of secondary malignant tumors.

Due to the fact that grapefruit contains a compound that can interfere with the activation of cyclophosphamide, it is not recommended to consume it, as well as its juice, during the treatment period.

special instructions

During the period of use of the drug, regular blood tests should be performed (especially the content of neutrophils and platelets should be monitored) to assess the degree of myelosuppression. Regular urine testing is also necessary for the presence of red blood cells, the presence of which may indicate the development of hemorrhagic cystitis.

Treatment with the drug should be interrupted:

when symptoms of cystitis with micro- or macrohematuria appear;
with a decrease in the number of leukocytes< 2500/мкл и/или тромбоцитов < 100 000/мкл;
if an infection occurs, if reducing the dose of the drug is not enough.

During treatment with Cyclophosphamide, it is necessary to use reliable methods of contraception and also refrain from drinking alcohol.

The anesthesiologist should be notified if the patient is prescribed Cyclophosphamide within 10 days after surgery under general anesthesia.

Drug interactions

The following medicines affect cyclophosphamide:

inducers of microsomal oxidation: reduce the half-life of cyclophosphamide and increase its activity;
allopurinol: enhances the toxic effect on the bone marrow;
colchicine, probenecid, allopurinol, sulfinpyrazone: there may be an increased risk of nephropathy caused by increased formation of uric acid (these drugs may need to be adjusted);
immunosuppressants (azathioprine, chlorambucil, glucocorticosteroids, cyclosporine, mercaptopurine, etc.): increase the risk of developing secondary tumors and infections;
lovastatin (for heart transplantation): possible increased risk of acute renal failure and acute necrosis of skeletal muscles;
myelosuppressive drugs, radiation therapy: risk of additive suppression of bone marrow function;
Cytarabine in high doses in preparation for bone marrow transplantation: increases the risk of fatal cardiomyopathy.

Cyclophosphamide affects the following drugs:

suxamethonium: enhances its effect due to a noticeable and long-term suppression of cholinesterase activity;
cocaine: reduces and slows down its metabolism, enhancing and prolonging its effect, as well as increasing the risk of toxic effects;
anticoagulants: can increase their activity due to a decrease in the synthesis of blood clotting factors in the liver and impaired platelet formation. However, it has also been noted to reduce anticoagulant activity through an unknown mechanism;
doxorubicin, daunorubicin: enhances their cardiotoxic effect.

Analogues

An analogue of Cyclophosphamide is Endoxan.

Terms and conditions of storage

Store in a dry place, away from light, at a temperature not exceeding 10 °C. Keep away from children.

Shelf life – 3 years.

Conditions for dispensing from pharmacies

Dispensed by prescription.

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Pharmacological properties

Indications

Method of administration of cyclophosphamide and dose

Contraindications for use

Restrictions on use

Use during pregnancy and breastfeeding

Side effects of cyclophosphamide

Interaction of cyclophosphamide with other substances

Overdose

Cyclophosphamide is a drug that has an antitumor effect. It works by alkylating action. With regular use of the drug, it is possible to have powerful immunosuppressive and cytostatic effects.

The drug can significantly reduce the rate of tumor development due to the transformation of cyclophosphamide into an active metabolite. It is he who has the alkylating effect. Please note that before starting such therapy, you should definitely consult with your doctor - independent therapy is prohibited.

Thanks to Cyclophosphamide, it is possible to have a powerful antitumor effect on the body. In addition, the active components of the drug help improve the body's immune abilities. This can be achieved due to the inactive transport form.

Under the action of phosphatase, they decompose, forming a specific active component. They attack the internal cells of malignant tumors, promoting the destruction of their DNA and RNA. In addition, it is possible to stop their mitotic division.

After cyclophosphamide is injected into a vein, the maximum concentration of active substances occurs after 2-3 hours. Moreover, on the first day after reaching this parameter, it rapidly decreases.

The bioavailability of the drug is 90%. The active components rapidly spread throughout the body, they settle in all internal organs. The half-life is on average 7 hours, if there are pathologies of the liver and kidneys - this parameter can be increased.

Indications for use

Cyclophosphamide is a drug with multiple effects. Typically, this drug is prescribed to treat the following conditions:

In addition, Cyclophosphamide is used as a combination therapy. It is successfully prescribed together with other antitumor drugs. This medicine is often taken for progressive autoimmune diseases, as well as for more successful engraftment of transplanted internal organs.

Instructions for use

Cyclophosphamide is a drug produced in the form of a white powder. It is intended for intravenous, intramuscular use, and is also placed in the oral cavity. Typically, the drug is used at a dose of 200 or 400 mg every other day orally.

Keep in mind that the course dose for all indications is 6-14 grams. Therapy takes about 2-3 weeks daily or every other day. If fluid has accumulated in the abdominal cavity due to a malignant neoplasm, then Cyclophosphamide is additionally administered into the oral cavity.

Internal administration provides maximum convenience if drug therapy is long-term. Cyclophosphamide has a powerful immunosuppressive effect. The drug acts mainly on lymphocytes. It is because of this that the powder is advisable to use for the treatment of lupus erythematosus, nonspecific aortoarteritis and rheumatoid arthritis.

Keep in mind that such therapy is not carried out if the number of leukocytes does not exceed 3.5 billion/l.

Please note that during treatment with Cyclophosphamide you should regularly check your blood chemistry. If there is a persistent decrease in leukocytes and platelets, then the drug is stopped. If pronounced leukopenia is diagnosed, the patient is given a blood transfusion or blood mass. Additionally, treatment is carried out with hematopoietic stimulants and vitamin complexes.

Contraindications for use

Cyclophosphamide is a fairly powerful drug that has a fairly wide range of limitations. Taking the drug in this case is strictly prohibited.

Contraindications include the following indications:

Hypersensitivity and individual intolerance to components;
Severe bone marrow disorders;
Cystitis;
Active infectious processes.

Cyclophosphamide is contraindicated during pregnancy and breastfeeding.

If therapy with this drug is vital, then the pregnancy is terminated in the first three months. If a woman has a longer period, then she is notified of the presence of a teratogenic effect.

The active components of Cyclophosphamide rapidly penetrate into breast milk and into the baby’s body. For the treatment of children, the current dose of the drug is reduced. Be sure to read the safety instructions before starting treatment.

Side effects

Cyclophosphamide is a drug that often causes side effects. This is due to its powerful action.

Often taking the drug causes the following side effects:

Nausea, vomiting, pain in the stomach;
Decrease in platelet and leukocyte levels;
Itching, redness of the skin, change in nail color, alopecia;
Cardiotoxicity, heart failure;
Interstitial pulmonary fibrosis;
Impaired spermatogenesis, amenorrhea;
Urticaria, anaphylactic shock;
Facial redness, increased sweating, secondary neoplasms.

Overdose

When consuming a large dose of Cyclophosphamide, an overdose of the active substance occurs. To prevent such consequences, you must follow all precautions. Also, do not forget about the recommendations that your doctor gave you.

Please note that Cyclophosphamide does not have an antidote. To stop pathological changes, the patient is indicated for hemodialysis - a blood purification procedure. Gastric lavage has no therapeutic value.

Keep in mind that after an overdose of Cyclophosphamide, the patient experiences suppression of bone marrow functionality. Leukocytopenia often occurs against this background. The extent of the pathological process depends on the severity of the overdose.

To prevent serious complications, it is worth checking the chemical composition of the blood in a timely manner. It is also necessary to do everything possible to prevent the development of neutropenia - constant prevention of infections is required.

For a more positive effect on the body, constant prevention of cystitis is required.

special instructions

To prevent negative consequences after Cyclophosphamide therapy, peripheral blood tests should be performed regularly. During the main therapy, analysis should be performed 2 times a week, during maintenance - 1. If the concentration of leukocytes decreases to 200/μl and platelets to 100,000/μl, therapy should be stopped.

Keep in mind that if Cyclophosphamide is taken in large doses, then uromitexane is prescribed to prevent the development of hemorrhagic cystitis. Also remember to drink as much clean water as possible.

To get rid of non-tumor pathologies, therapy should be carried out extremely carefully. This is especially important if treatment is carried out over a long period of time. During treatment you should completely stop drinking alcoholic beverages.

An anesthesiologist must know about the use of this medicine. Active components affect nerve endings.

Drug interactions

Due to the fact that Cyclophosphamide has a powerful effect on the body, it is worth adhering to a number of specific measures. They will help prevent dangerous consequences from occurring.

Please remember the following:

Cyclophosphamide significantly increases the activity of hypoglycemic drugs;
When cyclophosphamide and allopurinol are taken simultaneously, more pronounced myelodepression occurs;
If you take this medicine together with colchicine, probenecid, sulfinpyrazone, it is necessary to adjust the dose of anti-gout medications;
If you take uricosuric anti-gout medications, the likelihood of developing nephropathy significantly increases;
Rubromycin and Adriamycin significantly increase their cardiotoxicity during such therapy;
Concomitant therapy with cytarabine and cyclophosphamide can lead to cardiomyopathy and even death;
If Cyclophosphamide is taken together with lovastatin, acute necrosis of skeletal muscles and acute renal failure may occur;
Chlorpromazine and tricyclic antidepressants significantly increase the effect of the drug;
There is a potential for additive suppression of bone marrow function during radiation therapy.