Instructions for use cyclophosphane (Cyclophosphan). Cyclophosphus: Instructions for use cyclophosphamide Side effects

Cyclophosphamide (CYCLOPHOSPHAMIDE)

Composition and form of release of the drug

Vials (1) - packs cardboard.
Flakes (5) (for hospitals) - cardboard boxes.
Flakes (10) (for hospitals) - cardboard boxes.
Flakeons (50) (for hospitals) - cardboard boxes.

pharmachologic effect

Antitumor means of alkylating action. It has a cytostatic and immunosuppressive effect. The antitumor effect is implemented directly in the tumor cells, where the cyclophosphamide is biofamidated under the action of phosphatases with the formation of an active metabolite with an alkylating effect.

Pharmacokinetics

After a single in / in administration, the concentration of cyclophosphamide and its metabolites in quickly decreases in the first 24 hours, but can be determined for 72 hours. When taking inside the concentration of cyclophosphamide and its metabolites, almost the same as when in / in administration.

T 1/2 of plasma after a / in administration on average is 7 hours in adults and about 4 hours in children. Displays with urine and bile.

Indications

Contraindications

Cachexia, anemia, leukopenia, thrombocytopenia, heart failure, severe liver disease and / or kidney, pregnancy.

Dosage

Install individually, depending on the testimony and stage of the disease, the state of the blood formation system, the scheme of antitumor therapy.

Side effects

From side digestive system: nausea, vomiting, diarrhea, stomach pain; Rarely toxic hepatitis.

From the hematopopitation system: leukopenia, thrombocytopenia, anemia.

From the respiratory system: for long use High doses - pneumonite or interstitial pulmonary fibrosis.

From side of cardio-vascular system: Tachycardia, shortness of breath, acute myopericiditis; In some cases, there is severe failure (associated with hemorrhagic myocarditis and myocardial necrosis).

From the urinary system: Aseptic hemorrhagic cystitis, nephropathy (associated with hyperuricemia).

From the reproductive system: Violations menstrual cycle, Amenorrhea, azoospermia.

Allergic reactions: , urticaria, anaphylactic reactions.

Others: Alopecia, pain in the muscles and bones, headache.

Medicinal interaction

With the simultaneous use of cyclophosphamide, it may increase the effect of hypoglycemic drugs.

Combined use C can lead to a strengthening of myelotoxicity.

With simultaneous use with indirect anticoagulants It is possible to change the anticoagulant activity (as a rule, cyclophosphamide reduces the synthesis of coagulation factors in the liver and violates the process of platelet formation).

With the combined use of C, double-chip or doxorubicin, an increase in cardiotoxic action is possible.

With compulsified use with immunosuppressants, the risk of infections and secondary tumors increases.

With the simultaneous use of cycloofosphamide with a lovastatin, the risk of developing acute necrosis of skeletal muscles and acute renal failure.

Medicinal products that are inductors of microsomal enzymes cause an increased formation of active cyclophosphamide metabolites, which leads to an increase in its action.

special instructions

Caution is used in patients with gout or nephrolity in history, as well as after adrenaliactomy (correction of replacement hormone therapy and doses of cyclophosphamide).

Caution is used cyclophosphamide in patients with bone marrow patients with tumor cells, as well as in patients who received antitumor chemotherapy or radiation therapy.

In the process of treatment, systematic control of the pattern of peripheral blood is necessary: \u200b\u200bduring the main course 2 times / week; With supporting treatment - 1 time / week. With a decrease in the number of leukocytes to 2500 / μl and platelets to 100,000 / μl, treatment must be stopped.

Against the background of the treatment, hepatic transaminases and LDH are controlled, the level of bilirubin, the concentration of uric acid in the blood plasma, diuresis and the specific urine density, and also conduct tests for the detection of microhematuria.

When using cyclophosphamide in higher doses, with the aim of preventing hemorrhagic cystitis, it is advisable to the destination of the mole.

IN The carcinogenic and mutagenic effect of cyclophosphamide is established.

Pregnancy and lactation

Cyclophosphamide is contraindicated in pregnancy. If necessary, use during the lactation period should be resolved breastfeeding.

Women of childbearing age should apply reliable methods of contraception during therapy.

IN experimental studies The teratogenic and embryotoxic effect of cyclophosphamide has been established.

With violations of the kidney function

Contraindicated in severe kidney diseases.

When violations of the liver function

Contraindicated in severe liver diseases.

"Cyclophosphane" is an alkylating compound. This is a medicinal antitumor agent. Produced as a white or almost such crystalline powder. Next about this product.

"Cyclophosphane" - manufacturer

This medicinal product is manufactured at the Russian enterprise of Biochemistry. It is located in Saransk on Vasamenko Street, 15a.

Cost

In any pharmacy, you can purchase powder No. 1 "Cyclophosfan". Its price hesitates around 90-98 rubles.

Description of the dosage form

A solution is prepared from this powder. It is intended for intramuscular and intravenous administration.

Features of the composition

The composition of each bottle with a powder includes a substance of an active type called "Cyclophosphamide". It is certain. Namely it contains "cyclophosphane" 200 mg of the specified substance in one bottle. In this medicinal remedy there are no auxiliaries.

Description of pharmacological action

Based on the instructions for use, "cyclophosphane" is an alkylating cytostatic preparation. His chemical composition Similar with such substances as nitrogen analogs of the Iprit. pharmachologic effect "Cyclophosphane" lies in the implementation of the formation of cross-type crosslinks between DNA and RNA threads. Also, this drug contributes to inhibiting protein synthesis.

"Cyclophosphane" - analogues

In this case, they select those tools that coincide on the ATX Code of the Fourth category. Quite peculiar is "cyclophosphane". Analogues of this drug exist in a considerable amount. The most common are:

1. "Endocusan."
2. "Iphosfamide."
3. "Alkeran."
4. "Holoksan"
5. "Ribomustine".
6. Lakeran.

The selection of each of these drugs is carried out by the doctor individually. In this case, the state of health and portability of components is taken into account.

In what cases is applied?

Consider this item in more detail. Pretty peculiar is the use of such a drug as "cyclophosphane". Instructions for use in this regard will be an indispensable assistant. It indicates that this medicinal product is shown in the following cases:

1. In case of chronic and acute lympholecosis.
2. With multiple myeloma.
3. When manifest symptoms
4. In the event of mushroom-like Mikosa and Retinoblastoma.
5. In the presence of lymphogranulum, as well as ovarian and chest cancer.
6. When manifest symptoms of neuroblastoma.

In addition to all this, this drug is used in combination with other drug antitumor agents for treatment in the following cases:

1. With germinogenic tumors.
2. For cancer bladder and lung.
3. With sarcoma of soft type tissues.
4. In case of prostate cancer and cervix.
5. With the sarcoma of the Jinga.
6. In the event of the occurrence of Wilms tumors.
7. With a reticulosar.

Also, such a drug as "cyclophosphane", the reviews of which are positive, is effective as a means of immunosuppressive type in the manifestation of progressive autoimmune diseases. In this case, the occurrence of psoriatic and rheumatoid arthritis, autoimmune hemolytic anemia, collagenosis, nephrotic syndrome. Also, the specified means suppresses the reaction of the transplant rejection.

Contraindications

"Cyclophosphane" has certain contraindications. It can not be applied:

1. During a period of breastfeeding and pregnancy.
2. With a pronounced violation of the functions of the bone marrow.
3. In case of manifestation of hypersensitivity.
4. With urination delay.
5. In the presence of active infections.
6. During the manifestation of cystitis.

Caution requires "cyclophospham", the analogues of which are indicated above, assign in certain cases. Namely, if there are the following ailments:

1. Nephloolithiasis.
2. Heavy degree of heart disease, liver and kidney.
3. Gout.
4. Infiltration of bone marrow tumor cells.
5. Adrenalctomy.
6. Inhibition of the functionality of the bone marrow.

Description of side effects

"Cyclophosphus", synonyms (analogs) of which are indicated above, may contribute to the emergence of the following side effects:

Forms of interactions

When taking this drug, some elements that contribute to the liver can carry out the induced process of cyclophosphamide microsomal metabolism. This leads to certain factors. Namely to the large formation of alkylating metabolites. At the same time, the period is reduced for which the semi-anniversary of cycloofosphamide is carried out, and its activity increases. Reception of cycloofosphamide, which noticeably and longly suppresses the activity of cholinesterase, ensures an increase in the action of suucma. It also helps to reduce or slow down cocaine metabolism. As a result, the duration of its effect increases or increases and the risk of its toxic impact increases. This has a negative impact on the body as a whole. In addition, simultaneous use with allopurinol can help enhance the toxic effect on the bone marrow.

With a joint venture of cyclophosphamide with allopurinol, colchicine, probe, sulfintizon, the need for correction of doses of anti-dosing drugs during the treatment of gog and hyperuricemia may occur. In this case, an increase in the risk of nephropathy may appear, which is associated with increased education When using cyclophosphamide.

The latter substance may cause an increase in anticoagulant activity. Since the synthesis of factors contributing to blood coagulation and violation of platelets is reduced in the liver. However, a decrease in the activity of anticoagulants can occur through the mechanism of the unknown type.

Cyclophosphamide helps to enhance the cardiotoxic action of a downoworubicin and doxorubicin. Other immunosuppressants (chlorambucil, azathioprine, cyclosporine, glucocorticosteroids, mercaptopurin, etc.) can increase the possibility of the development of secondary tumors and infections.

The simultaneous use of lovastatin in patients with cardiac transplantation can increase the risk of diseases such as acute skeletal muscle necrosis and renal acute insufficiency.

If, in combination with this drug, myelosuppressive drugs or radiation therapy are used, then the adductive oppression of bone marrow functions is possible.

Simultaneous reception of cytarabin in large doses with a substance such as cyclophosphamide, at the preparatory stage to the transplantation process of bone marrow leads to a frequency increase in cardiomyopathy with the onset of death.

Main criteria

The process takes into account the following:

Precautionary measures

The reception of this drug is possible exclusively under the supervision of the doctor who has experience in chemotherapy. It is also necessary to observe the dosage mode. This should be especially carried out in combination therapy. Also, no need to double the next dose, if the previous one was missed. In the preparation of this drug, it is categorically not recommended to use diluents that contain benzyl alcohol. Since this can lead to the development of toxic lethal syndrome. Namely to the emergence of the oppression of the central nervous system, impaired respiration, renal failure, hypotension, convulsion, intracranial hemorrhage.

During the whole therapeutic course, it is recommended to conduct (for a week 1 time 100-125 ml). It is necessary to do this in order to implement the prevention of diseases such as hyperuricemia and nephropathy, which is due to the formation of an increased amount of uric acid. Such symptoms are quite often manifested at the beginning of the treatment period. Also before carrying out therapy with the specified drug and during 72 hours after its reception, it is recommended to carry out a certain use of liquid (about 3 liters per day), the use of allopurinol (in special cases) and the means that basic urine. To prevent the manifestations of hemorrhagic cystitis, it is often necessary to empty the bladder and take the "urometexane". If the initial signs of this disease appeared, then the medical course of the specified drug should be terminated until the symptoms have emerged.

To reduce the phenomena of the dyspeptic type, the cyclophosphamide can be taken during the first day in small doses. Full or partial alopecia, which can be observed during the treatment period, is reversible and after the course graduation is restored to the function of normal hair growth. However, their color and structure may be subject to change.

In the occurrence of chills, fever, cough or hoarseness, pain in the lower area of \u200b\u200bthe back or in the side, painful or difficult urination, hemorrhage or bleeding, black chair, blood in feces or urine must be immediately consulted by the doctor.

The possibility of thrombocytopenia leads to the need for special caution in conducting such actions as invasive procedures and dental interventions. At the same time, it should be regularly inspecting the skin and mucous membranes and places intravenous administrations. This is to identify signs of bleeding. It is also necessary to limit the frequency of venopunctions and refuse intramuscular injections. The blood content should be monitored in feces, vomit masses, urine. These patients are extremely careful necessary to carry out the shave process, manicure, teeth cleaning, toothpicks, etc. At the same time, it is categorically avoided by dropments and other damage. Also forbidden reception acetylsalicylic acid and alcohol, which increase the risk of occurrence in this case, it is necessary to delay the vaccination schedule (after 3-12 months from the end of the last chemotherapeutic course). It is desirable to eliminate contact with infectious patients. During the period of treatment it is necessary to apply adequate contraceptive measures.

When contacting the specified drug with mucous membrane or leather, it is necessary to thoroughly rinse this section with simple water or with soap, respectively.

When breastfeeding and pregnancy

In this regard, there are peculiar limitations that "cyclophosphane". The instruction indicates that the use of this drug during pregnancy is contraindicated. In this case, the category of impact on the fruit is denoted by "D" by FDA. For the period of treatment, it is necessary to stop conducting breastfeeding.

Overdose

In this case, there are certain nuances. The presence of a specific antidote in overdose of the specified drug is unknown. This is a reliable fact. In case of overdose, it is necessary to apply supporting measures, including the corresponding course of treatment. infectious diseases, as well as cardiotoxicity and / or myelosuppression.

Storage conditions

In this regard, it requires certain conditions such a drug as "cyclophosphane". The instructions for use says that it is necessary to store it at a temperature of not more than 10 ° C in a place that is dry and protected from light. At the same time, the access of children to it should be limited.

Shelf life

There is a certain period of time during which this drug can be used as "cyclophosphane". The application instruction indicates that its suitability is 3 years. In this case, a certain condition should be followed. It lies in the fact that it is strictly forbidden to use this drug After the expiration of the specified period.

Sales

In this direction, there is also a condition that has a "cyclophosphane". Instructions for use indicates that this drug is released in pharmacies only by a doctor's prescription.

Conclusion

This text has a lot useful information. Namely, what is "cyclophosphane", instructions for use, the price of this drug. However, it should be taken into account that before applying this drug, it is necessary to consult with a qualified physician.

Structure

Each bottle contains: active substance: cyclophosphamide - 200 mg.

Description

white or almost white crystalline powder.

pharmachologic effect

The antitumor means of alkylating action, according to the chemical structure is close to nitrogen analogues of the iprite. It has a cytostatic and immunosuppressive effect. It is an inactive transport form that decides under the action of phosphatases with the formation of the active component directly in the tumor cells, "attacks" nucleophilic centers of protein molecules, disrupts the synthesis of DNA and RNA, blocks mitotic division.

Indications for use

Leukemia: sharp or chronic lymphoblastic / lymphocyte and myeloid / myelogenic leukemia;

Malignant lymphomas, Hodgkin's disease (lymphogranulomatosis), non-Hodgkinsky lymphoma, plasmocyte;

Large malignant tumors With the presence of metastasis or without them: ovarian cancer, egg cancer, breast cancer, small-cell lung cancer, neuroblastoma, sarcoma of the Jinga, Rabdomiosarcoma in children, osteosarcoma;

Progressive autoimmune diseases»: rheumatoid arthritis, Psoriatic arthropathy, systemic red lupus, sclerodermia, systemic vasculitis (for example, with nephrotic syndrome), certain types of glomerulonephritis (for example, nephrotic syndrome), Miastic gravis, autoimmune hemolytic anemia, Cold agglutinin disease, venener granulomatosis.

Cycllorophosphane is also used as a means of suppressing immunity when organ transplantation and for air conditioning before the bone marrow transplantation with severe aplastic anemia, acute myeloid and acute lymphoblastic leukemia, chronic myeloid leukemia.

Method of application and dose

Application is possible only under the supervision of a physician who has experience in chemotherapy.

Cyclophosphane is introduced intravenously in the form of infusion, intramuscularly. Cyclophosphamide is part of many chemotherapeutic treatment schemes, in connection with which, when choosing a specific way of administration, regime and doses in each iN.didnote the case should be guided by the data of special literature.

Dosage should be selected individually for each patient.

The following dosage recommendations can be used for monotherapy with cyclophosphamide. With the joint appointment of other cytostatics of similar toxicity, a decrease in dose or an increase in the pause during treatment with the drug may be needed.

For continuous treatment of adults and children - from 3 to 6 mg / kg body weight, daily (equivalently from 120 to 240 mg / m 2 of the body surface area);

For intermittent treatment of adults and children - from 10 to 15 mg / kg body weight (equivalent to 400 to 600 mg / m 2 of the body surface area), at intervals from 2 to 5 days;

For intermittent treatment of adults and high dose - from 20 to 40 mg / kg body weight (equivalent to 800 to 1600 mg / m 2 area of \u200b\u200bbody surface), or with an even greater dose (for example, with air conditioning before the bone marrow transplant), with Intervals from 21 to 28 days. .

Preparation of solution

Immediately before applying to the contents of a bottle with a dosage of 200 mg, 10 ml of 0.9% sodium chloride solution is added. The substance is easily dissolved with energetic shaking after adding the solvent. If the substance does not dissolve immediately and completely, it is recommended to give a bottle to stand for a few minutes. The solution is suitable for intravenous applicationIt is better to produce an introduction in the form of intravenous infusion. With a short-term administration, the cyclophosphane solution is added to a ringer solution, a 0.9% solution of chloride sodium or 5% declaration solution to a total volume of approximately 500 ml. The duration of infusion is from 30 minutes to 2 hours, depending on the volume.

Medical cycles during intermittent therapy can be repeated every 3-4 weeks. The duration of therapy and intervals between courses depend on the indications used by the combination of chemotherapeutic drugs, general status Patient health, laboratory indicators and recovery of the number of blood shaped blood elements.

Leukocytes\u003e 4000 μl, and platelets\u003e 100,000 μl - 100% of the scheduled dose

Leukocytes 4000-2500 μl, and platelets 100,000-50000 μl - 50% dose of leukocytes<2500 мкл, а тромбоцитов <50000 мкл - подбор дозы до нормализации

indicators or acceptance of a separate decision.

Application in combination with other substances depressing blood formation requires a dose correction. The corresponding doses of cytotoxic drug regulation should be used on the quantitative composition of blood formation elements at the beginning of the cycle and the dose adjustment behind the low level of cytostatic substances. Recommendations for the selection of dose patients with hepatic insufficiency Heavy liver failure requires a dose reduction. The general recommendation is a reduction in the dose by 25% when the bilirubin content is from 3.1 to 5 mg / 100ml. .

Recommendations for the selection of dose to patients with renal failure A reduction in the dose by 50% is recommended at a level of glomerular filtration at a level of less than 10 ml / min. Cyclophosphamide can be removed from the body using dialysis. Children and teenagers

Dosage - according to the adopted treatment plan; Recommendations for the selection of the dose and the use of the drug in children and adolescents are the same as for adult patients. Elderly patients and physically weakened patients In general, given the increased frequency of cases of reduction of hepatic, renal or cardiac function, as well as the presence of concomitant diseases and the use of other drug therapy, the selection of the dose for this group of patients should be carried out with caution.

Side effect

In patients who receive cyclophosphamph, depending on the dosage, the following adverse reactions may occur, in most cases being reversible.

Infections and invasion. Usually, severe bone marrow oppression can lead to agranulocytic fever and secondary infections like pneumonia, may be progressing in sepsis (infections, threatening life), which in some cases may end themselves.

From the immune system. It is rare to have a reaction of hypersensitivity, accompanied by rash, chills, fever, tachycardia, bronchospasm, shortness of breath, swelling, blood flow and decrease in blood pressure. In rare cases, anaphylactoid reactions can progress to anaphylactic shock.

From the blood system and lymphatic system. Depending on the dosage, various forms of bone marrow oppression, such as leukopenia, neutropenia, thrombocytopenia with increased risk of bleeding and anemia can be occurring. It should be borne in mind that the heavy inhibition of bone marrow can lead to agranulocytic fever and the development of secondary (sometimes threatening life) infections. The minimum number of leukocytes and platelets is usually noted during the 1st and 2nd week of treatment. The bone marrow is restored relatively quickly, and the blood pattern is normalized, as a rule,

20 days after the start of treatment. Anemia can usually develop only after several treatment cycles. The most severe oppression of the bone marrow function should be expected in patients who were treated with chemical and / or radiation therapy, as well as in patients with renal failure.

Simultaneous treatment with other substances depressing blood formation requires a dose correction. The corresponding doses control tables should be used for cytotoxicity of drugs on the quantitative composition of blood at the beginning of the treatment cycle and dosing adjustment by low levels of cytostatic substances. From the nervous system. In rare cases, neurotoxic reactions were reported, such as paresthesia, peripheral neuropathy, polyneuropathy, as well as neuropathic pain, violation of taste and convulsions.

From the digestive tract. Such adverse reactions as nausea and vomiting are very frequent and depend on the dose. The average and severe forms of their manifestations are noted about 50% of patients. Anorexia, diarrhea, constipation and inflammation of mucous membranes from stomatitis to the formation of ulcers are marked with a lower frequency. In some cases, hemorrhagic colitis was reported, acute pancreatitis. In some cases, gastrointestinal bleeding has been reported. In case of nausea and vomiting, dehydration can sometimes develop. It has been reported on isolated cases of abdominal pain due to gastrointestinal disorders.

From the digestive system. It was rarely reported on the violation of the liver function (raising the level of serum transaminases, gammagludytranspend of transpeptidase, alkaline phosphatase, bilirubin).

Obricultural hepatic vein endophore was noted about 15-50% of patients who received high doses of cyclophosphamide in combination with beupulon or irradiation of the entire body with allogenic bone marrow transplantation. But on the contrary, this complication was noted in patients with aplastic anemia that received only high doses of cyclophosphane. Syndrome is usually developing in 1-3 weeks after transplantation and is manifested by a sharp increase in body weight, hepatomegaly, ascites and hyperbilirubinemia and portal hypertension. Hepatic encephalopathy can develop very rarely. Famous risk factors that contribute to the development of refrigerant veins in the patient, is the presence of a liver function, hepatotoxic drug therapy in combination with high doses chemotherapy, and especially if an element of co-induced therapy is an alkylating bursulfan compound.

From the side of the kidneys and the urinary system. After the isolation in the urine, the cyclophosphamide metabolites cause changes in the urinary system, namely in the urinary bubble. Hemorrhagic cystitis, microhematuria and macrohematuria are the most common dose-dependent complications in the treatment of cyclophosphane and require cancellation of therapy. Cystitis are developing very often, first they are sterile, but secondary infection may occur. Also marked swelling of the bladder walls, bleeding from the cell layer, interstitial inflammation with fibrosis, and sometimes - sclerosis of the bladder. Kidney dysfunction (especially in cases of violation of the kidney function in history) is an unclean side reaction when used in high doses. Treatment of urometexane or abundant drinking can reduce the frequency and severity of uroboxic adverse reactions.

In some cases, hemorrhagic cystitis with fatal outcome was reported. Outragia or chronic renal failure, toxic nephropathy, especially in patients with a reduced kidney function in history can be occurring.

From the reproductive system. Through the ankylistering effect, cyclophosphamide rarely cause a spermatogenesis (sometimes irreversible) and lead to azoospermia and / or permanent oligospermia. Rarely noted disorders of ovulation. In some cases, amenorrhea was reported and reducing the level of female sex hormones.

From the side of the cardiovascular system. Cardiotoxicity from minor changes in blood pressure, changes in ECG, arrhythmia, to secondary cardiomyopathy with a reduced function of the left ventricle and heart failure, which in some cases can cause a fatal outcome. Clinical symptoms of cardiotoxicity can manifest, for example, in the form of pain in the chest and the attacks of angina. Sometimes it was reported on the ventricular sucanementaricular arrhythmia. Very rarely, with cyclophosphane therapy, atrial or ventricular fibrillation can develop, as well as a heart stop. In very rare cases, myocardis reported, pericade and myocardial infarction. Cardiotoxicity is particularly enhanced after the use of a drug in high doses (120-240 mg / kg of body weight) and / or when it is combined with its use with other cardiotoxic drugs, for example, anthracycline or pentostatin. Strengthening of cardiotoxicity can also occur after the preliminary radiotherapy of the heart area.

From the side of the respiratory. Bronchospasm, shortness of breath or cough, which leads to hypoxia. Endoflects lungs may very rarely develop, sometimes as complications of lung fibrosis. It was very rarely reported on the toxic edema of lungs, pulmonary hypertension, lungs and pleural effusion. In some cases

pneumonite and interstitial pneumonia, passing into chronic interstitial pneumophibrosis, and respiratory distress syndrome and respiratory failure with death can also be developed. Benign and malignant neoplasms (including cysts and polyps). As always, with cytostatic treatment, the use of cyclophosphane is accompanied by the risk of developing secondary tumors and their predecessors as late complications. The risk of developing the urinary tract cancer, as well as myelodsplastic changes, partially mightble progress in sharp leukemia. Studies on animals have shown that the threat of a bladder cancer can be significantly reduced by appropriate use of Uromitexane. In rare cases, the tumor decay syndrome was reported due to a rapid response of large tumor sensitive to chemotherapy.

From the side of the skin and its derivatives / allergic reactions. The focal alopecia, which is a frequent side reaction (can progress to full baldness), wears, as a rule, is reversible. It has been reported on cases of changing the pigmentation of the skin of palms, nails and fingers, as well as the sole; dermatitis, expressed by inflammation of the skin and mucous membranes. Eritrozesty syndrome (feeling of tingling in palms and soles, to severe pain). Very rarely, after radiation therapy and subsequent treatment with cyclophosphamide reported general irritation and erythema on the irradiated area (radial dermatitis). In isolated cases - Stevens-Johnson syndrome and toxic epidermal necroliza, fever, shock.

On the side of the musculoskeletal system and connective tissue. Muscular weakness, rhabdomiolysis.

From the endocrine system and metabolism. Very rarely - SNSAG (inadequate secretion syndrome ADG), Schwartz-barter syndrome with hyponatremia and a delay in the removal of fluid, as well as the corresponding symptoms (confusion of consciousness, convulsions). In some cases, anorexia was reported, rarely on dehydration and very rarely - on the delay in the withdrawal of fluid and hyponatremia.

From the authorities of vision. Worsening vision. Due to the reaction of increased sensitivity, such symptoms as conjunctivitis and swelling of the eyelid were very rarely reported.

Vascular disorders. The main disease can cause certain very rare complications, such as thromboembolism and peripheral ischemia, DVS or hemolytic uremic syndrome, the frequency of these complications may increase in cyclophosphamide chemotherapy.

General disorders. Fever in the treatment of cyclophosphane is a very frequent adverse reaction in the development of hypersensitivity and neutropenia (associated with infection). Asthenic states, malaise - frequent complications in oncological patients. Very rarely as a result of extravasation, reactions in the place of administration of the drug in the form of erythema, inflammation or phlebitis can be observed. Overdose

Since no specific antidote cyclophosphamide is unknown, it should be particularly careful when applied. Cycloofosphamide can be removed from the body using dialysis, therefore, during overdose, fast hemodialysis is shown. Clearance of dialysis 78 ml / min was calculated by the cyclophosphamide concentration, was not metabolized in dialysis (normal kidney clearance is approximately 5-11 ml / min). Other sources report 194 ml / min. After 6:00 dialysis, 72% of the entered dose of cyclophosphamide was found in dialyzate. With overdose, among other reactions, it should be assumed to oppress the function of the bone marrow, more often than leukopenia. The severity and duration of the oppression of the functions of the bone marrow depends on the degree of overdose. Careful control of blood indicators and patient states are needed. When developing neutropenia follows

take measures to prevent infections, infections should be treated with the help of appropriate antibiotics. When thrombocytopenia occurs, platelet replenishment should be ensured. In order to prevent uroboxic phenomena, it is necessary to take measures to prevent cystitis using uromitexane. Contraindications

Well-known increased sensitivity to cyclophosphamid;

Severe disorders of the bone marrow function (especially in patients who have been treated with cytotoxic drugs and / or radiotherapy);

Bladder inflammation (cystitis);

Urination delay;

Active infections.

Interaction with other medicines

Enhances the action of suxamerase (long-term suppression of the activity of cholinesterase), reduces or slows down cocaine metabolism, reinforcing and / or increasing its duration of its action, increasing the risk of toxicity. The cyclophosphamide suppresses the activity of cholinesterase than the potential effect of acetylcholine. Enhances the cardiotoxic effect of doxorubicin and downorubicin. The inductors of the microsomal oxidation of the liver increase the formation of alkylating metabolites of cyclophosphamphamide, reduce the period of its semi-exploration and enhance its activity. Myelotoxic drugs, incl. Allopurinol, radiation therapy causes an increase in the myelotoxic effect of cyclophosphosphamide. Uricosuric drugs raise the risk of nephropathy (may

requires the dose correction of uricosuric JTC). Grapefruit juice disrupts activation and thereby the action of cyclophosphamide. Other immunosuppressants (including azathioprine, chlorambucil, glucocorticosteroids, cyclosporine, mercaptopurine) increase the risk of developing infections and secondary tumors. The simultaneous reception of lovastatin in patients with heart transplantation increases the risk of acute necrosis of skeletal muscles and acute renal failure. Simultaneous reception of cytarabina in high doses in preparation for bone marrow transplantation leads to an increase in the frequency of cardiomyopathy, followed by lethal.

Features of application

When using cyclophosphane and preparation of the solution, it is necessary to follow the safety regulations when working with cytotoxic substances.

Impact on the ability to control vehicles and other potentially hazardous mechanisms. During treatment with the drug, it is necessary to refrain from class activities requiring increased concentration of attention. Features of application.

Apply only for appointment and under the control of the doctor!

Before starting treatment, it is necessary to eliminate possible obstacles to the imagination of urinary tract, violation of the electrolyte balance, sanitize possible infections (cystitis).

From the blood system and lymphatic system. It should be expected to be a serious oppression of the functions of the bone marrow, especially in patients who were treated with chemical and / or radiotherapy, as well as in patients with disturbed kidney function. Therefore, for all patients, permanent hematological control with regular counting of uniform elements is shown during treatment. The calculation of leukocytes and platelets and the determination of the hemoglobin content should be carried out before each administration of the drug, as well as at certain intervals. In the process of treatment, it is necessary to systematically monitor the number of leukocytes: with initial treatment - with an interval of 5-7 days, if their number is reduced to<3000 в мм 3 , то раз в два дня или ежедневно. При длительном лечении обычно достаточно проводить анализ крови раз в две недели. Без крайней необходимости Циклофосфан

it is impossible to prescribe to patients with an amount of leukocytes less than 2500 / μl and / or platelet numbers less than 50,000 / μl. In the case of agranulocytic fever and / or leukopenia, antibiotics and / or antifungal drugs should be prescribed prophylactically. It should be regularly analyzed by the urinary residue on the content of erythrocytes.

From the immune system. Patients with a weakened immune system, for example, patients with diabetes, chronic renal or hepatic

insecurity also require special care. Cyclophosphane, like other cytostatics, should be used with caution in the treatment of weakened patients and elderly patients, as well as after radiotherapy.

From the kidney and the urinary system. Before starting treatment, attention should be paid to the state of the urinary system.

Appropriate treatment with uroprotector Uromitexane, as well as the reception of a sufficient amount of fluid, can significantly reduce the frequency and severity of the effect of the drug. It is important to reveal the urinary bladder release.

If the treatment with micro or macrohematuria is observed in the treatment of cyclophosphane, the treatment with the drug should be terminated until the state normalization. Patients with kidney diseases in the treatment of cyclophosphane require careful care.

Cardial disorders. There is evidence of the gain of the cardiotoxic effect of cyclophosphane in patients after pre-radiotherapy of the heart and / or concomitant treatment with anthraciklines or pentostatin. It should be remembered about the need for regular inspections of the electrolyte composition of blood, pay special attention to patients with heart disease in history.

GTS. To reduce the frequency and severity of such effects as nausea and vomiting, it is necessary for the purpose of prevention to prescribe antiwest drugs. Alcohol can enhance these side effects, therefore, patients who receive treatment with cyclophosphane should be recommended to refuse to receive alcohol.

To reduce the frequency of stomatitis, attention should be paid attention to the oral hygiene.

From the digestive system. Apply the drug for the treatment of patients with impaired liver function should only after a thorough estimate in each case. Such patients need careful care. Alcohol abuse can increase the risk of liver dysfunction.

Reproductive system disorders / genetic disorders. Cyclophosphane treatment can cause genetic anomalies in men and women. Therefore, during the treatment and within six months after its end, pregnancy should be avoided. During this time, sexual men and women need to use effective methods of contraception.

In men, treatment can increase the risk of developing irreversible infertility, so it. It should be reported about the need to preserve sperm before the start of treatment.

General disorders / disorders at the place of administration. Since the cytostatic effect of cycloofosphane is after its bioactivation, which occurs in the liver, the risk of damage to the tissues with an unintentional instrumental administration of the drug solution is insignificant.

In patients with diabetes mellitus, it is necessary to regularly check blood sugar levels in order to adjust the anti-diabetic therapy in time.

Precautions

During the treatment period, it is necessary to carefully observe the patient's condition due to the possibility of the appearance of toxic effects in any of the listed states: leukopenia, thrombocytopenia, bone marrow infiltration with tumor cells, previously conducted radiation or chemotherapy, renal / hepatic insufficiency.

During the main course of treatment, it is necessary to control 2 times a week the overall picture of blood (especially the number of neutrophils and platelets) to assess the degree of myelosuppression), with supporting therapy 1 time per week, as well as urine analysis for the presence of red blood cell, which can precede the development of hemorrhagic cystitis. When symptoms of cystitis with micro or macrohematuria appear, as well as with a decrease in the number of leukocytes to 2500 / μl and / or platelets to 100 thousand / μl, the treatment should be discontinued.

In the event of infections, treatment must be interrupted or should be reduced to the dose of the drug.

Women and men during treatment should use reliable methods of contraception.

During the period of treatment, it is necessary to refrain from taking ethanol, as well as from grapefruit eating (including juice).

When the cyclophosphane is appointed during the first 10 days after surgery with the use of general anesthesia, it is necessary to inform the anesthesiologist. After adrenalectomy, it is necessary to correct the doses of both glucocorticosteroids (as substitutionary therapy) and cyclophosphane. It can increase anticoagulant activity as a result of a decrease in the synthesis in the liver of coagulation factors and violations of platelets, as well as as a result of an unknown mechanism.

For the prevention of hemorrhagic cystitis, it is recommended to assign an adequate amount of liquid and uroprotectors (messenger). Hematuria usually stops a few days after the end of treatment with cyclophosphane. With severe forms of hemorrhagic cystitis, it is necessary to cancel cyclophosphane.

According to ECG and echo-kg in patients undergoing the episodes of the cardiotoxic effects of high doses of cyclophosphane, no residual phenomena was detected by myocardial.

Girls, as a result of treatment with cyclophosphamph in a prepubertal period, secondary sexual signs developed normally and menstruation were normal; Subsequently, they were capable of conception. The sexual attraction and the potency in men is not disturbed. In boys, during treatment with the drug in the prepubertal period, the secondary sexual signs developed normally, however, oligo-or azoospermia can be marked and increased gonadotropin secretion.

After a previously conducted treatment, the drug may occur with secondary malignant tumors, most often it is a bladder tumor (usually

patients with hemorrhagic cystitis in history), myelos or lymphoproliferative diseases. Secondary tumors most often developed in patients as a result of the treatment of primary myeloproliferative malignant or non-malignant diseases in violation of immune processes. In some cases, secondary tumors are developing several years after discontinuation of treatment.

Storage conditions

In the place protected from light at a temperature not higher than 25 ° C.

Keep out of the reach of children.

Registration number: P N001579 / 01-140808

Trade name of the drug: Cyclophosfan

International UnPatented Name (MNN): cyclophosphamide

Dosage form: Powder for the preparation of a solution for intravenous and intramuscular administration

Structure: Each Powder bottle contains
Active substance: cyclophosphamide 200 mg
Excipients: not

Description: White or almost white crystalline powder.

Pharmacotherapeutic group: antitumor agent, alkylating connection.
ATX code L01AA01.

Pharmacological properties
Pharmacodynamics
Cycloofosphamide is an alkylating cytostatic drug, chemically close to nitrogen analogues of iprite.
It is assumed that the mechanism of action includes the formation of transverse strokes between DNA and RNA threads, as well as inhibition of protein synthesis.

Pharmacokinetics
Cycllorophosphamide is metabolized mainly in the liver under the action of a microsomal oxidase system, forming active alkylating metabolites (4-cyclophosphamide and adradophosphamide), some of which are subjected to further transformation to inactive metabolites, part is transported into cells where phosphatas are influenced into metabolites with a cytotoxic effect. . The concentration of metabolites reaches a maximum in a plasma 2-3 hours after intravenous administration. The connection of the unchanged preparation with blood plasma proteins is insignificant (12-14%), but some metabolites are binding to more than 60%. Through the hemat andphalic barrier penetrates a limited extent.
The cyclophosphamide is excreted from the body by kidneys mainly in the form of metabolites, however, from 5 to 25% of the administered dose is distinguished with urine unchanged, as well as with biliary. The half-life is 3-12 hours.

Indications for use
Acute lymphoblastic and chronic lympholoicosis, lymphogranulomatosis, non-Hodgkinsky lymphoma, multiple myeloma, breast cancer, ovaries, neuroblastoma, retinoblastoma, mushroom micaosis. Cycllorophosphamide is also used in combination with other antitumor drugs for the treatment of lung cancer, germinogenic tumors, cervical cancer, bladder cancer, soft tissue cancer, reticulosarcomers, sarcoma of the Jinga, Wilms Tumors, prostate cancer.
As an immunosuppressive means, cyclophosphamide is used in progressive autoimmune diseases (rheumatoid arthritis, psoriatic arthritis, collagenoses, autoimmune hemolytic anemia, nephrotic syndrome) and to suppress the transplant reaction reaction.

Contraindications

• Increased sensitivity to cyclophosphamid or any other component of the dosage form.
• A pronounced violation of the bone marrow function.
• Cystitis.
• Urination delay.
• Pregnancy and breastfeeding period.
• Active infections.

Carefully : With severe heart disease, liver and kidney, adrenalectomy, gout (in history), nephroolithiasis, inhibition of bone marrow function, bone marrow infiltration with tumor cells preceding radiation or chemotherapy.

Method of application and dose
Cyclophosphane is introduced intravenously in the form of infusion, intramuscularly.
The cyclophosphamide is part of many chemotherapeutic treatment schemes, and therefore, when choosing a specific route of administration, regime and doses in each individual case, the data of special literature should be guided.
The most frequently used doses and modes for adults and children:
50-100 mg / m 2 daily within 2-3 weeks,
100-200 mg / m 2 2 or 3 times a week for 3-4 weeks,
600-750 mg / m 2 1 time in 2 weeks,
1500-2000 mg / m 2 1 time at 3-4 weeks before the total dose - 6-14 g.
When using cyclophosphane in combination with other antitumor drugs, a dose is reduced both cyclophosphane and other drugs.
Preparation of solution
To prepare a solution for injection to dry substance in the vial, a corresponding amount of 0.9% sodium solution of chloride is added, as indicated in the table:

After adding a solvent, the vial is intensively shaken in order to complete the dissolution of the drug. If fast and complete dissolution is not achieved, you should leave the bottle to stand for several minutes.
For. Preparation of the solution for infusions to the obtained solution of the drug cyclofosphus add a solution of ringer, 0.9% solution of sodium chloride or declaration solution so that the total fluid volume is about 500 ml.

Side effects
From the hematopoietic system: leukopenia, neutropenia; Rarely, thrombocytopenia, anemia. The greatest decrease in the number of leukocytes and platelets is usually observed on the 7-14 day of treatment. Recovery during leukopenia usually begins 7-10 days after discontinuation of treatment with the drug.
From the digestive system: nausea, vomiting, anorexia, less often stomatitis, discomfort or abdominal area, diarrhea or constipation, there are separate reports on the development of hemorrhagic colitis, jaundice.
Rare cases of violation of the liver function were noted, manifested by an increase in transaminase activity, alkaline phosphatase and bilirubin content in serum. In 15-50% of patients receiving high, doses of cyclophosphamide in combination with beupulon and. Total irradiation during allogeneic bone marrow transplantation develops obliterating endoflebitis of hepatic veins. A similar reaction in very rare cases is also observed in patients receiving high doses of one cyclophosphamide in patients with aplastic anemia. This syndrome is usually developing in 1-3 weeks after bone marrow transplantation and is characterized by a sharp increase in body weight, hepatomegaly, ascites and hyperbilirubinemia.
Hepatic encephalopathy can also be observed.
From the skin and skin appendages: Alopecia is often developing. The hair rustling begins after the preparation is completed or even during prolonged treatment; Hair may differ in their structure and color. Sometimes during the treatment, rash appears on the skin, skin pigmentation and nail changes.
From the urinary system: Hemorrhagic urethritis / cystitis, necrosis of renal tubules (up to death), bladder fibrosis (incl. Common) with or without cystitis. Atypical urinary bubble epithelial cells can be detected in the urine.
When the high doses of cyclophosphamide is prescribed, in rare cases, there may be a violation of the kidney function, hyperuricemia, nephropathy associated with increased formation of uric acid.
Infection: In patients with severe forms of immunosuppression, serious infections may develop.
From the cardiovascular system: Cardiotoxicity was observed with the introduction of high doses of 4.5-10 g / m 2 (120 to 270 mg / kg) of the drug for several days, usually as part of intensive combined antitumor or drug therapy during organ transplantation. At the same time, severe and sometimes reduced episodes of congestive heart failure, due to hemorrhagic myocarditis, were observed.
From the respiratory system: interstitial pulmonary fibrosis (with the introduction of high doses of the drug for a long time).
From the reproductive system: Disruption of oogenesis and spermatogenesis. The drug may cause sterility both in men and in women, which in some cases may have an irreversible character.
Amenorrhea has a significant part of women, regular menstruation is usually restored for several months after discontinuation of treatment. In girls, as a result of treatment with cyclophosphamide during a prepubertal period, secondary sexual signs developed normally and menstruation were normal; Subsequently, they were capable of conception.
In men, as a result of treatment with drug, oligospermia or azoospermia can develop, associated with an increase in the level of gonadotropin at normal secretion of testosterone. The sexual attraction and potency in such patients is not violated. For boys, during treatment with a preparation in a prepubertal period, secondary sex, signs are developing normally, however, oligospermia or azoospermia and increased secretion of gonadotropins can be marked. Atrophy of the testicles of various degrees may be celebrated. In some patients, azoospermia caused by the drug has a reversible nature, however, the restoration of the disturbed function can occur only a few years after the cessation of treatment.
Allergic reactions: skin rash, urticaria, itching of the skin, rarelyanofilact reactions; Cross sensitivity is possible with other alkylating compounds.
Others: syndrome similar to the syndrome of inadequate secretion of antidiuretic hormone (ADG); Blood tides to face skin or face hyperemia, headache, high sweating; Development of secondary malignant tumors.

Overdose
Specific antidot for overdose of the drug is unknown. In cases of overdose, supporting measures should be used, including the corresponding treatment of infections, manifestations of myelosuppression and / or cardiotoxicity.

Interaction with other drugs and other forms of interaction
Inductors of microsomal oxidation in the liver can induce the microsomal metabolism of cyclophosphamide, which leads to an increased formation of alkylating metabolites, thereby reducing the period of semi-anniversary of cyclophosphamide and increasing its activity. The use of cyclophosphamide, causing a noticeable and long-term suppression of the activity of cholinesterase, enhances the effect of suxametononia, and also reduces or slows down the cocaine metabolism, thereby reinforcing and / or increasing the duration of its effect and increasing the risk of toxic effect. With simultaneous use with allopurinol, a toxic effect on the bone marrow may be enhanced. With the simultaneous use of cyclophosphamide and allopurinol, colchicine, probe, sulfinpyrazone, it may be necessary to correct the doses of oppression drugs in the treatment of hyperuricemia and gout; The use of uricosuric oppression drugs may increase the risk of nephropathy associated with the increased formation of uric acid when using cyclophosphamide.
Cyclophosphamide can increase anticoagulant activity as a result of a reduction in the synthesis of blood coagulation factors and platelet impaired, but can also reduce the activity of anticoagulants through an unknown mechanism. Since grapefruit contains a compound that can violate the activation of cyclophosphamide and thereby its action, patients are not recommended to eat grapefruit or drinking grapefruit juice.
Cycloofosphamide enhances the cardiotoxic effect of doxorubicin and downorubicin. Other immunosuppressants (azatioprine, chlorambucil, glucocorticosteroids, cyclosporine, mercaptopurine, etc.) increase the risk of developing infections and secondary tumors.
With the simultaneous application of lovastatin in patients with heart transplantation, it is possible to increase the risk of acute necrosis of skeletal muscles and acute renal failure.
In combination with other myelosuppressive drugs or radiation therapy, the additive oppression of the bone marrow function is possible.
The simultaneous use of cycloofosphamide cyclubabine with cyclophosphamide during the preparation for bone marrow transplantation led to an increase in the frequency of cardiomyopathy, followed by fatal.

special instructions
During treatment with the drug, it is necessary to regularly carry out blood test (especially paying attention to the content of neutrophils and platelets) to assess the degree of myelosuppression, and regularly conduct urine analysis for the presence of erythrocytes, the appearance of which can precede the development of hemorrhagic cystitis.
When signs of cystitis with micro or macrohematuria, the treatment with cyclophosphane should be discontinued.
With a decrease in the number of leukocytes< 2500/мкл и/или тромбоцитов < 100000/мкл лечение Циклофосфаном следует прекратить.
In the event of infections in the process of cyclophosphamfin therapy, treatment must be either interrupted, or a dose of the drug should be reduced. Women and men during treatment with cyclophosphane should use reliable methods of contraception.
During the treatment period, it is necessary to refrain from the reception of alcoholic beverages. If during the first ten days after an operation conducted under general anesthesia, the patient is prescribed cyclophosphane, it is necessary to inform the anesthesiologist about it.
The patient after adrenaliactomy is necessary to adjust the doses of both glucocorticosteroids used for substitution therapy and the drug cyclophosphane.

Form release
Powder for preparing a solution for intravenous and intramuscular administration in bottles of 200 mg.
By 1; 5 or 10 bottles in a pack with instructions for medical use.
50 bottles are placed in boxes with an attachment from 3 to 5 medical instructions (for hospitals).

Storage conditions
List A. In the dry, protected from light, inaccessible for children, at a temperature not higher than 10 ° C.

Shelf life
3 years.
Do not use the expiration date specified on the package.

Conditions of vacation from pharmacies
On prescription

Manufacturer
OJSC "Biochemistry"
Russia, 430030, Saransk, ul. VASENKO, 15 A.
Claims for the quality of the drug to send to the manufacturer's address.

The active ingredient of the drug cyclophosphamide refers to the clinical and pharmacological classification of cytostatic agents, antitumor drugs, alkylantic compounds.

Cyclophosphamide
Instructions for use

Tradename
Cyclophosphamide (depending on the manufacturer may be called cyclophosphane or endoxan)

International name
Cyclophosphamide.

Latin
Cyclophosphamideum.

N Olope chemical formula substance
C7N15CL2N2O2R

BUT active active ingredient

The active substance of the medical drug is cyclophosphamide, the drug is white or with a yellow crystalline powder with an existing molecular weight of 279.1. Powder is practically not dissolved by acetone or ether, it is difficult to divorce in dioxane solutions, four carbon chloride, ethylene glycly, alcohol or pure benzene. It is well soluble in water, including in water for injection.

Pharmacological classification
The active ingredient drug of the cyclophosphamide refers to the clinical and pharmacological classification of cytostatic agents, antitumor drugs, alkylantic compounds

Pharmacology
The active substance of the drug cyclophosphamide has a strong cytostatic effect, aimed at inhibiting or complete cessation of fission of tumor cells, parallel to immunosuppressive assistance to the body alkybling structural elements of DNA. Cells of malignant neoplasms are divided and developed faster than the cells of ordinary tissues, in connection with this, the first reacts much more to various DNA injuries, especially for alkowning. Thus, the active substance has a strongly pronounced antitumor effect.
The chemical transformation of the active actant in the liver is expressed in obtaining two main metabolites, they are the main organizers of the alkybent processes. The effect of alkybent metabolites is directed to protein molecules. In particular, on their nucleophilic kernels, connecting the threads of DNA by transverse membranes along their entire length and prevent the reproductions of the mitosis nature of tumor cells.
The properties of the active substance are aimed at suppressing the growth of oncological cells. Moreover, antitumor activity has a wide range of action.
Immunosuppressive activity is expressed in selective inhibition of betta-lymphocytes, not tasty proliferation of the remaining lymphocytic clones involved in the immune recovery. But it should be borne in mind that the long-term use of the drug, which has two years or more, can lead to the development of a remote effect, i.e., to the emergence of malignant nebulaections of a secondary nature, such as lympho and myeloproliferative oncological diseases, kartenomes of renal pelvis or bladder kartzenomes. In particular, such phenomena were observed in patients with signs of hemorrhagic cystitis. And the kidney loching cancer was observed in a single case in a patient with a cerebral type vasculitis. More often, the described cases of oppressing the normal operation of the genital glands are noted, mostly reversible, but there were single precedents of fixed infertility. Basically, it depends on the dose of the received drug and the duration of its application.
In the case of therapy with a medical drug with cyclophosphamide of children aged preceding sexual maturation (prepressant period), in the future, female patients, sexual maturation passes in normal mode with cyclic menstruation, without changes and pathologies with the possibility of further pregnancy. In male patients, signs of azoospermia or oligospermia were noted, an increase in the production of gonadotropin and kidney atrophy.

In isolated cases, there are records for the development of ovarian fibrosis in female patients and the absolute destruction of the genital cells in the prepubertal period after the long-term use of the drug. When conducting cytostatic therapy, men before the time of the fetal conception time was reflected in the newborn in the form of congenital pathologies such as the vice of the development of the heart muscle and the damage to the development of a baby. In women, such cases were born both healthy children and with listed vices, including with the lack of fingers on the legs and / or hands and various hernias. In addition, babies were born with a significant weight loss.

Animal experiences revealed carcinogenic properties during pregnancy. In particular, the introduction of the drug pregnant rabbits, monkeys, rats and mice were also given the results of a teratogenic nature with the introduction of doses, while recalculating the relevant therapeutic people.

The active active ingredient for oral (inside) reception is well absorbed by reaching overall bioavailability to 77%, but little binds to blood plasma proteins, no more than 15%, although for non-core metabolites this indicator can be more than 65%. Biotransformation is fully in the liver, both in the initial activation stage and under subsequent metabolic processes, forming an ultimately active metabolites.

It has the property of overcoming a placental obstacle and getting into breast milk. The half-life period in the blood plasma lasts from 2.5 to 12.5 hours. In the case of intravenous administration of the drug, the maximum concentration of active substance metabolites in the blood plasma is several hours, on average from two to three.
The active active ingredient is excreted mainly by the kidneys with urine as the main and non-core metabolites in the form of acid chlororacus, acrolein and others. Unchanged with the help of kidney dialysis from 3 to 26%. It is characteristic that with an additional diagnosis of oncological patient renal failure, there is no amplification of the toxic properties of the drug.
In recent decades, there are cases of very effective treatment with the drug cyclophosphamide of patients with a diagnosis of glomerulonephritis, a systemic red lupus, as well as the presence of nonspecific aortoatheritis, dermatomyositis, vegetable granuloma, and even multiple sclerosis.

Cyclophosphamide Application

The drug-based cyclophosphamide is used with severe oncological diseases of people: small-cell lung cancer, ovarian cancer, carcenaries of the uterus and the very body of the uterus, breast cancer, carcenaries of the bladder, in men with prostate cancer, during the ovarian seminine.
It is also used in diagnosed retino and neuro-blustoms, angio, reticulous and lymphatic sarcoma, with a lympholoicosis and a chronic myelolomicosis, with sharp leukes of lymphoblastic, myeloblastic or monoblastic type. It is also an effective cytostatic in lymphogranulomatosis, non-Held lymphomas of various etiologies, with myelomic diseases, Wilms tumors, malignant ying tumor, with sarcoma of soft tissues and osteogenic type. Effectively drug and at nokological germinogenic neoplasms, with mushroom mushrooms.
The high efficiency of the drug was noted at various autoimmune diseases, which include all possible systemic diseases of the connective tissue, taking into account the articular diseases of the type of rheumatoid arthritis, psoriatic and gouty arthritis, at an autoimmune hemolytic type anemia, with nephrotic syndrome (as immunosuppressor), as well as in the case The risk of transplant rejection as a prophylactic and overwhelming reaction of this rejection.

Contraindications
Due to the severity of diseases, for the treatment of which the drug is intended for cyclophosphamide. Application, contraindications are practically no, with the exception of the individual intolerance of the active active substance or any of the LS aids and some severe kidney diseases associated with the violation of their activities, bone marrow hypoplasia, during leukopenia. if the number of leukocytes is lower than the index 3.5 * 109 / l, or during thrombocytopenia, if the indicators of the number of platelets are below 120 * 109 / l, the drug is also contraindicated with pronounced anemia, pronounced cachexia and terminal stages of any oncological diseases, as the drug May aggravate the state.
A contraindicated drug remedy for pregnancy in any trimester and when feeding a baby breast milk.

Cyclophosphamide use of pregnant and lactating women
In the Point Application Cyclophosphamide, the instruction warns that the substance is contraindicated with both pregnant and lactating women, in case of justified risk, during the feeding of a baby, it is necessary to translate a child to artificial nutrition. During the treatment with a cytostatic agent, women need to be carefully protected using the most reliable contraceptives. The studies conducted on pregnant animals showed the embryonic acid and teratogenicity of the active substance on the fruit.

Side effects
Stomach and intestines. From the head of the gastrointestibility, the likelihood of stomatitis, dryness of the mucous membranes of the oral cavity, nausea row. The urges of vomiting, the attacks of diarrhea, the occurrence of pain in the stomach, possible bleeding in any of the segments of the stomach or intestines, rarely observed cases of hemorogic colitis, jaundice or toxic hepatitis. It is possible to reduce appetite up to its complete loss and anorexia.
Heart, vessels, blood formation organs and hemostasis. From these bodies, the manifestation of myelodepresses, myelosuppression, leukopenia or agranulocytosis is possible, the emergence of anemia, less often - thrombocytopenia. There were also cases of hemorrhages and bleeding, blood tides to the head, signs of cardiotoxicity. Cases of heart failure, pericarditis, myiopericarditis of a hemorogic nature, rapid heartbeat are likely.
Nervous system and sense organs. There are cases of reduction of vision, hearing impairment, asthenia. Sudden dizziness and attacks of severe headaches. In rare cases, signs of consciousness confusion are possible.
Respiratory system. The appearance of sudden shortness of breath, pneumonitis, interscoming pneumosclerosis is possible.
GOOD SYSTEM. Diseases are happening by hemorrhagic cystitis, urethritis or urinary bubble fibrosis, sometimes hematuria attacks, difficulties occur during urination, painful attacks. There were cases of edema of the limbs, especially legs, nephropathy, hyperurickozuria or hyperuricemia. Rarely described cases of the occurrence of necrosis of the kidney, amenorrhea, oppression of the normal operation of ovaries or azoospermia.
Skin covering. Often the offensive of alopecia, less often - hyperpigmentation on nails and palms, cases of microcharger exclusions, allergic reactions in the form of rashes, urticaria, itching or pain in the injection places.
Individual cases of pain syndromes in various parts of the body and joints, lip swelling, symptoms of anaphylactic reactions were noted.

Interaction with other drugs
Interaction with the drug Alopurinol with complex therapy increases the risk of brain inhibition from both drugs, so receiving two of these drugs is possible only after agreeing with a specialist and accounting for all possible risks.
Joint therapy with the drug Busulfan (Mileran buy) It may lead to a mutual strengthening of already manifest side effects, or to the emergence of new, including the veneroply disease or even tamponades of the heart muscle.
Interaction with the drug Colchicin (Colchicin to buy) It may lead to a serious risk of the emergence or development of nephropathy from the first and to increase the concentration of uric acid salts in the patient's blood as an influence from the drug cyclophosphamide.
Mercaptopurin (Purur-net) leads to an increase in the risk of secondary tumors, as a consequence of enhancing immunosuppressive influence. It is also likely to enhance the risk of the emergence or development of infections of various nature.
Recommended Simultaneous Use of Medication Mesna (Uromitexane to buy) with an active active substance cyclophosphamide, since their interaction significantly reduces the risk of violation of the functions of the patient's urinary system.
Interaction with the drug Methotrexat (Methotrexate to buy) It is dual character. On the one hand, the concentration of the free actant in the blood plasma increases, the positive effect of cytostatic therapy increases, and on the other hand, the toxic effect is enhanced.
Complex therapy with the drug Metformin (Metformin to buy) leads to increased hypoglycemic effect of metformin, which positively affects the therapy of articular rheumatoid diseases and similar to it.
The drug, when interacting with which the risks of the occurrence of secondary infections or tumors are possible - Chlorambucil (Lakeran buy), Comprehensive application with which is possible only in case of justified reasons.

Dosage and application
It is used strictly for its intended purpose and under the supervision of the attending physician, which is a specialist in the field of treatment with cytostatic medicines. The dose of the course is from 7 to 14 mg / kg, and the application method depends on the entire treatment regimen.

Storage
Store the drug in hermetically visited container with positive temperatures up to 30 degrees Celsius in strictly protected from children.