Endoxan tablets 50mg, No. 50

• acute lymphoblastic and chronic lymphocytic leukemia;

• lymphogranulomatosis;

• non-Hodgkin lymphomas;

• multiple myeloma;

• mammary cancer;

• ovarian cancer;

• neuroblastoma;

• retinoblastoma;

• fungal mycosis.

Endoxan is also used in combination with other anticancer drugs for the treatment of lung cancer, germ cell tumors, cervical cancer, bladder cancer, soft tissue sarcoma, reticulosarcoma, Ewing's sarcoma, Wilms tumor, and prostate cancer.

As an immunosuppressive agent, Endoxan is used in progressive autoimmune diseases (rheumatoid arthritis, psoriatic arthritis, collagenosis, autoimmune hemolytic anemia, nephrotic syndrome) and to suppress the graft rejection reaction.

Inside 30 minutes before meals or 2 hours after meals.

Endoxan is part of many chemotherapeutic treatment regimens, and therefore, when choosing a specific route of administration, regimen and doses in each individual case, one should be guided by the data of special literature.

Inside Endoxan is usually prescribed at a dose of 1-3 mg / kg (50-200 mg) / day for 2-3 weeks.

When using the drug in combination with other anticancer drugs, it may be necessary to reduce the dose of both Endoxan and other drugs.

Cyclophosphamide

• severe bone marrow dysfunction;

• cystitis;

• delay in urination;

• active infections;

• pregnancy;

• lactation;

• hypersensitivity to cyclophosphamide or other excipients included in the dosage form.

With caution: in severe diseases of the heart, liver and kidneys, adrenalectomy, gout (history), nephrourolithiasis, bone marrow suppression, bone marrow infiltration with tumor cells, preceding radiation or chemotherapy.

Clinical and pharmacological group: Antineoplastic drug

Pharmaco-therapeutic group: Antineoplastic agent, alkylating compound

pharmachologic effect

Cyclophosphamide is an alkylating cytostatic drug chemically close to the nitrogen analogs of mustard gas.

The mechanism of action is believed to include the formation of cross-links between DNA and RNA strands, as well as inhibition of protein synthesis.

Pharmacokinetics

Cyclophosphamide is almost completely absorbed from the gastrointestinal tract. The content of the drug in the blood after intravenous administration and oral administration are the same. It is metabolized mainly in the liver under the action of the microsomal oxidase system, 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 a cytotoxic effect.

The binding of the unchanged drug to blood plasma proteins is insignificant (12-14%), but some metabolites bind by more than 60%. Through the BBB penetrates to a limited extent.

Cyclophosphamide is excreted from the body by the kidneys mainly in the form of metabolites, however, 5-25% of the administered dose is excreted unchanged in the urine, as well as in the bile. T1 / 2 is 7 hours for adults and 4 hours for children.

Indications

• acute lymphoblastic and chronic lymphocytic leukemia;

• lymphogranulomatosis;

• non-Hodgkin lymphomas;

• multiple myeloma;

• mammary cancer;

• ovarian cancer;

• neuroblastoma;

• retinoblastoma;

• fungal mycosis.

Endoxan is also used in combination with other anticancer drugs for the treatment of lung cancer, germ cell tumors, cervical cancer, bladder cancer, soft tissue sarcoma, reticulosarcoma, Ewing's sarcoma, Wilms tumor, and prostate cancer.

As an immunosuppressive agent, Endoxan is used in progressive autoimmune diseases (rheumatoid arthritis, psoriatic arthritis, collagenosis, autoimmune hemolytic anemia, nephrotic syndrome) and to suppress the graft rejection reaction.

Dosage regimen

Inside 30 minutes before meals or 2 hours after meals.

Endoxan is part of many chemotherapeutic treatment regimens, and therefore, when choosing a specific route of administration, regimen and doses in each individual case, one should be guided by the data of special literature.

Inside Endoxan is usually prescribed at a dose of 1-3 mg / kg (50-200 mg) / day for 2-3 weeks.

When using the drug in combination with other anticancer drugs, it may be necessary to reduce the dose of both Endoxan and other drugs.

Side effect

From the hematopoietic system: leukopenia, neutropenia; rarely - thrombocytopenia, anemia. The greatest decrease in the number of leukocytes and platelets is usually observed on days 7-14 of treatment. Recovery of blood counts in leukopenia usually begins 7-10 days after stopping treatment.

From the digestive system: nausea, vomiting, anorexia, less often stomatitis, discomfort or pain in the abdominal region, diarrhea or constipation. There are separate reports on the development of hemorrhagic colitis, jaundice.

There have been rare cases of liver dysfunction, manifested by an increase in the activity of hepatic transaminases, the level of alkaline phosphatase and the content of bilirubin in the blood serum. In 15-50% of patients receiving high doses of cyclophosphamide in combination with busulfan and total radiation during allogeneic bone marrow transplantation, hepatic vein obliterating endophlebitis develops. 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 usually develops 1Ц3 weeks after bone marrow transplantation and is characterized by abrupt weight gain, hepatomegaly, ascites, and hyperbilirubinemia. Hepatic encephalopathy may also occur.

On the part of the skin and cutaneous appendages: alopecia often develops. Hair regrowth begins after completion of drug treatment or even during prolonged treatment; hair may vary in structure and color. Sometimes, during treatment, a rash appears on the skin, skin pigmentation and nail changes are observed.

From the urinary system: hemorrhagic urethritis, cystitis, necrosis of the renal tubules. In rare cases, this condition can be severe and even fatal. Fibrosis of the bladder, sometimes widespread, with or without cystitis, may also develop. Atypical bladder epithelial cells can be found in the urine. These side effects depend on the dose of Endoxan and the duration of treatment. The prevention of cystitis is facilitated by hydration and the use of the drug mesna. Usually, in severe forms of hemorrhagic cystitis, it is necessary to stop treatment with the drug. When prescribing high doses of cyclophosphamide, in rare cases, impaired renal function, hyperuricemia, nephropathy associated with increased production of uric acid can be observed.

Infections: Patients with severe immunosuppression can develop serious infections.

From the side of the cardiovascular system: cardiotoxicity was observed when high doses of 4.5-10 g / m2 (120 to 270 mg / kg) of the drug were administered for several days, usually as part of intensive combined anticancer or drug therapy for organ transplantation. At the same time, severe and sometimes fatal episodes of congestive heart failure due to hemorrhagic myocarditis were noted.

From the respiratory system: interstitial pulmonary fibrosis (with the introduction of high doses of the drug for a long time).

Reproductive system disorders : violation of oogenesis and spermatogenesis. The drug can cause sterility in both men and women, which in some cases can be irreversible.

A significant proportion of women develop amenorrhea, and regular menstruation usually returns within a few months after stopping treatment. In girls, as a result of treatment with cyclophosphamide during the prepubertal period, secondary sexual characteristics developed normally and menstruation was normal; subsequently they were able to conceive.

In men, as a result of treatment with the drug, oligospermia or azoospermia may develop, associated with an increase in the level of gonadotropins with normal secretion of testosterone. Sexual desire and potency in such patients are not impaired.In boys, during treatment with the drug in the prepubertal period, secondary sexual characteristics develop normally, however, oligospermia or azoospermia and increased secretion of gonadotropins may be noted. Testicular atrophy of varying degrees may occur. In some patients, the azoospermia caused by the drug is reversible, but the restoration of the impaired function may occur only several years after the termination of treatment.

Carcinogenicity: in some patients who were previously treated with the drug in monotherapy or in combination with other anticancer drugs and / or other methods of treatment, secondary malignant tumors developed. Most often these were bladder tumors (usually in patients who had previously suffered from hemorrhagic cystitis), myeloproliferative or lymphoproliferative diseases. Secondary tumors most often developed in patients as a result of treatment of primary myeloproliferative malignant tumors or non-malignant diseases, with impaired immune processes. In some cases, a secondary tumor developed several years after stopping treatment with the drug.

When assessing the ratio of the expected positive results and the possible risk of using the drug, one should always keep in mind the likelihood of induction of a malignant tumor by the drug.

Allergic reactions: skin rash, hives, or itching; rarely - anaphylactic reactions.

Miscellaneous: One case of possible cross-sensitivity with other alkylating agents has been reported. Cyclophosphamide may interfere with normal wound healing. Perhaps the development of a syndrome similar to the syndrome of inappropriate secretion of ADH. Redness, swelling, or pain at the injection site. Flushing or flushing of the face, headache, excessive sweating.

Contraindications for use

• severe bone marrow dysfunction;

• cystitis;

• delay in urination;

• active infections;

• pregnancy;

• lactation;

• hypersensitivity to cyclophosphamide or other excipients included in the dosage form.

With caution: in severe diseases of the heart, liver and kidneys, adrenalectomy, gout (history), nephrourolithiasis, bone marrow suppression, bone marrow infiltration with tumor cells, preceding radiation or chemotherapy.

Application during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

The drug can cause sterility in both men and women, which in some cases can be irreversible.

A significant proportion of women develop amenorrhea, and regular menstruation usually returns within a few months after stopping treatment. In girls, as a result of treatment with cyclophosphamide during the prepubertal period, secondary sexual characteristics developed normally and menstruation was normal; subsequently they were able to conceive.

In men, as a result of treatment with the drug, oligospermia or azoospermia may develop, associated with an increase in the level of gonadotropins with normal secretion of testosterone. Sexual desire and potency in such patients are not impaired.In boys, during treatment with the drug in the prepubertal period, secondary sexual characteristics develop normally, however, oligospermia or azoospermia and increased secretion of gonadotropins may be noted. Testicular atrophy of varying degrees may occur. In some patients, the azoospermia caused by the drug is reversible, but the restoration of the impaired function may occur only several years after the termination of treatment.

Application for violations of liver function

With caution: in case of severe liver disease.

Application for impaired renal function

Contraindicated:

• cystitis;

• delay in urination.

With caution: in case of severe kidney disease.

special instructions

During treatment with the drug, it is necessary to regularly conduct a blood test (especially paying attention to the content of neutrophils and platelets) to assess the degree of myelosuppression, and also regularly conduct a urinalysis for the presence of red blood cells, the appearance of which may precede the development of hemorrhagic cystitis.

If signs of cystitis with micro- or gross hematuria appear, treatment with Endoxan should be discontinued.

With a decrease in the number of leukocytes to 2500 / ?l and / or platelets to 100,000 / ?l, treatment with Endoxan should be discontinued.

In the event of infections during therapy with Endoxan, treatment should either be interrupted or the dose of the drug should be reduced.

When using high doses of Endoxan in order to prevent the development of hemorrhagic cystitis, the drug mesna is prescribed.

During the period of treatment, one should refrain from taking alcoholic beverages.

If during the first 10 days after the operation performed under general anesthesia, the patient is prescribed Endoxan, it is necessary to inform the anesthesiologist about this.

After adrenalectomy, the patient needs to adjust the doses of both corticosteroids used for replacement therapy and the drug Endoxan.

Women and men should use reliable methods of contraception during treatment with Endoxan

Overdose

The specific antidote for drug overdose is unknown. In cases of overdose, supportive measures should be used, including appropriate treatment of infections, manifestations of myelosuppression or cardiotoxicity.

Drug interactions

Inducers of microsomal oxidation in the liver can induce microsomal metabolism of cyclophosphamide, which leads to increased formation of alikylating metabolites, thereby reducing the half-life of cyclophosphamide and increasing its activity.

The use of cyclophosphamide, which causes a noticeable and long-term suppression of cholinesterase activity, enhances the effect of suxamethonium, and also reduces or slows down the metabolism of cocaine, thereby increasing and / or increasing the duration of its effect and increasing the risk of toxic effects.

With simultaneous use with allopurinol, in addition, the toxic effect on the bone marrow may increase.

With the simultaneous use of cyclophosphamide, allopurinol, colchicine, probenecid, sulfinpyrazone, dose adjustment of anti-gout drugs may be required. The use of uricosuric anti-gout drugs may increase the risk of nephropathy associated with increased production of uric acid when using cyclophosphamide.

Cyclophosphamide may increase anticoagulant activity as a result of decreased hepatic synthesis of coagulation factors and impaired platelet formation, but it may also decrease anticoagulant activity through an unknown mechanism.

Because grapefruit contains a compound that can interfere with cyclophosphamide activation and thus its action, patients are advised not to eat grapefruit or drink grapefruit juice.

Cyclophosphamide enhances the cardiotoxic effect of doxorubicin and daunorubicin.

Other immunosuppressants (azathioprine, chlorambucil, GCS, cyclosporine, mercaptopurine) increase the risk of developing infections and secondary tumors.

With the simultaneous use of lovastatin in patients with heart transplantation, an increase in the risk of acute skeletal muscle necrosis and acute renal failure is possible.

Medicines that cause myelosuppression, as well as radiation therapy - possibly additive suppression of bone marrow function.

The simultaneous use of high doses of cytarabine with cyclophosphamide in preparation for bone marrow transplantation led to an increase in the incidence of cardiomyopathy with subsequent death.

Storage conditions of the drug Endoxan

List A. The drug should be stored at a temperature not exceeding 25 ? C out of the reach of children.

Shelf life of Endoxan

Shelf life is 3 years.

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

BAXTER (USA)