Endoxan
Endoxan: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. In case of impaired renal function
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Endoxan
ATX code: L01AA01
Active ingredient: cyclophosphamide (cyclophosphamide)
Producer: Almirall Prodespharma (Spain), Baxter Oncology, GmbH (Germany)
Description and photo updated: 2018-26-11
Prices in pharmacies: from 152 rubles.
Buy
Endoxan is an antineoplastic drug.
Release form and composition
Endoxan dosage forms:
- sugar-coated tablets: white, round, biconvex, with a white core (10 pcs. in blisters, in a cardboard box 5 blisters);
- powder for the preparation of a solution for intravenous (iv) administration: white crystalline mass (200 mg, 500 mg or 1000 mg each in a glass colorless vial with a capacity of 20 ml, 50 ml or 75 ml, respectively, in a cardboard box 1 bottle).
1 tablet contains:
- active substance: cyclophosphamide - 50 mg;
- auxiliary components: sodium carmellose, corn starch (maize starch), calcium monohydrogen phosphate (calcium hydrogen phosphate), lactose, calcium carbonate, gelatin, glycerol, sucrose, magnesium stearate, silicon dioxide (silicon dioxide), polysorbate, macrogol, dioxididone, titanium talc.
The content of the active ingredient - cyclophosphamide monohydrate - in 1 bottle is 213.8 mg, 534.5 mg or 1069 mg, which is equivalent to the content of 200 mg, 500 mg or 1000 mg of cyclophosphamide.
Pharmacological properties
Pharmacodynamics
Endoxan is an antineoplastic drug with the active ingredient cyclophosphamide, which is an alkylating cytostatic compound, the chemical characteristics of which are close to the nitrogen analogues of mustard gas.
The mechanism of action of the drug is due to the formation of cross-links between DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) strands and inhibition of protein synthesis.
Pharmacokinetics
After taking Endoxan inside, cyclophosphamide is almost completely absorbed from the gastrointestinal tract. The content of the active substance in the blood against the background of parenteral and oral administration is the same.
Cyclophosphamide metabolism mainly occurs in the liver. As a result of exposure to the microsomal oxidase system, active alkylating metabolites are formed: 4-OH cyclophosphamide and aldophosphamide. Some of them are transported into cells and, under the influence of phosphatases, are transformed into metabolites that have a cytotoxic effect. The other part is converted to inactive metabolites.
After intravenous administration, C max (maximum concentration) of metabolites is reached in plasma in 2–3 hours.
Plasma protein binding of cyclophosphamide in unchanged form - 12-14%, some metabolites - up to 60%.
The blood-brain barrier overcomes a limited amount of the drug.
T 1/2 (half-life) in adults - 7 hours, in children - 4 hours.
It is excreted through the kidneys mainly in the form of metabolites. Unchanged through the kidneys and intestines, 5% to 25% of the dose taken is excreted.
Indications for use
According to the instructions, Endoxan is indicated as monotherapy for the following diseases:
- ovarian cancer;
- lymphogranulomatosis;
- acute lymphoblastic and chronic lymphocytic leukemia;
- non-Hodgkin lymphomas;
- mammary cancer;
- multiple myeloma;
- retinoblastoma;
- neuroblastoma;
- fungal mycosis.
In combination with other antineoplastic agents, Endoxan is used to treat lung cancer, soft tissue sarcoma, germ cell tumors, bladder cancer, prostate cancer, cervical cancer, reticulosarcoma, Wilms tumor, Ewing's sarcoma.
As an immunosuppressive therapy, Endoxan is prescribed for organ transplantation (in order to suppress the rejection reaction) and the progression of autoimmune diseases such as psoriatic arthritis, rheumatoid arthritis, autoimmune hemolytic anemia, collagenosis, and nephrotic syndrome.
Contraindications
- active infections;
- severe dysfunction of the bone marrow;
- cystitis;
- delay in urination;
- period of pregnancy;
- breast-feeding;
- hypersensitivity to the components of the drug.
With caution, it is necessary to prescribe Endoxan to patients with severe heart disease, gout (in history), with severe liver and / or kidney dysfunction, nephrourolithiasis, adrenalectomy, bone marrow suppression, after radiation or chemotherapy, with bone marrow infiltration with tumor cells.
Instructions for the use of Endoxan: method and dosage
Pills
Endoxan tablets are taken orally 0.5 hours before or 2 hours after meals.
The doctor determines the dosage form, regimen and dose of the drug individually, taking into account the clinical indications of the patient.
Recommended dosage for monotherapy: 1–3 mg per 1 kg of patient weight per day. The duration of the course is from 14 to 21 days.
When prescribing tablets in combination with other antineoplastic agents, the dose of Endoxan can be reduced.
Powder for preparation of solution for intravenous administration
The prepared powder solution is intended for intravenous administration.
To prepare the solution, the contents of the vial should be dissolved in 0.9% sodium chloride solution or water for injection at a concentration of 20 mg per 1 ml.
The doctor prescribes the dosage regimen of Endoxan individually, taking into account clinical indications and depending on the chosen chemotherapy regimen.
The recommended dosage for adults and children depends on the frequency of the procedures:
- daily: at the rate of 50-100 mg per 1 m 2 of body surface. The duration of the course is from 14 to 21 days;
- 2-3 times within 7 days: 100-200 mg per 1 m 2 of body surface within 21-28 days;
- 1 time in 14 days: 600-750 mg per 1 m 2;
- 1 time in 21-28 days: 1500-2000 mg per 1 m 2, the total dose of the course is from 6000 to 14000 mg.
In case of intravenous administration of the drug in combination with other antineoplastic agents, one should consider a possible decrease in the dose of Endoxan and / or concomitant therapy drugs.
Side effects
- from the hematopoietic system: neutropenia, leukopenia; rarely - anemia, thrombocytopenia;
- from the digestive system: nausea, anorexia, vomiting; rarely - stomatitis, discomfort in the abdominal region, pain in the abdominal region, diarrhea, constipation, an increase in the activity of hepatic transaminases, the level of alkaline phosphatase and the concentration of bilirubin in the blood serum; in some cases - jaundice, hemorrhagic colitis; very rarely (in patients with aplastic anemia with monotherapy with cyclophosphamide in high doses) - obliterating endophlebitis of the hepatic veins; with a combination of high doses of cyclophosphamide with busulfan and against the background of total irradiation during allogeneic bone marrow transplantation, 15-50% of patients may develop obliterating endophlebitis of the hepatic veins;
- from the urinary system: cystitis, hemorrhagic urethritis, necrosis of the renal tubules; rarely - severe functional disorders, including fatal ones, hyperuricemia, increased uric acid concentration, nephropathy; in some cases - fibrosis of the bladder of varying degrees of prevalence (in combination with or without cystitis); the presence of atypical epithelial cells of the bladder in the urine;
- on the part of the cardiovascular system: cardiotoxicity (against the background of intravenous administration of doses of 120-270 mg per 1 kg of patient's weight for several days, more often with intensive combined antitumor or drug therapy associated with organ transplantation), congestive heart failure due to hemorrhagic myocarditis, including fatal ones;
- dermatological reactions: often - alopecia; rarely - skin rash, skin pigmentation, changes in the structure of nails;
- infections: in severe forms of immunosuppression - the development of serious infectious pathologies;
- on the part of the respiratory system: with the introduction of high doses of Endoxan for a long time - interstitial pulmonary fibrosis;
- on the part of the reproductive system: impaired spermatogenesis, impaired oogenesis, sterility (in some cases irreversible); often - amenorrhea, oligospermia, azoospermia, testicular atrophy;
- allergic reactions: skin rash, itching, urticaria; rarely - anaphylactic reactions;
- carcinogenic effect: the development of secondary malignant neoplasms - often in the form of a tumor of the bladder (in patients who previously had hemorrhagic cystitis), lymphoproliferative and myeloproliferative pathologies;
- local reactions: with parenteral administration - pain, redness or swelling at the injection site;
- others: flushing of the face, facial flushing, excessive sweating, headache; possibly - syndrome of inadequate secretion of antidiuretic hormone, cross-sensitivity with other alkylating agents, slowing down of the wound healing process.
Overdose
Symptoms: increased side effects.
Treatment: there is no specific antidote. Prescribing supportive therapy, including measures aimed at treating infections, cardiotoxicity, or manifestations of myelosuppression.
special instructions
The use of Endoxan should be accompanied by regular blood and urine tests. The indices of the content of neutrophils and platelets, which allow assessing the degree of myelosuppression, require special attention. If the leukocyte count is 2500 / μl, and the platelet count is 100,000 / μl, treatment should be stopped. The content of red blood cells in the urine may indicate the development of hemorrhagic cystitis. In case of laboratory or visual confirmation of symptoms of cystitis, treatment should be discontinued.
A decrease in the number of leukocytes and platelets is most pronounced, usually after 7-14 days of treatment. With leukopenia, blood counts begin to recover 7–10 days after stopping the use of Endoxan.
Cases of hepatic vein obliterating endophlebitis may occur 7 days or more after bone marrow transplantation. The characteristic symptoms of the development of this syndrome include an increase in the patient's body weight, ascites, hepatomegaly, hyperbilirubinemia, and hepatic encephalopathy.
With alopecia, hair begins to grow back after stopping therapy, or already during a long course of treatment. Hair texture and color may change.
The severity of side effects from the urinary system depends on the dose and duration of Endoxan use. For the prevention of cystitis, it is recommended to use hydration and Mesna. In severe forms of hemorrhagic cystitis, Endoxan must be canceled.
The development of secondary tumors often occurs when the immune processes are impaired during the use of the drug for the treatment of non-malignant neoplasms and primary myeloproliferative malignant tumors. The development of a secondary tumor can be observed several years after the discontinuation of cyclophosphamide.
When prescribing Endoxan, a careful assessment of the ratio of the expected therapeutic effect and the degree of risk of induction of a malignant tumor from the use of the drug should be carried out.
If an infectious disease occurs while using Endoxan, treatment should be interrupted or the advisability of continuing therapy at a lower dose of the drug should be considered.
Alcohol consumption during anticancer therapy is contraindicated.
Endoxan should be prescribed after surgery with general anesthesia for the first 10 days only with the participation of an anesthesiologist.
After adrenalectomy, dose adjustment of substitution therapy drugs and cyclophosphamide is required.
Application during pregnancy and lactation
The use of Endoxan is contraindicated during gestation and lactation.
The cytotoxic effect of cyclophosphamide can cause sterility in men and women, in some cases it is irreversible and leads to absolute infertility.
Against the background of the use of Endoxan in women, amenorrhea often develops, it is transient and a few months after the cancellation of therapy, the menstrual cycle is usually restored. In girls, menstruation is normal, the development of secondary sexual characteristics in the prepubertal period is not disturbed, and the ability to conceive remains.
The use of Endoxan in men does not affect sex drive and potency. In the treatment of boys in the prepubertal period, secondary sexual characteristics develop normally. Endoxan can cause the development of oligospermia or azoospermia caused by an increase in the level of gonadotropins with normal testosterone secretion, various degrees of testicular atrophy. Drug-induced azoospermia can be reversible; in some cases, restoration of impaired function may take several years after anticancer therapy is discontinued.
During the period of use of Endoxan, conception should be avoided using reliable methods of contraception.
With impaired renal function
The use of the drug is contraindicated for cystitis, urinary retention.
Endoxan is prescribed with caution for severe kidney disease, including nephrourolithiasis.
For violations of liver function
Endoxan should be used with caution in severe liver diseases.
Drug interactions
With the simultaneous use of Endoxan:
- inducers of enzymes of microsomal oxidation: induction of metabolism of cyclophosphamide in the liver causes an increase in its activity and the formation of active alkylating metabolites;
- suxamethonium, cocaine: a significant and prolonged suppression of cholinesterase activity by cyclophosphamide contributes to an increase in the effect of suxamethonium and an increase in the risk of the toxic effect of cocaine;
- allopurinol: an increase in the toxic effect of allopurinol, including on the bone marrow, is possible;
- colchicine, probenecid, allopurinol, sulfinpyrazone: increase the risk of nephropathy due to an increase in uric acid levels; it is recommended to consider the feasibility of adjusting the doses of uricosuric anti-gout agents;
- anticoagulants: may decrease the activity of anticoagulants;
- grapefruit, including grapefruit juice: may interfere with the action of cyclophosphamide, therefore, during the period of treatment, grapefruit should be excluded from the diet;
- doxorubicin, daunorubicin: their cardiotoxic action is enhanced;
- glucocorticosteroids, cyclosporine, azathioprine, chlorambucil, mercaptopurine: immunosuppressants increase the risk of secondary tumors and infections;
- lovastatin: may increase the risk of developing acute renal failure and acute skeletal muscle necrosis in heart transplantation;
- radiation therapy, drugs that reduce the level of leukocytes and platelets in the blood: an additive effect on the suppression of bone marrow function;
- Cytarabine: The use of high doses of cytarabine in preparation for bone marrow transplantation increases the risk of fatal cardiomyopathy.
Analogs
Endoxan analogs are: Alkeran, Ledoxina, Endoxan-Asta, Cyclophosphamide, Cyclophosphamide, Cytoxan, Leukeran.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 25 ° C.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Endoxan
Reviews about Endoxan do not allow determining the degree of therapeutic efficacy of the drug. Basically, in them, patients indicate a side effect of the drug. When administered intravenously, patients feel a rush of blood to the face, increased sweating, headache. The drug causes serious disorders of the hematopoietic system, hepatobiliary system, requiring concomitant therapy.
Price for Endoxan in pharmacies
The price of Endoxan for a package containing 1 bottle in a dose of 200 mg can be from 178 rubles, 500 mg - from 484 rubles, 1000 mg - from 539 rubles. The cost of tablets (50 pcs in a package) is from 867 rubles.
Endoxan: prices in online pharmacies
|
Drug name Price Pharmacy |
|
Endoxan 200 mg powder for solution for intravenous administration 1 pc. 152 RUB Buy |
|
Endoxan 500 mg powder for solution for intravenous administration 1 pc. 449 r Buy |
|
Endoxan 1000 mg powder for solution for intravenous administration 1 pc. RUB 517 Buy |
|
Endoxan 50 mg sugar-coated tablets 50 pcs. 779 r Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
