The drug "Endoxan" belongs to the group of antitumor drugs. Depending on the form of release, it can be taken orally or parenterally. What type of drug to prescribe and in what dosage, only the attending physician decides, based on the real circumstances of the patient's condition.
The composition and properties of the drug
The main active substance of the drug "Endoxan" instructions for use calls cyclophosphamide. One tablet contains 50 mg. The medicine belongs to the group of antitumor drugs and is a biconvex tablet with a white shell and a core of the same shade.
As additional components, this pharmaceutical product contains calcium carbonate and hydrogen phosphate, sodium caramellose, glycerol, gelatin, lactose, corn starch, macrogol, magnesium stearate, polysorbate, sucrose, talc,
silicon dioxide and titanium.
What is the pharmacology of the drug?
The main active substance of the drug, namely cyclophosphamide, has an alkylating and cytostatic effect. By its nature, it is close to mustard gas, being its nitrogen counterpart.
The mechanism of action of cyclophosphamide is based on the formation of cross-links between DNA and RNA molecules and the suppression of the synthesis of protein bodies.
Pharmacokinetics of the drug
The main active substance of the drug “Endoxan” has an almost complete degree of absorption from the digestive tract. Its concentration in the blood after oral and intravenous administration is the same. Cyclophosphamide metabolism occurs mainly in the liver, where the formation of active alkylating metabolites occurs under the action of the oxidase microsomal mechanism. Some of them are converted into inactive forms, another group is transferred to cells, where, under the influence of enzymes, phosphatases are transformed into substances with cytotoxic properties.
The degree of binding of the initial form of the drug with blood proteins is negligible and is 12-14%. However, the same indicator in metabolites is already 60%.
Excretion of cyclophosphamide is carried out through the kidneys mostly in the form of metabolites. About 5-25% of the drug is excreted in its original form with urine and bile.
The parameter T1 / 2 in the drug is 7 hours for adult patients and 4 hours in children.
At what dose should I take the medicine?
The drug "Endoxan" in tablet form is taken orally before meals for half an hour or after eating, after 2 hours.
Due to the fact that this pharmaceutical product is included in a large number of chemotherapeutic regimens, the choice of the method of its administration and dosage is considered individually by the doctor.
"Endoxan" - tablets - the instruction recommends taking at a dosage of 1-3 mg / kg body weight per day, which can be from 50 to 200 mg of cyclophosphamide for 24 hours. The duration of treatment is 2-3 weeks.
If the drug is taken in conjunction with other drugs with antitumor properties, then the dosage of all the elements of therapy is subject to correction.
Can an overdose occur?
The presence of a specific antidote in the drug “Endoxan” does not confirm the instructions for use. If the required dose is exceeded, it is recommended to use maintenance therapy in the form of appropriate treatment for infectious diseases, removal of cardiotoxicity and the elimination of signs of myelosuppression.
How is the medicine combined with other drugs?
If the patient takes drugs that provoke microsomal oxidation in the liver, then when combined with the drug “Endoxan”, the instruction indicates an increase in the synthesis of metabolites with alkylating activity, a decrease in the half-life of cyclophosphamide and an increase in its effectiveness.
This drug suppresses the activity of cholinesterase and the metabolic pathway of cocaine, increasing its toxicity, and increases the effectiveness of suxamethonium.
If “Endoxan” is used in conjunction with “Allopurinol”, then its enhanced negative effect on the bone marrow is observed.
In the case of simultaneous treatment with cyclophosphamide, colchicine, probenecid, sulfinpyrazone, the doctor usually adjusts the dose of drugs against gout. This is associated with an increased risk of nephropathy with the combined use of "Endoxan" with uricosuric medicines.
Cyclophosphamide reduces the synthesis of factors in the liver, which are responsible for blood coagulation and platelet formation, therefore, with simultaneous treatment with anticoagulants, the activity of the latter decreases.
For patients taking the drug “Endoxan”, the instructions for use recommend that grapefruit juice be excluded from the diet, as it contains components that violate the activation and effectiveness of the main active ingredient of the drug.
With the combined use of cyclophosphamide with Doxorubicin or with Daunorubicin, the cardiotoxic effect of these drugs is enhanced.
The combination with other immunosuppressants, such as Azathioprine, Cyclosporin, Chlorambucil, GCS, and Mercapturin leads to an increase in the occurrence of infections and secondary tumors.
In the case of combined use of Endoxan and Lovastin in patients with heart transplantation, there may be a risk of skeletal muscle necrosis and acute renal failure.
If treatment with cyclophosphamide is combined with myelosuppressants or with radiation therapy, then an increase in suppression of bone marrow functioning is possible.
The concomitant use of "Endoxan" with increased doses of cytarabine during preparatory procedures for bone marrow transplantation increases the incidence of fatal cardiomyopathy.
How does this medicine affect reproductive function?
The drug "Endoxan", patient reviews confirm this, can provoke sterility in patients of both sexes, which may be irreversible.
In most cases, amenorrhea is observed in women, however, the regularity of menstruation is usually restored several months after the end of treatment with cyclophosphamide. If therapy was carried out in girls of prepubertal age, deviations in the development of secondary sexual manifestations were not observed. Menses were normal, the ability to conceive was not lost.
When treating men with Endoxan, the instruction indicates that in a number of cases azoospermia or oligospermia were recorded. This is due to the increased production of gonadotropins at a rate of testosterone release. The level of libido and potency in men does not decrease. If treatment with cyclophosphamide was performed in boys of prepubertal age, then the secondary sexual manifestations were normal. However, cases of azoospermia, oligospermia and increased gonadotropins have been noted. Testicular atrophy may also occur. It is worth noting that azoospermia is reversible, although the restoration of this function may occur several years after the end of treatment.
What side effects does the drug have?
Taking the medicine “Endoxan”, the instructions for use confirm this, can cause some disorders of the hematopoiesis system:
- Leukopenia, neutropenia - quite often.
- Less common are anemia and thrombocytopenia.
After 1-2 weeks from the start of treatment, the patient has a maximum decrease in white blood cells and platelets in the blood. These indicators are restored to normal after 7-10 days after the end of therapy.
In the treatment of cyclophosphamide, adverse reactions from the gastrointestinal tract may occur:
- Nausea and vomiting.
- Anorekisya.
- Stomatitis.
- Pain in the abdominal region.
- Violations of the stool.
- Jaundice.
- Hemorrhagic colitis.
Rarely are liver dysfunctions associated with increased enzyme activity and increased bilirubin levels. In a fairly large group of patients who have aplastic anemia and receive high doses of Endoxan, or by combining it with busulfan, endoflebitis of the veins of the liver is noted. This phenomenon can develop after 1-3 weeks from the time of bone marrow transplantation and is manifested in a sharp increase in body weight, ascites, hepatomegaly and hyperbilirubinemia, and hepatic encephalopathy.
When taking the drug, unwanted reactions from the skin may occur:
- Reversible alopecia.
- Rash.
- Pigmentation of skin and nails.
A violation of the urinary system can also be provoked during treatment with the drug “Endoxan”. Instructions, reviews of doctors and patients indicate the following conditions:
- Cystitis in combination with or without bladder fibrosis.
- Hemorrhagic urethritis.
- Necrotic phenomena of the renal tubules up to death.
Bladder epithelium may be found in the patient's urine. If the form of hemorrhagic cystitis is severe, stop taking the drug. The best prevention of this condition is taking the drug "Mesna". If the doses of “Endoxan” are increased, then kidney dysfunction in the form of nephropathy and hyperuremia may develop.
If the patient has a severe degree of immunosuppression, then during treatment with cyclophosphamide severe infections can be observed.
The following side effects may also develop:
- Cardiotoxicity (when taking high doses), severe degrees of heart failure.
- Pulmonary fibrosis of an interstitial nature.
- Violation of normal oogenesis and spermatogenesis, reversible and irreversible sterility.
- The development of secondary malignant neoplasms: bladder cancer, myeloproliferation and lymphoproliferation.
- Allergy in the form of a rash, itching, urticaria, sometimes in the form of an anaphylactic reaction.
- Poor wound healing.
- Redness of the face, excessive sweating, headache.
The presence of serious side effects from taking the drug always raises the question of possible benefits versus the likely risks for an individual patient.
What diseases is this drug prescribed for?
Endoxan tablets can be prescribed to a patient if he has the following diseases:
- Lymphogranulomatosis.
- Multiple myeloma
- Mammary cancer.
- Lymphoblastic lymphocytic leukemia in acute or chronic form.
- Non-Hodgkin type lymphomas.
- Retinoblastoma.
- Neuroblastoma
- Mycosis of a fungal nature.
Indicates the acceptability of use as part of a complex anticarcinogenic therapy attached to the drug “Endoxan”. The manufacturer recommends it be included in the treatment of cancer of the cervix and bladder, oncology of the lung and prostate gland, sarcoma and reticulosarcoma, Ewing and Wilms diseases.
A cyclophosphamide-based drug can be used as an immunosuppressant in progressive autoimmune diseases: psoriatic and rheumatoid arthritis, hemolytic anemia, collagenosis, nephrotic syndrome, as well as to avoid transplant rejection.
When is the drug contraindicated?
The drug "Endoxan" has a lot of contraindications, including:
- Pregnancy and lactation.
- Cystitis.
- Infections in active form.
- Violation of the functioning of the bone marrow of a pronounced form.
- The presence of hypersensitivity to the main and additional substances of the drug.
- Urinary retention.
With extreme caution, doctors prescribe this drug for severe diseases of the heart, kidneys and liver, gout, adrenalectomy, the presence of infiltration processes in the bone marrow, nephrourolithiasis.
Special instructions for treatment
While taking the “Endoxan” preparation, the patient’s blood (concentration of platelets and neutrophils) and urine (red blood cells) are subject to mandatory control.
In some cases, it is recommended to stop treatment with Endoxan. Instructions for use of the tablet recommends doing this under the following conditions:
- The manifestation of cystitis.
- Lowering the concentration of leukocytes and platelets to critical values.
- The occurrence of infections (dose adjustment is possible).
If "Endoxan" is used in large doses, then the patient is prescribed the medicine "Mesna" for the prevention of hemorrhagic type cystitis.
When treating with this drug, one should refrain from drinking alcohol and use reliable methods of contraception.
If the patient is prescribed Endoxan within 10 days after surgery with general anesthesia, then the anesthesiologist is informed about this.
After an adrenalectomy, a dose adjustment of “Endoxan” and other GCS preparations is carried out.
Analogues of the drug
If there are serious contraindications and risks, then the instruction “Endoxan” suggests refusing to take the medicine. Analogs may be prescribed by your doctor as a suitable alternative. Among them:
- Ledoxin.
- Cyclophosphamide.
- "Cytoxan".
- Cyclophosphamide - Teva.
- Cyclophosphamide-Lance.
- "Endoxan - ASTA."
This information is a simplified version of the instructions for the drug "Endoxan". The purpose of this drug is made only by the attending physician.