Cyclophosphan-LNS rapidly soluble, lyophilizate 200 mg

Cyclophosphamide is an alkylating cytostatic drug chemically similar to the nitrogen analogues of mustard gas.

Indications

Acute lymphoblastic and chronic lymphocytic leukemia, lymphogranulomatosis, non-Hodgkin’s lymphoma, multiple myeloma, breast cancer, ovarian cancer, neuroblastoma, retinoblastoma, mycosis fungoides.

Pharmacological effect

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

Special instructions

Cyclophosphamide-LENS® should be used under the supervision of a physician experienced in working with anticancer drugs. 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, as well as regularly conduct a urine test for the presence of red blood cells, the appearance of which may precede the development of hemorrhagic cystitis.

Active ingredient

Cyclophosphamide

Composition

Each bottle contains:

Contraindications

– Hypersensitivity to cyclophosphamide or any other component of the dosage form.
– Severe impairment of bone marrow function.
– Cystitis.
– Urinary retention.
– Pregnancy and breastfeeding.
– Active infections.

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

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 days 7-14 of treatment. Recovery from leukopenia usually begins 7-10 days 4 after stopping treatment with the drug.

From the digestive system: nausea, vomiting, anorexia, less often stomatitis, discomfort or pain in the abdominal area, diarrhea or constipation. There are isolated reports of the development of hemorrhagic colitis and jaundice. Rare cases of liver dysfunction have been reported, manifested by an increase in the activity of transaminases, alkaline phosphatase and bilirubin content in the blood serum. In 15-50% of patients receiving high doses of cyclophosphamide in combination with busulfan and total irradiation during allogeneic bone marrow transplantation, obliterating endophlebitis of the hepatic veins develops.

A similar reaction in very rare cases has also been observed in patients receiving high doses of cyclophosphamide alone in patients with aplastic anemia. This syndrome usually develops 1–3 weeks after bone marrow transplantation and is characterized by sudden weight gain, hepatomegaly, ascites, and hyperbilirubinemia. Hepatic encephalopathy may also occur.

From the skin and skin appendages: alopecia often develops. Hair regrowth begins after completion of treatment with the drug or even during prolonged treatment; hair may differ in its structure and color. Sometimes during treatment, skin rashes, skin pigmentation and changes in nails appear.

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 may also develop, sometimes of a widespread nature, in combination with or without cystitis. Atypical bladder epithelial cells may be found in the urine. These side effects depend on the dose of cyclophosphamide and the duration of treatment. Cystitis can be prevented by hydration and the use of mesna. 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, and nephropathy associated with increased formation of uric acid may occur.

Infections: Patients with severe immunosuppression may develop serious infections.

From 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 over several days, usually as part of intensive combination antitumor or drug therapy for organ transplantation. In this case, severe and sometimes fatal episodes of congestive heart failure caused by hemorrhagic myocarditis were observed.

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

From the reproductive system: disturbance 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 treated with cyclophosphamide during the prepubertal period, secondary sexual characteristics developed normally and menses were normal; they were subsequently 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 testosterone secretion. 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 observed. Testicular atrophy of varying degrees may be observed. In some patients, azoospermia caused by the drug is reversible, but restoration of impaired function may occur only several years after cessation of treatment.

Carcinogenicity. Some patients who were previously treated with the drug in monotherapy or in combination with other anticancer drugs and/or other treatments developed secondary malignant tumors. 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 when immune processes were disrupted. 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, you should always keep in mind the likelihood of the drug inducing a malignant tumor.

Allergic reactions: skin rash, urticaria or itching, rarely – anaphylactic reactions.

Other. One case of possible cross-sensitivity with other alkylating agents has been described. Cyclophosphamide may interfere with normal wound healing. It is possible to develop a syndrome similar to the syndrome of inappropriate secretion of antidiuretic hormone (ADH). Redness, swelling, or pain at the injection site. Flushing or redness of the face, headache, increased sweating.

Interaction

Inducers of microsomal oxidation in the liver can induce microsomal metabolism of cyclophosphamide, which leads to increased formation of alkylating metabolites, thereby reducing the half-life of cyclophosphamide and increasing its activity. The use of cyclophosphamide, which causes a marked and long-lasting suppression of cholinesterase activity, enhances the effect of suxamethonium and also reduces or slows down the metabolism of cocaine, thereby enhancing and/or increasing the duration of its effect and increasing the risk of toxicity.

Overdose

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

Recommendations for use

Cyclophosphamide-LENS® is administered intravenously as a bolus or as an infusion, intramuscularly. Cyclophosphamide is included in many chemotherapy treatment regimens, and therefore, when choosing a specific route of administration, regimen and doses in each individual case, one should be guided by data from special literature. The most commonly used doses and regimens for adults and children:

50-100 mg/m2 daily for 2-3 weeks,

100-200 mg/m2 2 or 3 times a week for 3-4 weeks,

600-750 mg/m2 once every 2 weeks,

1500-2000 mg/m2 once every 3-4 weeks up to a total dose of 6-14 g.

When using Cyclophosphamide-LENS® in combination with other anticancer drugs, it may be necessary to reduce the dose of both Cyclophosphamide-LENS® and other drugs. Before intravenous administration, Cyclophosphamide-LENS® is dissolved in water for injection or 0.9% sodium chloride solution at a concentration of 20 mg/1 ml.

Functional features

Cyclophosphamide 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.

Storage conditions

In a place protected from light and out of reach of children at a temperature not exceeding 10 °C.

Shelf life

3 years.
Do not use after the expiration date stated on the package.

Manufacturer

Lance Farm, Russia