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 lymph leukemia, lymphogranulematosis, non-Hodgkin’s lymphoma, multiple myeloma, breast cancer, ovarian cancer, neuroblastoma, retinoblastoma, fungal mycosis.

Active ingredient

Cyclophosphamide

Interaction

Microsomal oxidation inducers 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 causing marked and prolonged inhibition of cholinesterase activity enhances the effects of suxamethonium and also reduces or slows cocaine metabolism, thereby increasing and/or increasing the duration of its effects and increasing the risk of toxic effects.

Directions for use

Cyclophosphan-LNS® is administered intravenously by jetting or as an infusion, intramuscularly. Cyclophosphamide is included in many chemotherapeutic treatment regimens, therefore, when choosing a particular route of administration, regimen and doses in each individual case, one should be guided by the data of 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 to a cumulative dose of 6-14 g.

When using Cyclophosphan-LENS® in combination with other antitumor drugs, dose reduction may be required for both Cyclophosphan-LENS® and other drugs. Before intravenous administration Cyclophosphan-LENS® is dissolved in water for injection or 0.9% sodium chloride solution at the concentration of 20 mg/1 ml.

Special Instructions

Cyclophosphan-LNS® should be used under the supervision of a physician experienced in the use of antitumor drugs. During treatment with the drug, regular blood tests should be performed (especially paying attention to the content of neutrophils and platelets) to assess the degree of myelosuppression, and regular urine tests for the presence of erythrocytes, the appearance of which may precede the development of hemorrhagic cystitis.

Features

Cyclophosphamide is metabolized mainly in the liver under the action of microsomal oxidase system, forming active alkylating metabolites (4-ON cyclophosphamide and aldophosphamide), some of which undergo further transformation to inactive metabolites, some of which are transported into cells, where under the influence of phosphatases they turn into metabolites that have cytotoxic effect.

Contraindications

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

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

Side effects

Blood 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 in leukopenia usually begins 7-10 days 4 after discontinuation of treatment with the drug.

Digestive system disorders: nausea, vomiting, anorexia, less often stomatitis, discomfort or pain in the abdominal area, diarrhea or constipation. There are some reports of hemorrhagic colitis and jaundice. There are rare cases of liver dysfunction, manifested by increased activity of transaminases, alkaline phosphatase and serum bilirubin. In 15-50 % of patients receiving high doses of cyclophosphamide in combination with busulfan and total irradiation during allogeneic bone marrow transplantation hepatic vein endophlebitis develops.

A similar reaction in very rare cases is also seen 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 a dramatic increase in body weight, hepatomegaly, ascites, and hyperbilirubinemia. Hepatic encephalopathy may also be observed.

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

Urinary system disorders: hemorrhagic urethritis/cystitis, renal tubule necrosis. In rare cases, this condition may be severe and even fatal. Bladder fibrosis may also develop, sometimes widespread, 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. Prevention of cystitis is promoted by hydration and the use of mesna. In severe forms of hemorrhagic cystitis, treatment with the drug should be discontinued. When prescribing high doses of cyclophosphamide in rare cases renal dysfunction, hyperuricemia, nephropathy associated with increased uric acid formation may be observed.

Infections: serious infections may develop in patients with severe forms of immunosuppression.

Cardiovascular system disorders: cardiotoxicity has been observed when high doses of 4.5-10 g/m2 (120 to 270 mg/kg) of the drug have been administered for several days, usually as part of an intensive combined antitumor or drug therapy in organ transplantation. Severe and sometimes fatal episodes of congestive heart failure due to hemorrhagic myocarditis have been reported.

Respiratory system: interstitial pulmonary fibrosis (when administering high doses of the drug for a long time).

Reproductive system disorders: disruption of oogenesis and spermatogenesis. The drug may cause sterility in both men and women, which in some cases may be irreversible. A large proportion of women develop amenorrhea, with regular menstruation usually restored within a few months of stopping treatment. Girls treated with cyclophosphamide during prepuberty developed normal secondary sexual characteristics and menstruation; they were subsequently able to conceive. Men may develop oligospermia or azoospermia as a result of treatment with the drug, associated with increased gonadotropin levels 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 gonadotropin secretion may be noted. Testicular atrophy of varying degrees may be noted. In some patients azoospermia caused by the drug is reversible, but recovery of impaired function may not occur until several years after discontinuation of treatment.

Carcinogenicity. Some patients who were previously treated with the drug in monotherapy or in combination with other antitumor drugs and/or other treatments developed secondary malignant tumors. Most often these were bladder tumors (usually in patients with previous hemorrhagic cystitis), myeloproliferative or lymphoproliferative diseases. Secondary tumors most often developed in patients as a result of treatment of primary myeloproliferative malignancies or non-malignant diseases, with immune disorders. In some cases a secondary tumor developed several years after discontinuation of treatment with the drug. When evaluating the ratio of expected positive results to possible risk of using the drug, we should always keep in mind the possibility of malignancy induction by the drug.

Allergic reactions: skin rash, urticaria or pruritus, rarely anaphylactic reactions.

Others. One case of possible cross-sensitivity with other alkylating agents has been described. Cyclophosphamide may interfere with normal wound healing. Syndrome similar to inadequate antidiuretic hormone (ADH) secretion syndrome may develop. Redness, swelling or pain at the injection site. Blood rush to the face or reddening of the face, headache, increased sweating.

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.