Xyclomed

Xyclomed

cyclophosphamide

Manufacturer:

Korea United Pharma

Distributor:

Qualimed
Full Prescribing Info
Contents
Cyclophosphamide.
Description
Each vial contains Cyclophosphamide, USP 500 mg; Cyclophosphamide, USP 1 g.
Action
Pharmacology: Pharmacodynamics: Cyclophosphamide has been demonstrated to have a cytostatic effect in many tumour types. The active metabolites of cyclophosphamide are alkylating agents which transfer alkyl groups to DNA during the process of cell division, thus preventing normal synthesis of DNA.
Pharmacokinetics: Cyclophosphamide is well absorbed following an oral dose with a mean half-life of 4-8 hours for both oral and parenteral administration.
It is an inactive pro drug with alkylating metabolites produced by hepatic metabolism, reaching peak levels 4-6 hours after an i.v. injection. Hepatic enzymes may be induced. The parent compound binds poorly to plasma protein but the active metabolites are significantly protein-bound. The drug is widely distributed and crosses the blood-brain barrier, the placental barrier and is found in ascites. The metabolites are excreted renally.
Indications/Uses
Cyclophosphamide is used for malignant diseases such as Burkitt's and other Non-Hodgkin's lymphomas, some leukemias, and multiple myeloma. It is also used in the treatment of malignant lymphomas, neuroblastoma, adenocarcinoma of the ovary, retinoblastoma, carcinoma of the breast and Wilm's tumour.
Dosage/Direction for Use
The drug should be used only under constant supervision by experienced physicians because concomitant therapy with other antineoplastic agents may cause potential risks and fatal complication.
The drug is used for continuous reduction or reduction induction of disease.
Induction Dosage: The initial course of cyclophosphamide for patients with no hematologic deficiency usually consists of 40 to 50 mg/kg given intravenously in divided doses over a period of 2 to 5 days.
For the treatment of patients who were previously under X-ray therapy or anti-neoplastic agents which can decrease bone marrow function like cytotoxic drugs, and patients whose bone marrow are infiltrated tumor, the recommended dose is 1/2-1/3 of the initial dose.
Although leukopenia, related to the above dosage, may occur, generally it will disappear 7-10 days after the administration. White blood cell count should be monitored in the induction duration.
Maintenance Dosage: The recommended dose for delay or suppression of tumor growth is the following: 10 to 15 mg/kg/day given every 7 to 10 days intravenously.
3 to 5 mg/kg/day twice a week intravenously.
It is generally advisable to administer the largest maintenance dose that reasonably can be tolerated by the patient, unless the disease is unusually sensitive to cyclophosphamide.
Measure of total white blood cell count is a good objective guide for maintenance dosage control. If decreases in the total white blood cell count to 3000-4000 cells/mm3 develop commonly in patients, the drug can be used without risk of serious infection or other complication.
Preparation and Handling of Solutions: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to medication, whenever solution and container permit.
Cyclophosphamide Injection should be prepared for parenteral use by adding Sterile Water for Injection to the vial. Use the quantity of diluent shown below to reconstitute the product (see Table).

Click on icon to see table/diagram/image

Solutions of Cyclophosphamide Injection may be injected intravenously, intramuscularly, intraperitoneally, or intrapleurally or they may be infused intravenously in the following diluent: Dextrose Injection (5% dextrose), Dextrose and Sodium Chloride Injection (5% dextrose and 0.9% sodium chloride), 5% Dextrose and Ringer's Injection, Sodium Chloride Injection (0.45% sodium chloride), Sodium Lactate Injection (1/6 molar sodium lactate).
Reconstituted Cyclophosphamide Injection does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions.
The reconstituted solution should be used immediately, not exceeding 6 hours.
Extemporaneous liquid preparations of Cyclophosphamide for oral administration may be prepared by dissolving Cyclophosphamide Injection in Aromatic Elixir. The concentration of the solution is 1-5 mg of cyclophosphamide per mL. Such preparations should be stored under refrigeration and used within 14 days.
Overdosage
No specific antidote for cyclophosphamide is known. Overdosage should be managed with general supportive measures.
Contraindications
The drug is contraindicated in patients under pentostatin therapy.
Warnings
Death from cardiotoxicity due to the concomitant cyclophosphamide administration with pentostatin has been reported in foreign countries. Therefore, concomitant cyclophosphamide administration with pentostatin is not recommended.
Special Precautions
The drug should be administered with caution in the following patients: Patients with leukopenia; thrombocytopenia; tumor cell infiltration of bone marrow; previously under X-ray therapy; previously treated with other cytotoxic agents; impaired hepatic function; impaired renal function.
Cyclophosphamide may suppress active mechanism of immune system. Therefore, the dose-controlling or discontinuance of administration in the patients with microbiosis, fungal infection or viral infection should be considered. The administration of cyclophosphamide to the patients who were recently treated with steroidal drugs, the patients with concomitant administration with steroidal drugs, and especially, the patients with zoster herpes infection may be fatal, and should be cautioned.
The drug may interfere with normal wound healing.
Since cyclophosphamide has been reported to be more toxic in adrenalectomized dogs, adjustment of the doses of both replacement steroids and cyclophosphamide may be necessary for the adrenalectomized patient.
Use in Pregnancy & Lactation: Cyclophosphamide crosses the placenta and may cause teratogenesis. In the initial pregnancy, the drug should be used only when the expected benefits clearly outweigh the potential risks. Use in patients of child-bearing potential should be cautioned. Cyclophosphamide is excreted in breast milk. Breast feeding should be discontinued prior to the drug therapy.
Use In Pregnancy & Lactation
Cyclophosphamide crosses the placenta and may cause teratogenesis. In the initial pregnancy, the drug should be used only when the expected benefits clearly outweigh the potential risks. Use in patients of child-bearing potential should be cautioned.
Cyclophosphamide is excreted in breast milk. Breast feeding should be discontinued prior to the drug therapy.
Adverse Reactions
Cardiac Toxicity: Although a few instances of cardiac dysfunction have been reported following the use of recommended doses of cyclophosphamide, no causal relationship has been established.
Cardiotoxicity has been observed in some patients receiving high doses of cyclophosphamide (120-270 mg/kg) administered over a period of a few days, usually as a portion of an intensive antineoplastic multidrug regimen or in conjunction with transplantation procedures.
In a few instances with high doses of cyclophosphamide, severe, and sometimes fatal, congestive heart failure has occurred within a few days after the first cyclophosphamide dose.
Histopathologic examination has primarily shown hemorrhagic myocarditis. No residual cardiac abnormalities, as evidenced by electrocardiogram or echocardiogram appear to be present in patients surviving episodes of apparent cardiac toxicity associated with high doses of cyclophosphamide. Cyclophosphamide has been reported to potentiate doxorubicin-induced cardiotoxicity.
Secondary Malignancies: Secondary malignancies have developed in some patients treated with cyclophosphamide used alone or in association with other antineoplastic drugs and/or modalities. Most frequently, they have been urinary bladder, myeloproliferative, or lymphoproliferative malignancies.
Second malignancies most frequently were detected in patients treated for primary myeloproliferative malignancies or lymphoproliferative malignancies or nonmalignant disease in which immune processes are believed to be involved pathologically.
Second urinary bladder malignancies generally have occurred in patients who previously had hemorrhagic cystitis.
Renal pelvic and urethral tumor has also been reported in patients receiving long-term cyclophosphamide therapy.
In intraperitoneal or intravenous administration to rats, and intraperitoneal or hypodermic administration to mouse studies, there have been reports of tumors in several internal organs.
Although the clear relationship between the drug and malignancy in a patient has not been established, the possibility of cyclophosphamide-induced malignancy has been known on the basis of reliable data, therefore the possibility of cyclophosphamide-induced malignancy should be considered in any benefit-to-risk assessment for use of the drug.
Hematopoietic: Leukopenia is used as a guide for the expected effect and treatment. Thrombocytopenia or anemia may occur in a few patients and those symptoms reversibly occur. Acute leukemia has been reported in patients receiving long-term cyclophosphamide therapy.
Gastrointestinal Tract: Anorexia, nausea, vomiting are generally related to individual susceptibility to the drug as well as the dose of cyclophosphamide.
Oral mucosa ulcer, jaundice, hemorrhagic colitis during the therapy has been reported.
Urinary System: Hemorrhagic cystitis may develop in patients treated with cyclophosphamide, and it is considered to be due to urinary metabolite.
Non-hemorrhagic cystitis, fibrosis of the urinary bladder related to cyclophosphamide administration have been reported, and atypical urinary bladder epithelial cell have appeared in urinary sediment.
Sufficient water intake and frequent acceleration of urination prevent cystitis, and generally, although they occur, the administration doesn't have to be discontinued.
Hematuria usually resolves in a few days after cyclophosphamide treatment is stopped, but it may persist for several months, and in severe case, supplementation of lost blood may be needed. Protracted cases are successfully treated with application of electrocautery to telangiectatic areas of urinary bladder, diversion of urine flow, or cryosurgery.
Renal toxicity such as bleeding, conglobation in renal pelvis has been reported.
In the patients treated with the drug, gonadal suppression related to the dose and therapy duration has been reported. It may result in amenorrhea or aspermatism and maybe reversible, therefore, these adverse reactions should be considered.
Ovarian fibrosis after the cyclophosphamide administration has been reported.
Integumentary: Alopecia may occur in patients treated with frequent cyclophosphamide therapy. The hair can be expected to grow back after treatment with the drug or even during continued drug treatment, though it may be different in texture or color. Pigmentation of the skin and changes in nails can occur. General dermatitis may occur.
Respiratory System: Interstitial pulmonary fibrosis has been reported in patients receiving high doses of cyclophosphamide over a prolonged period.
Drug Interactions
Barbiturates: The rate of metabolism and the leukopenic activity of cyclophosphamide reportedly are increased by chronic administration of high doses of phenobarbital.
The patients should be alerted for possible combined drug actions, desirable or undesirable, involving cyclophosphamide even though cyclophosphamide has been used successfully concurrently with other drugs.
In one administration of pentostatin to a patient with cyclophosphamide therapy, confusion, dyspnea, hypotension, pulmonary edema developed and death of the patients has been reported. In animal (mouse) studies, concomitant administration with pentostatin (about 10 times of clinical dose), cyclophosphamide (around LD50) or ephosphamide (around LD50) has been confirmed that death rate increased more than each separate administration of those drugs.
Storage
Store at temperatures not exceeding 25°C.
ATC Classification
L01AA01 - cyclophosphamide ; Belongs to the class of alkylating agents, nitrogen mustard analogues. Used in the treatment of cancer.
Presentation/Packing
Powd for inj (vial, white crystalline powder) 500 mg x 10's. 1 g x 10's.
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