Cyclocel-500 Injection

Cyclophosphamide for injection is an alkylating drug indicated for treatment of adults and pediatric patients with: Malignant Diseases: malignant lymphomas: Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma ( 1.1 ) Minimal Change Nephrotic Syndrome in Pediatric Patients: biopsy proven minimal change nephrotic syndrome patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy ( 1.2 ) Limitations of Use: The safety and effectiveness for the treatment of nephrotic syndrome in …

• During or immediately after cyclophosphamide for injection administration, administer adequate amounts of fluid to reduce the risk of urinary tract toxicity
• Malignant Diseases: Adult and Pediatric Patients Intravenous: Initial course for patients with no hematologic deficiency: 40 mg per kg to 50 mg per kg in divided doses over 2 to 5 days
• Other regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly
• Oral: 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing
• Minimal Change Nephrotic Syndrome
• In Pediatric Patients Oral: 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg)
• Treatment beyond 90 days increases the probability of sterility in males
• Important Administration Instructions During or immediately after the administration of cyclophosphamide for injection, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity
• Therefore, cyclophosphamide for injection should be administered in the morning
• Recommended Dosage for Malignant Diseases
• Adults and Pediatric Patients Intravenous Use When used as the only oncolytic drug therapy, the recommended dosage for the initial course of cyclophosphamide for injection for patients with no hematologic deficiency is 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. …

Cyclophosphamide for injection (lyophilized powder) is a sterile white cake available in single does vials. 500 mg 1 g 2 g For Injection, lyophilized powder: 500 mg, 1 g and 2 g ( 3 )

• The safety and effectiveness of cyclophosphamide have been established
• In pediatric patients and information on this use is discussed throughout the labeling
• Pre-pubescent females who receive cyclophosphamide generally develop secondary sexual characteristics normally and have regular menses
• Ovarian fibrosis with apparently complete loss of germ cells after prolonged administration of cyclophosphamide in late pre-pubescence has been reported. …

There is insufficient data from clinical studies of cyclophosphamide available for patients 65 years of age and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac functioning, and of concomitant disease or other drug therapy.

• Hypersensitivity Cyclophosphamide for injection is contraindicated in patients who have a history of severe hypersensitivity reactions to cyclophosphamide, any of its metabolites, or to other components of the product
• Anaphylactic reactions including death have been reported with cyclophosphamide
• Cross-sensitivity with other alkylating agents can occur. …

7.1 Effect of Other Drugs on Cyclophosphamide Exposure Protease Inhibitors Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites and may enhance the toxicities of cyclophosphamide, including higher incidence of infections, neutropenia, and mucositis. Monitor for increased toxicities in patients receiving protease inhibitors. 7.2 Drugs that Potentiate Cyclophosphamide Toxicities Radiation therapy or drugs with similar toxicities to cyclophosphamide for injection can potentiate toxicities for cyclophosphamide. …

Myelosuppression, Immunosuppression, Bone Marrow Failure and Infections: Severe immunosuppression may lead to serious and sometimes fatal infections. Close hematological monitoring is required. ( 5.1 ) Urinary Tract and Renal Toxicity: Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria can occur. Urotoxicity can be fatal. Exclude or correct any urinary tract obstructions prior to treatment. ( 5.2 ) Cardiotoxicity: Myocarditis, myopericarditis, pericardial effusion, arrythmias and congestive heart failure, which may be fatal, have been reported. Monitor patients, especially those with risk factors for cardiotoxicity or pre-existing cardiac disease. …

The following adverse reactions are discussed in more detail in other sections of the labeling. Hypersensitivity [see Contraindications ( 4 )] Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections [see Warnings and Precautions ( 5.1 )] Urinary Tract and Renal Toxicity [see Warnings and Precautions ( 5.2 )] Cardiotoxicity [see Warnings and Precautions ( 5.3 )] Pulmonary Toxicity [see Warnings and Precautions ( 5.4 )] Secondary Malignancies [see Warnings and Precautions ( 5.5 )] Veno-occlusive Liver Disease [see Warnings and Precautions ( 5.6 )] Infertility [ see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.3 , 8.4 )] Impaired Wound Healing [see Warni …

8.1 Pregnancy Risk Summary Based on its mechanism of action and published reports of effects in pregnant patients or animals, cyclophosphamide for injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 ) and Nonclinical Toxicology ( 13.1 )]. …

No specific antidote for cyclophosphamide is known. Overdosage should be managed with supportive measures, including appropriate treatment for any concurrent infection, myelosuppression, or cardiac toxicity should it occur. Serious consequences of overdosage include manifestations of dose dependent toxicities such as myelosuppression, urotoxicity, cardiotoxicity (including cardiac failure), veno-occlusive hepatic disease, and stomatitis [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , and 5.6 )] . …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.