Adult Dosing

Chemotherapy for malignant Disease

• 40–50 mg/kg IV in divided doses over 2-5 days or 10-15 mg/kg q7–10 days
• Alternatively may give 3-5 mg/kg twice weekly

• Adjust dosage according to evidence of antitumor activity and/or leukopenia
• If on other cytotoxic drugs: reduce dose of cyclophosphamide
• Note: Dosing protocols may vary according to clinical condition, disease severity and individual patient characteristics. Many regimens are used. Some of the regimens commonly used are listed in dosing above. This dosing applies to patients with no hematologic deficiency

Goodpastures syndrome [Non-FDA Approved]

• For severe pulmonary hemorrhage, IV loading indicated – otherwise oral therapy appropriate. IV load is a total of 40-50 mg/kg divided over 2-5 days, then switched to oral cyclophosphamide

Pediatric Dosing

Chemotherapy for malignant Disease

• 40–50 mg/kg IV in divided doses over 2-5 days or 10-15 mg/kg q7–10 days
• Alternatively may give 3-5 mg/kg twice weekly

• Adjust dosage according to evidence of antitumor activity and/or leukopenia
• If on other cytotoxic drugs: reduce dose of cyclophosphamide
• Note: Dosing protocols may vary according to clinical condition, disease severity and individual patient characteristics. Many regimens are used. Some of the regimens commonly used are listed in dosing above. This dosing applies to patients with no hematologic deficiency

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment for malignant lymphomas, Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma, multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of the ovary, retinoblastoma, carcinoma of the breast

• Hypersensitivity to any of the ingredients of the product
• Patients with severely depressed bone marrow function

• N/A

Renal Dose Adjustment (Based on CrCl)

• <10 mL/min: Decrease dose by 25%

Hepatic Dose Adjustment

• Hepatic impairment: Use with caution; dose adjustments are not defined

• Secondary malignancies, including urinary bladder, myeloproliferative, or lymphoproliferative malignancies have developed in patients treated with cyclophosphamide alone or in combination with other antineoplastic drugs and/or modalities. Second malignancy may develop several years after the discontinuation of therapy
• Severe and sometimes fatal hemorrhagic cystitis may develop in patients treated with this drug. Fibrosis of the urinary bladder, sometimes extensive, also may develop with or without accompanying cystitis. Increased fluid intake and frequent voiding may help prevent cystitis; discontinue in severe hemorrhagic cystitis
• Cyclophosphamide can cause fetal harm when administered to a pregnant woman. If cyclophosphamide is used during pregnancy, or if a woman becomes pregnant during therapy, she should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant
• Interferes with oogenesis and spermatogenesis; causes sterility in both sexes
• Few instances of congestive heart failure have occurred, although no causal relationship is established
• Cyclophosphamide potentiates doxorubicin-induced cardiotoxicity
• Significant immunosuppression, leading to serious, sometimes fatal infections might develop
• Anaphylactic reactions, including death have been reported
• Avoid use as primary therapy in biopsy proven "minimal change" nephrotic syndrome in children; not indicated for nephrotic syndrome in adults or for any other renal disease
• Adjustment of the doses of replacement steroids and cyclophosphamide may be necessary in adrenalectomized patients
• Monitor hematologic profile; urine analysis and Cr at baseline

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• Leukopenia
• Thrombocytopenia
• Tumor cell infiltration of bone marrow
• Previous XRT
• Previous therapy with other cytotoxic agents
• Bone marrow suppression
• Adrenalectomy patients
• Wound healing

Pregnancy Category:D

Breastfeeding: Most sources consider breastfeeding to be contraindicated with antineoplastic therapy. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 17 November 2010). According to manufacturer's data, cyclophosphamide is excreted in breast milk. Manufacturer recommends discontinuation of nursing or discontinuation of therapy, by analyzing risk and benefit ratio in nursing mothers

• Note: Increased risk of carcinogenesis, mutagenesis, impairment of fertility and severe immunosuppression
• HEMA: Anemia, leucopenia, neutropenia with or without fever, thrombocytopenia, hyperurecemia
• GU: Amenorrhea, azoospermia, cystitis, hematuria, hemorrhagic cystitis and ureteritis, fertility impairment, oligospermia, ovarian fibrosis, renal tubular necrosis, sterility, testicular atrophy, urinary bladder fibrosis
• DERM: Alopecia, nail changes, skin pigmentation, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis
• GI: Nausea, vomiting, abdominal discomfort or pain, anorexia, diarrhea, hemorrhagic colitis, oral mucosal ulceration, jaundice
• CV: Acute cardiac toxicity, CHF, hemopericardium, hemorrhagic myocarditis, myocardial necrosis, pericarditis
• ENDO: Gonadal suppression, SIADH
• CNS: Asthenia, malaise
• RESP: Interstitial pneumonitis, interstitial pulmonary fibrosis
• MISC: Secondary malignancies/neoplasm, anaphylactic reactions, including death, hyperurecemia, superinfection

• Antoneoplastic alkylating agent; biotransformed to active alkylating metabolites in liver by a mixed function microsomal oxidase system; metabolities then interfere with the growth of susceptible rapidly proliferating malignant cells by cross-linking of tumor cell DNA
• Metabolized by liver by CYP2B6
• Excreted in urine (5-25% unchanged)
• Half-life: 3-12 hrs

US Trade Name(s)

• Cytoxan (Lyophilized)

US Availability

cyclophosphamide (generic)

• PWDR for INJ: 500 mg/vial
• PWDR for INJ: 1000 mg/vial
• PWDR for INJ: 2000 mg/vial

Cytoxan (Lyophilized)

• PWDR for INJ: 500 mg/vial
• PWDR for INJ: 1000 mg/vial
• PWDR for INJ: 2000 mg/vial

Canadian Trade Name(s)

• Procytox

Canadian Availability

Procytox

• PWDR for INJ: 200 mg/vial
• PWDR for INJ: 500 mg/vial
• PWDR for INJ: 1000 mg/vial
• PWDR for INJ: 2000 mg/vial

UK Trade Name(s)

• Only generic available

UK Availability

cyclophosphamide (generic)

• PWDR for INJ: 500 mg/vial
• PWDR for INJ: 1000 mg/vial
• PWDR for INJ: 2000 mg/vial

Australian Trade Name(s)

• Cycloblastin
• Endoxan

Australian Availability

Cycloblastin

• PWDR for INJ: 1000 mg/vial

Endoxan

• PWDR for INJ: 500 mg/vial
• PWDR for INJ: 1000 mg/vial
• PWDR for INJ: 2000 mg/vial

[Outline]

Hematology/Oncology

Antineoplastics

Alkylating Agents