Complete SPL Sections
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Malignant Diseases Cyclophosphamide Injection is indicated for the treatment of adult and pediatric patients with: • malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin's disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma • multiple myeloma • leukemias: chronic lymphocytic leukemia, chronic granulocytic leukemia (it is usually ineffective in acute blastic crisis), acute myelogenous and monocytic leukemia, acute lymphoblastic (stem-cell) leukemia (cyclophosphamide given during remission is effective in prolonging its duration) • mycosis fungoides (advanced disease) • neuroblastoma (disseminated disease) • adenocarcinoma of the ovary • retinoblastoma • carcinoma of the breast Cyclophosphamide, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Cyclophosphamide Injection is a clear or colorless ready to dilute sterile solution in a multiple-dose vial available in the following presentations: • 500 mg/2.5 mL (200 mg/mL) • 1,000 mg/5 mL (200 mg/mL)
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
Hypersensitivity Cyclophosphamide is contraindicated in patients who have a history of severe hypersensitivity reactions to it, any of its metabolites, or to other components of the product. Anaphylactic reactions including death have been reported with cyclophosphamide. Possible cross-sensitivity with other alkylating agents can occur. Urinary Outflow Obstruction Cyclophosphamide is contraindicated in patients with urinary outflow obstruction [see Warnings and Precautions (5.2) ] .
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
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) ] • Alcohol Content [see Warnings and Precautions (5.7) ] • Infertility [see Warnings and Precautions (5.9) and Use in Specific Populations (8.3 and 8.4) ] • Impaired Wound Healing [see Warnings and Precautions (5.10) ] • Hyponatremia [see Warnings and Precautions (5.11) ]
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
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 )]. Patients who received an overdose should be closely monitored for the development of toxicities, and hematologic toxicity in particular. Cyclophosphamide and its metabolites are dialyzable. Therefore, rapid hemodialysis is indicated when treating any suicidal or accidental overdose or intoxication. Cystitis prophylaxis with mesna may be helpful in preventing or limiting urotoxic effects with cyclophosphamide overdose.
11 DESCRIPTION
DESCRIPTION SECTION
Cyclophosphamide is an alkylating drug. It is an antineoplastic drug chemically related to the nitrogen mustards. The chemical name for cyclophosphamide is 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate, and has the following structural formula: Cyclophosphamide has a molecular formula of C 7 H 15 Cl 2 N 2 O 2 P•H 2 O and a molecular weight of 279.1 g/mol. Cyclophosphamide is soluble in water, saline, or ethanol. Cyclophosphamide Injection is a 200 mg/mL sterile clear colorless solution for intravenous use and is available as 500 mg and 1,000 mg strength vials. • 500 mg vial contains 534.5 mg cyclophosphamide monohydrate equivalent to 500 mg cyclophosphamide and 83.9% (v/v) dehydrated alcohol. • 1,000 mg vial contains 1,069 mg cyclophosphamide monohydrate equivalent to 1,000 mg cyclophosphamide and 83.9% (v/v) dehydrated alcohol.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
15 REFERENCES
REFERENCES SECTION
1. OSHA Hazardous drugs. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
Cyclophosphamide Injection is a 200 mg/mL clear or colorless ready-to-dilute sterile solution containing cyclophosphamide, USP. Cyclophosphamide Injection NDC Number Presentation Pack Factor 0338-9777-01 500 mg per 2.5 mL Multiple-Dose Vial 1 vial per carton 0338-9779-01 1,000 mg per 5 mL Multiple-Dose Vial 1 vial per carton The container closure is not made with natural rubber latex. Store the vials refrigerated at 2°C to 8°C (36°F to 46°F). Cyclophosphamide is a hazardous product. Follow special handling and disposal procedures. 1
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Advise the patient of the following: Myelosuppression, Immunosuppression, and Infections Inform patients of the possibility of myelosuppression, immunosuppression, and infections. Explain the need for routine blood cell counts. Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever [see Warnings and Precautions (5.1) ]. Urinary Tract and Renal Toxicity Advise the patient to report urinary symptoms (patients should report if their urine has turned a pink or red color) and the need for increasing fluid intake and frequent voiding [see Warnings and Precautions (5.2) ]. Cardiotoxicity Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Warnings and Precautions (5.3) ] . Pulmonary Toxicity Warn patients of the possibility of developing non-infectious pneumonitis. Advise patients to report promptly any new or worsening respiratory symptoms [see Warnings and Precautions (5.4) ] . Alcohol Content Explain to patients the possible effects of the alcohol content in Cyclophosphamide Injection, including possible effects on central nervous system. Patients in whom alcohol should be avoided or minimized should consider the alcohol content of Cyclophosphamide Injection. Alcohol could impair their ability to drive or use machines immediately after infusion [see Warnings and Precautions (5.7) ]. Embryo-Fetal Toxicity Inform female patients of the risk to a fetus and potential loss of the pregnancy. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment and for up to 1 year after completion of therapy [see Warning and Precautions (5.8) and Use in Specific Populations (8.1 , 8.3) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after completion of therapy [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1 , 8.3) ] . Lactation Advise lactating women not to breastfeed during treatment and for 1 week after the last dose of Cyclophosphamide Injection [see Use in Specific Populations (8.2) ]. Infertility Advise males and females of reproductive potential that Cyclophosphamide Injection may impair fertility [see Warnings and Precautions (5.9) and Use in Specific Populations (8.3 , 8.4) ]. Common Adverse Reactions Explain to patients that side effects such as nausea, vomiting, stomatitis, impaired wound healing, amenorrhea, premature menopause, sterility and hair loss may be associated with cyclophosphamide administration. Other undesirable effects (including, e.g., dizziness, blurred vision, visual impairment) could affect the ability to drive or use machines [see Adverse Reactions (6.1) ] . Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA Baxter is a registered trademark of Baxter International Inc. Product of USA 07-19-00-7612
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Container Label NDC 0338- 9777 -01 Cyclophosphamide Injection 500 mg/2.5 mL (200 mg/mL) Must Dilute Before Intravenous Use HAZARDOUS DRUG Rx Only Multiple Dose Vial Dosage: See prescribing information. Each mL contains 214 mg cyclophosphamide mono- hydrate equivalent to 200 mg of cyclophosphamide USP. Store vial refrigerated at 2° to 8°C (36° to 46°F). Manufactured for: Baxter Healthcare Corporation FPO Barcode (01)00303389777014 Carton Label For Intravenous Infusion Use: Dilute to a concentration of 2 mg/mL. For Direct Injection Use: Dilute to a concentration of 20 mg/mL. See Prescribing Information for a list of diluents. Recommended Dosage: See prescribing information Store vial refrigerated at 2°C to 8°C (36°F to 46°F). For multiple-dose use. Each mL contains 214 mg cyclophosphamide monohydrate equivalent to 200 mg of cyclophosphamide USP, and 83.9% (v/v) dehydrated alcohol USP. The container closure is not made with natural rubber latex. NDC 0338- 9777 -01 Cyclophosphamide Injection 500 mg/2.5 mL (200 mg/mL) Must Dilute Before Intravenous Use Sterile, Nonpyrogenic Preservative-free Baxter Logo Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA FPO Barcode (01)20303389777018 NDC 0338- 9777 -01 Rx Only Cyclophosphamide Injection 500 mg/2.5 mL (200 mg/mL) Must Dilute Before Intravenous Use HAZARDOUS DRUG Multiple-Dose Vial Refrigerate NVCP500VUS 07-04-00-1281 NDC 0338- 9777 -01 Cyclophosphamide Injection 500 mg/2.5 mL (200 mg/mL) Must Dilute Before Intravenous Use Sterile, Nonpyrogenic Preservative-free Baxter Logo Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA Container Label NDC 0338- 9779 -01 Cyclophosphamide Injection 1,000 mg/5 mL (200 mg/mL) Must Dilute Before Intravenous Use HAZARDOUS DRUG Rx Only Multiple Dose Vial Dosage: See prescribing information. Each mL contains 214 mg cyclo phosphamide monohydrate equivalent to 200 mg of cyclophosphamide USP. Store vial refrigerated at 2° to 8°C (36° to 46°F). Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA FPO Barcode (01)00303389779018 Carton Label For Intravenous Infusion Use: Dilute to a concentration of 2 mg/mL. For Direct Injection Use: Dilute to a concentration of 20 mg/mL. See Prescribing Information for a list of diluents. Recommended Dosage: See prescribing information. Store vial refrigerated at 2°C to 8°C (36°F to 46°F). For multiple-dose use. Each mL contains 214 mg cyclophosphamide monohydrate equivalent to 200 mg of cyclophosphamide USP, and 83.9% (v/v) dehydrated alcohol USP. The container closure is not made with natural rubber latex. NDC 0338- 9779 -01 Cyclophosphamide Injection 1,000 mg/5 mL (200 mg/mL) Must Dilute Before Intravenous Use Sterile, Nonpyrogenic Preservative-free Baxter Logo Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA FPO Barcode (01)20303389779012 NDC 0338- 9779 -01 Rx Only Cyclophosphamide Injection 1,000 mg/5 mL (200 mg/mL) Must Dilute Before Intravenous Use HAZARDOUS DRUG Multiple-Dose Vial Refrigerate NVCP1000VUS 07-04-00-1282 NDC 0338- 9779 -01 Cyclophosphamide Injection 1,000 mg/5 mL (200 mg/mL) Must Dilute Before Intravenous Use Sterile, Nonpyrogenic Preservative-free Baxter Logo Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA