Home › Drugs › Cyclophosphamide Injection, Solution

Cyclophosphamide Injection, Solution

FDA Drug Information • Also known as: Cyclophosphamide

Brand Names
Cyclophosphamide
Route
INTRAVENOUS
Dosage Form
INJECTION
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION 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. Cyclophosphamide Structural Formula.jpg

    • What Is Cyclophosphamide Injection, Solution Used For?

    1 INDICATIONS AND USAGE 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. Cyclophosphamide Injection is an alkylating drug indicated for treatment of adult 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 )

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION Malignant Diseases: Adult and Pediatric Patients ( 2.2 )

  • Intravenous: Initial course for patients with no hematologic deficiency: 40 mg/kg to 50 mg/kg in divided doses over 2 to 5 days. Other regimens include 10 mg/ kg to 15 mg/ kg given every 7 to 10 days or 3 mg/ kg to 5 mg/ kg twice weekly.
  • See full prescribing information for instructions on preparation, handling, and administration. ( 2.3 ) 2.1 Important Dosing Information During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, Cyclophosphamide Injection should be administered in the morning. 2.2 Recommended Dosage for Malignant Diseases Adults and Pediatric Patients Intravenous When used as the only oncolytic drug therapy, the initial course of Cyclophosphamide Injection for patients with no hematologic deficiency usually consists of 40 mg/kg to 50 mg/kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg/kg to 15 mg/kg given every 7 to 10 days or 3 mg/kg to 5 mg/kg twice weekly. Dosages may also be adjusted based on antitumor activity and/or leukopenia. The total leukocyte count may be used to manage dosage. When Cyclophosphamide Injection is included in combined cytotoxic regimens, it may be necessary to reduce the dose of Cyclophosphamide Injection as well as that of the other drugs. 2.3 Preparation, Handling and Administration Cyclophosphamide Injection is a hazardous drug. 1 Follow applicable special handling and disposal procedures. Caution should be exercised when handling and preparing Cyclophosphamide Injection. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide Injection. Cyclophosphamide Injection Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use Cyclophosphamide Injection vials if there are signs of particulate matter. Cyclophosphamide Injection does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique. For Direct Intravenous Injection Aseptically withdraw the prescribed dose from the vial. Dilute the prescribed dose of Cyclophosphamide Injection to a concentration of 20 mg per mL by using any of the following diluents:
  • 0.9% Sodium Chloride Injection, USP
  • 0.45% Sodium Chloride Injection, USP
  • 5% Dextrose Injection, USP
  • 5% Dextrose and 0.9% Sodium Chloride Injection, USP Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly. For Intravenous Infusion Aseptically withdraw the prescribed dose from the vial. Dilute the prescribed dose of Cyclophosphamide Injection to a concentration of 2 mg per mL by using any of the following...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS 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) ] Most common adverse reactions reported are neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials and Postmarketing Experience The following adverse reactions associated with the use of cyclophosphamide were identified in clinical studies or post-marketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions were neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea. Cardiac: cardiac arrest, ventricular fibrillation, ventricular tachycardia, cardiogenic shock, pericardial effusion (progressing to cardiac tamponade), myocardial hemorrhage, myocardial infarction, cardiac failure (including fatal outcomes), cardiomyopathy, myocarditis, pericarditis, carditis, atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, bradycardia, tachycardia, palpitations, QT prolongation. Congenital, Familial and Genetic: intra-uterine death, fetal malformation, fetal growth retardation, fetal toxicity (including myelosuppression, gastroenteritis). Ear and Labyrinth: deafness, hearing impaired, tinnitus. Endocrine: water intoxication. Eye: visual impairment, conjunctivitis, lacrimation. Gastrointestinal: gastrointestinal hemorrhage, acute pancreatitis, colitis, enteritis, cecitis, stomatitis, constipation, parotid gland inflammation, nausea, vomiting, diarrhea. General Disorders and Administrative Site Conditions: multiorgan failure, general physical deterioration, influenza-like illness, injection/infusion site reactions (thrombosis, necrosis, phlebitis, inflammation, pain, swelling, erythema), pyrexia, edema, chest pain, mucosal inflammation, asthenia, pain, chills, fatigue, malaise, headache, febrile neutropenia. Hematologic: myelosuppression, bone marrow failure, disseminated intravascular coagulation and hemolytic uremic syndrome (with thrombotic microangiopathy). Hepatic: veno-occlusive liver disease, cholestatic hepatitis, cytolytic hepatitis, hepatitis, cholestasis; hepatotoxicity with hepatic failure, hepatic encephalopathy, ascites, hepatomegaly, blood bilirubin increased, hepatic function abnormal, hepatic enzymes increased. Immune: immunosuppression, anaphylactic shock and hypersensitivity reaction. Infections: The following manifestations have been associated with myelosuppression and immunosuppression caused by cyclophosphamide: increased risk for and severity of pneumonias (including fatal outcomes), other bacterial, fungal, viral, protozoal and, parasitic infections; reactivation of latent infections, (including viral hepatitis, tuberculosis), Pneumocystis jiroveci , herpes zoster, Strongyloides , sepsis and septic shock. Investigations: blood lactate dehydrogenase increased, C-reactive protein increased. Metabolism and Nutrition: hyponatremia, fluid...

    • Drug Interactions

    7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on Cyclophosphamide Exposure Protease Inhibitors Cyclophosphamide is a pro-drug that is activated by cytochrome P450s [see Clinical Pharmacology (12.3) ]. Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites. Use of protease inhibitor-based regimens was found to be associated with a higher Incidence of infections and neutropenia in patients receiving cyclophosphamide, doxorubicin, and etoposide (CDE) than use of a Non-Nucleoside Reverse Transcriptase Inhibitor-based regimen. 7.2 Drugs that Can Potentiate Cyclophosphamide Toxicities Combined or sequential use of Cyclophosphamide Injection and other drugs or agents with similar toxicities to Cyclophosphamide Injection and can potentiate these effects and are listed in Table 2 . Table 2: Drugs that Can Potentiate Cyclophosphamide Toxicities Toxicity Drug or other treatment Increased hematotoxicity and/or immunosuppression

  • ACE inhibitors: ACE inhibitors can cause leukopenia.
  • Natalizumab
  • Paclitaxel: Increased hematotoxicity has been reported when cyclophosphamide was administered after paclitaxel infusion.
  • Thiazide diuretics
  • Zidovudine Increased cardiotoxicity
  • Anthracyclines
  • Cytarabine
  • Pentostatin
  • Radiation therapy of the cardiac region
  • Trastuzumab Increased pulmonary toxicity
  • Amiodarone
  • G-CSF, GM-CSF (granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor) Increased nephrotoxicity
  • Amphotericin B
  • Indomethacin: Acute water intoxication has been reported with concomitant use of indomethacin Increase in other toxicities:
  • Azathioprine: Increased risk of hepatotoxicity (liver necrosis)
  • Busulfan: Increased incidence of hepatic veno-occlusive disease and mucositis has been reported.
  • Protease inhibitors: Increased incidence of mucositis Increased risk of hemorrhagic cystitis
  • Radiation treatment: Increased risk of hemorrhagic cystitis may result from a combined effect of cyclophosphamide and past or concomitant radiation treatment. 7.3 Effect of Cyclophosphamide With Other Drugs Etanercept A higher incidence of non-cutaneous malignant solid tumors in patients with Wegener’s granulomatosis occurred with the addition of etanercept to cyclophosphamide treatment. Metronidazole Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. In an animal study, the combination of cyclophosphamide with metronidazole was associated with increased cyclophosphamide toxicity. Tamoxifen Concomitant use of tamoxifen and chemotherapy may increase the risk of thromboembolic complications. Coumarins Both increased and decreased warfarin effect have been reported in patients receiving warfarin and cyclophosphamide. Cyclosporine Lower serum concentrations of cyclosporine have been observed in patients receiving a combination of cyclophosphamide and cyclosporine than in patients receiving only cyclosporine. This interaction may result in an...

    • Contraindications

    4 CONTRAINDICATIONS 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) ] .

  • Severe hypersensitivity to cyclophosphamide ( 4 )
  • Urinary outflow obstruction ( 4 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Based on its mechanism of action and published reports of effects in pregnant patients or animals, Cyclophosphamide Injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ] . Exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn [see Data] . Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys [see Data] . Advise pregnant women and females of reproductive potential of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% - 4% and of miscarriage is 15% - 20% of clinically recognized pregnancies. Data Human Data Malformations of the skeleton, palate, limbs and eyes as well as miscarriage have been reported after exposure to cyclophosphamide in the first trimester. Fetal growth retardation and toxic effects manifesting in the newborn, including leukopenia, anemia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis have been reported after exposure to cyclophosphamide. Animal Data Administration of cyclophosphamide to pregnant mice, rats, rabbits and monkeys during the period of organogenesis at doses at or below the dose in patients based on body surface area resulted in various malformations, which included neural tube defects, limb and digit defects and other skeletal anomalies, cleft lip and palate, and reduced skeletal ossification.

    Overdosage

    10 OVERDOSAGE 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.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING 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

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.