NAME OF DRUG
cyclophosphamide

CLASSIFICATION

Cytotoxic Agent- non-vesicant
Alkylating Agent

ALTERNATE NAMES

CYTOXAN, PROCYTOX

INDICATIONS

• myeloproliferative and lymphoproliferative disorders
• has some use in solid malignancies

• cyclophosphamide disrupts DNA replication and transcription of RNA, resulting in the disruption of nucleic acid function
• it exhibits phosphorylating properties, and also possesses potent immunosuppressive activity
• the serum half-life after IV administration is reported to range from 4-6.5 hours; however, the drug and/or its metabolites can be detected in the serum for up to 72 hours after administration
• cyclophosphamide is enzymatically metabolized in the liver and mainly excreted in the urine
• 36-99% of a dose is eliminated within 48 hours; of this, 30% is unchanged drug

• ALL cytotoxic agents are prepared in pharmacy and will be sent to the ward with a label indicating storage conditions and the expiry date.  All cytotoxic waste including bags, sets, tubing, gloves, etc. must be properly disposed of in the cytotoxic waste containers on the nursing unit.

• compatible with NS, D5S, D5W
• incompatible with other drugs

ROUTES OF ADMINISTRATION

• IM
• IV direct - each 100 mg or fraction thereof over at least 1 minute
• IV intermittent - in 50-100 mL of compatible IV solution over 20-60 minutes
• IV infusion - the dose can be administered in a convenient volume
• intrapleural
• intraperitoneal

Intrapleural and Intraperitoneal routes restricted to physician only

A Parenteral Chemotherapy/Immunotherapy pre-printed order form (PPO # 45) must be used for prescribing if this cytotoxic agent
is not already on an existing PPO.

G - Cytotoxic Agents - see Drug Table G for specific administration guidelines.
H - The IV infusion rate must be controlled by an automated infusion control device.

DOSAGE

Dose and schedule depend on protocol and patient response.

• doses up to 50 mg/kg/dose or 200 mg/kg/course of treatment are used

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

• facial flushing, faintness, diaphoresis, and oropharyngeal sensation have occurred following IV administration
• extravasation (see Appendix VII for extravasation protocol for non-vesicants)

IMPORTANT IMPLICATIONS

• delayed (1-2 weeks) myelosuppression, especially neutropenia; can be dose limiting
• bladder toxicity, manifested as cystitis can be serious
• urine output should be closely followed; patients should receive >3 litres of fluid on the day of therapy to promote frequent urination and prevent toxic metabolites from "sitting" in the bladder
• the drug should be administered before 1600H to decrease the amount of drug in the bladder overnight
• nausea and vomiting usually occur 6-8 hours after drug administration (especially with high doses); antiemetics usually help
• interstitial pulmonary fibrosis can occur after chronic, long term therapy
• inappropriate ADH secretion has occurred, generally in patients receiving higher than normal doses.  Hyponatremia resulting from impaired excretion of water associated with progressive weight gain without edema occurs.
• cardiotoxicity has been rarely reported - it occurs in patients receiving high doses >50 mg/kg and those receiving other cardiotoxic drugs in combination
• reversible alopecia frequently occurs (70-80%) within 1-3 months
• patients may have increased sensitivity to neuromuscular blocking agents (i.e. succinylcholine); advise the anesthesiologist if the patient is to undergo surgery
• cyclophosphamide may interfere with normal wound healing

VGH Site only:
Notify security-84 immediately upon accidental spillage.
DO NOT ATTEMPT CLEAN-UP

• See also Appendix VI

Rev. Dec 2007