Cyclophosphamide

Cyclophosphamide is used to treat various types of cancer. It is a chemotherapy drug that works by slowing or stopping cell growth.

Cyclophosphamide also works by decreasing your immune system's response to various diseases. It is used to treat a certain type of kidney disease in children after other treatments have not worked.

Cyclophosphamide may also be used for various conditions such as lupus and rheumatoid arthritis, and to prevent organ transplant rejection.

Cyclophosphamide is available under the following different brand names: Cytoxan.

Dosage Forms and Strengths

Powder for injection

• 500 mg
• 1 g
• 2 g

Tablet

• 25 mg
• 50 mg

Dosage Considerations – Should be Given as Follows:

Malignant Diseases

Adult and Pediatric

• Intravenous (IV) (intermittent therapy): 40-50 mg/kg (400-1800 mg/m²) divided over 2-5 days; may be repeated at intervals of 2-4 weeks
• IV (continuous daily therapy): 60-120 mg/m²/day (1-2.5 mg/kg/day)
• Oral (intermittent therapy): 400-1000 mg/m² divided over 4-5 days
• Oral (continuous daily therapy): 50-100 mg/m²/day or 1-5 mg/kg/day

Nephrotic Syndrome

• 2-3 mg/kg/day for up to 12 weeks when corticosteroids unsuccessful

Non-Hodgkin Lymphoma

• 600-1500 mg/m² intravenously (IV) with other antineoplastics (part of CHOP regimen); dose intensification possible

Breast Cancer

• 600 mg/m² intravenously (IV) with other antineoplastics; dose intensification possible

Systemic Lupus Erythematosus, Pediatric

• 500-750 mg/m² intravenously (IV) monthly; not to exceed 1 g/m²

Juvenile Idiopathic Arthritis/Vasculitis (Off-label)

• 10 mg/kg intravenously (IV) every 2 weeks

Lupus Nephritis (Off-Label)

• Induction therapy for lupus nephritis (American College of Rheumatology Guidelines 2012)
• Low-dose: 500 mg intravenously (IV) every 2 weeks for 6 doses plus corticosteroids, then maintenance with mycophenolate mofetil or azathioprine
• High-dose: 500-1000 mg/m² IV monthly for 6 doses plus corticosteroids

Dosing Modifications

• Hepatic impairment: Give 75% of normal dose if transaminase levels are greater than 3 times upper limit of normal (ULN) or bilirubin is 3.1-5 mg/dL
• Renal impairment: CrCl less than 10 mL/minute, give 75% of normal dose; CrCl greater than 10 mL/minute, give full dose

Common side effects of cyclophosphamide include:

• Hair loss
• Nausea and vomiting (may be severe)
• Gastrointestinal damage
• Low white blood cell count (leukopenia)
• Missed menstrual periods
• Sterility
• Facial flushing
• Headache
• Rash
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Nasal congestion
• Loss of appetite
• Stomach pain or upset
• Diarrhea
• A wound that will not heal
• Changes in skin color (darkening)
• Changes in nails

Other side effects of cyclophosphamide include:

• Cardiomyopathy, congestive heart failure (CHF) (high dose)
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis (rare)
• Hemorrhagic cystitis
• Absence of viable sperm in semen
• Low concentration of sperm in semen
• Interstitial pneumonia
• Infectious disease
• Secondary malignancies: Urinary bladder, myeloproliferative, lymphoproliferative

Serious side effects of cyclophosphamide include:

• Pink/bloody urine
• Unusual decrease in the amount of urine
• Mouth sores
• Unusual tiredness or weakness
• Joint pain
• Easy bruising or bleeding

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Cyclophosphamide has no known severe interactions with other drugs.

Serious interactions of cyclophosphamide include:

• adenovirus types 4 and 7 live, oral
• carbamazepine
• etanercept
• hydrochlorothiazide
• idarubicin
• idelalisib
• influenza virus vaccine trivalent, adjuvanted
• ivacaftor
• palifermin
• tofacitinib

Cyclophosphamide has moderate/mild interactions with at least 56 different drugs.

Mild interactions of cyclophosphamide include:

• lepirudin
• ruxolitinib

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

This medication contains cyclophosphamide. Do not take Cytoxan if you are allergic to cyclophosphamide or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Severe myelosuppression
• Hypersensitivity

Effects of Drug Abuse

• None

Short-Term Effects

• Acute heart failure, often occurring within 1 to 10 days of treatment, has been reported.
• See "What Are Side Effects Associated with Using Cyclophosphamide?"

Long-Term Effects

• Risk of potentially fatal and irreversible interstitial pulmonary fibrosis if given over prolonged periods.
• See "What Are Side Effects Associated with Using Cyclophosphamide?"

Cautions

• Use with caution in patients with hepatic or renal impairment, leukopenia, thrombocytopenia, recent radiation therapy or chemotherapy.
• Pelvic irradiation potentiates hemorrhagic cystitis.
• Potential for radiation recall when used in conjunction with radiation therapy.
• Risk of potentially fatal and irreversible interstitial pulmonary fibrosis if given over prolonged periods.
• May cause infertility in male patients who received high doses as children.
• Monitor for secondary malignancies.
• Heart Failure risk:
• Acute heart failure, often occurring within 1 to 10 days of treatment, has been reported
• Subclinical decreases in left ventricular ejection fraction (LVEF) in up to 50% of cases have also been seen
• The onset of heart failure usually resolves over 3 to 4 weeks; However, fatalities caused by heart failure have been reported
• Large individual doses (greater than 120–170 mg/kg or 1.55 mg/m 2 per day), old age, mediastinal radiation, and anthracycline use have been identified as risk factors

Pregnancy and Lactation

• Use cyclophosphamide during pregnancy only in LIFE-THREATENING emergencies when no safer drug is available. There is positive evidence of human fetal risk.
• Cyclophosphamide is excreted in breast milk; do not nurse.