Dosing and uses of Cytoxan (cyclophosphamide)
Adult dosage forms and strengths
powder for injection
- 500mg
- 1g
- 2g
tablet
- 25mg
- 50mg
Malignant Diseases
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)
PO (intermittent therapy): 400-1000 mg/m² divided over 4-5 days
PO (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 IV with other antineoplastics (part of CHOP regimen); dose intensification possible
Breast Cancer
600 mg/m² IV with other antineoplastics; dose intensification possible
Juvenile Idiopathic Arthritis/Vasculitis (Off-label)
10 mg/kg IV every 2 weeks
Lupus Nephritis (Off-Label)
Induction therapy for lupus nephritis (American College of Rheumatology Guidelines 2012)
Low-dose: 500 mg 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
Systemic Sclerosis (Orphan)
Prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplant
Orphan designation sponsor
- Accentia Biopharmaceuticals, 324 South Hyde Avenue, Suite 350, Tampa, FL 33606
Dosing Modifications
Hepatic impariment: Give 75% of normal dose if transaminase levels are >3 times upper limit of normal or bilirubin is 3.1-5 mg/dL
Renal impairment: CrCl <10 mL/min, give 75% of normal dose; CrCl >10 mL/min, give full dose
Pediatric dosage forms and strengths
powder for injection
- 500mg
- 1g
- 2g
tablet
- 25mg
- 50mg
Malignant Diseases
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)
PO (intermittent therapy): 400-1000 mg/m² divided over 4-5 days
PO (continuous daily therapy): 50-100 mg/m²/day
Juvenile Idiopathic Arthritis/Vasculitis
10 mg/kg IV every 2 weeks
Nephrotic Syndrome
2-3 mg/kg/day for up to 12 weeks when corticosteroids unsuccessfuL
Systemic Lupus Erythematosus
500-750 mg/m² IV monthly; not to exceed 1 g/m²
Interactions
>10%
Alopecia (40-60%)
Nausea and vomiting
GI toxicity
Leukopenia
Amenorrhea
Sterility
1-10%
Facial flushing
Headache
Rash
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Nasal congestion
Frequency not defined
Cardiomyopathy, CHF (high dose)
Stevens-Johnson syndrome
Toxic epidermal necrolysis (rare)
Hemorrhagic cystitis
Azoospermia
Oligozoospermia
Interstitial pneumonia
Infectious disease
Secondary malignancies: Urinary bladder, myeloproliferative, lymphoproliferative
Warnings
Contraindications
Severe myelosuppression
Hypersensitivity
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 LVEF in up to 50% of cases have also been seen
- The onset of HF usually resolves over 3 to 4 weeks; However, fatalities caused by HF 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
Pregnancy category: d
Lactation: Drug excreted in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cytoxan (cyclophosphamide)
Mechanism of action
Metabolites interfere with malignant cell growth by cross-linking tumor cell DNA; drug does not have specificity for any phase of the cell cycle; also has potent immunosuppressive activity
Absorption
Bioavailability: 75%
Onset: 2-3 hr
Peak plasma time: Cyclophosphamide, 1 hr; metabolites, 2-3 hr
Distribution
Protein bound: Cyclophosphamide, low; metabolites, >60%
Vd: 0.48-0.71 L/kg
Metabolism
Metabolized by liver
Metabolites: 4-hydroperoxycyclophosphamide, 4-aldophosphamide
Elimination
Half-life: 3-12 hr
Excretion: Urine
Administration
Give dose early in day
Patients should drink plenty of fluids with PO doses
Patients should empty bladder frequently to prevent hemorrhagic cystitis
Sometimes, mesna is used concomitantly as prophylaxis against hemorrhagic cystitis
Monitor blood counts during therapy (WBC count may decrease to 2000-3000/μL without serious risk of infection)
May be administered IM, intraperitoneally, intrapleurally, by IV piggy-back, or by continuous IV infusion
IV Incompatibilities
Y-site: Amphotericin B cholesteryl sulfate
IV Compatibilities
Additive: Cisplatin/etoposide, fluorouracil, hydroxyzine, methotrexate, methotrexate/fluorouracil, mitoxantrone, ondansetron
Syringe: Bleomycin, cisplatin, doxapram, doxorubicin, droperidol, furosemide, heparin, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine
Y-site (partial list): Allopurinol, amifostine, bleomycin, most cephalosporins, cisplatin, diphenhydramine, doxorubicin, doxorubicin liposomal, filgrastim, fluorouracil, furosemide, gemcitabine, linezolid, lorazepam, mitomycin, morphine, paclitaxel, prochlorperazine, propofol, sodium bicarbonate, trimethoprim/sulfamethoxazole, vancomycin, vinblastine, vincristine
IV Preparation
Maximum concentration of cyclophosphamide is limited to 20 mg/mL because of solubility
IV push: Reconstitute with NS (do not use SWI, because it is hypotonic)
Infusion: Reconstitute with SWI to concentration of 20 mg/mL
May dilute further with D5W, NS, lactated Ringer solution, or other compatible fluids
IV Administration
Infusions may be administered over 1-2 hours
Doses >500 mg up to ~1 g may be administered over 20-30 minutes
To minimize bladder toxicity, increase normal fluid intake during and for 1-2 days after cyclophosphamide therapy; most adult patients will require fluid intake of at least 2 L/day; high-dose regimens should be accompanied by vigorous hydration with or without mesna therapy
Storage
Store intact vials at room temperature
