Dosing & Uses
Dosage Forms & 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)
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
Dosage Forms & 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
Nephrotic Syndrome
2-3 mg/kg/day for up to 12 weeks when corticosteroids unsuccessful
Systemic Lupus Erythematosus
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

>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
Adverse Effects
Frequency Not Defined
Neutropenia
Fever
Nausea
Vomiting
Anorexia
Abdominal discomfort or pain
Diarrhea
Hemorrhagic colitis
Oral mucosal ulceration
Jaundice
Alopecia
Skin rash
Pigmentation of skin and changes in nails
Postmarketing Reports
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: Intrauterine 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
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
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, hypersensitivity reaction
Infections: Myelosuppression and immunosuppression may increase 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 retention, blood glucose increased, blood glucose decreased
Musculoskeletal and connective tissue: Rhabdomyolysis, scleroderma, muscle spasms, myalgia, arthralgia
Neoplasms: Acute leukemia, myelodysplastic syndrome, lymphoma, sarcomas, renal cell carcinoma, renal pelvis cancer, bladder cancer, ureteric cancer, thyroid cancer
Nervous system: Encephalopathy, convulsion, dizziness, neurotoxicity has been reported and manifested as reversible posterior leukoencephalopathy syndrome, myelopathy, peripheral neuropathy, polyneuropathy, neuralgia, dysesthesia, hypoesthesia, paresthesia, tremor, dysgeusia, hypogeusia, parosmia
Pregnancy: Premature labor
Psychiatric: Confusional state
Renal and urinary: Renal failure, renal tubular disorder, renal impairment, nephropathy toxic, hemorrhagic cystitis, bladder necrosis, cystitis ulcerative, bladder contracture, hematuria, nephrogenic diabetes insipidus, atypical urinary bladder epithelial cells
Reproductive system: Infertility, ovarian failure, ovarian disorder, amenorrhea, oligomenorrhea, testicular atrophy, azoospermia, oligospermia
Respiratory: Pulmonary veno-occlusive disease, acute respiratory distress syndrome, interstitial lung disease as manifested by respiratory failure (including fatal outcomes), obliterative bronchiolitis, organizing pneumonia, alveolitis allergic, pneumonitis, pulmonary hemorrhage; respiratory distress, pulmonary hypertension, pulmonary edema, pleural effusion, bronchospasm, dyspnea, hypoxia, cough, nasal congestion, nasal discomfort, oropharyngeal pain, rhinorrhea
Skin and subcutaneous tissue: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, palmoplantar erythrodysesthesia syndrome, radiation recall dermatitis, toxic skin eruption, urticaria, dermatitis, blister, pruritus, erythema, nail disorder, facial swelling, hyperhidrosis
Tumor lysis syndrome: May induce tumor-lysis syndrome and hyperuricemia in patients with rapidly growing tumors
Vascular: Pulmonary embolism, venous thrombosis, vasculitis, peripheral ischemia, hypertension, hypotension, flushing, hot flush
Warnings
Contraindications
Severe myelosuppression
Hypersensitivity
Urinary outflow obstruction
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 & Lactation
Pregnancy
Based on mechanism of action and published reports of effects in pregnant patients or animals, drug can cause fetal harm when administered to pregnant woman; exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn; drug is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys; advise pregnant women and females of reproductive potential of the potential risk to the fetus
Verify the pregnancy status of females of reproductive potential prior to the initiation of therapy
Contraception
- Therapy can cause fetal harm; advise females of reproductive potential to use effective contraception during treatment for up to 1 year after completion of therapy
- Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after completion of therapy
Infertility
- Amenorrhea, transient or permanent, associated with decreased estrogen and increased gonadotropin secretion develops in a proportion of women treated with cyclophosphamide
- Affected patients generally resume regular menses within a few months after cessation of therapy; risk of premature menopause with cyclophosphamide increases with age
- Oligomenorrhea has also been reported in association with cyclophosphamide treatment
- Men treated with cyclophosphamide may develop oligospermia or azoospermia, which are normally associated with increased gonadotropin but normal testosterone
Lactation
Drug is present in breast milk; neutropenia, thrombocytopenia, low hemoglobin, and diarrhea have been reported in infants breast fed by women treated with cyclophosphamide; because of potential for serious adverse reactions in a breastfed child from therapy, advise lactating women not to breastfeed during treatment and for 1 week after last dose
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
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
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Formulary
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