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 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 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 dosePregnancy 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. 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 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 BRAND FORM. UNIT PRICE PILL IMAGE cyclophosphamide intravenous- 1 gram vialcyclophosphamide intravenous- 2 gram vialcyclophosphamide intravenous- 1 gram vialcyclophosphamide intravenous- 500 mg vialcyclophosphamide intravenous- 2 gram vialcyclophosphamide intravenous- 2 gram vialcyclophosphamide intravenous- 500 mg vialcyclophosphamide intravenous- 1 gram vialcyclophosphamide intravenous- 1 gram vialcyclophosphamide intravenous- 1 gram vialcyclophosphamide intravenous- 500 mg vialcyclophosphamide intravenous- 500 mg vialcyclophosphamide intravenous- 1 gram vialcyclophosphamide intravenous- 200 mg/mL vialcyclophosphamide intravenous- 200 mg/mL vialcyclophosphamide intravenous- 2 gram vialcyclophosphamide intravenous- 500 mg vialcyclophosphamide intravenous- 200 mg/mL vialcyclophosphamide intravenous- 500 mg vialcyclophosphamide intravenous- 500 mg vialcyclophosphamide oral- 25 mg capsulecyclophosphamide oral- 25 mg capsulecyclophosphamide oral- 25 mg capsulecyclophosphamide oral- 50 mg capsulecyclophosphamide oral- 25 mg capsulecyclophosphamide oral- 50 mg capsulecyclophosphamide oral- 50 mg capsuleCopyright © 2010 First DataBank, Inc.Select a drug:cyclophosphamide intravenouscyclophosphamide oralPrint Patient Educationcyclophosphamide intravenous CYCLOPHOSPHAMIDE - INJECTION (sye-klo-FOSS-fuh-mide) COMMON BRAND NAME(S): Cytoxan USES: 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. HOW TO USE: This medication is usually given by injection into a vein by a health care professional. The dosage is based on your medical condition, weight, response to treatment, and other treatments (such as other chemotherapy drugs, radiation) you may be receiving. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During treatment with this medication, it is important that you take in more fluids than usual and pass urine often to help avoid kidney and bladder side effects. Intravenous fluids should be given with this medication. Also, ask your doctor how much fluid you should drink and how often to empty your bladder each day, and follow these instructions carefully. SIDE EFFECTS: Nausea, vomiting, loss of appetite, stomach ache, diarrhea, or darkening of the skin/nails may occur. Nausea and vomiting can be severe. In some cases, drug therapy may be necessary to prevent or relieve nausea and vomiting. Changes in diet such as eating several small meals or limiting activity may help lessen some of these effects. If these effects last or get worse, notify your doctor or pharmacist promptly.Although these effects are uncommon, immediately report any pain, swelling, or redness at the injection site.Temporary hair loss may occur. Hair growth should return after treatment has ended or may even return during treatment. However, new hair may have a different color or texture.People using this medication may have serious side effects. However, you have been prescribed this drug because your doctor has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.Tell your doctor right away if you have any serious side effects, including: signs of kidney or bladder problems (such as change in the amount of urine, pink/bloody urine), mouth sores, joint pain, stopping of menstrual periods, existing wounds that are slow healing, black/bloody stools, severe stomach/abdominal pain, yellowing eyes or skin, dark urine, mental/mood changes, muscle weakness/spasm.This medication may rarely cause very serious effects on the heart, especially when used in high doses, or in combination with radiation treatment or certain other chemotherapy drugs (such as doxorubicin). Get medical help right away if you develop: chest pain, jaw/left arm pain, trouble breathing, irregular heartbeat, symptoms of heart failure (such as shortness of breath, swelling ankles/feet, unusual tiredness, unusual/sudden weight gain).This medication decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising/bleeding. Tell your doctor right away if you develop any of the following symptoms: unusual tiredness, pale skin, signs of infection (such as sore throat that doesn't go away, fever, chills), easy bruising/bleeding.Cyclophosphamide may lessen the chance of having children in both men and women. Sterility is usually temporary with this medication, but can be permanent in some cases. Consult your doctor for more details.Although cyclophosphamide is used to treat cancer, in some patients it may increase the risk of developing another form of cancer, sometimes months to years after treatment. Consult your doctor for more details. It is important to be closely monitored by your doctor during treatment. You should also see your doctor regularly after treatment is finished. Tell your doctor right away if you develop: unusual growths or lumps, swollen glands, unexplained or sudden weight loss, night sweats, pain in the pelvis, painful or frequent urination.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side