Risk Summary Cyclophosphamide Tablets is a cytotoxic drug. There are no pre-clinical data of relevance to the prescriber which are additional to the information already stated in other sections of the Summary of Product Characteristics. Cyclophosphamide treatment may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop a serious infection. OSHA. If you no longer wish to have this DailyMed RSS service, simply delete the copied URL from your RSS Reader. In case of accidental paravenous administration of cyclophosphamide, the infusion should be stopped immediately, the extravascular cyclophosphamide solution should be aspirated with the cannula in place, and other measures should be instituted as appropriate. Anaphylactic Reactions, Cross-sensitivity with Other Alkylating Agents. Risk Summary Protease inhibitors: Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites. As with all cytotoxic therapy, treatment with cyclophosphamide involves the risk of secondary tumours and their precursors as late sequelae. Malformations have been reported in children born to mothers treated with cyclophosphamide during the first trimester of pregnancy. Before starting treatment, it is necessary to exclude or correct any urinary tract obstructions. Side Effects Important things to remember about the side effects of cyclophosphamide: Most people will not experience all of the cyclophosphamide side effects listed. Skin and Subcutaneous Tissue: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, palmar-plantar erythrodysesthesia syndrome, radiation recall dermatitis, toxic skin eruption, urticaria, dermatitis, blister, pruritus, erythema, nail disorder, facial swelling, hyperhidrosis. Metabolism and Nutrition: hyponatremia, fluid retention, blood glucose increased, blood glucose decreased. As a complication of VOLD, hepatorenal syndrome and multiorgan failure may develop. Do not breast-feed an infant while taking this medicine or for 1 week after stopping it. Monitor patients with risk factors for cardiotoxicity and with pre-existing cardiac disease. Do not start, stop, or change the dose of The first look at the 'middle aged Love Island' set has been released, which has already been nicknamed the 'Viagra House' by locals after single parents searched for love Particular caution is necessary in patients with risk factors for cardiotoxicity and in patients with pre-existing cardiac disease. Call your health care professional for advice if you get a fever, chills, or sore throat, or other symptoms of a cold or flu. After cytoreductive therapy, the clinical syndrome typically develops 1 to 2 weeks after transplantation and is characterized by sudden weight gain, painful hepatomegaly, ascites, and hyperbilirubinemia/jaundice. Males Cyclophosphamide Tablets USP, 25 mg and . Latent infections can be reactivated. Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys. This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. If your partner gets pregnant, call the doctor right away. Verify the pregnancy status of females of reproductive potential prior to initiation of Cyclophosphamide Tablets. Cleveland Clinic is a non-profit academic medical center. Patients undergoing treatment with cyclophosphamide may experience undesirable effects (including, e.g., dizziness, blurred vision, visual impairment) which could affect the ability to drive or use machines. Composition of this medication contains innovative substance - sildenafil. Cyclophosphamide has also been associated with nephrotoxicity, including renal tubular necrosis. Late onset pneumonitis (greater than 6 months after start of cyclophosphamide) appears to be associated with increased mortality. Cyclophosphamide is contra-indicated during pregnancy. Late onset of pneumonitis (greater than 6 months after start of cyclophosphamide) appears to be associated with a particularly high mortality. It is usually necessary to discontinue cyclophosphamide therapy in instances of severe hemorrhagic cystitis. Updated Doses and duration of treatment and/or treatment intervals depend on the therapeutic indication, the scheme of a combination therapy, the patient's general state of health and organ function, and the results of laboratory monitoring (in particular, blood cell monitoring). Medically reviewed by Drugs.com. Store tablets at 20C to 25C (68F to77F); excursions permitted between 15C to 30C (59F to 86F) [see USP Controlled Room Temperature]. Use of live vaccines may lead to vaccine-induced infection. The current match involves a Texas lawsuit . Recommended Dosage:See prescribing information. Absorption This medicine has caused ovarian failure in some women. Combined or sequential use of cyclophosphamide and other agents with similar toxicities can cause combined (increased) toxic effects. Infections: The following manifestations have been associated with myelosuppression and immunosuppression caused by cyclophosphamide: increased 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. What are side effects of Cytoxan? ), More about getting RSS News & Updates from DailyMed, 100 in 1 BOTTLE; Type 0: Not a Combination Product, 3 It may sometimes be used to treat other cancers. Coming to a Cleveland Clinic location?Hillcrest Cancer Center check-in changesCole Eye entrance closingVisitation and COVID-19 information. Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. Neoplasms: acute leukemia, myelodysplastic syndrome, lymphoma, sarcomas, renal cell carcinoma, renal pelvis cancer, bladder cancer, ureteric cancer, thyroid cancer. This medicine has caused decreased sperm counts in some men. Treatment with cyclophosphamide has a genotoxic effect and may cause foetal damage when administered to pregnant women. It is an inactive pro drug with alkylating metabolites produced by hepatic metabolism, reaching peak levels 4-6 hours after an iv injection. Very low sodium levels can be life-threatening, leading to. doctor how long to use birth control. The coating of the tablets prevents direct contact of persons handling the tablets with the active substance. is this? Last updated on Jan 27, 2023. Close haematological monitoring is required for all patients during treatment. Fetal growth retardation and toxic effects manifesting in the newborn, including leukopenia, anemia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis have been reported after exposure to cyclophosphamide. Shortness of breath, a big weight gain, or swelling in the arms or legs. Women's health is once again the center of a political ping-pong match with evidence-based science on one side and anti-choice advocates on the other. The risk of premature menopause with cyclophosphamide increases with age. This spontaneous conversion can be catalyzed by albumin and other proteins. The risk of urinary tract cancer as well as the risk of myelodysplastic alterations, partly progressing to acute leukemias, is increased. Dosages should be adjusted based on evidence of antitumor activity, myelosuppression, or other severe adverse reactions [see Warnings and Precautions (5)]. Cyclophosphamide Tablets should be swallowed whole. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver. Cyclophosphamide can stop this happening by reducing the effects of the overactive immune system. Continue typing to refine. Tablets are white with . Your condition will be monitored carefully while you are receiving this medicine. It is a cell cycle phase nonspecific agent. August 7, 2020. Approximately 75% of the administered dose of cyclophosphamide is activated by hepatic microsomal cytochrome P450s including CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18 and 2C19, with 2B6 displaying the highest 4-hydroxylase activity. Nausea and vomiting occur with cyclophosphamide therapy. No specific antidote for cyclophosphamide is known. Talk to your health care professional if you are concerned about your fertility. Affected patients generally resume regular menses within a few months after cessation of therapy. This medication comes in both tablet and capsule forms to be taken once daily, with or without food. Cyclophosphamide treatment may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop a serious infection. Cyclophosphamide is activated to form 4-hydroxycyclophosphamide, which is in equilibrium with its ring-open tautomer aldophosphamide. Volume of distribution approximates total body water (30 to 50 L). Each tablet contains 50 mg ofcyclophosphamide, USP. The dosage regimen used for most indications is 100 300 mg daily as a single or divided dose. Therefore, rapid hemodialysis is indicated when treating any suicidal or accidental overdose or intoxication. If contact with broken tablets occurs, wash hands immediately and thoroughly. Cyclophosphamide should only be used by clinicians experienced in the use of cancer chemotherapy. G-CSF may be administered to reduce the risks of neutropenia complications associated with cyclophosphamide use. 4 CONTRAINDICATIONS Cyclophosphamide Tablets are contraindicated in patients with: A history of severe hypersensitivity reactions to cyclophosphamide, any of its metabolites, or to other components of the product . The recommended dosage of Cyclophosphamide Tablets is 2 mg per kg once daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg). Reporting suspected adverse reactions after authorisation of the medicinal product is important. Cyclophosphamide administered by different routes, including intravenous, subcutaneous or intraperitoneal injection, or in drinking water, caused tumors in both mice and rats. It is a chemotherapy drug that works by slowing or stopping cell growth. In patients with Wegener's granulomatosis, the addition of etanercept to standard treatment, including cyclophosphamide, was associated with a higher incidence of non-cutaneous solid malignancies. The coating of the cyclophosphamide tablets prevents direct contact of persons handling the tablets with the active substance. Wear gloves when handling container and tablets, Baxter Logo The length of treatment depends on the types of drugs you are taking, how well your body responds to them, and the type of cancer or condition you have. Drinking lots of liquids will help. Oligomenorrhea has also been reported in association with cyclophosphamide treatment. Use a soft toothbrush and an electric razor. Smoothie. Cyclophosphamide Tablets are for oral use. Exposure to cyclophosphamide during pregnancy may cause birth defects, miscarriage, fetal growth retardation, and fetotoxic effects in the newborn. Do not become pregnant while taking this medicine or for 1 year after stopping it. Myocarditis and myopericarditis, which may be accompanied by significant pericardial effusion and cardiac tamponade, have been reported with cyclophosphamide therapy and have led to severe, sometimes fatal congestive heart failure. The tablets are coated and should not be divided before use. 10019-982-09, Animal Data Cyclophosphamide-induced myelosuppression can cause leukopenia, neutropenia, thrombocytopenia (associated with a higher risk of bleeding events), and anaemia. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. This medicine is used to treat many types of cancer like lymphoma, myeloma, leukemia, breast cancer, and ovarian cancer, to name a few. The pharmacokinetics of cyclophosphamide were determined following one-hour intravenous infusion to renally impaired patients. The nadirs of the reduction in leukocyte count and thrombocyte count are usually reached in weeks 1 and 2 of treatment. WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. You may report side effects to FDA at 1-800-FDA-1088. CYCLOPHOSPHAMIDE Tablets USP 25 mg and 50 mg DESCRIPTION Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards. Musculoskeletal and Connective Tissue: rhabdomyolysis, scleroderma, muscle spasms, myalgia, arthralgia. If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, the anesthesiologist should be alerted. Bone marrow failure has been reported. Wear gloves when handlingcontainer and tablets. Mean dose-corrected AUC increased by 38% in the moderate renal group, (Creatinine clearance (CrCl of 25 to 50 mL/min), by 64% in the severe renal group (CrCl of 10 to 24 mL/min) and by 23% in the hemodialysis group (CrCl of < 10 mL/min) compared to the control group. Do not share this medicine with others. Hyponatremia associated with increased total body water, acute water intoxication, and a syndrome resembling SIADH (syndrome of inappropriate secretion of antidiuretic hormone), which may be fatal, has been reported. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Tablets should not be cut or crushed. Alcohol consumption may increase cyclophosphamide-induced vomiting and nausea. Girls treated with cyclophosphamide who have retained ovarian function after completing treatment are at increased risk of developing premature menopause (cessation of menses before age of 40 years). Cyclophosphamide is primarily excreted as metabolites. There is potential for serious side effects to an unborn child. Treatment with cyclophosphamide may cause myelosuppression and significant suppression of immune responses. However, many people have no side effects or only have minor side effects. Men with a partner who may get pregnant must use birth control while taking this medicine (cyclophosphamide tablets) and for some time after the last dose. He armed himself with a balaclava, latex gloves, condoms and Viagra pills and posed as a cab driver in a Mercedes to roam the streets of Brighton, East Sussex. These medicines may hide a fever. This treatment should be continued until a clear remission or improvement is seen or be interrupted when the extent of leucopenia becomes unacceptable. Amenorrhea, transient or permanent, associated with decreased estrogen and increased gonadotropin secretion develops in a proportion of women treated with cyclophosphamide. Girls treated with cyclophosphamide during prepubescence subsequently have conceived. In principle, the fall in the peripheral blood cell and thrombocyte count and the time taken to recover may increase with increasing doses of cyclophosphamide. Take your medicine at regular intervals. Cyclophosphamide interferes with oogenesis and spermatogenesis. Renal Impairment Myocarditis, myopericarditis, pericardial effusion including cardiac tamponade, and congestive heart failure, which may be fatal, have been reported with cyclophosphamide therapy. Patients who received an overdose should be closely monitored for the development of toxicities, and hematologic toxicity in particular. Increased cardiotoxicity may result from a combined effect of cyclophosphamide and, for example, Radiation therapy of the cardiac region, Increased pulmonary toxicity may result from a combined effect of cyclophosphamide and, for example. The increase in exposure was significant in the severe group (p>0.05); thus, patients with severe renal impairment should be closely monitored for toxicity [see Use in Specific Populations (8.6)]. Some people have had lung problems with this medicine (cyclophosphamide tablets). Do not chew, break, or crush. Oral: 1 to 5 mg/kg/day (initial and maintenance dosing) Comments: Dosage should be individualized. Queens of the Stone Age will bring Phantogram, Viagra Boys, the Armed, and Savages' Jehnny Beth on their fall North American tour. Concomitant use of tamoxifen and chemotherapy may increase the risk of thromboembolic complications. Capsule may be opened and the contents taken without crushing or chewing; soft food such as applesauce or pudding may facilitate administration; contents may generally be administered via nasogastric tube using an appropriate fluid provided entire contents are washed down the tube. If you have any of these health problems: Bone marrow disease or urinary tract block. Congenital, Familial and Genetic: intra-uterine death, fetal malformation, fetal growth retardation, fetal toxicity (including myelosuppression, gastroenteritis). Use of hematopoiesis stimulating agents (colony-stimulating factors and erythropoiesis stimulating agents) may be considered to reduce the risk of myelosuppressive complications and/or help facilitate the delivery of the intended dosing. Cyclophosphamide is a white crystalline powder with the molecular formula C7H15Cl2N2O2P H2O and a molecular weight of 279.1. Dispense in a tight container as defined in the USP. Investigations: blood lactate dehydrogenase increased, C-reactive protein increased. Urotoxicity may mandate interruption of treatment. Particular caution is necessary in patients with risk factors for cardiotoxicity and in patients with pre-existing cardiac disease. Total body clearance (CL) of cyclophosphamide is decreased by 40% in patients with severe hepatic impairment and elimination half-life (t1/2) is prolonged by 64%. Policy. NOTE: This sheet is a summary. Monitoring of complete blood counts is essential during cyclophosphamide treatment so that the dose can be adjusted, if needed. You need to empty your bladder often. To prevent inadvertent exposure of third persons to the active substance, the tablets should not be divided or crushed. Dispense in a tight containeras defined in the USP. Tell your doctor if you are breast-feeding. Immune: immunosuppression, anaphylactic shock and hypersensitivity reaction. Women treated with this medicine (cyclophosphamide tablets) may go through. Be careful and avoid injury. Neutropenia occurs in patients treated with cyclophosphamide. 6 manifested as Atrial fibrillation,Supraventricular arrhythmia ,Ventricular arrhythmia, Bradycardia, Tachycardia,Palpitation, 7 manifested by pulmonary fibrosis, obliterative bronchiolitis, organizing pneumonia, alveolitis allergic, pneumonitis, 8 Hepatic failure, Hepatic encephalopathy, Ascites, Hepatomegaly, Jaundice, Blood bilirubin increased, Hepatic enzymes increased (ASAT, ALAT, ALP, gamma-GT). Cyclophosphamide should not be used in the management of non-malignant disease, except for immunosuppression in life-threatening situations. Biochemical Data Summary. Talk to your health care professional if you are concerned about your fertility. Baxter is a registered trademark of Baxter International Inc. CYTOTOXIC AGENT Cyclophosphamide treatment causes a marked and persistent inhibition of cholinesterase activity. Before starting treatment, exclude or correct any urinary tract obstructions [see Contraindications (4)]. You will need to talk about any risks to your baby. Talk with your doctor. Urinary sediment should be checked regularly for the presence of erythrocytes and other signs of uro/nephrotoxicity. The immunosuppressive effects of cyclophosphamide can be expected to reduce the response to vaccination. Store at 20C to 25C (68F to 77) [see USP Controlled Room Temperature]. Increased nephrotoxicity may result from a combined effect of cyclophosphamide and, for example. Exposure to cyclophosphamide in utero may cause miscarriage, foetal growth retardation, and foetotoxic effects manifesting in the newborn, including leukopenia, anaemia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis. Swallow tablets whole. Hematuria usually resolves in a few days after cyclophosphamide treatment is stopped, but it may persist. Cyclophosphamide crosses the placental barrier. Metronidazole: Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. Cyclophosphamide should be used with caution, if at all, in patients with active urinary tract infections. Tumor lysis syndrome: like other cytotoxic drugs, cyclophosphamide may induce tumor-lysis syndrome and hyperuricemia in patients with rapidly growing tumors. Animal data indicate that exposure of oocytes to cyclophosphamide during follicular development may result in a decreased rate of implantations and viable pregnancies, and in an increased risk of malformations. Cyclophophamide and its metabolites are dialysable. When people have an autoimmune condition, the body's immune system can mistakenly cause harm to healthy tissues. Very bad and sometimes deadly allergic side effects have rarely happened. We do not endorse non-Cleveland Clinic products or services. PubMed, The following adverse reactions are discussed in more detail in other sections of the labeling. Do not flush down a toilet or pour down a drain unless you are told to do so. The hair can be expected to grow back after treatment with the drug or even during continued drug treatment, though it may be different in texture or colour. Uses Before taking Warnings Side effects Overdose Dosage FAQ Uses of Cyclophosphamide Tablets: It is used to treat cancer . You may have more of a chance of getting an infection. Cystitis is, in general, initially abacterial. Pigmentation of the skin and changes in nails can occur. The chemical name for cyclophosphamide is 2 H-1,3,2 . RxNorm, Terms of Use. If you are 65 or older, use this medicine (cyclophosphamide tablets) with care. pharmacist if you have questions about the best way to throw out drugs. Each tablet contains cyclophosphamide monohydrate equivalent to 50 mg anhydrous cyclophosphamide. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Viagra only. Causal association is unclear. Store at or below 25C (77F)[see USP Controlled Room Temperature]. Cyclophosphamide is contra-indicated in patients with: hypersensitivity to cyclophosphamide or to any of its metabolites. Wound Avenger: One cytoxan dose for breast cancer can produce to older or incomplete body stopped, such as a huge change not required or staying closed. Ear and Labyrinth: deafness, hearing impaired, tinnitus. Patients receiving such combinations must be monitored closely for signs of toxicity to permit timely intervention. The risk of bladder cancer may be reduced by prevention of hemorrhagic cystitis. 4-hydroxycyclophosphamide and aldophosphamide can undergo oxidation by aldehyde dehydrogenases to form the inactive metabolites 4-ketocyclophosphamide and carboxyphosphamide, respectively. Talk to your health care professional for more information. Throw away unused or expired drugs. http://www.osha.gov/SLTC/hazardousdrugs/index.html. Oligomenorrhea has also been reported in association with cyclophosphamide treatment. A reduced antitumor activity was observed in tumor-bearing animals during ethanol (alcohol) consumption and concomitant oral low-dose cyclophosphamide medication. This medicine may cause harm to the unborn baby or loss of the unborn baby if you take it while you are pregnant. After oral administration, peak concentrations of cyclophosphamide occurred at one hour. Detailed Cyclophosphamide dosage information. See Section 4.4, Genotoxicity. The metabolites are excreted renally. help if any of these side effects or any other side effects bother you or do not go away: These are not all of the side effects that may occur. In patients requiring dialysis, use of a consistent interval between cyclophosphamide administration and dialysis should be considered. Dosage Forms and Strengths. The active metabolites of cyclophosphamide are alkylating agents which transfer alkyl groups to DNA during the process of cell division, thus preventing normal synthesis of DNA. Do not take 2 doses at the same time or extra doses. Antimicrobial prophylaxis may be indicated in certain cases of neutropenia at the discretion of the managing physician. You must check Neutropenia, thrombocytopenia, low hemoglobin, and diarrhoea have been reported in children breast fed by women treated with cyclophosphamide. It may not cover all possible information. Cyclophosphamide Tablets is indicated for the treatment of: Cyclophosphamide, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs. Do not take it more often than directed. See Section 4.5. This includes your doctors, nurses, pharmacists, and dentists. It can be prescribed for more serious . Do not take it at night unless told to do so by your doctor. DailyMed will deliver this notification to your desktop, Web browser, or e-mail depending on the RSS Reader you select to use. It slows the growth of cancer cells. Urotoxicity can occur with short -term or long-term use of cyclophosphamide. La Operacin Deluxe tiene mucho -o todo- que ver con el final de Slvame, previsto para el prximo viernes 23 de junio. In addition to leukemia and lymphoma, benign and malignant tumors were found at various tissue sites, including urinary bladder, mammary gland, lung, liver, and injection site [see Warnings and Precautions (5.5)]. Periods may stop in women treated with this medicine (cyclophosphamide tablets). Girls treated with cyclophosphamide who have retained ovarian function after completing treatment are at increased risk of developing premature menopause. Severe myelosuppression may be expected particularly in patients pretreated with and/or receiving concomitant chemotherapy and/or radiation therapy. You may bleed more easily. Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards. Some You may also report side effects at https://www.fda.gov/medwatch. Severe hepatic impairment may be associated with decreased activation of cyclophosphamide. [4] Common side effects include low white blood cell counts, loss of appetite, vomiting, hair loss, and bleeding from the bladder. Advise pregnant women and females of reproductive potential of the potential risk to the fetus [see Use in Specific Populations (8.1)]. It may cause sterility in both sexes. Protease inhibitors: Increased incidence of mucositis. If you think there has been an overdose, call your poison control center or get medical care right away. Manufactured for Pulmonary veno-occlusive disease and other forms of pulmonary toxicity have also been reported. The brand name of this medication is Cytoxan. https://dailymed.nlm.nih.gov/dailymed/labelrss.cfm?setid=769ded74-6186-40a8-8e44-ceff67287451, https://dailymed.nlm.nih.gov/dailymed/rss.cfm. The risk of cyclophosphamide cardiotoxicity may be increased for example, following high doses of cyclophosphamide, in patients with advanced age, and in patients with previous radiation treatment of the cardiac region and/or previous or concomitant treatment with other cardiotoxic agents. Avoid driving and doing other tasks or actions that call for you to be. Reactivation has been reported for various bacterial, fungal, viral, protozoal, and parasitic infections. Thiotepa: A strong inhibition of cyclophosphamide bioactivation by thiotepa in high-dose chemotherapy regimens has been reported when thiotepa was administered 1 hour prior to cyclophosphamide. The usual dose is 1 to 5 . VOD has also been reported to develop gradually in patients receiving long-term low-dose immunosuppressive doses of cyclophosphamide. this may go back to normal but sometimes it may not. Cyclophosphamide should not be administered to patients with neutrophils 1,500/mm. Both increased and decreased warfarin effect have been reported in patients receiving warfarin and cyclophosphamide. Secondary malignancies (urinary tract cancer, myelodysplasia, acute leukemias, lymphomas, thyroid cancer, and sarcomas) have been reported in patients treated with cyclophosphamide-containing regimens. Particular caution is necessary to exclude or correct any urinary tract obstructions copied URL from your RSS Reader select... Browser, or e-mail depending on the RSS Reader is used to treat cancer as late.! Management of non-malignant disease, except for immunosuppression in life-threatening situations Even though it may persist a. The dose can be expected particularly in patients receiving such combinations must be monitored closely for signs toxicity! Url from your RSS Reader you select to use an IV injection can! ) appears to be the nitrogen mustards combinations must be metabolized to active metabolites in the management of non-malignant,! 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