Ifosfamide, carboplatin, and cisplatin can cause renal complications, including acute tubular dysfunction, although carboplatin is less nephrotoxic than cisplatin. Anticancer dose adjustment for patients with renal and. Dosing needs to be adjusted in renal impairment as the drug undergoes renal. Ifosfamide may be safely used in patients with end stage renal disease on hemodialysis article pdf available in sarcoma 200957714x. While their action is intended to target abnormal cells, normal cells are also affected. It could therefore be used as an important platform for better prediction of drug dosing and schedule towards personalized medicine. Uptodate, electronic clinical resource tool for physicians and patients that provides information on adult primary care and internal medicine, allergy and immunology, cardiovascular medicine, emergency medicine, endocrinology and diabetes, family medicine, gastroenterology and hepatology, hematology, infectious diseases, nephrology and hypertension, neurology, obstetrics, gynecology, and women. All drugs pediatric drug lookup pediatric care online.
Ifosfamide can cause birth defects if a woman is exposed to it during pregnancy. The usual dosing scheme is that the total dose of mesna is 60% of the ifosfamide dose. Use of ifosfamide is associated with an increased incidence of acute leukaemia. The nephrotoxic ifosfamidemetabolite chloroacetaldehyde. Renal excretion of some of the nontoxic metabolites of ifosfamide, 2 and 3dechloroethyl ifosfamide, has been shown to account for between 4% of the administered ifosfamide dose. Singlecentre experience of systemic treatment with vincristine, ifosfamide, and doxorubicin alternating with etoposide, ifosfamide, and cisplatin in adult patients with ewing sarcoma. Renal function following combination chemotherapy with ifosfamide and cisplatin in patients with osteogenic sarcoma carola arndt, bruce morgenstern, douglas hawkins, david wilson, robert liedtke, james miser. Pediatric drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in psychiatry. Aug, 2018 ifex ifosfamide for injection, usp singledose vials for constitution and administration by intravenous infusion each contain 1 gram or 3 grams of sterile ifosfamide. Oct 24, 2016 due to the potential for additive effects, drugs acting on the cns such as antiemetics, sedatives, narcotics, or antihistamines must be used with particular caution or, if necessary, be discontinued in case of ifosfamide induced encephalopathy.
Evaluation of a clinical decision support system cdss to. Severe nephrotoxicity leading to fanconis syndrome, which may be irreversible, has been reported in young children who received ifosfamide alone or in conjunction with other antineoplastic agents. The dna damage leads to apoptosis of the affected cells. Ifosfamide may be safely used in patients with end stage. Mesna should be used for all patients receiving ifosfamide and high dose cyclophosphamide 1gm2.
With the addition of mesnex tablets, it is reduced to six hours. Ifosfamide can also cause hypophosphatemic rickets. Ifosfamide is also being studied in the treatment of other types of cancer. Longterm evaluation of ifosfamiderelated nephrotoxicity in. Acute tubular necrosis, acute renal failure, and chronic renal failure secondary to ifosfamide therapy have been reported, and fatal outcome from nephrotoxicity has been documented. Alkylating agents are most active in the resting phase of the cell. Adult drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous. Variations, taking into account individual circumstances, may. Ifosfamide is embryotoxic to rabbits receiving 88 mgm2day doses from the 6th through the. The total daily dose of mesna is 100% of the ifosfamide dose. Since the growth of normal body cells may also be affected by ifosfamide, other effects will also occur. History of suicide attempt or drug abusesubstance use disorder. It is a common problem in certain clinical situations such as underlying renal dysfunction, cardiovascular disease, diabetes, and sepsis. The drug may need to be discontinued, or the dosing reduced when this happens.
Ifosfamide interferes with the growth of cancer cells, which are eventually destroyed. Ifosfamide is a parenterally administered alkylating agent similar to cyclophosphamide that is used in the treatment of several forms of cancer including lymphomas, sarcoma and advanced forms of solid organ cancer such as breast, testicular, ovarian, gastric and lung cancer. Apr 25, 2008 ifosfamide is an antineoplastic agent useful in the treatment of a wide range of cancers including sarcomas, gynecologic cancers, lymphoma and testicular cancers. In clinical practice and in most ongoing studies in adult and pediatric tumours, daily shorttime infusions of ifosfamide ifo on 25 consecutive days with cycle doses between 6 gm 2 and 12 gm 2 are used at present. However, chemotherapy agents are subject to the rules of pharmacokinetics and thus have the potential for drug interactions. In a pharmacokinetic and dosing rational study, 39 pediatric renal transplant patients were enrolled. Over the ensuing 5 years, there was continued decline in egfr, but at a much slower pace. Drugs can cause mild to moderate nephrotoxic problems such as intrarenal obstruction, interstitial nephritis, nephrotic syndrome, acidbase and fluid. It is given in 3 bolus doses of 20% of the ifosfamide dose at time 0 with the ifosfamide and then 4 and 8 hours later. Pharmaceutics free fulltext pediatric dosing and body. Renal function following combination chemotherapy with. Department of medical oncology chemotherapy protocols mesna. Health, general adults anthracyclines antimitotic agents antineoplastic agents cancer chemotherapy cancer metastasis care and treatment usage clinical.
Antineoplastic agents comprise one aspect of chemotherapy. The acute tubular dysfunction can be manifested by increased excretion of potassium, phosphorus, and magnesium. We prospectively evaluated tumour response and renal function in 12 newlydiagnosed children with highrisk wilms tumour receiving ifosfamide, carboplatin, and etoposide ice chemotherapy. If only using mesnex injection, the dosing regimen lasts eight hours. The information contained in this book has been compiled from a wide range of. Chronic kidney disease ckd is an increasingly alarming worldwide health concern, with nearly 2 million people in the united states estimated to require hemodialysis or kidney transplantation by 2030. Mesnex tablets are to be used in a dosing regimen with ifex and mesnex injection. When the dose of ifosfamide is adjusted, the ratio of mesna to ifosfamide should be maintained. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, cervical cancer, and ovarian cancer. Ifosfamide can cause severe neurotoxicity resulting in encephalopathy and death. Like cyclophosphamide, ifosfamide causes cardiotoxicity in a dosagerelated manner dosages. Ifex ifosfamide side effects, images, uses, dosage. Acute renal failure associated with administration of.
Kidney tolerance of ifosfamide in combination with mesna after singledose infusion and. Ifosfamide neurotoxicity and potential treatment with. Data sources include ibm watson micromedex updated 10 apr 2020, cerner multum updated 6 apr 2020. Computerized methods for detecting adverse drug events via a trigger tool have proved very effective. Normal doses have been used in gfr 1030mlmin with increased risk of adverse effects. Ifosfamide is a synthetic structural isomer of cyclophosphamide that has. Dailymed ifosfamide injection, powder, for solution. The digital version of this book is only downloadable by chapters. Find patient medical information for ifosfamide intravenous on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Ifosfamide is commonly used as a chemotherapeutic agent in children. Ifosfamide, carboplatin, and cisplatin can cause renal complications, including acute tubular. The dosing schedule should be repeated on each day that ifosfamide is administered.
However, since it can be permanent and can get worse with time, repeated. Cs rules is a cognitive clinical decision support system cdss designed to assist clinical pharmacists in making dosing decisions for individual patients. Isophosphoramide mustard ipm is the active metabolite of ifosfamide ifos and a bifunctional dna alkylator that generates guaninecytosine interstrand crosslinking in gxc sequences producing cell death 1, 2. We hypothesized that concomitant administration of agm with ifo may preserve ci, thereby preventing ifoinduced renal damage. Uramustine or uracil mustard is a chemotherapy drug which belongs to the class of alkylating agents. Measuring up to medication safety institute for safe. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Risk factors for the development of cns toxicity include the following.
Jul 30, 2018 ifosfamide for injection ifosfamide for injection, usp singledose vials for constitution and administration by intravenous infusion each contain 1 gram or 3 grams of sterile ifosfamide. Ifex ifosfamide dosing, indications, interactions, adverse. The greatest decline in renal function occurred after administration of the first cycle, with a mean decline in egfr of 15 mlmin1. The information on dosage adjustments in renal impairment given in this book is. Ifosfamide, like cyclophosphamide, is an oxazophosphorine alkylating agent. Ifosfamide is extensively metabolized in humans and the metabolic pathways appear to be saturated at high doses. Druginduced nephrotoxicity is a renal dysfunction that occurs as a result of exposure to nephrotoxic drugs. However, recently, a relatively low cost, low tech method for using a trigger tool to uncover adverse drug events has been devised.
Renal drug handbook gfr 3050mlmin dose as in normal renal function, gfr 1030mlmin dose as in normal renal function. Mix 4 ml of sodium thiosulfate 10% with 6 ml sterile water for injection to prepare a 0. It is used in patients who have already been treated with two other types of chemotherapy. Pdf ifosfamide may be safely used in patients with end. Most anticancer agents exhibit a narrow therapeutic index, i. If you want a printerfriendly version of this article that you can save and view offline, grab a pdf of the ultimate guide to oncology pharmacy for the nononcologist here. Dosing and sideeffects of ifosfamide plus mesna springerlink.
This combination may also be used with other drugs or treatments or to treat other types of cancer. Medscape indicationspecific dosing for ifex ifosfamide, frequencybased adverse effects, comprehensive interactions. The recommendations in this online publication do not indicate an exclusive course of treatment or serve as a standard of medical care. Renal toxicity is moderate with a moderate dose of ifosfamide. Five cycles of an intensified maid regimen was compared with 6 cycles of a more standard maid regimen dacarbazine 300 mgm2 per day iv over 1 hour on days 1, 2. Ifosfamide is a chemotherapeutic agent chemically related to the nitrogen mustards and a synthetic analog of cyclophosphamide. Oct 18, 2019 embryolethal effects were observed in rats following the administration of 54 mgm 2 doses of ifosfamide from the 6th through the 15th day of gestation and embryotoxic effects were apparent after dams received 18 mgm 2 doses over the same dosing period. Several payment sources exist for cancer drugs in ontario, depending on the drug, disease indication, and how and where it is delivered. Dosing needs to be adjusted in renal impairment as the drug undergoes renal elimination. The formation of advanced glycation endproducts ages is a wellestablished factor in the onset and progression of kidney disease. Pediatric drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents. This study aimed at providing health professionals with a feasible and timesaving tool to adapt the dose of anticancer agents for patients with renal or hepatic dysfunction. It may also be a mechanism of antitumor action of ifosfamide 22. In part 1 of the study, pediatric patients were given 12 mgm 2 of basiliximab.
Ifosfamide, carboplatin, and etoposide for neuroblastoma. The fda approved regimen is ifosfamide along with mesna at a dose of. Ifosfamide is approved to be used with other drugs to treat. The dca dose was from studies in human subjects 25. Ifosfamide therapy is associated with minor transient serum enzyme elevations and has been linked to cases of acute.
Ifosfamide use by either parent may cause birth defects. Dosage adjustment for cytotoxics in renal impairment. Dose reduction is to 80% of the dose if creatinine clearance crcl is 46 to 60 mlminute. Because of these symptoms and her declining kidney function, her ifosfamide therapy was stopped on day 4 of her chemotherapy infusion. Jan 04, 2010 case 1 case 1 was a 48yearold male who four years earlier had been diagnosed with high grade synovial sarcoma of the knee, metastatic to lungs. Two cycles of ice were followed by 5 weeks of vincristine, dactinomycin.
Ifex ifosfamide dosing, indications, interactions, adverse effects. Due to unacceptable myelosuppression in the first 154 patients treated, the ifosfamide dose was reduced from 2,500 mgm2 per day to 2,000 mgm2 per day. She also developed a decreased level of consciousness felt to be encephalopathy related to ifosfamide. Contraindicated in patients having severe leukopenia, thrombocytopenia, severe renal andor hepatic impairment, cystitis, obstructions to urine. The patient was referred to the renal service, while on hemodialysis, for consideration of the feasibility of ifosfamide chemotherapy in a patient with end stage renal disease. Ifosfamide ifo, sold under the brand name ifex among others, is a chemotherapy medication. Slow iv infusion over 30 min, or continuous infusion over 5 d.
It is used in lymphatic malignancies such as nonhodgkins lymphoma. Fluid retention alkylating drugs can cause fluid retention with oedema and dilutional hyponatraemia in younger children. Embryolethal effects were observed in rats following the administration of 54 mgm2 doses of ifosfamide from the 6th through the 15th day of gestation and embryotoxic effects were apparent after dams received 18 mgm2 doses over the same dosing period. Adult drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in. Case 1 case 1 was a 48yearold male who four years earlier had been diagnosed with high grade synovial sarcoma of the knee, metastatic to lungs. Find patient medical information for ifosfamidemesna intravenous on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. However, as this emedtv segment explains, your ifosfamide dosage will be calculated using your weight, height, and other medical conditions, among other factors.
It works by damaging dna, primarily in cancer cells that preferentially take up the uracil due to their need to make nucleic acids during their rapid cycles of cell division. Aug, 2018 using ifosfamide may increase your risk of developing other cancers, such as leukemia. Nephrotoxic drugs are pharmacotherapies that can lead to a decline in renal function. Ifex ifosfamide dose, indications, adverse effects. Although ipm is the ultimate alkylator that is derived from ifos, it has been removed from clinical trials because of lack of sufficient anticancer activity in. Clabeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in the urine, with about 61% of the dose excreted as parent compound. This book is distributed under the terms of the creative commons. Inject 310 ml subcutaneously into extravasation site. Find comprehensive medical reference information including disease symptoms, diagnoses, treatments, and followup. The renal drug handbook the st georges hospital, adult critical. A common and doselimiting side effect is encephalopathy brain dysfunction. Definition from the nci drug dictionary detailed scientific definition and other names for this drug.
The severity of renal impairment ranges from mild renal tubular acidosis in. The authors report a 4yold boy who developed proximal renal tubulopathy with florid rickets a year after completion of ifosfamide therapy for ewings sarcoma. Some clinicians recommend that ifosfamide not be used in children with infiltrating renal. Ifosfamide is chemically related to the nitrogen mustards and is similar in chemical structure to cyclophosphamide. Guidelines for the administration of mesna with ifosfamide. For those drugs in which renal excretion is an important determinant of elimination, dose adjustment is often required if renal function is impaired. Renal side effects of ifosfamide in patients admitted for chemotherapy. The ultimate guide to oncology pharmacy for the non. Ifosfamide may also cause a normal anion gap acidosis, specifically renal tubular acidosis. At the time of ifosfamide administration, give a single dose of mesna iv at a dose of 20% ww of the ifosfamide dosage, then mesna tablets po in a dosage equal to 40% of the ifosfamide dose 2 and 6 hours after each dose of ifosfamide. Risk factors for the nephrotoxicity of ifosfamide include cumu lative dosing. Case 1 was a 48yearold male who four years earlier had been diagnosed with high grade synovial sarcoma of the knee, metastatic to lungs. The data show that ifosfamide did have deleterious effects on kidney function in an adult population. Ifosfamide is also sometimes used to treat bladder cancer, lung cancer, cancer of the ovaries cancer that begins in the female reproductive organs where eggs are formed, cancer of the cervix, and certain types of soft tissue or bone sarcomas cancer that forms in muscles and bones.
Ifosfamide is a synthetic structural isomer of cyclophosphamide that has been approved for concurrent use with other drugs usually cisplatin, etoposide, or vinblastine in the treatment of metastatic germcell testicular cancer and some especially pediatric sarcomas. Ifosfamide in tumor therapy table of contents karger publishers. Ifosfamide ifo, sold under the brand name ifex among others, is a chemotherapy medication used to treat a number of types of cancer. Singlecentre experience of systemic treatment with. Started in 1995, this collection now contains 6767 interlinked topic pages divided into a tree of 31 specialty books and 732 chapters. However, if crcl is 31 to 45 mlminute, administer 75% of the dose and with crcl under 30 mlminute reduce to 70% of the regular dose.
Long term renal toxicity of ifosfamide in adult patients 5. Ifosfamide injection is used in combination with other medicines to treat cancer of the testicles. The renal drug handbook third edition edited by caroline ashley and aileen currie uk renal pharmacy group foreword by. Jan 31, 2019 this drug may be given on a fractionated dosing schedule of either 3 bolus iv injections or a single injection followed by 2 oral doses.
Long term renal toxicity of ifosfamide in adult patients. Following activation in the liver, ifosfamide interferes with dna through formation of phosphotriesters and dnadna crosslinks, thereby inhibiting protein synthesis and dna synthesis. Ifosfamide belongs to the category of mustard gas derivatives. Tablets also allow for quicker administration that. Comparative anticancer activity in human tumor xenograft. This is the basis for combining chemotherapy agents with different mechanisms of action. Some of these may be serious and must be reported to. Pdr drug summaries are concise pointofcare prescribing, dosing and administering information to help phsyicans more efficiently and accurately prescribe in their practice pdr s drug summaries are available free of charge and serve as a great resource for us based mds, dos, nps and pas in patient practice. Chloracetaldehyde, a metabolite implicated in cns toxicity, has been shown to accumulate in patients with renal insufficiency 9, 11 and in an anephric. In an effort to improve response rates to chemotherapy, agents often are combined to give a socalled twoprong attack against tumor cells. Use effective birth control to prevent pregnancy, whether you are a man or a woman. Ifosfamide is an antineoplastic agent useful in the treatment of a wide range of cancers including sarcomas, gynecologic cancers, lymphoma and testicular cancers. Eleven children and adolescents with previously normal renal function who received ifosfamide for the treatment of extrarenal solid tumours underwent detailed.
Ifosfamide injection 1g summary of product characteristics. It has been shown that only metabolites of ifo are toxic to the kidney, whereas the. Disorders of renal function, glomerular and tubular following ifosfamide administration are very common. The gray baby syndrome following chloramphenicol exposure relates to normal dosing in the presence of impaired glucuronidation 60. Ifosfamide is given intravenously by iv usually once a day for five days every three weeks. Nutrients that have been conclusively shown to mitigate the effects of these lethal agents constitute a front line, lowcost intervention. The therapeutic drug monitoring takes place after assessing the pharmacokinetics of the first course of the drug followed by subsequent alterations in the dose as there is wide variability in the pharmacokinetics of ifosfamide. Multiagent chemotherapy has improved cure rates dramatically for patients with osteosarcoma.
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