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Clinical Pharmacy Mar 1990The chemistry, pharmacology, pharmacokinetics, and adverse effects of ifosfamide and mesna are described separately, followed by a discussion of the adverse effects of... (Review)
Review
The chemistry, pharmacology, pharmacokinetics, and adverse effects of ifosfamide and mesna are described separately, followed by a discussion of the adverse effects of concurrent ifosfamide and mesna, the clinical spectrum of ifosfamide, and the dosage and administration of the two drugs. Ifosfamide, an active analogue of cyclophosphamide, differs from other direct alkylating substances in that it requires biotransformation in the liver before it can exert its alkylating effects. The bioavailability of ifosfamide after oral administration exceeds 95%. The adverse effects of ifosfamide include hematologic, urinary tract, GI tract, and CNS toxicity. Mesna is a thiol compound designed to function as a regional detoxificant of urotoxic oxazaphosphorine cytostatics such as ifosfamide. The drug is rapidly oxidized in the plasma to its dimeric form, dimesna, one third of which is converted back to mesna by glutathione reductase. The mean total urinary availability of mesna administered orally is 76%. Mesna may produce gastrointestinal and allergic reactions. The adverse effects of concurrent ifosfamide and mesna include urinary tract and renal toxicity. Although current FDA-approved labeling is limited to refractory germ cell testicular cancer, ifosfamide has also shown efficacy in the treatment of lymphoma, lung cancer, and sarcomas. Optimum dosage and scheduling remain to be determined; studies suggest that a fractionated dosage schedule provides antineoplastic activity with tolerable toxicity. Ifosfamide, used in combination with mesna for uroprotection, provides a useful therapeutic option for the management of patients with testicular cancer, soft tissue sarcomas, or high-grade malignant lymphomas.
Topics: Animals; Humans; Ifosfamide; Mercaptoethanol; Mesna; Neoplasms
PubMed: 2107997
DOI: No ID Found -
Cancer Treatment Reviews Jun 1987
Review
Topics: Cystitis; Expectorants; Humans; Mercaptoethanol; Mesna; Neoplasms
PubMed: 3119211
DOI: 10.1016/0305-7372(87)90041-7 -
Seminars in Oncology Dec 1992Oral administration of mesna can facilitate outpatient ifosfamide therapy. Blood and urinary mesna concentrations are more steady and prolonged after oral delivery... (Review)
Review
Oral administration of mesna can facilitate outpatient ifosfamide therapy. Blood and urinary mesna concentrations are more steady and prolonged after oral delivery compared with after intravenous delivery. The incidence of hematuria observed during partial oral mesna therapy is no greater than that during intravenous mesna therapy. The pharmacology, pharmacokinetics, efficacy, safety, and reported schedules of administration are reviewed.
Topics: Administration, Oral; Animals; Humans; Ifosfamide; Mesna
PubMed: 1485175
DOI: No ID Found -
Expert Opinion on Investigational Drugs Jun 2010To date, surgical dissection is based only on mechanical forces. The use of a chemical product that is able to ease tissue dissection represents an important advance.... (Review)
Review
IMPORTANCE OF THE FIELD
To date, surgical dissection is based only on mechanical forces. The use of a chemical product that is able to ease tissue dissection represents an important advance. MESNA (sodium-2-mercaptoethanesulfonate) has recently been validated for chemically assisted tissue dissection during surgery or invasive procedures. No other drugs are available for this.
AREAS COVERED IN THIS REVIEW
An extensive literature search was conducted that included published articles and abstracts on the use of MESNA during surgery or invasive procedures in the experimental and clinical setting, since 1997. Clinically validated settings are ear, nose and throat (ENT), gynecological and orthopedic fields.
WHAT THE READER WILL GAIN
A state-of-the-art overview of intraoperative applications of MESNA, and a consideration of the possible mechanisms underlying chemically assisted tissue dissection.
TAKE HOME MESSAGE
MESNA has been successfully used to ease abdominal myomectomies and excision of endometrial cysts; in ENT surgery, topical MESNA could be widely used, from ear and skull base to head and neck diseases, in both outpatient and operating-room settings. In revision lumbar spine surgery, its use resulted in significantly easier surgery and reduction of postoperative complications. Given the high efficacy and favorable complications rate, future applications in the surgical field are expected to increase.
Topics: Animals; Dissection; Humans; Mesna; Postoperative Complications; Protective Agents; Surgical Procedures, Operative
PubMed: 20433403
DOI: 10.1517/13543784.2010.485192 -
Annals of Allergy, Asthma & Immunology... Jul 2022
Topics: Cyclophosphamide; Drug Hypersensitivity; Humans; Mesna
PubMed: 35476968
DOI: 10.1016/j.anai.2022.04.023 -
Seminars in Oncology Jun 1996Mesna can be given orally to simplify outpatient ifosfamide therapy. Oral administration of mesna solution or tablets has been approved in Canada, Denmark, Germany,... (Review)
Review
Mesna can be given orally to simplify outpatient ifosfamide therapy. Oral administration of mesna solution or tablets has been approved in Canada, Denmark, Germany, Italy, The Netherlands, and the United Kingdom, and programs for registration are ongoing in other European countries and in the United States. This review summarizes dosing schedules and the incidence of hematuria in 47 clinical studies, in which oral mesna was given to at least 1,986 patients who received more than 6,475 courses of ifosfamide. Various doses and schedules of oral mesna, usually in combination with intravenously injected mesna, provided effective uroprotection for a wide range of ifosfamide regimens.
Topics: Administration, Oral; Ambulatory Care; Antineoplastic Agents, Alkylating; Cystitis; Drug Administration Schedule; Europe; Hematuria; Hemorrhage; Humans; Ifosfamide; Injections, Intravenous; Mesna; Tablets; United States
PubMed: 8677457
DOI: No ID Found -
Drugs Sep 1991Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450... (Review)
Review
Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
Topics: Drug Evaluation; Drug Therapy, Combination; Female; Humans; Ifosfamide; Male; Mesna; Neoplasms
PubMed: 1720382
DOI: 10.2165/00003495-199142030-00006 -
Lancet (London, England) Apr 1987
Topics: Antineoplastic Combined Chemotherapy Protocols; Epilepsy, Tonic-Clonic; Female; Humans; Ifosfamide; Male; Mercaptoethanol; Mesna; Middle Aged; Psychoses, Substance-Induced
PubMed: 2882385
DOI: 10.1016/s0140-6736(87)90343-6 -
Clinical and Experimental Dermatology Jun 2012We present the case of a 41-year-old man who developed a photodistributed eruption 1 month after being started on 2-mercaptoethane sulfonate sodium (mesna) for treatment...
We present the case of a 41-year-old man who developed a photodistributed eruption 1 month after being started on 2-mercaptoethane sulfonate sodium (mesna) for treatment of cyclophosphamide-induced haemorrhagic cystitis. The patient had a background history of Wegener granulomatosis, and had been taking cyclophosphamide at a stable dose of 150 mg daily for the previous 3 years. Complete resolution of the rash occurred within 8 weeks of cessation of mesna. This is the first reported case, to our knowledge, of mesna-induced photodistributed dermatosis. Early recognition of this condition will ensure prompt cessation of the culprit medication, and consideration of alternative management of haemorrhagic cystitis.
Topics: Adult; Cystitis; Drug Eruptions; Humans; Male; Mesna; Photosensitivity Disorders; Protective Agents
PubMed: 22103595
DOI: 10.1111/j.1365-2230.2011.04233.x -
Supportive Care in Cancer : Official... Mar 1998The purpose of this study was to make evidence-based recommendations regarding the mode, dosage and schedule of delivery of concomitant mesna... (Review)
Review
The purpose of this study was to make evidence-based recommendations regarding the mode, dosage and schedule of delivery of concomitant mesna (sodium-2-mercaptoethanesulfonate) to protect against ifosfamide-induced uroepithelial toxicity. A critical review of the literature from 1966 to 1996 was undertaken on mesna administration via the intravenous, oral, or combined modality routes. Outcome measures of urinary symptoms and macrohematuria were emphasized, since these endpoints of urotoxicity are most clinically relevant. The quality of evidence obtained from published clinical research was evaluated based on guidelines developed by the Canadian Task Force on the Periodic Health Examination. Recommendations are now made according to the strength of available evidence on the proper usage of mesna as a protective agent against ifosfamide-induced urotoxicity. There is good evidence that the use of mesna significantly reduces urinary symptoms of dysuria and frequency, as well as the incidences of macrohematuria and microhematuria, when administered concurrently with any dosage of ifosfamide regardless of tumor site. Mesna, given intravenously or orally, is superior to standard prophylaxis with vigorous hydration and alkalinization of urine. A commonly used schedule of intravenous mesna involves a dose equal to 60% of the total ifosfamide dose, divided into three aliquots and administered at 0 h, 4 h and 8 h after ifosfamide. Combined oral and intravenous mesna delivered in some tested schedules is equivalent to intravenous mesna alone, but the optimal schedule and dosage of combined formulation have not yet been established. There is fair indirect but no direct evidence that oral mesna alone is equivalent to intravenous mesna or combined modality use. Further research issues, such as patient compliance with oral mesna and other routes of mesna delivery, are discussed. Ongoing study in the appropriate use of mesna is needed to maximize its value as a uroprotective agent in the clinical setting.
Topics: Antineoplastic Agents, Alkylating; Drug Administration Schedule; Humans; Ifosfamide; Kidney; Mesna; Renal Insufficiency
PubMed: 9540174
DOI: 10.1007/s005200050149