Hemorrhagic cystitis prevention

Few side effects can be alleviated by the use of antidotes. An example is the prevention of hemorrhagic cystitis caused by cyclophosphamide by the concomitant infusion of mesna. 

Cyclophosphamide Hemorrhagic cystitis due to acrolein metabolite (prevent with MESNA)... 

The use of effective prevention strategies can decrease the incidence of hemorrhagic cystitis to less than 5% in patients receiving cyclophosphamide or ifosfamide. There are three methods to reduce the risk administration of mesna, hyperhydration, and bladder irrigation with catheterization. 

West NJ. Prevention and treatment of hemorrhagic cystitis. Pharmacotherapy 1997 17 696-706. 

Prevention of hemorrhagic cystitis in patients receiving ifosfamide IV 20% of ifosfa-mide dose at time of ifosfamide administration and 4 hr and 8 hr after each dose of if-osfamide. Total dose 60% of ifosfamide dosage. Range 60%-160% of the daily ifosfa-mide dose. 

Mechlorethamine Forms DNA cross-links, resulting in inhibition of DNA synthesis and function Hodgkin s and non-Hodgkin s lymphoma Nausea and vomiting Moderate depression of peripheral blood count excessive doses produce severe bone marrow depression with leukopenia, thrombocytopenia, and bleeding alopecia and hemorrhagic cystitis occasionally occur with cyclophosphamide cystitis can be prevented with adequate hydration busulfan is associated with skin pigmentation, pulmonary fibrosis, and adrenal... 

In animal studies, NAC has been shown to prevent hemorrhagic cystitis that results from administration of cyclophosphamide or its position isomer ifosfamide. Hemorrhagic cystitis results from the toxic effect of acrolein, a metabolic product of cyclophosphamide or its position isomer ifosfamide. The mechanism whereby NAC prevents this toxicity may be prevention of the intracellular depletion of antioxidants, such as GSH, by acrolein. Concomitant administration of NAC with cyclophosphamide or ifosfamide does not impair antineoplastic activity, because both anticancer drugs are inactive until they are metabolized by the liver to their phosphoramide mustard metabolites. 

Blijham GH. 1986. Prevention of oxazaphosphorine-induced hemorrhagic cystitis by N-acetylcysteine and MESNA. Pharma Weekbl 121 658-663. (Dutch)... 

Hemorrhagic cystitis and bladder cancer are well-known complications of cyclophosphamide. The damage to the urinary bladder epithelium is caused by acrolein, a metabolite of cyclophosphamide that is excreted in the urine. In bone marrow transplant recipients, prior administration of busulfan, which itself causes hemorrhagic cystitis, can increase this risk (23). Mesna (2-mercaptoethane sodium sulfonate) is used to prevent this adverse effect. It is excreted by the kidney, and it binds and detoxifies acrolein in the urine mesna also prevents the breakdown of acrolein precursors. Intravesical prostaglandin E2 has been suggested as an alternative treatment (23). 

Mesna is used to prevent or ameliorate hemorrhagic cystitis produced by the anticancer drugs cyclophosphamide and ifosfamide. It is excreted by the kidney and binds and detoxifies acrolein in the urine mesna also prevents the breakdown of acrolein precursors. It is also used as a mucolytic. 

Droller MJ, Sral Rand Santos G. Prevention of cyclophosphamide-induced hemorrhagic cystitis. Urology, 20 256-258,1982... 

Drug therapy may also cause renal insufficiency due to lower urinary tract obstruction. Ureteral obstruction can be caused by calculi or retroperitoneal fibrosis. Bladder dysfunction with urinary outflow obstruction can result, particularly in males with prostatic hypertrophy, from anticholinergic drugs including tricyclic antidepressants and disopyramide. Bladder outlet and ureteral obstruction may result from bladder fibrosis following hemorrhagic cystitis with cyclophosphamide or ifosfamide therapy. Concurrent treatment with mesna can prevent cystitis and this complication. 

Droller MJ, Sral R and Santos G. Prevention of cyclophosphamide-induced hemorrhagic cystitis. Urology 1982 20 256-258. Link H, Neef V, Niethammer D and Wilms K. Prophylaxis of haemorrhagic cystatis due to cyclophos-phamide-conditioning for bone marrow transplantation. Blut 1981 48 329-330. 

Mesna is a cytoprotective agent. It is used to reduce the incidence of ifosfamide-induced hemorrhagic cystitis. Mesna disulfide is reduced to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfa-mide metabolites, resulting in their detoxification. It is indicated in prevention of ifosfamide-induced hemorrhagic cystitis. 

Encourage patients taking cyclophosphamide to drink plenty of fluids and void often to prevent hemorrhagic cystitis. 

Because acrolein is formed, the same precautions against hemorrhagic cystitis that were previously outlined for cyclophosphamide must be taken hydrate well, irrigate thoroughly, and administer with mesna. As previously stated, mesna will not prevent chloroacetaldehyde-induced toxicity. 

Electrolyte balance In a retrospective analysis of data obtained from 84 patients with lupus nephritis or non-Hodgkin s lymphoma, 112 treatment episodes with low-dose intravenous pulse cyclophosphamide (500-750 mg/m ) were evaluated [28. All received 0.45% saline as hydration to prevent hemorrhagic cystitis. There was cyclophosphamide-induced hyponatremia during 15 treatment episodes in 12 patients. Patients with hyponatremia were significantly older than those without, although no factors independently predicted hyponatremia in a multivariate analysis, including cyclophosphamide dose. Cyclophosphamide potentiates the renal action of vasopressin, thereby reducing the ability of the kidney to excrete water, which should warrant the use of hypotonic solutions for prophylactic hydration to prevent hyponatremia. 

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