解毒劑 Prevention of the urinary tract toxicity of oxazaphosphorines (Endoxan)

Antidote
Mesna is oxidized to dimesna in blood, which in turn is reduced in the kidney back to mesna, supplying a free thiol group which binds to and inactivates acrolein, the urotoxic metabolite of ifosfamide and cyclophosphamide.

Distribution:
1. Vd: 0.65 ± 0.24 L/kg; distributed to total body water
2. Protein binding: 69-75%
Metabolism:
1. Rapidly oxidized to mesna disulfide (dimesna) in the intravascular compartment. Mesna and dimesna do not undergo hepatic metabolism.
2. Half-life elimination: (Mesna) ~22 min; (Dimesna) ~70 min
Excretion:
Urine (32% as mesna; 33% as dimesna)

Known hypersensitivity to mesna or any component of the formulation.

B

Breastfeeding is not recommended during therapy and for at least 1 week after the last mesna injection.

Common:
Flushing, dizziness, headache, skin rash, constipation, diarrhea, flatulence, nausea, vomiting, injection site reaction, rthralgia, back pain, conjunctivitis, cough, flu-like symptoms, rhinitis, fever
Postmarketing:
Anaphylaxis, erythema, hypersensitivity reaction, hypertension, hypotension, increased serum transaminases, increased ST segment on ECG, limb pain, malaise, myalgia, tachycardia, tachypnea, thrombocytopenia

Each mesna dose is equal to 20% of the ifosfamide dose, at hour 0, hour 4, and at hour 8 after the ifosfamide dose:

Hour	0	4	8
Oxazaphosphorine dose	40mg/kg BW	-	-
Uromitexan dose	8mg/kg BW	8mg/kg BW	8mg/kg BW

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied)

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied)