部份中文Mesna处方资料（仅供参考）
药品英文名
Mesna
药品别名
美安、美钠、美斯钠、巯乙磺酸钠、Uromitexan  
药理作用
环磷酰胺类化疗药在体内产生的丙烯醛和4-羟基代谢物对泌尿道有一定的毒性，美司钠可与丙烯醛的双链结合，形成稳定的硫醚化合物；另外，美司钠可降低尿中4-羟基代谢产物的降解速度，形成一种相对稳定的对膀胱无毒性的4-羟基环磷酰胺或4-羟基异环磷酰胺与美司钠缩合而成的产物，从而起到良好的解毒作用。此外，美司钠可使痰中黏蛋白的二巯键断裂，从而降低痰黏度，为局部吸入或滴入的速效、强效的黏痰稀释剂。本品是含有半胱氨酸的化合物，本身无抗肿瘤作用，但却是抗肿瘤治疗中一种极为重要的辅助用药。
药动学
美司钠口服吸收良好，但与静脉注射相比排出略慢。本药注射后，药物主要分布于肾脏，并立即开始清除，大部分在8h内清除。并可迅速在组织中转化为无生物活性的二硫化物，经肾小球滤过后，在肾小管上皮又转化成美司钠。原形药和代谢物血浆半衰期分别为15～30min和70min，24h内约有80%的药物从尿中排泄。
适应证
1.用于接受异环磷酰胺(IFO)或环磷酰胺(CTX) 和曲磷胺治疗的患者，作为泌尿系统保护剂，预防上述药物的代谢产物所致以出血性膀胱炎等为主的泌尿道毒性。
2.本药气雾剂适用于大量黏痰阻塞引起的呼吸困难。
禁忌证
对本品或含有巯基的化合物过敏者禁用。
注意事项
1.抑郁症患者慎用。
2.在尿酮体诊断试验中，本品可使之出现假阳性。
3.在尿红细胞诊断试验中，本品可使之出现假阳性或假阴性。
4.妊娠及哺乳妇女慎用。
5.应用本药可引起尿酮试验假阳性反应。
6.本药的保护作用不限于预防泌尿系统的损害。
不良反应
1.常规剂量给药，一般无不良反应，若单一剂量超过60mg/kg时，可能出现恶心、呕吐、腹痛和腹泻，可加重IFO的中枢神经系统症状。
2.极少数有静脉刺激或皮肤、黏膜过敏反应。
3.头痛、乏力、四肢痛、抑郁、低血压和皮炎。
用法用量
1.静脉注射：常用量为IFO或CTX剂量的20%，例如用异环磷酰胺2.0g，美司钠每次给400mg。可分别于0h、4h及8h各静脉注射1次。如抗癌药持续24h输注，本品首次静脉注射抗癌药用量20%，继而在24h中输注与抗癌药用量相等的本品，在以后的12h中再输注60%的本品。
2.雾化吸入：每次1～3ml，用于黏痰阻塞引起的呼吸困难。
3.气管滴入：同雾化吸入。
药物相应作用
本品与顺铂、氮芥不相容，不可混用。美司钠与华法林合用，出血的危险性增加，作用机制尚不清楚。
专家点评
在一项随机安慰剂对照研究中，静脉注射本品使环磷酰胺引起的中度或严重性血尿发生率约为6.7%，而安慰剂组为32%，皮下给药具有实用性，可有效代替静脉注射。美司钠对肿瘤无治疗作用，能与CTX和IFO的毒性代谢物丙烯醛结合成无毒化合物，由尿中排出体外，降低这两种药物的膀胱刺激症状。
价格规格
400mgx10支
1000mgx1瓶
1000mgx5瓶
5000mgx1瓶

Mesna Injection 100mg per mL

SAGENTRx only

Mesna is a detoxifying agent to inhibit the hemorrhagic cystitis induced by ifosfamide. The active ingredient mesna is a synthetic sulfhydryl compound designated as sodium-2-mercaptoethane sulfonate with a molecular formula of CHNaOS and a molecular weight of 164.18. Its structural formula is as follows:

Mesna Injection is a sterile, nonpyrogenic, aqueous solution of colorless to light pink appearance in clear glass multidose vials for intravenous administration. Mesna injection contains 100 mg/mL mesna, 0.25 mg/mL edetate disodium, sodium hydroxide for pH adjustment and q.s with Water for Injection. Mesna injection multidose vials also contain 10.4 mg/mL of benzyl alcohol as a preservative. The solution has a pH range of 6.5 to 7.4.

Mesna was developed as a prophylactic agent to reduce the risk of hemorrhagic cystitis induced by ifosfamide.

Analogous to the physiological cysteine-cystine system, mesna is rapidly oxidized to its major metabolite, mesna disulfide (dimesna). Mesna disulfide remains in the intravascular compartment and is rapidly eliminated by the kidneys.

In the kidney, the mesna disulfide is reduced to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfamide metabolites (acrolein and 4-hydroxy-ifosfamide) resulting in their detoxification. The first step in the detoxification process is the binding of mesna to 4-hydroxy-ifosfamide forming a nonurotoxic 4-sulfoethylthioifosfamide. Mesna also binds to the double bonds of acrolein and to other urotoxic metabolites.

In multiple human xenograft or rodent tumor model studies of limited scope, using IV or IP routes of administration, mesna in combination with ifosfamide (at dose ratios of up to 20-fold as single or multiple courses) failed to demonstrate interference with antitumor efficacy.

At doses of 2 to 4 g/m, the terminal elimination half-life of ifosfamide is about 4 to 8 hours. As a result, in order to maintain adequate levels of mesna in the urinary bladder during the course of elimination of the urotoxic ifosfamide metabolites, repeated doses of mesna are required.

After intravenous administration of an 800-mg dose, the half-lives of mesna and dimesna in the blood are 0.36 hours and 1.17 hours, respectively. Approximately 32% and 33% of the administered dose was eliminated in the urine in 24 hours as mesna and dimesna, respectively. The majority of the dose recovered was eliminated within 4 hours. Mesna has a plasma clearance of 1.23 L/h/kg.

The half-life of mesna ranged from 1.2 to 8.3 hours after administration of intravenous plus oral doses of mesna. The urinary bioavailability of oral mesna ranged from 45 to 79% of intravenously administered mesna. Food does not affect the urinary availability of orally administered mesna. Approximately 18 to 26% of the combined intravenous and oral mesna dose appears as free mesna in the urine. When compared to intravenously administered mesna, the intravenous plus oral dosing regimen increases systemic exposures (150%) and provides more sustained excretion of mesna in the urine over a 24-hour period. Approximately 5% of the mesna dose is excreted during the 12 to 24 hour interval, as compared to negligible amounts in patients given the IV regimen. The fraction of the administered dose of mesna excreted in the urine is independent of dose. Protein binding of mesna is in a moderate range (69 to 75%).

An analysis was conducted in four male and four female volunteers; no differences in plasma pharmacokinetics were detected.

Pharmacokinetic data of mesna in pediatric and geriatric patients are not available.

No clinical studies were conducted to eva luate the effect of hepatic impairment or renal impairment on the pharmacokinetics of mesna.

No clinical drug interaction studies have been conducted with mesna.

Hemorrhagic cystitis produced by ifosfamide is dose dependent (Table 1). At a dose of 1.2 g/m ifosfamide administered daily for 5 days, 16 to 26% of the patients who received conventional uroprophylaxis (high fluid intake, alkalinization of the urine, and the administration of diuretics) developed hematuria (>50 RBC/hpf or macrohematuria) (Morgan, Einhorn, Costanzi). In contrast, none of the patients who received mesna injection together with this dose of ifosfamide developed hematuria (Einhorn). In two randomized studies, (Fukuoka, Scheef), higher doses of ifosfamide, from 2 to 4 g/m administered for 3 to 5 days, produced hematuria in 31 to 100% of the patients. When mesna was administered together with these doses of ifosfamide, the incidence of hematuria was less than 7%.

Table 1. Percent of Mesna Patients Developing Hematuria (≥ 50 RBC/hpf or macrohematuria)

* Ifosfamide dose 1.2 g/m2 d x 5
**Ifosfamide dose 2 to 4 g/m2 d x 3-5
Study	Conventional Uroprophylaxis (number of patients)	Standard Mesna IV Regimen (number of patients)
Uncontrolled studies
MORGAN*	16% (7/44)	-
COSTANZI*	26% (11/43)	-
EINHORNa*	18% (7/38)	0% (0/21)
EINHORNb*	-	0% (0/32)
Controlled studies
FUKUOKA**	31% (14/46)	6% (3/46)
SCHEEF**	100% (7/7)	0% (0/8)

Mesna is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis.

Mesna is contraindicated in patients known to be hypersensitive to mesna or other thiol compounds.

Allergic reactions to mesna ranging from mild hypersensitivity to systemic anaphylactic reactions have been reported. Patients with autoimmune disorders who were treated with cyclophosphamide and mesna appeared to have a higher incidence of allergic reactions.

The majority of these patients received mesna orally.

Mesna has been developed as an agent to reduce the risk of ifosfamide-induced hemorrhagic cystitis. It will not prevent or alleviate any of the other adverse reactions or toxicities associated with ifosfamide therapy.

Mesna does not prevent hemorrhagic cystitis in all patients. Up to 6% of patients treated with mesna have developed hematuria (>50 RBC/hpf or WHO grade 2 and above). As a result, a morning specimen of urine should be examined for the presence of hematuria (microscopic evidence of red blood cells) each day prior to ifosfamide therapy. If hematuria develops when mesna is given with ifosfamide according to the recommended dosage schedule, depending on the severity of the hematuria, dosage reductions or discontinuation of ifosfamide therapy may be initiated.

In order to reduce the risk of hematuria, mesna must be administered with each dose of ifosfamide as outlined in the DOSAGE AND ADMINISTRATION section. Mesna is not effective in reducing the risk of hematuria due to other pathological conditions such as thrombocytopenia.

Because of the benzyl alcohol content, the multidose vial should not be used in neonates or infants and should be used with caution in older pediatric patients.

Healthcare providers should advise patients taking mesna to drink at least a quart of liquid a day. Patients should be informed to report if their urine has turned a pink or red color.

A false positive test for urinary ketones may arise in patients treated with mesna. In this test, a red-violet color develops which, with the addition of glacial acetic acid, will return to violet.

No clinical drug studies have been conducted.

No long-term studies in animals have been performed to eva luate the carcinogenic potential of mesna.

Mesna was not genotoxic in the in vitro Ames bacterial mutagenicity assay, the in vitro mammalian lymphocyte chromosomal aberration assay or the in vivo mouse micronucleus assay.

No studies on male or female fertility were conducted. No signs of male or female reproductive organ toxicity were seen in 6-month oral rat studies (at doses up to 2000 mg/kg/day) or 29-week oral dog studies (520 mg/kg/day; both studies approximately 10-fold higher than the maximum recommended human dose on a body surface area basis).

Reproduction studies have been performed in rats and rabbits at oral doses of 1000 mg/kg in rabbits and 2000 mg/kg in rats (approximately 10 times the maximum recommended total daily IV-oral-oral human dose on a body surface area basis) and have revealed no evidence of harm to the fetus due to mesna. There are however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

It is not known whether mesna or dimesna is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from mesna, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Because of the benzyl alcohol content in mesna injection, the multidose vial should not be used in neonates or infants and should be used with caution in older pediatric patients.

Clinical studies of mesna did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. However, the ratio of ifosfamide to mesna should remain unchanged.

Mesna adverse reaction data are available from four phase I studies in which single IV bolus doses of 600 to 1200 mg mesna injection without concurrent chemotherapy were administered to a total of 53 subjects.

The most frequently reported side effects (observed in two or more patients) for patients receiving single doses of mesna IV were headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperaesthesia, influenza-like symptoms, and coughing.

In two phase I multiple-dose studies where patients received mesna tablets alone or IV mesna followed by repeated doses of mesna tablets, flatulence and rhinitis were reported. In addition, constipation was reported by patients who had received repeated doses of IV mesna.

Because mesna is used in combination with ifosfamide or ifosfamide-containing chemotherapy regimens, it is difficult to distinguish the adverse reactions which may be due to mesna from those caused by the concomitantly administered cytotoxic agents.

Adverse reactions reasonably associated with mesna administered IV and orally in four controlled studies in which patients received ifosfamide or ifosfamide-containing regimens are presented in Table 3.

Table 2. Incidence of Adverse Events and Incidence of Most Frequently Reported Adverse Events in Controlled Studies

* All grades
Mesna Regimen	IV-IV-IV	IV-Oral-Oral
N exposed	119 (100.0%)	119 (100.0%)
Incidence of AEs	101 (84.9%)	106 (89.1%)
Most Frequently Reported Adverse events (Preferred Terms)
	N (%)	N (%)
Nausea	65 (54.6)	64 (53.8)
Vomiting	35 (29.4)	45 (37.8)
Constipation	28 (23.5)	21 (17.6)
Leukopenia	25 (21.0)	21 (17.6)
Fatigue	24 (20.2)	24 (20.2)
Fever	24 (20.2)	18 (15.1)
Anorexia	21 (17.6)	19 (16.0)
Thrombocytopenia	21 (17.6)	16 (13.4)
Anemia	20 (16.8)	21 (17.6)
Granulocytopenia	16 (13.4)	15 (12.6)
Asthenia	15 (12.6)	21 (17.6)
Abdominal Pain	14 (11.8)	18 (15.1)
Alopecia	12 (10.1)	13 (10.9)
Dyspnea	11 (9.2)	11 (9.2)
Chest Pain	10 (8.4)	9 (7.6)
Hypokalemia	10 (8.4)	11 (9.2)
Diarrhea	9 (7.6)	17 (14.3)
Dizziness	9 (7.6)	5 (4.2)
Headache	9 (7.6)	13 (10.9)
Pain	9 (7.6)	10 (8.4)
Sweating Increased	9 (7.6)	2 (1.7)
Back Pain	8 (6.7)	6 (5.0)
Hematuria*	8 (6.7)	7 (5.9)
Injection Site Reaction	8 (6.7)	10 (8.4)
Edema	8 (6.7)	9 (7.6)
Edema Peripheral	8 (6.7)	8 (6.7)
Somnolence	8 (6.7)	12 (10.1)
Anxiety	7 (5.9)	4 (3.4)
Confusion	7 (5.9)	6 (5.0)
Face Edema	6 (5.0)	5 (4.2)
Insomnia	6 (5.0)	11 (9.2)
Coughing	5 (4.2)	10 (8.4)
Dyspepsia	4 (3.4)	6 (5.0)
Hypotension	4 (3.4)	6 (5.0)
Pallor	4 (3.4)	6 (5.0)
Dehydration	3 (2.5)	7 (5.9)
Pneumonia	2 (1.7)	8 (6.7)
Tachycardia	1 (0.8)	7 (5.9)
Flushing	1 (0.8)	6 (5.0)

Allergic reactions, decreased platelet counts associated with allergic reactions, hypertension, hypotension, increased heart rate, increased liver enzymes, injection site reactions (including pain and erythema), limb pain, malaise, myalgia, ST-segment elevation, tachycardia, and tachypnea have been reported as part of postmarketing surveillance.

There is no known antidote for mesna. Oral doses of 6.1 and 4.3 g/kg were lethal to mice and rats, respectively. These doses are approximately 15 and 22 times the maximum recommended human dose on a body surface area basis. Death was preceded by diarrhea, tremor, convulsions, dyspnea, and cyanosis.

For the prophylaxis of ifosfamide induced hemorrhagic cystitis, mesna may be given on a fractionated dosing schedule of three bolus intravenous injections as outlined below.

Mesna is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration and 4 and 8 hours after each dose of ifosfamide. The total daily dose of mesna is 60% of the ifosfamide dose.

The recommended dosing schedule is outlined below:

	0 Hour	4 Hour	8 Hour
Ifosfamide	1.2 g/m2	-	-
Mesna	240 mg/m2	240 mg/m2	240 mg/m2

The mesna multidose vials may be stored and used for up to 8 days.

For IV administration the drug can be diluted by adding the mesna injection solution to any of the following fluids obtaining final concentrations of 20 mg mesna/mL:

For example:

One mL of mesna injection multidose vial 100 mg/mL may be added to 4 mL of any of the solutions listed above to create a final concentration of 20 mg mesna/mL.

Diluted solutions are chemically and physically stable for 24 hours at 25°C (77°F).

Mesna is not compatible with cisplatin or carboplatin.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Mesna Injection is supplied as follows:

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). [See USP Controlled Room Temperature.]