部份中文甲磺酸多拉司琼处方资料(仅供参考)
The empirical formula is C19H20N2O3 • CH3SO3H • H2O, with a molecular weight of 438.50. Approximately 74% of dolasetron mesylate monohydrate is dolasetron base.
Clinical Studies Prevention of Postoperative Nausea and Vomiting ANZEMET Injection administered intravenously at a dose of 12.5 mg approximately 15 minutes before the cessation of general balanced anesthesia (short-acting barbiturate, nitrous oxide, narcotic and analgesic, and skeletal muscle relaxant) was significantly more effective than placebo in preventing postoperative nausea and vomiting. No increased efficacy was seen with higher doses. One trial compared single intravenous ANZEMET Injection doses of 12.5, 25, 50, and 100 mg with placebo in 635 women surgical patients undergoing laparoscopic procedures. ANZEMET Injection at a dose of 12.5 mg was statistically superior to placebo for complete response (no vomiting, no rescue medication) (p=.0003). Complete response rates were 50% and 31%, respectively. Another trial compared single intravenous ANZEMET Injection doses of 12.5, 25, 50, and 100 mg with placebo in 1030 (722 women and 308 men) surgical patients. In women, the 12.5 mg dose was statistically superior to placebo for complete response. The complete response rates were 50% and 40%, respectively. However, in men, there was no statistically significant difference in complete response between any ANZEMET dose and placebo. Treatment of Postoperative Nausea and/or Vomiting Two randomized, double-blinded trials compared single intravenous ANZEMET Injection doses of 12.5, 25, 50, and 100 mg with placebo in 124 male and 833 female patients who had undergone surgery with general balanced anesthesia and presented with early postoperative nausea or vomiting requiring antiemetic treatment. In both studies, the 12.5 mg intravenous dose of ANZEMET was statistically superior to placebo for complete response (no vomiting, no escape medication). No significant increased efficacy was seen with higher doses. INDICATIONS AND USAGE ANZEMET Injection is indicated for the following: (1) the prevention of postoperative nausea and vomiting (PONV) in adults and children 2 years and older. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, ANZEMET Injection is recommended even where the incidence of postoperative nausea and/or vomiting is low. When prophylaxis has failed, a repeat dose should not be initiated as rescue therapy. (2) the treatment of postoperative nausea and/or vomiting in adults and children 2 years and older. Close CONTRAINDICATIONS ANZEMET Injection is contraindicated in patients known to have hypersensitivity to the drug. ANZEMET Injection solution administered intravenously is contraindicated in adult and pediatric patients for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy due to dose dependent QT prolongation. Mean QTc effects over 20 ms are expected in this patient population (see CLINICAL PHARMACOLOGY and WARNINGS). WARNINGS QTc Interval ProlongationANZEMET prolongs the QT interval in a dose dependent fashion. Torsade de Pointes has been reported during post-marketing experience. Avoid ANZEMET in patients with congenital long QT syndrome, hypokalemia or hypomagnesemia. Hypokalemia and hypomagnesemia must be corrected prior to ANZEMET administration. Monitor these electrolytes after administration as clinically indicated. Use ECG monitoring in patients with congestive heart failure and bradycardia (see CLINICAL PHARMACOLOGY). PR and QRS Interval ProlongationANZEMET has been shown to cause dose dependent prolongation of the PR and QRS interval and reports of second or third degree atrioventricular block, cardiac arrest and serious ventricular arrhythmias including fatalities in both adult and pediatric patients. At particular risk are patients with underlying structural heart disease and preexisting conduction system abnormalities, elderly, patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response, patients with myocardial ischemia or patients receiving drugs known to prolong the PR interval (such as verapamil) and QRS interval (e.g., flecainide or quinidine). ANZEMET should be used with caution and with ECG monitoring in these patients. ANZEMET should be avoided in patients with complete heart block or at risk for complete heart block, unless they have an implanted pacemaker (see CLINICAL PHARMACOLOGY). Serotonin SyndromeThe development of serotonin syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of another 5-HT3 receptor antagonist alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Anzemet and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Anzemet and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Anzemet is used concomitantly with other serotonergic drugs (see DRUG INTERACTIONS, Patient Counseling Information). PRECAUTIONS GeneralDolasetron should be administered with caution in patients who have or may develop prolongation of cardiac conduction intervals, particularly QTc. These include patients with hypokalemia or hypomagnesemia, patients taking diuretics with potential for inducing electrolyte abnormalities, patients with congenital QT syndrome, patients taking anti-arrhythmic drugs or other drugs which lead to QT prolongation, and cumulative high dose anthracycline therapy. Cross hypersensitivity reactions have been reported in patients who received other selective 5-HT3 receptor antagonists. These reactions have not been seen with dolasetron mesylate. Drug InteractionsThe potential for clinically significant drug-drug interactions posed by dolasetron and hydrodolasetron appears to be low for drugs commonly used in surgery, because hydrodolasetron is eliminated by multiple routes. See PRECAUTIONS, General for information about potential interaction with other drugs that prolong the QTc interval. When oral dolasetron (200 mg once daily) was coadministered with cimetidine (300 mg four times daily) for 7 days, the systemic exposure (i.e., AUC) of hydrodolasetron increased by 24% and the maximum plasma concentration of hydrodolasetron increased by 15%. When oral dolasetron (200 mg once daily) was coadministered with rifampin (600 mg once daily) for 7 days, the systemic exposure of hydrodolasetron decreased by 28% and the maximum plasma concentration of hydrodolasetron decreased by 17%. Caution should be exercised when ANZEMET Injection is coadministered with drugs that prolong ECG intervals and/or cause hypokalemia or hypomagnesemia (see WARNINGS). In patients taking furosemide, nifedipine, diltiazem, ACE inhibitors, verapamil, glyburide, and propranolol, no effect was shown on the clearance of hydrodolasetron. Clearance of hydrodolasetron decreased by about 27% when dolasetron mesylate was administered intravenously concomitantly with atenolol. ANZEMET did not influence anesthesia recovery time in patients. Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Carcinogenesis, Mutagenesis, Impairment of FertilityIn a 24-month carcinogenicity study, there was a statistically significant (P<0.001) increase in the incidence of combined hepatocellular adenomas and carcinomas in male mice treated with 150 mg/kg/day and above. In this study, mice (CD-1) were treated orally with dolasetron mesylate 75, 150 or 300 mg/kg/day (225, 450 or 900 mg/m2/day). For a 50 kg person of average height (1.46 m2 body surface area), these doses represent 3.4, 6.8 and 13.5 times the recommended clinical dose (66.6 mg/m2, intravenous) on a body surface area basis. No increase in liver tumors was observed at a dose of 75 mg/kg/day in male mice and at doses up to 300 mg/kg/day in female mice. In a 24-month rat (Sprague-Dawley) carcinogenicity study, oral dolasetron mesylate was not tumorigenic at doses up to 150 mg/kg/day (900 mg/m2/day, 13.5 times the recommended human dose based on body surface area) in male rats and 300 mg/kg/day (1800 mg/m2/day, 27 times the recommended human dose based on body surface area) in female rats. Dolasetron mesylate was not genotoxic in the Ames test, the rat lymphocyte chromosomal aberration test, the Chinese hamster ovary (CHO) cell (HGPRT) forward mutation test, the rat hepatocyte unscheduled DNA synthesis (UDS) test or the mouse micronucleus test. Dolasetron mesylate was found to have no effect on fertility and reproductive performance at oral doses up to 100 mg/kg/day (600 mg/m2/day, 9 times the recommended human dose based on body surface area) in female rats and up to 400 mg/kg/day (2400 mg/m2/day, 36 times the recommended human dose based on body surface area) in male rats. Pregnancy Teratogenic EffectsPregnancy Category B Teratology studies have not revealed evidence of impaired fertility or harm to the fetus due to dolasetron mesylate. These studies have been performed in pregnant rats at intravenous doses up to 60 mg/kg/day (5.4 times the recommended human dose based on body surface area) and pregnant rabbits at intravenous doses up to 20 mg/kg/day (3.2 times the recommended human dose based on body surface area). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing MothersIt is not known whether dolasetron mesylate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ANZEMET Injection is administered to a nursing woman. Pediatric Use Prevention of chemotherapy-induced nausea and vomiting (CINV) Dolasetron is contraindicated in pediatric patients for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy. (see CONTRAINDICATIONS). Prevention and treatment of post-operative nausea and vomiting (PONV) Safety and effectiveness in pediatric patients (2 years and older) for prevention and treatment of postoperative nausea and vomiting is based on pharmacokinetic studies and efficacy data in adults. Safety and effectiveness in pediatric patients under 2 years of age have not been established. Two open-label, noncomparative pharmacokinetic studies have been performed in a total of 30 pediatric patients undergoing surgery with general anesthesia. These patients received ANZEMET Injection either intravenously or orally in juice. Pediatric patients from 2 to 12 years of age participated in these trials, which included an intravenous ANZEMET Injection dose of 1.2 mg/kg, and an oral dose of 1.2 mg/kg. There is no experience in pediatric patients under 2 years of age. Overall, ANZEMET Injection was well tolerated in these pediatric patients. No efficacy information was collected in the pediatric postoperative nausea and vomiting studies. Geriatric Use Prevention of chemotherapy-induced nausea and vomiting (CINV) Dolasetron is contraindicated in geriatric patients for prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy (see CONTRAINDICATIONS). Prevention and treatment of post-operative nausea and vomiting (PONV) Controlled clinical studies in the prevention and treatment of post-operative nausea and vomiting did not include sufficient numbers of patients aged 65 years or older – only 57 (2%) geriatric patients (43 received intravenous ANZEMET Injection) out of 3289 total patients participated in the controlled PONV trials – to determine whether they respond differently from younger patients. Other reported clinical experiences have not identified differences in responses between geriatric and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients are at particular risk for prolongation of the PR, QRS, and QT interval; therefore, caution should be exercised and ECG monitoring should be performed when using ANZEMET for prevention of postoperative nausea and vomiting in this population (see WARNINGS). The pharmacokinetics, including clearance of intravenous ANZEMET Injection, in elderly and younger patients are similar (see CLINICAL PHARMACOLOGY, Pharmacokinetics in Humans). Dosage adjustment is not needed in patients over the age of 65. ADVERSE REACTIONS Postoperative PatientsIn controlled clinical trials with 2550 adult patients, headache and dizziness were reported more frequently with 12.5 mg ANZEMET Injection than with placebo. Rates of other adverse events were similar. Following is a listing of all adverse events reported in ≥2% of patients receiving either placebo or 12.5 mg ANZEMET Injection for the prevention or treatment of postoperative nausea and vomiting in controlled clinical trials (Table 2). Table 2. Adverse Events ≥2% from Placebo-Controlled Postoperative Nausea and Vomiting Studies
Body as a Whole: Chills/shivering. Cardiovascular: Sinus arrhythmia, hypotension, orthostatic hypotension. The following events also occurred and with a similar frequency as placebo and/or active comparator: Mobitz I AV block, chest pain, syncope, severe bradycardia, and palpitations. See PRECAUTIONS section for information on potential effects on ECG. In addition, the following asymptomatic treatment-emergent ECG changes were seen at rates less than or equal to those for active or placebo controls: bradycardia, tachycardia, T wave change, ST-T wave change, extrasystole (APCs or VPCs), bundle branch block (left and right). Furthermore, severe hypotension, bradycardia and syncope have been reported immediately or closely following IV administration. Dermatologic: Rash. Gastrointestinal System: Constipation, dyspepsia, abdominal pain. Hearing, Taste and Vision: Taste perversion, abnormal vision. Hypersensitivity: Anaphylactic reaction, urticaria. Liver and Biliary System: Transient increases in AST (SGOT) and/or ALT (SGPT). The increases did not appear to be related to dose or duration of therapy and were not associated with symptomatic hepatic disease. Similar increases were seen with patients receiving active comparator. Musculoskeletal: Myalgia, arthralgia. Nervous System: Vertigo; flushing, paraesthesia. Psychiatric: Agitation, anxiety, abnormal dreaming. Respiratory System: Bronchospasm. Vascular (Extracardiac): Local pain or burning on IV administration. Postmarketing ExperienceThere are reports of wide complex tachycardia or ventricular tachycardia and of ventricular fibrillation cardiac arrest following intravenous administration. OVERDOSAGE There is no known specific antidote for dolasetron mesylate, and patients with suspected overdose should be managed with supportive therapy. Individual doses as large as 5 mg/kg intravenously or 400 mg orally have been safely given to healthy volunteers or cancer patients. Following a suspected overdose of ANZEMET Injection, a patient found to have second-degree or higher AV conduction block with ECG should undergo cardiac telemetry monitoring. It is not known if dolasetron mesylate is removed by hemodialysis or peritoneal dialysis. Single intravenous doses of dolasetron mesylate at 160 mg/kg in male mice and 140 mg/kg in female mice and rats of both sexes (6.3 to 12.6 times the recommended human dose based on body surface area) were lethal. Symptoms of acute toxicity were tremors, depression and convulsions. A 59-year-old man with metastatic melanoma and no known pre-existing cardiac conditions developed severe hypotension and dizziness 40 minutes after receiving a 15 minute intravenous infusion of 1000 mg (13 mg/kg) of dolasetron mesylate. Treatment for the overdose consisted of infusion of 500 mL of a plasma expander, dopamine, and atropine. The patient had normal sinus rhythm and prolongation of PR, QRS and QTc intervals on an ECG recorded 2 hours after the infusion. The patient's blood pressure was normal 3 hours after the event and the ECG intervals returned to baseline on follow-up. The patient was released from the hospital 6 hours after the event. A 7-year-old boy received 6 mg/kg dolasetron mesylate orally before surgery. No symptoms occurred and no treatment was required. DOSAGE AND ADMINISTRATION The recommended dose of ANZEMET Injection should not be exceeded. Prevention or Treatment of Postoperative Nausea and/or Vomiting Adults The recommended intravenous dosage of ANZEMET Injection is 12.5 mg given as a single dose approximately 15 minutes before the cessation of anesthesia (prevention) or as soon as nausea or vomiting presents (treatment). Pediatric Patients Intravenous Administration The recommended intravenous dosage in pediatric patients 2 to 16 years of age is 0.35 mg/kg, with a maximum dose of 12.5 mg, given as a single dose approximately 15 minutes before the cessation of anesthesia or as soon as nausea or vomiting presents. Safety and effectiveness in pediatric patients under 2 years of age have not been established. Oral Administration of the Intravenous Product ANZEMET Injection solution may be mixed into apple or apple-grape juice for oral dosing in pediatric patients. When ANZEMET Injection solution is administered orally, the recommended oral dosage in pediatric patients 2 to 16 years of age is 1.2 mg/kg up to a maximum 100-mg dose given within 2 hours before surgery. The diluted product may be kept up to 2 hours at room temperature before use. Use in the Elderly, in Renal Failure Patients, or in Hepatically Impaired Patients No dosage adjustment is recommended; however, ECG monitoring is recommended for elderly and renally impaired patients (see WARNINGS and CLINICAL PHARMACOLOGY, Pharmacokinetics in Humans). ADMINISTRATIONANZEMET Injection can be safely infused intravenously as rapidly as 30 seconds or diluted in a compatible intravenous solution (see below) to 50 mL and infused over a period of up to 15 minutes. ANZEMET Injection should not be mixed with other drugs. Flush the infusion line before and after administration of ANZEMET Injection. STABILITYAfter dilution, ANZEMET Injection is stable under normal lighting conditions at room temperature for 24 hours or under refrigeration for 48 hours with the following compatible intravenous fluids: 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.45% sodium chloride injection, 5% dextrose and Lactated Ringer's injection, Lactated Ringer's injection, and 10% mannitol injection. Although ANZEMET Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative. After dilution, do not use beyond 24 hours, or 48 hours if refrigerated. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit. HOW SUPPLIED ANZEMET Injection (dolasetron mesylate) is supplied as a clear, colorless solution in single and multidose vials.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6600DFEA-FCF2-4F89-AB45-66282DEE969F ---------------------------------------------------- 注:以下产品[针剂和片剂:美国上市包装]不同规格和不同价格,采购以咨询为准 ---------------------------------------------------- ANZEMET 100MG/5ML SDV SA 1/EA DOLASETRON MESYLATE 00088-1206-32 ANZEMET 500MG/25ML MDV SA 1/EA DOLASETRON MESYLATE 00088-1209-26 ANZEMET SDV 100MG 5ML DOLASETRON MESYLATE 00088-1206-32 ANZEMET TAB 100MG BOTTLE 5 DOLASETRON MESYLATE 00088-1203-05 ANZEMET VL 12.5MG 6 DOLASETRON MESYLATE 00088-1208-06 ANZEMET TAB 100MG BOTTLE 5 DOLASETRON MESYLATE 30698-0121-05 ANZEMET TAB 50MG BOTTLE DS 5 DOLASETRON MESYLATE 30698-0120-05 |
ANZEMET Injection(甲磺酸多拉司琼注射剂)简介:
部份中文甲磺酸多拉司琼处方资料(仅供参考)【药品名称】甲磺酸多拉司琼注射液【英文名称】Dolasetron Mesylate Injection 【汉语拼音】Jiahuangsuan Duolasiqiong Zhusheye 【化学名称】本品主要成份 ... 责任编辑:p53 |
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