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| {{DrugProjectFormSinglePage
| | #REDIRECT[[Dolasetron]] |
| |authorTag={{KS}}
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| |aOrAn=a
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| |indicationType=treatment
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| |adverseReactions=<!--Black Box Warning-->
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| |blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
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| |blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
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| * Content
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| <!--Adult Indications and Dosage-->
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| <!--FDA-Labeled Indications and Dosage (Adult)-->
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| |fdaLIADAdult===Indications==
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| ANZEMET Tablets are indicated for the prevention of [[nausea]] and [[vomiting]] associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses in adults and children 2 years and older.
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| ==Dosage==
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| The recommended doses of ANZEMET Tablets should not be exceeded.
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| '''Adults'''
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| * The recommended oral dosage of ANZEMET (dolasetron mesylate) is 100 mg given within one hour before chemotherapy.
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| '''Use in the Elderly, Renal Failure Patients, or Hepatically Impaired Patients'''
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| * No dosage adjustment is recommended, however; ECG monitoring is recommended for elderly and renally impaired patients.
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| |offLabelAdultGuideSupport======Condition1=====
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| * Developed by:
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| * Class of Recommendation:
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| * Strength of Evidence:
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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| <!--Non–Guideline-Supported Use (Adult)-->
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| |offLabelAdultNoGuideSupport======Condition1=====
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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| <!--Pediatric Indications and Dosage-->
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| <!--FDA-Labeled Indications and Dosage (Pediatric)-->
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| |fdaLIADPed======Condition1=====
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Off-Label Use and Dosage (Pediatric)-->
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| <!--Guideline-Supported Use (Pediatric)-->
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| |offLabelPedGuideSupport======Condition1=====
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| * Developed by:
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| * Class of Recommendation:
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| * Strength of Evidence:
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Non–Guideline-Supported Use (Pediatric)-->
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| |offLabelPedNoGuideSupport======Condition1=====
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Contraindications-->
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| |contraindications=* Condition1
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| <!--Warnings-->
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| |warnings='''QT Interval Prolongation'''
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| * ANZEMET 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]], [[hypomagnesemia]], or [[hypokalemia]]. 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]], [[bradycardia]], renal impairment, and elderly patients.
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| '''PR and QRS Interval Prolongation'''
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| * ANZEMET 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.
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| '''Serotonin Syndrome'''
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| * The 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.
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| * 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, and/or 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.
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| |clinicalTrials=* In controlled clinical trials, 943 adult cancer patients received ANZEMET Tablets. These patients were receiving concurrent chemotherapy, predominantly cyclophosphamide and doxorubicin regimens. The following adverse events were reported in ≥2% of patients receiving either ANZEMET 25 mg or ANZEMET 100 mg tablets for prevention of cancer chemotherapy induced nausea and vomiting in controlled clinical trials (Table 3).
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| [[File:Dolasetron table3.png|thumb|none|600px|This image is provided by the National Library of Medicine.]] | |
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| * In clinical trials, the following reported adverse events, assessed by investigators as treatment-related or causality unknown, occurred following oral or intravenous administration of ANZEMET in < 2% of adult patients receiving concomitant cancer chemotherapy:
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| '''Cardiovascular''':
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| * [[Hypotension]]; [[edema]], [[peripheral edema]]. The following events also occurred and with a similar frequency as placebo and/or active comparator: Mobitz I AV block, [[chest pain]], orthostatic hypotension, [[myocardial ischemia]], [[syncope]], severe [[bradycardia]], and palpitations.
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| * 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, T wave change, ST-T wave change, sinus arrhythmia, extrasystole (APCs or VPCs), poor R-wave progression, bundle branch block (left and right), nodal arrhythmia, U wave change, atrial flutter/fibrillation.
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| * Furthermore, severe [[hypotension]], [[bradycardia]] and [[syncope]] have been reported immediately or closely following IV administration.
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| '''Dermatologic''': [[Rash]], increased sweating.
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| '''Gastrointestinal System''': [[Constipation]], [[dyspepsia]], [[abdominal pain]], [[anorexia]]; [[pancreatitis]].
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| '''Hearing, Taste and Vision''': Taste perversion, abnormal vision, [[tinnitus]], [[photophobia]].
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| '''Hematologic''': [[Hematuria]], [[epistaxis]], prothrombin time prolonged, PTT increased, [[anemia]], [[purpura]]/hematoma, [[thrombocytopenia]].
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| '''Hypersensitivity''': [[Anaphylactic reaction]], facial [[edema]], [[urticaria]].
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| '''Liver and Biliary System''': Transient increases in AST (SGOT) and/or ALT (SGPT) values have been reported as adverse events in less than 1% of adult patients receiving ANZEMET in clinical trials. 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. [[Hyperbilirubinemia]], increased GGT.
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| '''Metabolic and Nutritional''': Alkaline phosphatase increased.
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| '''Musculoskeletal''': [[Myalgia]], [[arthralgia]].
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| '''Nervous System: Flushing''', [[vertigo]], [[paresthesia]], [[tremor]]; [[ataxia]], twitching.
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| '''Psychiatric''': Agitation, sleep disorder, depersonalization; confusion, [[anxiety]], abnormal dreaming.
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| '''Respiratory System''': [[Dyspnea]], bronchospasm.
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| Urinary System: Dysuria, polyuria, acute renal failure.
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| Vascular (Extracardiac): Local pain or burning on IV administration; peripheral ischemia, thrombophlebitis/phlebitis.
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| |postmarketing=* There are reports of wide complex [[tachycardia]] or [[ventricular tachycardia]] and of [[ventricular fibrillation]] cardiac arrest following intravenous administration
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| |drugInteractions=* The potential for clinically significant drug-drug interactions posed by dolasetron and hydrodolasetron appears to be low for drugs commonly used in chemotherapy because hydrodolasetron is eliminated by multiple routes.
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| * 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%.
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| * Caution should be exercised when ANZEMET is coadministered with drugs, including those used in chemotherapy, that prolong ECG intervals and/or cause hypokalemia or hypomagnesemia.
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| * In patients taking furosemide, nifedipine, diltiazem, ACE inhibitors, verapamil, glyburide, propranolol, and various chemotherapy agents, 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. Dolasetron mesylate did not inhibit the antitumor activity of four chemotherapeutic agents (cisplatin, 5-fluorouracil, doxorubicin, cyclophosphamide) in four murine models.
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| * Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular abnormalities) 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).
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| |useInPregnancyFDA='''Teratogenic Effects'''
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| '''Pregnancy Category B'''
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| * 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 oral doses up to 100 mg/kg/day (8 times the recommended human dose based on body surface area) and pregnant rabbits at oral doses up to 100 mg/kg/day (16 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.
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| |useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
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| There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
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| |useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
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| |useInNursing=* It 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 Tablets are administered to a nursing woman.
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| |useInPed=* Safety and effectiveness in pediatric patients (2 years and older) 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.
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| * ANZEMET Tablets are expected to be as safe and effective as when ANZEMET Injection is given orally to pediatric patients. ANZEMET Tablets are recommended for children old enough to swallow tablets
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| |useInGeri=* 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 in this population.
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| * In controlled clinical trials in the prevention of chemotherapy-induced nausea and vomiting, 301 (29%) of 1026 patients were 65 years of age or older. Of the 301 geriatric patients in the trial, 282 received oral ANZEMET Tablets. No overall differences in safety or effectiveness were observed between geriatric and younger patients, and other reported clinical experience has not identified differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
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| * The pharmacokinetics, including clearance of oral ANZEMET Tablets, in elderly and younger patients are similar. Dosage adjustment is not needed in patients over the age of 65.
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| |useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
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| |useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
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| |useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
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| |useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
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| |useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
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| |useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
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| |administration=* Oral
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| * Intravenous
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| |monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
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| * Description
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| <!--IV Compatibility-->
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| |IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
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| <!--Overdosage-->
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| |overdose=* 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.
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| * 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.
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| * It is not known if dolasetron mesylate is removed by hemodialysis or peritoneal dialysis.
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| * 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.
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| * 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.
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| |drugBox=<!--Mechanism of Action-->
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| |mechAction=*
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| <!--Structure-->
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| |structure=*
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| : [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
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| <!--Pharmacodynamics-->
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| |PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
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| <!--Pharmacokinetics-->
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| |PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
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| |nonClinToxic='''Carcinogenesis, Mutagenesis, Impairment of Fertility'''
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| * In 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, 6, and 12 times the recommended clinical dose (74 mg/m2) 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.
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| * 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, 12 times the recommended human dose based on body surface area) in male rats and 300 mg/kg/day (1800 mg/m2/day, 24 times the recommended human dose based on body surface area) in female rats.
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| * 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.
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| * 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, 8 times the recommended human dose based on body surface area) in female rats and up to 400 mg/kg/day (2400 mg/m2/day, 32 times the recommended human dose based on body surface area) in male rats.
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| |clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
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| <!--How Supplied-->
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| |howSupplied=* [[File:Dolasetron supply.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
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| |storage=* Store at controlled room temperature 20–25°C (68–77°F). Protect from light.
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| |packLabel=<!--Patient Counseling Information-->
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| |fdaPatientInfo=* Patients should be informed that ANZEMET may cause serious cardiac arrhythmias such as [[QT prolongation]] or [[heart block]]. Patients should be instructed to tell their health care provider right away if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode.
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| * Patients should be informed that the chances of developing serious cardiac arrhythmias such as QT prolongation and Torsade de Pointes or heart block are higher in the following people:
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| :*Patients with a personal or family history of abnormal heart rhythms, such as congenital long QT syndrome
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| :*Patients with a personal history of sick sinus syndrome, atrial fibrillation with slow ventricular response or myocardial ischemia
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| :*Patients who take medications that may prolong the PR interval, such as certain antihypertensives or medications that may prolong the QRS interval, such as antiarrythmic medications
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| :*Patients who take medications, such as diuretics, which may cause electrolyte abnormalities
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| :*Patients with hypokalemia or hypomagnesemia. Some types of chemotherapy cause hypokalemia and hypomagnesemia
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| :*Elderly patients and renally impaired patients
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| * ANZEMET should be avoided in these patients, since they may be more at risk for cardiac arrhythmias such as QT prolongation and Torsade de Pointes.
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| * Advise patients of the possibility of serotonin syndrome with concomitant use of Anzemet and another serotonergic agent such as medications to treat depression and migraines. Advise patients to seek immediate medical attention if the following symptoms occur: changes in mental status, autonomic instability, neuromuscular symptoms with or without gastrointestinal symptoms.
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| |alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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| |brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
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| <!--Look-Alike Drug Names-->
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| |lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
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| <!--Drug Shortage Status-->
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| |drugShortage=
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| {{PillImage
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| {{LabelImage
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| |fileName={{PAGENAME}}11.png
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| {{LabelImage
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| |fileName={{PAGENAME}}11.png
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| }}
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| <!--Pill Image-->
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| <!--Label Display Image-->
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| <!--Category-->
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| [[Category:Drug]]
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