gigantic [.0001:<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/m 2 /day). For a 50 kg person of average height (1.46 m 2 body surface area), these doses represent 3, 6, and 12 times the recommended clinical dose (74 mg/m 2 ) 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/m 2 /day, 12 times the recommended human dose based on body surface area) in male rats and 300 mg/kg/day (1800 mg/m 2 /day, 24 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/m 2 /day, 8 times the recommended human dose based on body surface area) in female rats and up to 400 mg/kg/day (2400 mg/m 2 /day, 32 times the recommended human dose based on body surface area) in male rats. Pregnancy: Teratogenic Effects. Pregnancy 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 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. Nursing Mothers 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. Pediatric Use (See PRECAUTIONS, General ) 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. 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 (see CLINICAL PHARMACOLOGY, Pharmacokinetics in Humans ). Geriatric Use 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 (see WARNINGS ). 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. The pharmacokinetics, including clearance of oral Anzemet Tablets, 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 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). Table 3. Adverse Events 2% from Chemotherapy-Induced Nausea and Vomiting Studies Anzemet Event 25 mg (N=235) 100 mg (N=227) Headache 42 (17.9%) 52 (22.9%) Fatigue 6 (2.6%) 13 (5.7%) Diarrhea 5 (2.1%) 12 (5.3%) Bradycardia 12 (5.1%) 9 (4.0%) Dizziness 3 (1.3%) 7 (3.1%) Pain 0 7 (3.1%) Tachycardia 7 (3.0%) 6 (2.6%) Dyspepsia 7 (3.0%) 5 (2.2%) Chills/Shivering 3 (1.3%) 5 (2.2%) 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: Cardiovascular: 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. 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, 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. Furthermore, severe hypotension, bradycardia and syncope have been reported immediately or closely following IV administration. Dermatologic: Rash, increased sweating. Gastrointestinal System: Constipation, dyspepsia, abdominal pain, anorexia; pancreatitis. Hearing, Taste and Vision: Taste perversion, abnormal vision, tinnitus, photophobia. Hematologic: Hematuria, epistaxis, prothrombin time prolonged, PTT increased, anemia, purpura/hematoma, thrombocytopenia. Hypersensitivity: Anaphylactic reaction, facial edema, urticaria. 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. Metabolic and Nutritional: Alkaline phosphatase increased. Musculoskeletal: Myalgia, arthralgia. Nervous System: Flushing, vertigo, paresthesia, tremor; ataxia, twitching. Psychiatric: Agitation, sleep disorder, depersonalization; confusion, anxiety, abnormal dreaming. Respiratory System: Dyspnea, bronchospasm. Urinary System: Dysuria, polyuria, acute renal failure. Vascular ( Extracardiac ): Local pain or burning on IV administration; peripheral ischemia, thrombophlebitis/phlebitis. Postmarketing Experience: There 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 QT c 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. Anzemet Dosage and Administration The recommended doses of Anzemet Tablets should not be exceeded. Adults The recommended oral dosage of Anzemet (dolasetron mesylate) is 100 mg given within one hour before chemotherapy. Pediatric Patients The recommended oral dosage in pediatric patients 2 to 16 years of age is 1.8 mg/kg given within one hour before chemotherapy, up to a maximum of 100 mg. Safety and effectiveness in pediatric patients under 2 years of age have not been established. In children for whom the 100 mg tablet is not appropriate based on their weight or ability to swallow tablets, the Anzemet Injection solution may be mixed into apple or apple-grape juice for oral dosing in pediatric patients. The diluted product may be kept up to 2 hours at room temperature before use. However, Anzemet Injection solution when 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. Use in the Elderly, Renal Failure Patients, or 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 ). How is Anzemet Supplied Anzemet Tablets (dolasetron mesylate) Strength Quantity NDC Number Description 50 mg 5 ct Bottle 30698-120-05 Light pink, film coated, round tablet imprinted with A on one side and 50 on the other. 100 mg 5 ct Bottle 30698-121-05 Pink, film coated, elongated oval tablet imprinted with 100 on one side and Anzemet on the other. Store at controlled room temperature 20-25 C (68-77 F). Protect from light. Patient Counseling Information 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. 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: Patients with a personal or family history of abnormal heart rhythms, such as congenital long QT syndrome Patients with a personal history of sick sinus syndrome, atrial fibrillation with slow ventricular response or myocardial ischemia 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 Patients who take medications, such as diuretics, which may cause electrolyte abnormalities Patients with hypokalemia or hypomagnesemia. Some types of chemotherapy cause hypokalemia and hypomagnesemia Elderly patients and renally impaired patients 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. 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. Prescribing Information as of June 2016 Distributed by: Validus Pharmaceuticals LLC Parsippany, New Jersey 07054 info@validuspharma.com www.validuspharma.com 1-866-982-5438 (1-866-9VALIDUS) 2016 Validus Pharmaceuticals LLC (Rev. June 2016) 60035-01 PRINCIPAL DISPLAY PANEL NDC 30698-120-05 Anzemet Tablets (dolasetron Mesylate) 50 mg 5 Tablets Rx Only PRINCIPAL DISPLAY PANEL NDC 30698-121-05 Anzemet Tablets (dolasetron Mesylate) 100 mg 5 Tablets Rx Only Anzemet dolasetron mesylate tablet, film coated Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:30698-120 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DOLASETRON MESYLATE (DOLASETRON) DOLASETRON MESYLATE 50 mg Inactive Ingredients Ingredient Name Strength CARNAUBA WAX CROSCARMELLOSE SODIUM HYPROMELLOSES LACTOSE MAGNESIUM STEARATE POLYETHYLENE GLYCOLS POLYSORBATE 80 STARCH, PREGELATINIZED CORN FERRIC OXIDE RED TITANIUM DIOXIDE WHITE WAX SHELLAC PROPYLENE GLYCOL FERROSOFERRIC OXIDE Product Characteristics Color PINK (light pink) Score no score Shape ROUND Size 7mm Flavor Imprint Code A;50 Contains Packaging # Item Code Package Description 1 NDC:30698-120-05 5 TABLET, FILM COATED in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020623 09/11/1997 Anzemet dolasetron mesylate tablet, film coated Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:30698-121 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DOLASETRON MESYLATE (DOLASETRON) DOLASETRON MESYLATE 100 mg Inactive Ingredients Ingredient Name Strength CARNAUBA WAX CROSCARMELLOSE SODIUM HYPROMELLOSES LACTOSE MAGNESIUM STEARATE POLYETHYLENE GLYCOLS POLYSORBATE 80 STARCH, PREGELATINIZED CORN FERRIC OXIDE RED TITANIUM DIOXIDE WHITE WAX SHELLAC PROPYLENE GLYCOL FERROSOFERRIC OXIDE Product Characteristics Color PINK Score no score Shape OVAL Size 13mm Flavor Imprint Code 100;Anzemet Contains Packaging # Item Code Package Description 1 NDC:30698-121-05 5 TABLET, FILM COATED in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020623 09/11/1997 Labeler - Validus Pharmaceuticals LLC (801194619) Revised: 06/2016 Validus Pharmaceuticals LLC Next Interactions Print this page Add to My Med List More about Anzemet (dolasetron) Side Effects During Pregnancy Dosage Information Drug Images Drug Interactions Support Group Pricing & Coupons 0 Reviews Add your own review/rating Drug class: 5HT3 receptor antagonists Consumer resources Anzemet ... +5 more Professional resources Anzemet (AHFS Monograph) Anzemet Injection (FDA) Related treatment guides Nausea/Vomiting, Postoperative Nausea/Vomiting, Chemotherapy Induced ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only B Pregnancy Category No proven risk in humans N/A CSA Schedule Not a controlled drug 10 + years Approval History FDA approved 1997 Drug Class 5HT3 receptor antagonists Related Drugs 5HT3 receptor antagonists ondansetron , Zofran , Zofran ODT , Aloxi , granisetron , palonosetron Nausea / Vomiting, Chemotherapy Induced lorazepam , ondansetron , Zofran , Ativan , dexamethasone , metoclopramide , Reglan , Decadron , Marinol , dronabinol , More... Nausea / Vomiting, Postoperative ondansetron , Zofran , metoclopramide , Reglan , Zofran ODT , Emend , Aloxi , granisetron , palonosetron , droperidol , Kytril , aprepitant , More... Anzemet Rating No Reviews - Be the first! 10 /10 No Reviews - Be the first! 10 Rate it! Anzemet Images Anzemet 50 mg (ANZEMET 50 ) View all images} } stumble on
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