Dolasetron Mesylate (1 brand name, 2 dosage forms, 2 routes)
Available dosage forms: TABLET, INJECTABLE.
Routes of administration: ORAL, INJECTION.
Brand Names
- ANZEMET
Indications and Usage
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.
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 100 mg 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 ).
Contraindications
ANZEMET Tablets are contraindicated in patients known to have hypersensitivity to the drug.
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, abd
Drug Interactions
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. See PRECAUTIONS, General for information about potential interaction with other drugs that prolong the QTc interval. When oral dolasetron (200 mg once daily) was co-administered 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 co-administered 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 is co-administered with drugs, including those used in chemotherapy, that prolong ECG intervals and/or cause hypokalemia or hypomagnesemia (see WARNINGS ). 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. 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 re-uptake inhibitors (SSRIs) and serotonin and noradrenaline re-uptake inhibitors (SNRIs).
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.