Prevention of chemotherapy-associated nausea and vomiting (moderate emetic potential): Oral: 100 mg within 1 hour before chemotherapy.
Guideline recommendations: Prevention of chemotherapy-induced nausea and vomiting: American Society of Clinical Oncology (ASCO [Hesketh 2020]):
High emetic risk, including cisplatin-based and most anthracyclines combined with cyclophosphamide regimens: Oral: 100 mg on the day(s) chemotherapy is administered (antiemetic regimen also includes dexamethasone, an NK1 receptor antagonist, and olanzapine).
Moderate emetic risk: Oral: 100 mg on the day(s) chemotherapy is administered (antiemetic regimen also includes dexamethasone [and an NK1 receptor antagonist for carboplatin AUC ≥4]).
Low emetic risk: Oral: 100 mg (as a single agent) prior to chemotherapy on the day(s) chemotherapy is administered.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary; however, ECG monitoring is recommended in patients with renal impairment.
No dosage adjustment necessary.
(For additional information see "Dolasetron: Pediatric drug information")
Chemotherapy-induced nausea and vomiting (CINV); prevention:
Children ≥2 years and Adolescents ≤16 years: Oral: 1.8 mg/kg as a single dose within 1 hour before chemotherapy; maximum dose: 100 mg/dose.
Adolescents >16 years: Oral: 100 mg as a single dose within 1 hour before chemotherapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥2 years and Adolescents: No dosage adjustment necessary; however, ECG monitoring is recommended in patients with renal impairment.
Children ≥2 years and Adolescents: No dosage adjustment necessary.
Refer to adult dosing. ECG monitoring is also recommended.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as mesylate:
Anzemet: 50 mg, 100 mg [DSC]
No
Oral: Administer within 1 hour prior to chemotherapy.
Oral: Administer within 1 hour prior to chemotherapy; may be administered with or without food.
Chemotherapy-associated nausea and vomiting: Prevention of nausea and vomiting associated with initial and repeat course of moderately emetogenic cancer chemotherapy in adults and children ≥2 years of age.
Chemotherapy-associated nausea and vomiting (high emetic potential); Chemotherapy-associated nausea and vomiting (low emetic potential)
Anzemet may be confused with Aldomet, Antivert, Avandamet
Dolasetron may be confused with alosetron, granisetron, ondansetron, palonosetron
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with concurrent chemotherapy.
>10%: Nervous system: Headache (18% to 23%)
1% to 10%:
Cardiovascular: Bradycardia (4% to 5%; including severe bradycardia), edema (<2%), facial edema (<2%), flushing (<2%), hypotension (<2%), peripheral edema (<2%), peripheral ischemia (<2%), phlebitis (<2%), tachycardia (3%), thrombophlebitis (<2%)
Dermatologic: Diaphoresis (<2%), skin rash (<2%), urticaria (<2%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (<2%)
Gastrointestinal: Abdominal pain (<2%), anorexia (<2%), constipation (<2%), diarrhea (2% to 5%), dysgeusia (<2%), dyspepsia (2% to 3%), pancreatitis (<2%)
Genitourinary: Dysuria (<2%), hematuria (<2%)
Hematologic and oncologic: Anemia (<2%), hematoma (<2%), prolonged prothrombin time (<2%), prolonged partial thromboplastin time (<2%), purpuric disease (<2%), thrombocytopenia (<2%)
Hepatic: Hyperbilirubinemia (<2%), increased serum alkaline phosphatase (<2%)
Hypersensitivity: Anaphylaxis (<2%)
Nervous system: Abnormal dreams (<2%), agitation (<2%), anxiety (<2%), ataxia (<2%), chills (≤2%), confusion (<2%), depersonalization (<2%), dizziness (1% to 3%), fatigue (3% to 6%), pain (3%), paresthesia (<2%), shivering (≤2%), sleep disorder (<2%), twitching (<2%), vertigo (<2%)
Neuromuscular & skeletal: Arthralgia (<2%), myalgia (<2%), tremor (<2%)
Ophthalmic: Photophobia (<2%), visual disturbance (<2%)
Otic: Tinnitus (<2%)
Renal: Acute renal failure (<2%), polyuria (<2%)
Respiratory: Bronchospasm (<2%), dyspnea (<2%), epistaxis (<2%)
<1%: Hepatic: Increased serum alanine aminotransferase (transient), increased serum aspartate aminotransferase (transient)
Frequency not defined: Cardiovascular: Abnormal T waves on ECG, appearance of U waves on ECG, atrial fibrillation, atrial flutter, atrioventricular nodal arrhythmia, bundle branch block (left and right), chest pain, extrasystoles (APCs or VPCs), ischemic heart disease, Mobitz I second degree atrioventricular block, orthostatic hypotension, palpitations, sinoatrial nodal rhythm disorder, slow R wave progression, ST segment changes on ECG, syncope
Postmarketing: Cardiovascular: Atrioventricular block, prolongation P-R interval on ECG (dose dependent), prolonged QT interval on ECG (dose dependent), torsades de pointes, ventricular arrhythmia, widened QRS complex on ECG (dose dependent)
Hypersensitivity to dolasetron or any component of the formulation.
Concerns related to adverse effects:
• Cardiovascular effects: Dolasetron is associated with dose-dependent QT interval prolongation; torsades de pointes has been reported. Dolasetron has been determined to cause dose-dependent PR and QRS interval prolongation; second- or third-degree atrioventricular block, cardiac arrest, and serious ventricular arrhythmias (with fatalities) have been observed in adult and pediatric patients. The risk for ECG changes is increased in patients with underlying structural heart disease, preexisting conduction system abnormalities, sick sinus syndrome, atrial fibrillation with slow ventricular response, myocardial ischemia, elderly patients, patients receiving drugs known to prolong the QT interval (eg, Class I or II antiarrhythmics), PR interval (eg, verapamil), or QRS interval (eg, flecainide or quinidine), patients receiving diuretics with the potential to cause electrolyte abnormalities, or patients who have received cumulative high-dose anthracycline therapy. Use with caution (and monitor ECG) in patients at risk for ECG changes. Avoid dolasetron use in patients with congenital long QT syndrome, hypokalemia or hypomagnesemia, and complete heart block or in those at risk for complete heart block who do not have an implanted pacemaker. Correct hypokalemia and hypomagnesemia prior to treatment initiation. Following dolasetron administration, monitor serum potassium and magnesium as clinically indicated. Monitor ECG in patients with heart failure, bradycardia, renal impairment, and in elderly patients. The IV formulations of 5-HT3 antagonists have more association with ECG interval changes, compared to oral formulations. Reduction in heart rate may also occur with the 5-HT3 antagonists.
• Hypersensitivity: Anaphylactic reaction, facial edema, and urticaria have been reported. Use with caution in patients allergic to other 5-HT3 receptor antagonists; cross-reactivity has been reported with other 5-HT3 receptor antagonists.
• Serotonin syndrome: Serotonin syndrome has been reported with 5-HT3 receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, and/or IV methylene blue). Some of the cases have been fatal. The majority of serotonin syndrome reports due to 5-HT3 receptor antagonists have occurred in a post-anesthesia setting or in an infusion center. Serotonin syndrome has also been reported following overdose of another 5-HT3 receptor antagonist. Monitor for signs of serotonin syndrome, including mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); gastrointestinal symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. If serotonin syndrome occurs, discontinue 5-HT3 receptor antagonist treatment and begin supportive management.
Special populations:
• Older adlt: ECG monitoring is recommended in older adult patients.
• Pediatric: Use with caution in children and adolescents who have or may develop QTc prolongation; rare cases of supraventricular and ventricular arrhythmias, cardiac arrest, and MI have been reported in this population.
• Renal impairment: ECG monitoring is recommended in patients with renal impairment.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC, 1984). See manufacturer’s labeling.
Other warnings/precautions:
• Chemotherapy-related emesis: Antiemetics are most effective when used prophylactically (MASCC/ESMO [Roila 2016]). If emesis occurs despite optimal antiemetic prophylaxis, reevaluate emetic risk, disease status, concurrent morbidities, and current medications to assure antiemetic regimen is optimized (ASCO [Hesketh 2020]).
Substrate of CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Mequitazine: Dolasetron may enhance the arrhythmogenic effect of Mequitazine. Management: Concurrent administration of intravenous dolasetron with mequitazine is contraindicated. Risk X: Avoid combination
Panobinostat: Dolasetron may enhance the arrhythmogenic effect of Panobinostat. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Serotonergic Agents (High Risk): Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
TraMADol: Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Adverse events have not been observed in animal reproduction studies.
It is not known if dolasetron is present in breast milk. The manufacturer recommends exercising caution when administering dolasetron to breastfeeding females.
Monitor serum potassium and magnesium; ECG (in patients with heart failure or bradycardia, elderly, renally impaired, those at risk of developing hypokalemia and/or hypomagnesemia). Monitor for signs/symptoms of serotonin syndrome.
Dolasetron is a selective serotonin receptor (5-HT3) antagonist which blocks serotonin both peripherally (primary site of action) and centrally at the chemoreceptor trigger zone
Absorption: Rapid and complete.
Distribution: Hydrodolasetron: Children: 5.9 to 7.4 L/kg; Adults: 5.8 L/kg.
Protein binding: Hydrodolasetron: 69% to 77% (~50% bound to alpha1-acid glycoprotein).
Metabolism: Hepatic; rapid reduction by carbonyl reductase to hydrodolasetron (active metabolite); further metabolized by CYP2D6, CYP3A, and flavin monooxygenase.
Bioavailability: Not affected by food; Children: 59% (formulation not specified); Adults: ~75%.
Half-life elimination:
Hydrodolasetron:
Children: 5.5 hours; Adolescents: 6.4 hours; Adults: 8.1 hours.
Severe renal impairment: 11 hours.
Severe hepatic impairment: 11 hours.
Time to peak, plasma: ~1 hour.
Excretion: Urine ~67% (dolasetron: <1% excreted unchanged in urine; hydrodolasetron: 53% to 61% of the total dose); Feces ~33%.
Altered kidney function: The apparent clearance of hydrodolasetron decreases 44% with severe renal impairment.
Hepatic function impairment: The apparent clearance of hydrodolasetron decreases 42% with severe hepatic impairment.
Tablets (Anzemet Oral)
50 mg (per each): $35.47
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