Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as mesylate:
Anzemet: 20 mg/mL (0.625 mL [DSC], 5 mL [DSC], 25 mL [DSC])
Tablet, Oral, as mesylate:
Anzemet: 50 mg, 100 mg
Pharmacology
Mechanism of Action
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
Pharmacokinetics/Pharmacodynamics
Absorption
Oral: Rapid and complete
Distribution
Hydrodolasetron: Children: 5.9 to 7.4 L/kg; Adults: 5.8 L/kg
Metabolism
Hepatic; rapid reduction by carbonyl reductase to hydrodolasetron (active metabolite); further metabolized by CYP2D6, CYP3A, and flavin monooxygenase
Excretion
Urine ~67% (dolasetron: <1% excreted unchanged in urine; hydrodolasetron: 53% to 61% of the total dose); Feces ~33%
Time to Peak
Hydrodolasetron: IV: 0.6 hours; Oral: ~1 hour
Half-Life Elimination
Dolasetron: IV: ≤10 minutes
Hydrodolasetron:
Oral: Children: 5.5 hours; Adolescents: 6.4 hours; Adults: 8.1 hours
IV: Children: 4.8 hours; Adults: 7.3 hours
Severe renal impairment: 11 hours
Severe hepatic impairment: 11 hours
Protein Binding
Hydrodolasetron: 69% to 77% (~50% bound to alpha1-acid glycoprotein)
Use in Specific Populations
Special Populations: Renal Function Impairment
The apparent clearance of hydrodolasetron decreases 44% (oral) and 47% (IV) with severe renal impairment.
Special Populations: Hepatic Function Impairment
The apparent oral clearance of hydrodolasetron decreases 42% (oral) with severe hepatic impairment.
Use: Labeled Indications
Chemotherapy-associated nausea and vomiting (oral): Prevention of nausea and vomiting associated with initial and repeat course of moderately emetogenic cancer chemotherapy in adults and children ≥2 years
Postoperative nausea and vomiting (injection): Prevention and treatment of postoperative nausea and vomiting (PONV) in adults and children ≥2 years
Limitations of use: Routine PONV prophylaxis is not recommended if there is little expectation that nausea and/or vomiting will occur postoperatively. In patients in whom nausea and/or vomiting must be avoided postoperatively, dolasetron (injection) is recommended even if the anticipated incidence of postoperative nausea and/or vomiting is low. If prophylaxis has failed, a repeat dose should not be utilized as rescue therapy.
Use: Off Label
Chemotherapy-associated nausea and vomiting (high emetic potential)yes
In addition to the approved use (prevention of nausea and vomiting associated with moderately emetogenic chemotherapy), antiemetic guidelines from the American Society of Clinical Oncology (ASCO) also recommend offering a 5-HT3 receptor antagonist (including oral dolasetron) in combination with other antiemetic agents for the prevention of highly emetic chemotherapy, including cisplatin-containing chemotherapy or chemotherapy regimens containing an anthracycline and cyclophosphamide.
Chemotherapy-associated nausea and vomiting (low emetic potential)yes
In addition to the approved use (prevention of nausea and vomiting associated with moderately emetogenic chemotherapy), antiemetic guidelines from the American Society of Clinical Oncology (ASCO) also recommend offering a 5-HT3 receptor antagonist (including oral dolasetron) as a single agent for the prevention of low emetic chemotherapy.
Contraindications
Tablet: Known hypersensitivity to dolasetron or any component of the formulation
Injection: Known hypersensitivity to dolasetron or any component of the formulation; intravenous administration is contraindicated when used for prevention of chemotherapy-associated nausea and vomiting
Dosage and Administration
Dosing: Adult
Note: Anzemet injection has been discontinued in the US for more than 1 year.
Note: Use of intravenous dolasetron is contraindicated for the prevention of chemotherapy induced nausea and vomiting.
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 2017]):
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
Postoperative nausea and vomiting:
Prevention: IV: 12.5 mg ~15 minutes before cessation of anesthesia (do not exceed the recommended dose)
Treatment: IV: 12.5 mg as soon as nausea or vomiting present (do not exceed the recommended dose)
Dosing: Geriatric
Refer to adult dosing. ECG monitoring is also recommended.
Dosing: Pediatric
Note: Anzemet injection has been discontinued in the US for more than 1 year.
Chemotherapy-induced nausea and vomiting (CINV); prevention: Note: Due to increased risk of QTc prolongation, IV administration of dolasetron for CINV is contraindicated; however, the parenteral formulation may be administered orally to patients who cannot swallow tablets or in whom the tablet strength is an inappropriate dose.
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.
Postoperative nausea and vomiting: Note: If the prophylaxis dolasetron dose has failed, a repeat dose should not be administered as rescue or treatment.
Prevention:
Oral: Children and Adolescents 2 to 16 years: 1.2 mg/kg administered within 2 hours before surgery; maximum dose: 100 mg.
IV:
Children ≥2 years and Adolescents ≤16 years: 0.35 mg/kg administered ~15 minutes before cessation of anesthesia; maximum dose: 12.5 mg/dose.
Adolescents >16 years: 12.5 mg administered ~15 minutes before cessation of anesthesia (do not exceed the recommended dose).
Treatment: IV:
Children ≥2 years and Adolescents ≤16 years: 0.35 mg/kg as soon as nausea or vomiting present; maximum dose: 12.5 mg/dose.
Adolescents >16 years: 12.5 mg as soon as nausea or vomiting present (do not exceed the recommended dose).
Reconstitution
IV: May be administered undiluted, or diluted in 50 mL of a compatible solution (ie, NS, D5W, D51/2NS, D5LR, LR, and 10% mannitol injection).
Extemporaneously Prepared
10 mg/mL Oral Suspension
A 10 mg/mL oral suspension may be prepared with tablets and either a 1:1 mixture of Ora-Plus and Ora-Sweet SF or a 1:1 mixture of strawberry syrup and Ora-Plus. Crush twelve 50 mg tablets in a mortar and reduce to a fine powder. Slowly add chosen vehicle to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well" and "refrigerate." Stable for 90 days refrigerated.
Johnson CE, Wagner DS, and Bussard WE, "Stability of Dolasetron in Two Oral Liquid Vehicles," Am J Health Syst Pharm, 2003, 60(21):2242-4.14619116
Administration
Oral: Administer within 1 hour prior to chemotherapy. When unable to administer in tablet form, dolasetron injection may be diluted in apple or apple-grape juice and taken orally; this dilution is stable for 2 hours at room temperature (Anzemet prescribing information 2013).
IV: IV injection may be given either undiluted as an IV push over 30 seconds or diluted in 50 mL of compatible fluid and infused over up to 15 minutes. Flush line before and after dolasetron administration.
Storage
Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Solutions diluted for infusion in NS, D5W, D51/2NS, D5LR, LR, or mannitol 10% are stable under normal lighting conditions at room temperature for 24 hours or under refrigeration for 48 hours.
Tablets: Store at 20°C to 25°C (68°F to 77°F). Protect from light.
Drug Interactions
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy
Mequitazine: Dolasetron may enhance the arrhythmogenic effect of Mequitazine. Management: Concurrent administration of intravenous dolasetron with mequitazine is contraindicated. Avoid combination
Panobinostat: Dolasetron may enhance the arrhythmogenic effect of Panobinostat. 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. 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. Exceptions: TraMADol. Monitor therapy
Tapentadol: Antiemetics (5HT3 Antagonists) may diminish the analgesic effect of Tapentadol. 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. Monitor therapy
Adverse Reactions
Adverse events may vary according to indication and route of administration.
>10%: Central nervous system: Headache (oral: 18% to 23%; IV: 9%)
1% to 10%:
Cardiovascular: Bradycardia (4% to 5%; may be severe after IV administration), tachycardia (≤3%), edema (<2%), facial edema (<2%), flushing (<2%), hypotension (<2%; may be severe after IV administration), orthostatic hypotension (<2%), peripheral edema (<2%), peripheral ischemia (<2%), phlebitis (<2%), sinus arrhythmia (<2%), thrombophlebitis (<2%)
Central nervous system: Fatigue (oral: 3% to 6%), dizziness (1% to 6%), pain (≤3%), abnormal dreams (<2%), agitation (<2%), anxiety (<2%), ataxia (<2%), chills (≤2%), confusion (<2%), depersonalization (<2%), paresthesia (<2%), shivering (≤2%), sleep disorder (<2%), twitching (<2%), vertigo (<2%)
Dermatologic: Diaphoresis (<2%), skin rash (<2%), urticaria (<2%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (<2%)
Gastrointestinal: Diarrhea (oral: 2% to 5%), dyspepsia (≤3%), abdominal pain (<2%), anorexia (<2%), constipation (<2%), dysgeusia (<2%), pancreatitis (<2%)
Genitourinary: Dysuria (<2%), hematuria (<2%)
Hematologic and oncologic: Anemia (<2%), hematoma (<2%), prolonged prothrombin time (<2%), prolonged partial thromboplastin time (<2%), purpura (<2%), thrombocytopenia (<2%)
Hepatic: Hyperbilirubinemia (<2%), increased serum alkaline phosphatase (<2%)
Hypersensitivity: Anaphylaxis (<2%)
Local: Burning sensation at injection site (IV: <2%), pain at injection site (IV: <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%, postmarketing, and/or case reports: Abnormal T waves on ECG, appearance of U waves on ECG, atrial fibrillation, atrial flutter, atrioventricular block, bundle branch block (left and right), cardiac arrest, chest pain, extrasystoles (APCs or VPCs), increased serum ALT (transient), increased serum AST (transient), ischemic heart disease, nodal arrhythmia, palpitations, prolongation P-R interval on ECG (dose dependent), prolonged Q-T interval on ECG, serotonin syndrome, slow R wave progression, ST segment changes on ECG, syncope (may be severe after IV administration), torsades de pointes, ventricular arrhythmia, ventricular fibrillation cardiac arrest (IV), ventricular tachycardia (IV), wide complex tachycardia (IV), widened QRS complex on ECG (dose-dependent)
Warnings/Precautions
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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: ECG monitoring is recommended in geriatric 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 (Roila 2016). If emesis occurs despite optimal antiemetic prophylaxis, reevaluate emetic risk, disease, concurrent morbidities, and medications to assure antiemetic regimen is optimized (ASCO [Hesketh 2017]).
Monitoring Parameters
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.
Pregnancy
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, loss of strength and energy, or diarrhea. Have patient report immediately to prescriber severe dizziness, passing out, slow heartbeat, fast heartbeat, signs of serotonin syndrome (dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), or abnormal heartbeat (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
