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Dolasetron

Medically reviewed by Drugs.com. Last updated on Sep 14, 2020.

Pronunciation

(dol A se tron)

Index Terms

  • Dolasetron Mesylate
  • MDL 73,147EF

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as mesylate:

Anzemet: 50 mg, 100 mg

Brand Names: U.S.

  • Anzemet

Pharmacologic Category

  • Antiemetic
  • Selective 5-HT3 Receptor Antagonist

Pharmacology

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.

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: ~1 hour.

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.

Protein Binding

Hydrodolasetron: 69% to 77% (~50% bound to alpha1-acid glycoprotein).

Special Populations: Renal Function Impairment

The apparent clearance of hydrodolasetron decreases 44% with severe renal impairment.

Special Populations: Hepatic Function Impairment

The apparent clearance of hydrodolasetron decreases 42% with severe hepatic impairment.

Use: Labeled Indications

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.

Off Label Uses

Chemotherapy-associated nausea and vomiting (high emetic potential)

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)

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

Hypersensitivity to dolasetron or any component of the formulation.

Dosing: Adult

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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing. ECG monitoring is also recommended.

Dosing: Pediatric

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.

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.

Storage

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. 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

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

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 QT 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.

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 Considerations

Adverse events have not been observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat or prevent upset stomach and throwing up.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Loss of strength and energy

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Slow heartbeat

• Fast heartbeat

• Serotonin syndrome like 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

• Abnormal heartbeat

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.