Dosing and uses of Anzemet (dolasetron)
Adult dosage forms and strengths
injectable solution
- 20mg/mL
tablet
- 50mg
- 100mg
Cancer Chemotherapy Induced Nausea & Vomiting
Oral: 100 mg PO 1 hr before chemotherapy
Note: IV administration no longer indicated for CINV because of risk for QT prolongation
Post-op Nausea & Vomiting
Indicated for prevention and treatment of postoperative nausea and vomiting (PONV)
IV: 12.5 mg IV 15 minutes before cessation of anesthesia or as soon as N/V presents
Note: Oral tablet no longer indicated for PONV
Dosing considerations
Post-op nausea & vomiting
- As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively
- In patients where nausea and/or vomiting must be avoided postoperatively, a 5-HT3 receptor antagonist is recommended even where the incidence of postoperative nausea and/or vomiting is low
- When prophylaxis has failed, a repeat dose should not be initiated as rescue therapy
Pediatric dosage forms and strengths
injectable solution
- 20mg/mL
tablet
- 50mg
- 100mg
Cancer Chemotherapy Induced Nausea & Vomiting
<2 years: Safety and efficacy not established
2-16 years: 1.8 mg/kg PO 1 hr before chemotherapy; not to exceed 100 mg/dose
IV may be administered PO in children aged 2-16 years: 1.8 mg/kg PO 1 hr before chemotherapy; not to exceed 100 mg/dose
Note: IV administration no longer indicated for CINV because of risk for QT prolongation
Postoperative Nausea & Vomiting
Indicated for prevention and treatment of post-op nausea and vomiting (PONV) in children ≥2 years
<2 years: Safety and efficacy not established
IV: 0.35 mg/kg 15 minutes before cessation of anesthesia or as soon as N/V develops; not to exceed 12.5 mg/dose
IV may be administered PO in children aged 2-16 years: 1.2 mg/kg PO administered within 2 hr before surgery; not to exceed 100 mg/dose
Note: Oral tablet no longer indicated for PONV
Dosing considerations
Post-op nausea & vomiting
- As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively
- In patients where nausea and/or vomiting must be avoided postoperatively, a 5-HT3 receptor antagonist is recommended even where the incidence of postoperative nausea and/or vomiting is low
- When prophylaxis has failed, a repeat dose should not be initiated as rescue therapy
Administration
IV administered PO
- Injectable solution may be given PO mixed in apple-grape or apple juice
- Diluted product may be kept up to 2 hr at room temperature
Geriatric dosage forms and strengths
Cancer chemotherapy induced nausea & vomiting
Oral: 100 mg PO 1 hr before chemotherapy
Note: IV administration no longer indicated for CINV because of risk for QT prolongation
Post-op nausea & vomiting
IV: 12.5 mg IV 15 minutes before cessation of anesthesia or as soon as N/V presents
Note: Oral tablet no longer indicated for PONV
Anzemet (dolasetron) adverse (side) effects
>10%
Headache
Diarrhea
1-10%
Dizziness
Drowsiness
Fatigue
Bradycardia
HTn
Hypotension
Tachycardia
Abdominal pain
Dyspepsia
Abnormal liver function
Chills
Fever
Oliguria
Urinary retention
Pain
Pruritus
Warnings
Contraindications
Hypersensitivity
Coadministration with apomorphine; combination reported to cause profound hypotension and loss of consciousness
IV administration for chemotherapy-induced nausea/vomiting (CINV) because of risk for QT, PR, and QRS prolongation
Cautions
Patients at risk for prolongation of cardiac conduction intervals, particularly long QTc interval, congenital long QT syndrome, uncorrected hypokalemia or hypomagnesemia, or receiving other QT-prolonging drugs
Serotonin syndrome reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs including SSRIs, SNRIs, MAO inhibitors, lithium, tramadol, methylene blue IV, and mirtazapine
Correct hypokalemia and hypomagnesemia before administration
Use electrocardiogram (ECG) monitoring in patients with congestive heart failure, bradycardia, underlying heart disease, renal impairment, or who are elderly
Pregnancy and lactation
Pregnancy category: B
Lactation: not known whether distributed into breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Anzemet (dolasetron)
Mechanism of action
Selective 5-HT3 receptor antagonist; dolasetron binds to 5-HT3 receptors located on vagal neurons in GI tract, blocking signal to vomiting center in the brain, thus preventing N/V
Pharmacokinetics
Half-life: parent compound <10 min, hydrodolasetron (active) 4-9 hr
Peak plasma time: IV: 0.6 hr, PO: 1-1.5 hr
Bioavailability: 59-80% (PO)
Vd: 5.8-10 L/kg
Protein binding: 69-77%
Metabolism: dolasetron is metabolized to hydrodolasetron (active) by carbonyl reductase; hydrodolasetron is subsequently metabolized by CYP2D6 and CYP3A
Metabolites: hydrodolasetron (active)
Total body clearance: 9.4-13.4 mL/min/kg
Renal clearance: 2.6-3.4 mg/kg
Excretion: urine (53-61%); feces (25-33%)
Administration
IV Preparation
For infusion, dilute to 50 mL in NS/D5W/D5 in 0.5 NS/D5 in LR/LR/10% mannitol injection
Store vial at room temp
Dilution stable for 24 hr at room temp or 48 hr refrigerated
IV Administration
IVP 100 mg/30 sec Or
Dilute as above and infuse over up to 15 min
After dilution, use within 24 hr, or 48 hr if refrigerated
Do not mix with other drugs
Flush infusion line before and after administration
