No

Selective 5-HT₃ Receptor Antagonist

Prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including initial and repeat courses; prevention of postoperative nausea and vomiting and treatment of postoperative nausea and vomiting (injectable form only)

B

Patients known to have hypersensitivity to the drug

Dolasetron should be administered with caution in patients who have or may develop prolongation of cardiac conduction intervals, particularly QT_c intervals. These include patients with hypokalemia or hypomagnesemia, patients taking diuretics with potential for inducing electrolyte abnormalities, patients with congenital Q-T syndrome, patients taking antiarrhythmic drugs or other drugs which lead to Q-T prolongation, and cumulative high-dose anthracycline therapy.

Dolasetron can cause electrocardiographic interval changes, which are related in frequency and magnitude to blood levels of the metabolite, hydrodolasetron

Cardiovascular: Hypertension

Central nervous system: Headache, fatigue, dizziness, fever, chills and shivering

Gastrointestinal: Diarrhea, abdominal pain

Genitourinary: Urinary retention

Hepatic: Transient increases in liver enzymes

In animal toxicity studies, doses 6.3-12.6 times the recommended human dose based upon surface area were lethal and symptoms of acute poisoning included tremors, depression, and convulsions

There is no known specific antidote for dolasetron and patients with suspected overdose should be managed with supportive therapy

CYP2D6 and 3A3/4 enzyme substrate

After dilution, I.V. dolasetron is stable under normal lighting conditions at room temperature for 24 hours or under refrigeration for 48 hours with the following compatible intravenous fluids: 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.45% sodium chloride injection, 5% dextrose and lactated Ringer's injection, lactated Ringer's injection, and 10% mannitol injection

Dolasetron is a pseudopelletierine-derived serotonin antagonist. Serotonin antagonists block the serotonin receptors in the chemoreceptor trigger zone and in the gastrointestinal tract. Once the receptor site is blocked, antagonism of vomiting occurs.

Half-life: elimination:

MDL 74,156: 8 hours

Children <2 years: Not recommended for use

Nausea and vomiting associated with chemotherapy (including initial and repeat courses):

Children 2-16 years:

Oral: 1.8 mg/kg within 1 hour before chemotherapy; maximum: 100 mg/dose

I.V.: 1.8 mg/kg ~30 minutes before chemotherapy; maximum: 100 mg/dose

Adults:

Oral: 100 mg within 1 hour before chemotherapy

I.V.: 1.8 mg/kg ~30 minutes before chemotherapy or may give 100 mg

Prevention of postoperative nausea and vomiting:

Children 2-16 years:

Oral: 1.2 mg within 2 hours before surgery; maximum: 100 mg/dose

I.V.: 0.35 mg/kg (maximum: 12.5 mg) ~15 minutes before stopping anesthesia

Adults:

Oral: 100 mg within 2 hours before surgery

I.V.: 12.5 mg ~15 minutes before stopping anesthesia

Treatment of postoperative nausea and vomiting: I.V. only:

Children 2-16 years: 0.35 mg/kg as soon as needed

Adults: 12.5 mg as soon as needed

Dosing adjustment for elderly, renal/hepatic impairment: No dosage adjustment is recommended

Liver function tests, blood pressure and pulse, and EKG in patients with cardiovascular disease

May cause drowsiness or dizziness

None reported

No information available to require special precautions

No effects or complications reported

This drug is given to reduce the incidence of nausea and vomiting. You may experience headache, drowsiness, or dizziness; request assistance when getting up or changing position and do not perform activities requiring alertness. Report immediately unusual pain, chills, or fever; severe headache or diarrhea; chest pain, palpitations, or tightness; swelling of throat or feeling of tightness in throat; or difficulty urinating. Breast-feeding precautions: Consult prescriber if breast-feeding.

Dolasetron injection may be diluted in apple or apple-grape juice and taken orally

Injection, as mesylate: 20 mg/mL (0.625 mL, 5 mL)

Tablet, as mesylate: 50 mg, 100 mg

Dempsey E, Bourque S, Spenard J, et al, "Pharmacokinetics of Single Intravenous and Oral Doses of Dolasetron Mesylate in Healthy Elderly Volunteers," J Clin Pharmacol, 1996, 36(10):903-10.

Diemunsch P, Lesser J, Feiss P, et al, "Intravenous Dolasetron Mesilate Ameliorates Postoperative Nausea and Vomiting," Can J Anaesth, 1997, 44(2):173-81.

Fauser AA, Russ W, and Bischoff M, "Oral Dolasetron Mesilate (MDL 73, 147EF) for the Control of Emesis During Fractionated Total-Body Irradiation and High-Dose Cyclophosphamide in Patients Undergoing Allogeneic Bone Marrow Transplantation," Support Care Cancer, 1997, 5(3):219-22.

Graczyk SG, McKenzie R, et al, "Intravenous Dolasetron for the Prevention of Postoperative Nausea and Vomiting After Outpatient Laparoscopic Gynecologic Surgery," Anesth Analg, 1997, 84:325-30.

Grote TH, Pineda LF, Figlin RA, et al, "Oral Dolasetron Mesylate in Patients Receiving Moderately Emetogenic Platinum-Containing Chemotherapy. Oral Dolasetron Dose Response Study Group," Cancer J Sci Am, 1997, 3(1):45-51.

Kovac Al, Scuderi PE, et al, "Treatment of Postoperative Nausea and Vomiting With Single Intravenous Doses of Dolasetron Mesylate: A Multicenter Trial," Anesth Analg, 1997, 85:546-52.

Kris MG, Pendergrass KB, Navari RM, et al, "Prevention of Acute Emesis in Cancer Patients Following High-Dose Cisplatin With the Combination of Oral Dolasetron and Dexamethasone," J Clin Oncol, 1997, 15(5):2135-8.

Rubenstein EB, Gralla RJ, Hainsworth JD, et al, "Randomized, Double-Blind, Dose-Response Trial Across Four Oral Doses of Dolasetron for the Prevention of Acute Emesis After Moderately Emetogenic Chemotherapy. Oral Dolasetron Dose-Response Study Group," Cancer, 1997, 79(6):1216-24.