Dolasetron

Intravenous
Treatment and prophylaxis of postoperative nausea and vomiting

Oral
Nausea and vomiting associated with cancer chemotherapy

Oral
Prophylaxis of postoperative nausea and vomiting

IV infusion: Dilute in 50 ml of a compatible soln (i.e. NaCl 0.9%, dextrose 5%, Lactated Ringer’s soln, dextrose 5% and Lactated Ringer’s soln, dextrose 5% and NaCl 0.45%, and mannitol 10% inj).

Incompatible w/ aciclovir, alemtuzumab, aminocaproic acid, aminophylline, amphotericin B, ampicillin Na, carmustine, cefazolin Na, chloramphenicol Na succinate, clindamycin phosphate, dexamethasone, K phosphate, thiopentone Na, 5-fluorouracil, heparin Na, methylprednisolone succinate, Na bicarbonate, pantoprazole, trimethoprim w/ sulfamethoxazole.

Complete heart block (w/o pacemaker), congenital QT syndrome.

Patient w/ history of abnormal heart rhythms, structural heart disease, sick sinus syndrome, AF w/ slow ventricular response, myocardial ischemia, electrolyte abnormalities (i.e. hypokalaemia, hypomagnesemia). IV admin is not intended for prophylaxis of chemotherapy-associated nausea and vomiting. Pregnancy and lactation.

Significant: PR, QRS, and QT prolongation.
Nervous: Dizziness, headache, drowsiness, fatigue, syncope, flushing, paraesthesia, tremor, ataxia, twitching, agitation, anxiety, sleep disorder, depersonalization, confusion, abnormal dreaming.
CV: Bradycardia, HTN, orthostatic hypotension, tachycardia, peripheral oedema and ischaemia, phlebitis.
GI: Diarrhoea, dyspepsia, flatulence, taste disturbance, constipation, abdominal pain, anorexia, pancreatitis.
Resp: Bronchospasm, dyspnea, epistaxis.
Genitourinary: Oliguria, dysuria, polyuria, acute renal failure, urinary retention, hematuria.
Haematologic: Anemia, hematoma, thrombocytopenia, prolonged partial thromboplastin time (PTT) and prothrombin time.
Musculoskeletal: Myalgia, arthralgia.
Ophthalmologic: Abnormal vision, photophobia.
Otic: Tinnitus.
Dermatologic: Pruritus, urticaria, increased sweating, rash.
Others: Chills, fever, pain, pain at inj site.
Potentially Fatal: Serotonin syndrome. Rarely, cardiac arrest, 2nd or 3rd degree AV block, serious ventricular arrhythmia (e.g. torsade de pointes).

IV/Parenteral/PO: B

Monitor ECG, serum K and Mg concentration.

Symptoms: Severe hypotension, dizziness; PR, QRS, and QT prolongation. Management: Symptomatic and supportive treatment. Monitor cardiac function.

Increased risk of QT prolongation w/ other QT prolonging agents (e.g. pimozide, ziprasideone) and drugs known to cause electrolyte imbalance (e.g. diuretics). Decreased blood levels and therapeutic effects w/ rifampicin. Increased blood levels and effects w/ atenolol and cimetidine. Increased risk of conduction abnormalities when concurrently used w/ antiarrhythmic agents (e.g. verapamil, flecainide, quinidine).

Description:
Mechanism of Action: Dolasetron, a selective serotonin (5-HT₃) receptor antagonist, has antiemetic actions similar to ondansetron. It blocks serotonin both peripherally at the GI tract (main site of action) and centrally at the chemoreceptor trigger zone.
Pharmacokinetics:
Absorption: Rapid and completely absorbed (oral). Bioavalability: Approx 75%. Time to peak plasma concentration: Hydrodolasetron: Approx 1 hr (oral); 0.6 hr (IV).
Distribution: Widely distributed in the body. Volume of distribution: 5-7.9 L/kg. Plasma protein binding: 69-77%.
Metabolism: Rapidly metabolised hepatically via reduction by carbonyl reductase to hydrodolasetron (active metabolite); further metabolised by CYP2D6, CYP3A, and flavin monooxygenase enzymes.
Excretion: Via urine (approx 67%); faeces (approx 33%). Elimination half-life: Dolasetron: ≤10 min (IV); hydrodolasetron: 8.1 hr (oral); 7.3 hr (IV).

Source: National Center for Biotechnology Information. PubChem Database. Dolasetronum, CID=3033818, https://pubchem.ncbi.nlm.nih.gov/compound/Dolasetronum (accessed on Jan. 21, 2020)

Store between 20-25°C. Protect from light.

Antiemetics / Supportive Care Therapy

A04AA04 - dolasetron ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.

Anon. Dolasetron. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/02/2017.

Anzemet Injection (Sanofi-Aventis U.S. LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 27/02/2017.

Anzemet Tablet, Film Coated (Validus Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 27/02/2017.

Buckingham R (ed). Dolasetron Mesilate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com . Accessed 27/02/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Dolasetron Mesylate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 27/02/2017.