Oral Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: In cases associated with initial and repeat courses of moderately emetogenic cancer chemotherapy: 100 mg given within 1 hour prior to chemotherapy. Dosage and treatment recommendations may vary among countries (refer to local guidelines). Child: 2-16 years In cases associated with initial and repeat courses of moderately emetogenic cancer chemotherapy: 1.8 mg/kg given within 1 hour prior to chemotherapy. Max: 100 mg. Treatment recommendations may vary among countries (refer to local guidelines).
Special Precautions
Patient with underlying structural heart disease, pre-existing conduction abnormalities, sick sinus syndrome, atrial fibrillation with slow ventricular response, myocardial ischaemia. Patient receiving drugs known to prolong QT interval (e.g. class I or II antiarrhythmics), PR interval (e.g. verapamil) and QRS interval (e.g. quinidine, flecainide), diuretics that may cause electrolyte abnormalities, and cumulative high-dose anthracycline therapy. Avoid use in patients with congenital long QT syndrome, complete heart block (unless an implanted pacemaker is present), hypokalaemia or hypomagnesaemia. Renal impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Prolongation of QT, PR, and QRS interval (dose-dependent), torsades de pointes; hypersensitivity reactions (e.g. anaphylactic reaction, facial oedema, urticaria). Blood and lymphatic system disorders: Anaemia, thrombocytopenia. Cardiac disorders: Bradycardia, tachycardia. Ear and labyrinth disorders: Vertigo, tinnitus. Eye disorders: Visual disturbance, photophobia. Gastrointestinal disorders: Diarrhoea, dyspepsia, abdominal pain, constipation, dysgeusia, pancreatitis. General disorders and administration site conditions: Fatigue, chills or shivering, pain. Hepatobiliary disorders: Hyperbilirubinaemia. Investigations: Increased GGT and serum alkaline phosphatase; prolonged prothrombin time and partial thromboplastin time. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Twitching, arthralgia, myalgia. Nervous system disorders: Headache, dizziness, ataxia, paraesthesia, tremor. Psychiatric disorders: Anxiety, agitation, abnormal dreams, confusion, depersonalisation, sleep disorder. Renal and urinary disorders: Dysuria, haematuria, polyuria, acute renal failure. Respiratory, thoracic and mediastinal disorders: Dyspnoea, epistaxis, bronchospasm. Skin and subcutaneous tissue disorders: Rash, diaphoresis. Vascular disorders: Hypotension, flushing, haematoma. Potentially Fatal: Serotonin syndrome; 2nd- or 3rd-degree AV block, cardiac arrest, ventricular arrhythmias.
Correct hypokalaemia and hypomagnesaemia before initiating treatment. Monitor serum K and Mg (as clinically indicated) and ECG (in elderly, patients with heart failure, bradycardia, and renal impairment, and patients at risk of hypokalaemia and/or hypomagnesaemia). Observe for signs or symptoms of serotonin syndrome.
Drug Interactions
Reduced hydrodolasetron (active metabolite) exposure with rifampicin. Increased hydrodolasetron exposure with cimetidine. May cause additive ECG interval prolongation effect when used concomitantly with other drugs that prolong PR interval (e.g. verapamil), QRS interval (e.g. flecainide, quinidine), and drugs that may cause electrolyte disorders (e.g. diuretics). Potentially Fatal: Concomitant use with other serotonergic agents (e.g. SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol) may lead to serotonin syndrome.
Action
Description: Mechanism of Action: Dolasetron, a selective serotonin receptor (5-HT3) antagonist, has antiemetic actions similar to ondansetron. It blocks serotonin both peripherally in the gastrointestinal tract (main site of action) and centrally in the medullary chemoreceptor trigger zone. Pharmacokinetics: Absorption: Rapidly and completely absorbed. Bioavailability: Approx 75%. Time to peak plasma concentration: Approx 1 hour. Distribution: Plasma protein binding: Hydrodolasetron: 69-77%; approx 50% to α1-acid glycoprotein. Metabolism: Rapidly metabolised in the liver by carbonyl reductase via reduction to hydrodolasetron (major active metabolite), which is further metabolised by CYP2D6 via hydroxylation and by CYP3A and flavin monooxygenase via N-oxidation. Excretion: Via urine (approx 67%); faeces (approx 33%). Elimination half-life: 8.1 hours (hydrodolasetron).
Chemical Structure
Dolasetron Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3033818, Dolasetron. https://pubchem.ncbi.nlm.nih.gov/compound/Dolasetron. Accessed July 26, 2024.
A04AA04 - dolasetron ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.
References
Anon. Dolasetron. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 10/06/2024.Anzemet Tablet, Film Coated (Validus Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2024.Brayfield A, Cadart C (eds). Dolasetron Mesilate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/06/2024.Dolasetron. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 10/06/2024.
Sign Out
Lanjutkan dengan Google