pms-Ondansetron Special Precautions

Immune: Cross-reactive hypersensitivity has been reported between different 5-HT₃ antagonists. Patients who have experienced hypersensitivity reactions to one 5-HT₃ antagonist have experienced more severe reactions upon being challenged with another drug of the same class. The use of a different 5-HT₃ receptor antagonist is not recommended as a replacement in cases in which a patient has experienced even a mild hypersensitivity type reaction to another 5-HT₃ antagonist.
Cardiovascular: QTc Interval Prolongation: Ondansetron prolongs the QT interval (see Pharmacology: Pharmacodynamics: Electrocardiography under Actions). The magnitude of QTc prolongation will depend on the dose and the infusion rate. In addition, post-marketing cases of torsade de pointes have been reported in patients using ondansetron. Torsade de pointes is a polymorphic ventricular tachyarrhythmia. Generally, the risk of torsade de pointes increases with the magnitude of QTc prolongation produced by the drug. Torsade de pointes may be asymptomatic or experienced by the patient as dizziness, palpitations, syncope, or seizures. If sustained, torsade de pointes can progress to ventricular fibrillation and sudden cardiac death.
Avoid ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to either QT prolongation or electrolyte abnormalities (see Interactions). Hypokalemia, hypocalcemia, and hypomagnesemia should be corrected prior to ondansetron administration.
Additional risk factors for torsade de pointes in the general population include, but are not limited to, the following: female gender; age 65 years or older; baseline prolongation of the QT/QTc interval; presence of genetic variants affecting cardiac ion channels or regulatory proteins; family history of sudden cardiac death at < 50 years; cardiac disease (e.g., myocardial ischemia or infarction, left ventricular hypertrophy, cardiomyopathy, conduction system disease); history of arrhythmias (especially ventricular arrhythmias, atrial fibrillation, or recent conversion from atrial fibrillation); bradycardia (< 50 beats per minute); acute neurological events (e.g., intracranial or subarachnoid haemorrhage, stroke, intracranial trauma); nutritional deficits (e.g., eating disorders, extreme diets); diabetes mellitus; autonomic neuropathy.
Ondansetron hydrochloride is not effective in preventing motion-induced nausea and vomiting.
Neurologic: Serotonin syndrome/Neuroleptic Malignant Syndrome: Cases of life-threatening serotonin syndrome or neuroleptic malignant syndrome-like events have been reported with 5-HT₃ receptor antagonist antiemetics, including ondansetron hydrochloride dihydrate, when given in combination with other serotonergic and/or neuroleptic drugs. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). As these syndromes may result in potentially life-threatening conditions, treatment should be discontinued if such events occur and supportive symptomatic treatment should be initiated. If concomitant treatment of ondansetron hydrochloride with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see Interactions).
Hepatic/Biliary/Pancreatic: There is no experience in patients who are clinically jaundiced. The clearance of an 8 mg IV dose of ondansetron hydrochloride was significantly reduced and the serum half-life significantly prolonged in subjects with severe impairment of hepatic function. In patients with moderate or severe impairment of hepatic function, reductions in dosage are therefore recommended and a total daily dose of 8 mg should not be exceeded. This may be given as a single IV or oral dose.
Ondansetron does not itself appear to induce or inhibit the cytochrome P₄₅₀ drug-metabolizing enzyme system of the liver. Because ondansetron is metabolised by hepatic cytochrome P₄₅₀ drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of ondansetron. On the basis of available data, no dosage adjustment is recommended for patients on these drugs.
Gastrointestinal: As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.
Reproduction: Pregnancy status should be verified for females of reproductive potential prior to starting the treatment with pms-ONDANSETRON.
Females of reproductive potential should be advised that it is possible that ondansetron can cause harm to the developing fetus. Sexually active females of reproductive potential are recommended to use effective contraception (methods that result in less than 1% pregnancy rates) when using pms-ONDANSETRON and for two days after stopping treatment with pms-ONDANSETRON.
Use in Children: Insufficient information is available to provide dosage recommendations for children 3 years of age or younger.