fluvoxamine and Hypotension

Tizanidine is primarily metabolized via cytochrome P450 (CYP) 1A2 and therefore medications that inhibit the enzyme will affect the clearance of tizanidine, leading to increased plasma concentrations of tizanidine and potentially serious adverse events.. Our aim was to study the occurrence of adverse events reported in the FDA Adverse Event Reporting System (FAERS) involving the combination of tizanidine and drugs that inhibit the metabolic activity of CYP1A2.. A disproportionality analysis of FAERS reports from 2004 quarter 1 through 2020 quarter 3 was conducted to calculate the reporting odds ratio (ROR) of reports mentioning tizanidine in a suspect or interacting role or having any role, a CYP1A2 inhibitor, and the following adverse events: hypotension, bradycardia, syncope, shock, cardiorespiratory arrest, and fall or fracture.. A total of 89 reports were identified mentioning tizanidine, at least one CYP1A2 inhibitor, and one of the adverse events of interest. More than half of the reports identified tizanidine as having a suspect or interacting role (n = 59, 66.3%), and the reports more frequently involved women (n = 58, 65.1%). The median age was 56.1 years (standard deviation 17.1). Some of the important safety signals included interactions between tizanidine in a suspect or interacting role and ciprofloxacin (ROR for hypotension 28.1, 95% confidence interval [CI] 19.2-41.2) or fluvoxamine (ROR for hypotension 36.9, 95% CI 13.1-103.4), and also when reported in "any role" with ciprofloxacin (ROR for hypotension 6.3, 95% CI 4.7-8.5), fluvoxamine (ROR for hypotension 11.4, 95% CI 4.5-28.8), and zafirlukast (ROR for falls 16.0, 95% CI 6.1-42.1).. Reports involving tizanidine and a CYP1A2 inhibitor have higher odds of reporting hypotension. This study suggests that concurrent use of tizanidine with CYP1A2 inhibitors may lead to serious health consequences associated with low blood pressure such as falls and fractures.

Topics: Adverse Drug Reaction Reporting Systems; Ciprofloxacin; Clonidine; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; Drug Interactions; Female; Fluvoxamine; Humans; Hypotension; Male; Middle Aged; United States; United States Food and Drug Administration

Fluvoxamine is one of the typical selective serotonin-reuptake inhibitors. While its combined use with QT-prolonging drugs has been contraindicated because of the increase in plasma concentrations of such drugs, information is still limited whether fluvoxamine by itself may directly prolong the QT interval. We examined electropharmacological effects of fluvoxamine together with its pharmacokinetic profile by using the halothane-anesthetized dogs (n = 4). Fluvoxamine was intravenously administered in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20 min between the doses. The low dose provided therapeutic plasma drug concentration, whereas the middle and high doses attained approximately 10 and 100 times of the therapeutic ones, respectively. Supra-therapeutic concentration of fluvoxamine exerted the negative chronotropic, inotropic and hypotensive effects; and suppressed the atrioventricular nodal and intraventricular conductions, indicating inhibitory actions on Ca2+ and Na+ channels, whereas it delayed the repolarization in a reverse use-dependent manner, reflecting characteristics of rapidly activating delayed rectifier K+ current channel-blocking property. Fluvoxamine prolonged the terminal repolarization phase at 100 times higher concentration than the therapeutic, indicating its proarrhythmic potential. Thus, fluvoxamine by itself has potential to directly induce long QT syndrome at supra-therapeutic concentrations.

Topics: Animals; Arrhythmias, Cardiac; Calcium Channels; Contraindications; Depression, Chemical; Dogs; Dose-Response Relationship, Drug; Fluvoxamine; Heart Conduction System; Heart Rate; Hypotension; Infusions, Intravenous; Long QT Syndrome; Male; Myocardial Contraction; Selective Serotonin Reuptake Inhibitors; Sodium Channels

Hypotension occurred following a combined beta blocker (atenolol), angiotensin converting enzyme inhibitor (quinapil) and selective serotonin reuptake inhibitor (fluvoxamine) overdose. In another instance heart block and hypotension was noted in association with a diltiazem and atenolol adverse interaction. Crystalloid infusion was ineffective in both cases, but toxicity was rapidly reversed with aminophylline administration. Aminophylline's recognized inotropic and chronotropic properties make it a potentially valuable therapeutic agent in the treatment of antihypertensive medication toxicity.

Topics: Adrenergic beta-Antagonists; Aminophylline; Angiotensin-Converting Enzyme Inhibitors; Atenolol; Cardiotonic Agents; Drug Overdose; Female; Fluvoxamine; Humans; Hypotension; Isoquinolines; Middle Aged; Quinapril; Selective Serotonin Reuptake Inhibitors; Tetrahydroisoquinolines; Treatment Outcome

Deliberate drug overdose is a frequent occurrence in patients with schizophrenia. Typical antipsychotic medications can be lethal at doses 5 times the recommended therapeutic range. Clozapine, an atypical antipsychotic, can be toxic at doses 4 times a moderate dose. Little is known about the lethal effects of the novel antipsychotic risperidone, despite the fact that it is now one of the most widely prescribed antipsychotics in North America. To date, only 1 death attributable to risperidone overdose has been reported. The case presented here documents adverse cardiac effects in a 28-year-old man who intentionally ingested 24 mg of risperidone--4 times the recommended dose. A potential drug interaction with fluvoxamine and the role of active metabolites are discussed.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Drug Interactions; Drug Overdose; Electrocardiography; Fluvoxamine; Heart Block; Humans; Hypotension; Male; Risperidone; Schizophrenia; Suicide, Attempted