Intervallo QT lungo
Reazione avversa da farmaco (ADR)
|Sensazione di bruciore|
|Dermatite da contatto|
Varianti ✨Per l'analisi computazionale dettagliata delle varianti, si prega di selezionare l'abbonamento standard a pagamento.
Informazioni dei farmaci per i pazienti
Non abbiamo ulteriori avvertenze per la co-somministrazione di fluorouracile e astemizolo. Si prega di consultare le informazioni specialistiche pertinenti.
I cambiamenti riportati in seguito all'esposizione corrispondono ai cambiamenti nell'area sottesa alla curva concentrazione plasmatica-tempo [ AUC ]. Non ci aspettiamo nessun cambiamento nell'esposizione alla fluorouracile, quando è co-somministrata con la astemizolo (100%). Non ci aspettiamo nessun cambiamento nell'esposizione alla astemizolo, quando è co-somministrata con la fluorouracile (100%).
I parametri farmacocinetici della popolazione media sono utilizzati come punto di partenza per calcolare i cambiamenti del singolo individuo esposto alle interazioni farmacologiche
La fluorouracile ha una significativa biodisponibilità [ F ] orale pari al 64%, perciò attraverso un'interazione farmacologica la concentrazione plasmatica massima [Cmax] tende a cambiare di poco. L'emivita [ t12 ] del farmaco è piuttosto breve in 0.26666667 ore e lo stato stazionario [Css] si raggiunge molto velocemente. La finestra terapeutica è stretta e quindi il margine di sicurezza è piccolo. Anche piccoli cambiamenti nell'esposizione possono aumentare il rischio di tossicità. Il legame proteico [ Pb ] è molto debole al 10%. I processi metabolici che avvengono tramite il sistema enzimatico dei citocromi sono ancora in fase di studio..
La astemizolo ha una bassa biodisponibilità orale [ F ] del 3%, motivo per cui il livello plasmatico massimo [Cmax] tende a cambiare fortemente con un'interazione. L'emivita [ t12 ] del farmaco è di 22 ore e la concentrazione allo stato stazionario [Css] si raggiunge dopo circa 88 ore. Il legame proteico [ Pb ] è forte al 97%. Tra l'altro, il metabolismo avviene rispettivamente attraverso gli enzimi CYP2D6 e CYP3A4..
|Effetti serotoninergici a||0||Ø||Ø|
Valutazione: Sulla base dei dati a nostra disposizione, né la fluorouracile né la astemizolo potenziano l'attività serotoninergica.
|Kiesel & Durán b||0||Ø||Ø|
Valutazione: Sulla base dei dati a nostra disposizione, né la fluorouracile né la astemizolo causano un aumento dell'attività anticolinergica.
Intervallo QT lungo
Valutazione: La co-somministrazione di fluorouracile e astemizolo potrebbe causare tachicardia ventricolare a torsione di punta.
Effetti collaterali generali
|Effetti collaterali||∑ frequenza||flu||ast|
|Sensazione di bruciore||1.0 %||+||n.a.|
|Dermatite da contatto||1.0 %||+||n.a.|
|Sindrome mano-piede||1.0 %||+||n.a.|
|Angina pectoris||0.0 %||0.01||n.a.|
|Ulcera gastrointestinale||0.0 %||0.01||n.a.|
Abbiamo valutato il rischio individuale di effetti indesiderati in base alle risposte fornite ed alle informazioni scientifiche disponibili. Le informazioni contenute nel sito hanno esclusivamente scopo informativo e non sostituiscono il parere del medico. Si accomanda pertanto di chiedere sempre il parere del proprio medico curante e/o di specialisti riguardo qualsiasi indicazione riportata. Nella versione alpha test, il rischio di tutti i farmaci non è stato ancora completamente valutato.
Abstract: Astemizole is a long-acting, highly selective histamine1-receptor antagonist with minimal central and anticholinergic effects. Comparison studies have shown astemizole to be equal or superior to currently available antihistamines, beclomethasone nasal spray, and cromolyn sodium in relieving allergic symptoms of seasonal and perennial allergic rhinitis. Other uses include treatment of allergic conjunctivitis and chronic urticaria. Astemizole is not as effective for treatment of acute allergic symptoms because of its delayed onset of action. Astemizole and its active metabolite, desmethylastemizole, have long elimination half-lives permitting once-daily dosing. The incidence of sedation is lower than with conventional antihistamines, but increased appetite and weight gain do occur. Astemizole should be useful for both maintenance and prophylactic therapy in patients with chronic allergic conditions who cannot tolerate the sedative or anticholinergic effects of conventional antihistamines.
Abstract: Astemizole is an H1-histamine receptor antagonist with a long duration of action permitting once daily administration. Its efficacy in seasonal and perennial allergic rhinitis has been convincingly demonstrated, and several comparative studies suggest that astemizole is at least as effective as some other H1-histamine receptor antagonists. A few smaller studies have shown beneficial effects on the symptoms of allergic conjunctivitis and chronic urticaria (but not atopic dermatitis). While astemizole appears to share with other H1-histamine receptor antagonists a tendency to increase appetite and cause weight gain after prolonged use, it offers the important advantage of an absence of significant central nervous system depression or anticholinergic effects with usual doses. Thus, astemizole offers a worthwhile improvement in side effect profile over 'traditional' H1-histamine receptor antagonists, especially in patients bothered by the sedative effects of these drugs.
Abstract: An overdose of astemizole predisposes the myocardium to ventricular dysrhythmias, including torsades de pointes. Herein we describe a case of astemizole-induced torsades de pointes ventricular tachycardia and also review previous case reports in the literature. All the patients were young, and dysrhythmias developed only in those with corrected QT intervals greater than 500 ms. Although several mechanisms have been postulated, no clear explanation has been provided for why astemizole promotes myocardial dysrhythmias. Treatment of astemizole-induced torsades de pointes includes discontinuing use of astemizole, intravenous administration of magnesium sulfate and isoproterenol, temporary cardiac pacing, and, when necessary, direct current cardioversion. A cardiac cause of syncope or convulsions must not be overlooked, especially in patients taking H1 antagonists because they often have these symptoms before hospitalization or detection of torsades de pointes (or both).
Abstract: No Abstract available
Abstract: A 26 year-old woman was admitted to the hospital two hours after astemizole overdose. Electrocardiograph showed a prolonged QT interval. Torsade de pointes occurred 13 h after ingestion. Plasma levels of astemizole plus hydroxylated metabolites showed an apparent plasma half-life of 17 h. The possible occurrence of torsade de pointes in astemizole overdose, and the long elimination time of astemizole and hydroxylated metabolites, makes it necessary to maintain ECG monitoring until QT interval has returned to normal.
Abstract: AIMS: The aim of this study was to investigate the influence of chronic itraconazole treatment on the pharmacokinetics and cardiovascular effects of single dose astemizole in healthy subjects was studied. METHODS: Twelve male volunteers were taking orally 200 mg twice daily itraconazole or placebo for 14 days with a washout period of 4 weeks in between. Approximately 2 h after the morning dose of itraconazole or placebo on day 11, 10 mg astemizole was orally administered. The plasma concentrations of astemizole and desmethylastemizole were measured by radioimmunoassay up to 504 h after administration; electrocardiograms with analysis of the QTc interval were recorded up to 24 h post administration. RESULTS: Itraconazole treatment did not significantly change the peak concentration of astemizole (0.74 vs 0.81 ng ml-1) but it increased the area under the curve from 0 to 24 h (5.46 to 9.95 ng ml-1 h) and from 0 to infinity (17.4 to 48.2 ng ml-1 h), and the elimination half-life (2.1 to 3.6 days). The systemic bioavailability of desmethylastemizole was also increased. The QTc interval did not increase after astemizole administration and there was no difference in the QTc intervals between the itraconazole and placebo session. CONCLUSIONS: Chronic administration of itraconazole influences the metabolism of single dose astemizole in normal volunteers without changes of cardiac repolarization during the first 24 h after astemizole administration. However, the reduction in astemizole clearance under concomitant administration of itraconazole may result in a marked increase in astemizole plasma concentrations and QTc alterations during chronic combined intake of astemizole with itraconazole.
Abstract: Second-generation histamine H1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adverse effects that occur with older H1 receptor antagonists. This article evaluates second-generation antihistamines, including acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mizolastine and terfenadine, for significant features that affect choice. In addition to their primary mechanism of antagonising histamine at the H1 receptor, these agents may act on other mediators of the allergic reaction. However, the clinical significance of activity beyond that mediated by histamine H1 receptor antagonism has yet to be demonstrated. Most of the agents reviewed are metabolised by the liver to active metabolites that play a significant role in their effect. Conditions that result in accumulation of astemizole, ebastine and terfenadine may prolong the QT interval and result in torsade de pointes. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis, all agents are effective and the choice should be based on other factors. For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare at the dosages recommended by the manufacturer. For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although current evidence does not suggest a primary role for these agents in the management of asthma, it does support their use for asthmatic patients when there is coexisting allergic rhinitis, dermatitis or urticaria.
Abstract: AIMS: The aims of the present study were to investigate the metabolism of astemizole in human liver microsomes, to assess possible pharmacokinetic drug-interactions with astemizole and to compare its metabolism with terfenadine, a typical H1 receptor antagonist known to be metabolized predominantly by CYP3A4. METHODS: Astemizole or terfenadine were incubated with human liver microsomes or recombinant cytochromes P450 in the absence or presence of chemical inhibitors and antibodies. RESULTS: Troleandomycin, a CYP3A4 inhibitor, markedly reduced the oxidation of terfenadine (26% of controls) in human liver microsomes, but showed only a marginal inhibition on the oxidation of astemizole (81% of controls). Three metabolites of astemizole were detected in a liver microsomal system, i.e. desmethylastemizole (DES-AST), 6-hydroxyastemizole (6OH-AST) and norastemizole (NOR-AST) at the ratio of 7.4 : 2.8 : 1. Experiments with recombinant P450s and antibodies indicate a negligible role for CYP3A4 on the main metabolic route of astemizole, i.e. formation of DES-AST, although CYP3A4 may mediate the relatively minor metabolic routes to 6OH-AST and NOR-AST. Recombinant CYP2D6 catalysed the formation of 6OH-AST and DES-AST. Studies with human liver microsomes, however, suggest a major role for a mono P450 in DES-AST formation. CONCLUSIONS: In contrast to terfenadine, a minor role for CYP3A4 and involvement of multiple P450 isozymes are suggested in the metabolism of astemizole. These differences in P450 isozymes involved in the metabolism of astemizole and terfenadine may associate with distinct pharmacokinetic influences observed with coadministration of drugs metabolized by CYP3A4.
Abstract: OBJECTIVE: To evaluate the cardiotoxicity of LV5FU2 regimen (bolus plus infusional 5-fluorouracil/folinic acid) treatment by non-invasive methods such as echocardiography, plasma troponin I (TnI) level, QT interval and QT dispersion on ECG. METHODS: Twenty-two patients with gastrointestinal cancer who received LV5FU2 chemotherapy were evaluated prospectively during 12 cycles of chemotherapy. Plasma TnI assay and ECG recording analyses were performed before the first cycle, at 24 h, before each cycle until cycle 6 and every three cycles thereafter. The longest QT interval measurement on each recording corrected with Bazzett's formula was considered as QTmax and the difference between the QTmax and the shortest corrected QT interval was considered as QT dispersion (QTd). A complete M-mode, 2D and color Doppler echocardiogram was performed at baseline and at the first, third and sixth months of treatment. RESULTS: Echocardiography did not show any significant change in either systolic or diastolic functions. Also, TnI measurements were found to be below detectable level in all patients and in all measurements. Meanwhile, significant prolongations of QTmax and QTd were observed as early as 24 h after first administration of chemotherapy. These events persisted and became more important over the duration of chemotherapy (P < 0.05). CONCLUSIONS: The clinical implication of these findings as predictive factors for subsequent events such as malignant arrhythmias in patients taking 5-fluorouracil-based chemotherapy need longer follow-up and further detailed evaluations.
Abstract: Anticancer drugs are sometimes associated with QT prolongation. Classical, new and candidate agents to treat cancer may affect ventricular repolarization through a set of different mechanisms. Interference on human ether-a-go-go-related gene potassium ion channels (HERG K+) seems to be a common mechanism for many of these drugs. Anthracycline chemotherapy is associated with electrocardiographic alterations including prolongation of QT interval, development of ventricular late potentials and various arrhythmias. The effects of the interaction of anthracyclines with the monoclonal antibody against HER2/neu (Erb-2) trastuzumab could potentiate the cardiotoxic effects. Electrocardiographic changes have been also reported with the use of 5-fluorouracil. QTc alterations have also been reported with some platinum compounds. Taxanes (paclitaxel and docetaxel) have also been associated with cardiotoxicity, promoting both bradi- and tachyarrhythmias and other cardiac disturbances. Among the newest compounds, symptomatic or asymptomatic QTc aberrations were reported with multitargeted tyrosine-kinase inhibitors, anti HERG2, anti-VEGF, vascular disruption agents and histone deacetylase inhibitors. Patients with cancer are at increased risk of sudden death due to severe cardiac arrhythmias because of the high prevalence of predisposing risk factors such as electrolytic abnormalities, starvation and concomitant medications. The use of specific anticancer drug that may prolong the QT interval need to be properly evaluated in each case to reduce this risk.