Intervallo QT lungo
Reazione avversa da farmaco (ADR)
|Mal di testa|
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 loratadine e tranilcipromina. 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 loratadine, quando è co-somministrata con la tranilcipromina (100%). Non ci aspettiamo nessun cambiamento nell'esposizione alla tranilcipromina, quando è co-somministrata con la loratadine (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 loratadine ha una bassa biodisponibilità [ F ] orale, perciò nel corso di un interazione farmacologica la concentrazione plasmatica massima (Cmax) tende fortemente a cambiare. Il legame proteico [ Pb ] è forte al 98%. Tra l'altro, il metabolismo avviene rispettivamente attraverso gli enzimi CYP2D6 e CYP3A4. e il trasporto attivo avviene in particolare attraverso i trasportatori PGP e TRA8X8.
La tranilcipromina ha una significativa biodisponibilità [ F ] orale pari al 50%, perciò attraverso un'interazione farmacologica la concentrazione plasmatica massima [Cmax] tende a cambiare di poco. L'emivita [ t12 ] del farmaco è piuttosto breve in 2.5 ore e lo stato stazionario [Css] si raggiunge molto velocemente. Il legame con le proteine [ Pb ] non è noto. I processi metabolici che avvengono tramite il sistema enzimatico dei citocromi sono ancora in fase di studio..
|Effetti serotoninergici a||3||Ø||+++|
Avvertenze: Il rischio di sindrome serotoninergica è maggiore, ma senza delle risposte esatte alle domande sui sintomi cognitivi, neurovegetativi e neuromuscolari non è possibile formulare alcun tipo di raccomandazione.
Valutazione: La tranilcipromina aumenta significativamente l'attività serotoninergica. Sulla base dei dati a nostra disposizione, la loratadine non potenzia l'attività serotoninergica.
|Kiesel & Durán b||2||+||+|
Avvertenze e precauzioni: Per precauzione, si dovrebbe porre attenzione ai sintomi di tipo anticolinergico, soprattutto se il dosaggio è stato aumentato oppure se è al di sopra dell'intervallo terapeutico.
Valutazione: La loratadine e la tranilcipromina possiedono soltanto limitati effetti anticolinergici. Il rischio di sindrome anticolinergica è molto basso se si rispettano i dosaggi abituali.
Intervallo QT lungo
Non è noto se la loratadine e la tranilcipromina siano in grado di prolungare l'intervallo QT
Effetti collaterali generali
|Effetti collaterali||∑ frequenza||lor||tra|
|Mal di testa||38.5 %||12.0||30.1|
|Visione offuscata||10.1 %||n.a.||10.1|
Edema periferico: tranilcipromina
Crisi ipertensiva: tranilcipromina
Perdita di appetito: tranilcipromina
Disfunzione erettile: tranilcipromina
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: This histological and immunohistochemical study of 6 food handlers affected by immediate contact dermatitis due to foods shows that apparently normal skin of patients with this condition presents several histological and immunohistochemical abnormalities. Skin biopsies of normal hand skin showed focal parakeratosis and moderately dense dermal infiltrates. Immunohistochemistry showed an increased number of Langerhans cells in the epidermis and in the superficial dermis and a mononuclear dermal infiltrate consisting of peripheral T lymphocytes with a CD4/CD8 ratio of 5-6/1. Biopsies of the immediate vesicular reactions induced by foods showed spongiotic vesicles within the epidermis and a moderate to dense mononuclear dermal perivascular infiltrate. The immunohistochemical features were similar to those described in apparently normal skin. The mechanism of this immediate vesicular reaction requires further research. The rapid appearance of the lesions (after 20-30 min) probably excludes an immunological cell-mediated pathogenesis. A non-immunological mechanism due to direct liberation of mediators by foods is more readily conceivable than an immediate immunological type of contact reaction.
Abstract: OBJECTIVE: To evaluate the effects of coadministration of loratadine and erythromycin on the pharmacokinetics and electrocardiographic repolarization (QTc) pharmacodynamics of loratadine and its metabolite descarboethoxyloratadine in healthy volunteers. METHODS: Twenty-four healthy volunteers were studied in a prospective, double-blind crossover design while confined in a Clinical Research Center. The primary pharmacodynamic end point of the study was the difference between baseline and day 10 mean QTc intervals obtained from surface electrocardiograms. Plasma concentrations of loratadine, descarboethoxyloratadine, and erythromycin were measured on treatment day 10 for pharmacokinetic analysis. Subjects received in random sequence the following three treatments for 10 consecutive days during three separate study periods: 10 mg loratadine every morning plus 500 mg erythromycin stearate every 8 hours, or 10 mg loratadine every morning plus placebo every 8 hours, or placebo every morning plus 500 mg erythromycin stearate. RESULTS: Concomitant administration of loratadine and erythromycin was associated with increased plasma concentrations of loratadine (40% increase in area under the plasma concentration-time curve [AUC]) and descarboethoxyloratadine (46% increase in AUC) compared with loratadine alone. Analysis of variance showed no difference between the treatment groups in effect on QTc intervals compared with baseline, and no significant change from baseline was observed. No clinically relevant changes in the safety profile of loratadine were observed, and there were no reports of sedation nor syncope. CONCLUSION: Although concomitant administration of loratadine and erythromycin was associated with increased plasma concentrations of loratadine and descarboethoxyloratadine, no clinically relevant changes in the safety profile of loratadine were observed. In this study, 10 mg loratadine administered orally for 10 consecutive days was well tolerated when coadministered with therapeutic doses of erythromycin stearate.
Abstract: Excessive stimulation of serotonin 5HT1A receptors causes a syndrome of serotonin excess that consists of shivering, muscle rigidity, salivation, confusion, agitation and hyperthermia. The most common cause of this syndrome is an interaction between a monoamine oxidase inhibitor (MAOI) and a specific serotonin reuptake inhibitor. Venlafaxine is a new antidepressant agent that inhibits the reuptake of serotonin and norepinephrine. We report a venlafaxine-MAOI interaction that resulted in the serotonin syndrome in a 23-y-old male who was taking tranylcypromine for depression. He had been well until the morning of presentation when he took 1/2 tab of venlafaxine. Within 2 h he became confused with jerking movements of his extremities, tremors and rigidity. He was brought directly to a hospital where he was found to be agitated and confused with shivering, myoclonic jerks, rigidity, salivation and diaphoresis. His pupils were 7 mm and sluggishly reactive to light. Vital signs were: blood pressure 120/67 mm Hg, heart rate 127/min, respiratory rate 28/min, and temperature 97 F. After 180 mg of diazepam i.v. he remained tremulous with muscle rigidity and clenched jaws. He was intubated for airway protection and because of hypoventilation, and was paralyzed to control muscle rigidity. His subsequent course was remarkable for non-immune thrombocytopenia which resolved. The patient's maximal temperature was 101.2 F and his CPK remained < 500 units/L with no other evidence of rhabdomyolysis. His mental status normalized and he was transferred to a psychiatry ward. This patient survived without sequelae due to the aggressive sedation and neuromuscular paralysis.
Abstract: A number of novel serotonergic antidepressants have been introduced to clinical practice over the last decade. These medications are felt to be safe alternatives to the traditional tricyclic antidepressants and monoamine oxidase inhibitors, particularly in the overdose setting. Serious adverse reactions and drug interactions have been appreciated and fatalities have been reported. We describe the development of the serotonin syndrome in a 60 year old female on chronic tranylcypromine treatment following the inadvertent ingestion of a single dose of venlafaxine. Manifestations included and altered mental status that progressed to hyperthermia and coma. She recovered quickly and without complications. Health care providers and poison specialists need to be aware that this potentially serious syndrome can be precipitated by a single dose of a serotonin reuptake inhibitor in patients being treated with a monoamine oxidase inhibitor.
Abstract: AIMS: To evaluate whether ketoconazole or cimetidine alter the pharmacokinetics of loratadine, or its major metabolite, desloratadine (DCL), or alter the effects of loratadine or DCL on electrocardiographic repolarization in healthy adult volunteers. METHODS: Two randomized, evaluator-blind, multiple-dose, three-way crossover drug interaction studies were performed. In each study, subjects received three 10 day treatments in random sequence, separated by a 14 day washout period. The treatments were loratadine alone, cimetidine or ketoconazole alone, or loratadine plus cimetidine or ketoconazole. The primary study endpoint was the difference in mean QTc intervals from baseline to day 10. In addition, plasma concentrations of loratadine, DCL, and ketoconazole or cimetidine were obtained on day 10. RESULTS: Concomitant administration of loratadine and ketoconazole significantly increased the loratadine plasma concentrations (307%; 90% CI 205-428%) and DCL concentrations (73%; 62-85%) compared with administration of loratadine alone. Concomitant administration of loratadine and cimetidine significantly increased the loratadine plasma concentrations (103% increase; 70-142%) but not DCL concentrations (6% increase; 1-11%) compared with administration of loratadine alone. Cimetidine or ketoconazole plasma concentrations were unaffected by coadministration with loratadine. Despite increased concentrations of loratadine and DCL, there were no statistically significant differences for the primary electrocardiographic repolarization parameter (QTc) among any of the treatment groups. No other clinically relevant changes in the safety profile of loratadine were observed as assessed by electrocardiographic parameters (mean (90% CI) QTc changes: loratadine vs loratadine + ketoconazole = 3.6 ms (-2.2, 9.4); loratadine vs loratadine + cimetidine = 3.2 ms (-1.6, 7.9)), clinical laboratory tests, vital signs, and adverse events. CONCLUSIONS: Loratadine 10 mg daily was devoid of any effects on electrocardiographic parameters when coadministered for 10 days with therapeutic doses of ketoconazole or cimetidine in healthy volunteers. It is concluded that, although there was a significant pharmacokinetic drug interaction between ketoconazole or cimetidine and loratadine, this effect was not accompanied by a change in the QTc interval in healthy adult volunteers.
Abstract: Loratadine is known to be a substrate for both CYP3A4 and CYP2D6 based on a previous in vitro study. In view of the large interindividual variability in loratadine pharmacokinetics and the greater genetically determined variability of CYP2D6 activity than of CYP3A4 in vivo, we hypothesized that CYP2D6 polymorphisms may contribute to the pharmacokinetic variability of loratadine. The purpose of this study was to evaluate the effect of CYP2D6 genotype (specifically the CYP2D6*10 allele) on the pharmacokinetics of loratadine in Chinese subjects. Three groups of healthy male Chinese subjects were enrolled: group I, homozygous CYP2D6*1 (*1/*1, n=4); group II, heterozygous CYP2D6*10 (*1/*10 or *2/*10, n=6); and group III, homozygous CYP2D6*10 (*10/*10, n=7) carriers. Each subject received a single oral dose of 20 mg of loratadine under fasting conditions. Multiple blood samples were collected over 48 h, and the plasma concentrations of loratadine and its metabolite desloratadine were determined by high-performance liquid chromatography. In comparing homozygous CYP2D6*10 (group III) to heterozygous CYP2D6*10 (group II) to homozygous CYP2D6*1 (group I) subjects, loratadine oral clearance values were 7.17+/- 2.54 versus 11.06+/-1.70 versus 14.59+/-2.43 l/h/kg, respectively [one-way analysis of variance (ANOVA), p<0.01], and the corresponding metabolic ratios [area under the plasma concentration-time curve (AUC)(desloratadine)/AUC(loratadine)] were 1.55+/-0.73 versus 2.47+/- 0.46 versus 3.32+/- 0.49, respectively (one-way ANOVA, p<0.05), indicating a gene-dose effect. The results demonstrated that CYP2D6 polymorphism prevalent in the Chinese population significantly affected loratadine pharmacokinetics.
Abstract: BACKGROUND: Adverse effects of anticholinergic medications may contribute to events such as falls, delirium, and cognitive impairment in older patients. To further assess this risk, we developed the Anticholinergic Risk Scale (ARS), a ranked categorical list of commonly prescribed medications with anticholinergic potential. The objective of this study was to determine if the ARS score could be used to predict the risk of anticholinergic adverse effects in a geriatric evaluation and management (GEM) cohort and in a primary care cohort. METHODS: Medical records of 132 GEM patients were reviewed retrospectively for medications included on the ARS and their resultant possible anticholinergic adverse effects. Prospectively, we enrolled 117 patients, 65 years or older, in primary care clinics; performed medication reconciliation; and asked about anticholinergic adverse effects. The relationship between the ARS score and the risk of anticholinergic adverse effects was assessed using Poisson regression analysis. RESULTS: Higher ARS scores were associated with increased risk of anticholinergic adverse effects in the GEM cohort (crude relative risk [RR], 1.5; 95% confidence interval [CI], 1.3-1.8) and in the primary care cohort (crude RR, 1.9; 95% CI, 1.5-2.4). After adjustment for age and the number of medications, higher ARS scores increased the risk of anticholinergic adverse effects in the GEM cohort (adjusted RR, 1.3; 95% CI, 1.1-1.6; c statistic, 0.74) and in the primary care cohort (adjusted RR, 1.9; 95% CI, 1.5-2.5; c statistic, 0.77). CONCLUSION: Higher ARS scores are associated with statistically significantly increased risk of anticholinergic adverse effects in older patients.
Abstract: OBJECTIVES: To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men. DESIGN: Prospective cohort study. SETTING: A Department of Veterans Affairs primary care clinic. PARTICIPANTS: Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension. MEASUREMENTS: The outcomes were measured using the Hopkins Verbal Recall Test (HVRT) for short-term memory and the instrumental activity of daily living (IADL) scale for executive function at baseline and during follow-up. Anticholinergic medication use was ascertained using participants' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anticholinergic score. RESULTS: Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs. On average, a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point (95% confidence interval (CI)= 0.05-0.58) and 0.10-point (95% CI=0.04-0.17) decrease in the HVRT and IADLs, respectively, independent of other potential risk factors for cognitive impairment, including age, education, cognitive and physical function, comorbidities, and severity of hypertension. The association was attenuated but remained statistically significant with memory (0.29, 95% CI=0.01-0.56) and executive function (0.08, 95% CI=0.02-0.15) after further adjustment for concomitant non-anticholinergic medications. CONCLUSION: Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men. Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects.
Abstract: The present study demonstrated that in addition to CYP3A4 and CYP2D6, the metabolism of loratadine is also catalyzed by CYP1A1, CYP2C19, and to a lesser extent by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP3A5. The biotransformation of loratadine was associated with the formation of desloratadine (DL) and further hydroxylation of both DL and the parent drug (loratadine). Based on the inhibition and correlation studies contribution of CYP2C19 in the formation of the major circulating metabolite DL seems to be minor. Reported clinical results suggest that the steady state mean (%CV) plasma Cmax and AUC(24hr) of loratadine were 4.73 ng/ml (119%) and 24.1 ng.hr/ml (157%), respectively, after dosing with 10 mg loratadine tablets for 10 days. High inter-subject variability in loratadine steady-state data is probably due to the phenotypical characteristics of CYP2D6, CYP2C19, and CYP3A4. The relative abundance of CYP3A4 in the human liver exceeds that of CYP2C19 and CYP2D6 and therefore the contribution of CYP3A4 in the metabolism of loratadine should be major (approximately 70%).
Abstract: No Abstract available
Abstract: It has been over 50 years since a review has focused exclusively on the monoamine oxidase (MAO) inhibitor tranylcypromine (TCP). A new review has therefore been conducted for TCP in two parts which are written to be read preferably in close conjunction: part I - pharmacodynamics, pharmacokinetics, drug interactions, toxicology; and part II - clinical studies with meta-analysis of controlled studies in depression, practice of TCP treatment, place in therapy. The irreversible and nonselective MAO-A/B inhibitor TCP has been confirmed as an efficacious and safe antidepressant drug. For the first time, a meta-analysis of controlled clinical trials in depression demonstrated that TCP is superior to placebo (pooled logOR=0.509, 95%CI=0.026 to 0.993, 4 studies) and equal to other antidepressants (pooled logOR=0.208, 95%CI=-0.128 to 0.544, 10 studies). In treatment resistant depression (TRD) after tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), TCP was superior to placebo (logOR=2.826, 95%CI=1.494 to 4.158, one study) and non-established antidepressants (pooled logOR=1.976, 95%CI=0.907 to 3.045, 4 studies), and was equal to other MAO inhibitors and an antidepressant combination (pooled logOR=-0.366, 95%CI=-0.869 to 0.137, 4 studies). Controlled studies revealed that TCP might provide a special advantage in the treatment of atypical depression, which was supported by a recent PET study of MAO-A activity in brain. However, TCP treatment remains beset with the need for a mandatory tyramine-restricted diet and is therefore limited to use as a third-line antidepressant according to recent treatment algorithms and guidelines for depression treatment. On the other hand, the effort needed to maintain a tyramine-restricted diet may have been overestimated in the perception of both doctors and patients, which may have led to relative underuse of TCP. Interaction with serotonergic drugs bears the risk of severe serotonin toxicity (SST) and combination with indirect sympathomimetic drugs may result in hypertensive crisis which both adds to the risks of TCP. At the same time, TCP has low to no risks of central anticholinergic, sedative, cardiac conduction, body weight, hemostatic effects, or pharmacokinetic drug interactions. Neuroprotection by MAO inhibitors due to reduced oxidative stress is becoming increasingly studied. Taken together, TCP is being increasingly recognized as an important option in systematic treatment approaches for patients suffering from severe courses of depression, such as TRD and atypical depression, by offering a MAO-related pathophysiological rationale.
Abstract: BACKGROUND: Anticholinergic drugs put elderly patients at a higher risk for falls, cognitive decline, and delirium as well as peripheral adverse reactions like dry mouth or constipation. Prescribers are often unaware of the drug-based anticholinergic burden (ACB) of their patients. This study aimed to develop an anticholinergic burden score for drugs licensed in Germany to be used by clinicians at prescribing level. METHODS: A systematic literature search in pubmed assessed previously published ACB tools. Quantitative grading scores were extracted, reduced to drugs available in Germany, and reevaluated by expert discussion. Drugs were scored as having no, weak, moderate, or strong anticholinergic effects. Further drugs were identified in clinical routine and included as well. RESULTS: The literature search identified 692 different drugs, with 548 drugs available in Germany. After exclusion of drugs due to no systemic effect or scoring of drug combinations (n = 67) and evaluation of 26 additional identified drugs in clinical routine, 504 drugs were scored. Of those, 356 drugs were categorised as having no, 104 drugs were scored as weak, 18 as moderate and 29 as having strong anticholinergic effects. CONCLUSIONS: The newly created ACB score for drugs authorized in Germany can be used in daily clinical practice to reduce potentially inappropriate medications for elderly patients. Further clinical studies investigating its effect on reducing anticholinergic side effects are necessary for validation.