Verlängerung der QT-Zeit
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Eklärungen für Patienten zu den Wirkstoffen
Für die Kombination von Escitalopram und Abarelix liegen uns keine zusätzlichen Warnhinweise vor. Bitte konsultieren Sie zusätzlich die jeweiligen Fachinformationen.
|Escitalopram||1 [0.53,5.2] 1,2||1|
Die genannten Expositionsveränderungen beziehen sich jeweils auf Veränderungen der Plasmakonzentrations-Zeit-Kurve [ AUC ]. Für Escitalopram erwarten wir keine Veränderung der Exposition, wenn eine Kombination mit Abarelix (100%) erfolgt. Die AUC liegt dabei je nach CYP2C19, CYP2D6
Für die Berechnung der individuellen Expositionsveränderungen durch die Wechselwirkungen werden als Ausgangsbasis die pharmakokinetischen Parameter der durchschnittlichen Population verwendet.
Escitalopram hat eine mittlere orale Bioverfügbarkeit [ F ] von 79%, weshalb die maximalen Plasmaspiegel [ Cmax ] sich bei einer Interaktion tendentiell verändern. Die terminale Halbwertszeit [ t12 ] ist mit 26.6 Stunden eher lang und konstante Plasmaspiegel [ Css ] werden erst nach mehr als 106.4 Stunden erreicht. Die Proteinbindung [ Pb ] ist mit 56% eher schwach und das Verteilungsvolumen [ Vd ] ist mit 864 Liter sehr gross. da die Substanz eine tiefe hepatische Extraktionsrate von 0.21 besitzt, kann eine Verdrängung aus der Proteinbindung [Pb] im Rahmen einer Interaktion die Exposition erhöhen. Die Metabolisierung findet unter anderem über CYP2C19, CYP2D6 und CYP3A4 statt und der aktive Transport erfolgt insbesondere über PGP.
Für Abarelix ist die Bioverfügbarkeit nicht bekannt. Die terminale Halbwertszeit [ t12 ] ist mit 316.8 Stunden eher lang und konstante Plasmaspiegel [ Css ] werden erst nach mehr als 1267.2 Stunden erreicht. Die Proteinbindung [ Pb ] ist mit 97.5% stark. Die Metabolisierung über Cytochrome wird aktuell noch bearbeitet.
|Serotonerge Effekte a||2||++||Ø|
Empfehlung: Insbesondere nach einer Dosiserhöhung und bei Dosierungen im oberen therapeutischen Bereich sollte vorsichtshalber auf Symptome einer serotonergen Überstimulation geachtet werden.
Bewertung: Escitalopram moduliert das serotonerge System in moderatem Ausmass. Das Risiko für ein serotonerges Syndrom ist bei dieser Medikation eher als gering einzustufen, wenn die Dosierung sich im üblichen Bereich befindet. Gemäss unseren Erkenntnissen erhöht Abarelix nicht die serotonerge Aktivität.
|Kiesel & Durán b||0||Ø||Ø|
Bewertung: Gemäss unseren Erkenntnissen erhöhen weder Escitalopram noch Abarelix die anticholinerge Aktivität.
Verlängerung der QT-Zeit
Bewertung: In Kombination können Escitalopram und Abarelix potentiell ventrikuläre Arrhythmien vom Typ Torsades de pointes auslösen.
|Abnorme Ejakulation||11.5 %||11.5||n.a.|
Reduzierte Libido (5%): Escitalopram
Orgasmusstörung (4%): Escitalopram
Erektile Dysfunktion (3%): Escitalopram
Verstopfung (4.5%): Escitalopram
Erbrechen (3%): Escitalopram
Basierend auf Ihren
Abstract: The pharmacokinetics of escitalopram (S-citalopram) and its principal metabolite, S-demethylcitalopram (S-DCT), were investigated after intravenous and oral administration to healthy subjects. After intravenous infusion of escitalopram, the mean systemic clearance and volume of distribution were 31 L/h and 1,100 L, respectively. After oral administration of single or multiple doses, the absorption was relatively fast, with the maximum observed plasma or serum concentration (C(max)) attained after 3 to 4 hours. The mean half-lives were 27 and 33 hours, respectively; steady state was attained within 10 days. The area under the plasma or serum concentration time curve from time zero to 24 hours and C(max) was both linear and proportional to the dose. The apparent volume of distribution was around 20 L/kg. Comparison of the systemic and oral clearance implied a high absolute bioavailability. There was no evidence of interconversion from S-citalopram to R-citalopram either in plasma or in urine. Concurrent intake of food had no effect on the pharmacokinetics of escitalopram or its metabolite. All treatments were well tolerated.
Abstract: There is limited documentation of the importance of heterozygous cytochrome P450 (CYP) mutations on drug exposure. This study was designed to evaluate the influence of heterozygous mutations in CYP2C19 on the serum concentration of racemic citalopram and escitalopram (S-citalopram). Eighty-three samples from subjects with determined CYP2C19 and CYP2D6 genotype receiving racemic citalopram or S-citalopram as part of their clinical treatment were collected from a routine therapeutic drug monitoring database. Concentration/dose (C/D) ratios, parent drug/metabolite ratios, and serum concentrations in CYP2C19 homozygous extensive metabolizers (EMs) and heterozygous extensive metabolizers (HEMs) were compared. The median C/D ratio was significantly higher in the HEM group compared with the EM group, both for racemic citalopram (8.0 vs. 4.9, P < 0.01) and S-citalopram (5.3 vs. 2.6, P < 0.01). The median parent drug/metabolite ratio was significantly higher in the HEM group compared with the EM group, both for racemic citalopram (2.9 vs. 1.6, P < 0.01) and for S-citalopram (2.4 vs. 1.2, P < 0.01). A higher median non-dose-corrected serum concentration also was observed in HEMs compared with EMs both for S-citalopram (P < 0.01) and racemic citalopram (P = 0.066). This study shows that the metabolism of racemic citalopram and S-citalopram is significantly impaired in CYP2C19 HEMs. Higher absolute serum concentrations indicate that this is not compensated for by dose reductions in clinical practice.
Abstract: Escitalopram is the (S)-enantiomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram. Clinical studies have shown that escitalopram is effective and well tolerated in the treatment of depression and anxiety disorders. Following oral administration, escitalopram is rapidly absorbed and reaches maximum plasma concentrations in approximately 3-4 hours after either single- or multiple-dose administration. The absorption of escitalopram is not affected by food. The elimination half-life of escitalopram is about 27-33 hours and is consistent with once-daily administration. Steady-state concentrations are achieved within 7-10 days of administration. Escitalopram has low protein binding (56%) and is not likely to cause interactions with highly protein-bound drugs. It is widely distributed throughout tissues, with an apparent volume of distribution during the terminal phase after oral administration (V(z)/F) of about 1100L. Unmetabolised escitalopram is the major compound in plasma. S-demethylcitalopram (S-DCT), the principal metabolite, is present at approximately one-third the level of escitalopram; however, S-DCT is a weak inhibitor of serotonin reuptake and does not contribute appreciably to the therapeutic activity of escitalopram. The didemethyl metabolite of escitalopram (S-DDCT) is typically present at or below quantifiable concentrations. Escitalopram and S-DCT exhibit linear and dose-proportional pharmacokinetics following single or multiple doses in the 10-30 mg/day dose range. Adolescents, elderly individuals and patients with hepatic impairment do not have clinically relevant differences in pharmacokinetics compared with healthy young adults, implying that adjustment of the dosage is not necessary in these patient groups. Escitalopram is metabolised by the cytochrome P450 (CYP) isoenzymes CYP2C19, CYP2D6 and CYP3A4. However, ritonavir, a potent inhibitor of CYP3A4, does not affect the pharmacokinetics of escitalopram. Coadministration of escitalopram 20mg following steady-state administration of cimetidine or omeprazole led to a 72% and 51% increase, respectively, in escitalopram exposure compared with administration alone. These changes were not considered clinically relevant. In vitro studies have shown that escitalopram has negligible inhibitory effects on CYP isoenzymes and P-glycoprotein, suggesting that escitalopram is unlikely to cause clinically significant drug-drug interactions. The favourable pharmacokinetic profile of escitalopram suggests clinical utility in a broad range of patients.
Abstract: Escitalopram is the newest selective serotonin reuptake inhibitor (SSRI) available for use in the United States. It has been approved for the treatment of major depression and generalized anxiety disorder. It is the S-enantiomer of the SSRI citalopram and is highly serotonin specific as it has minimal effect on the reuptake of dopamine or norepinephrine. It is also a well-tolerated medication, with a side-effect profile comparable to the other SSRIs. While a number of side effects have been seen during escitalopram therapy, such as insomnia, nausea, and increased sweating, there are no reported cases of serotonin syndrome associated with escitalopram therapy to date. We present the case of a 24-year-old woman who developed serotonin syndrome after an increase in her escitalopram to 30 mg/day. We will review the diagnostic criteria of serotonin syndrome and the clinical scenarios in which serotonin syndrome can develop. We will also discuss the proposed treatments and role that polypharmacology may play in the development of this clinical entity.
Abstract: BACKGROUND: Drugs most commonly responsible for the acquired form of long QT syndrome are antibiotics and antidepressants. Escitalopram overdose leading to prolongation of the QTc interval has only twice been previously described in the literature. METHODS: We report a 33-year-old Caucasian woman who attempted suicide by ingesting 15-20 pills of lithium (300 mg each), 15-20 pills of escitalopram (20 mg each), and alcohol. An electrocardiogram (ECG) on admission to the medicine telemetry unit showed a QTc prolongation of 491 ms and normal sinus rhythm. Repeat ECG 18 hours after admission showed a QTc of 502 ms and sinus bradycardia. Serial ECGs were continued with the following results of QTc/hours after admission: 499 ms/2, 485 ms/25 (> 1 day), 469 ms/41, 461 ms/71, 476 ms/97 (> 4 days). After the QTc interval had declined to 461 ms after more than 2 days (71 hours), the patient was transferred to the inpatient psychiatry ward service. CONCLUSIONS: Prescribers may wish to exercise caution when administering escitalopram to patients who have suicidal ideations and depression. In the event of an overdose, QT prolongation can occur and ECG monitoring should take place for at least 2 days after ingestion in order to prevent life-threatening arrhythmias such as torsades de pointes (tdp). Other factors and drugs that could contribute to prolongation of the QT interval should be taken into account when determining the time period needed for ECG monitoring in the individual patient.
Abstract: According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the S-enantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10mg/kg) or escitalopram (5mg/kg) Serum and brain samples were collected 1-6h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. In brain, 3-fold higher concentrations of S- and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls. The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated.
Abstract: BACKGROUND: Anticholinergic drugs are often involved in explicit criteria for inappropriate prescribing in older adults. Several scales were developed for screening of anticholinergic drugs and estimation of the anticholinergic burden. However, variation exists in scale development, in the selection of anticholinergic drugs, and the evaluation of their anticholinergic load. This study aims to systematically review existing anticholinergic risk scales, and to develop a uniform list of anticholinergic drugs differentiating for anticholinergic potency. METHODS: We performed a systematic search in MEDLINE. Studies were included if provided (1) a finite list of anticholinergic drugs; (2) a grading score of anticholinergic potency and, (3) a validation in a clinical or experimental setting. We listed anticholinergic drugs for which there was agreement in the different scales. In case of discrepancies between scores we used a reputed reference source (Martindale: The Complete Drug Reference®) to take a final decision about the anticholinergic activity of the drug. RESULTS: We included seven risk scales, and evaluated 225 different drugs. Hundred drugs were listed as having clinically relevant anticholinergic properties (47 high potency and 53 low potency), to be included in screening software for anticholinergic burden. CONCLUSION: Considerable variation exists among anticholinergic risk scales, in terms of selection of specific drugs, as well as of grading of anticholinergic potency. Our selection of 100 drugs with clinically relevant anticholinergic properties needs to be supplemented with validated information on dosing and route of administration for a full estimation of the anticholinergic burden in poly-medicated older adults.
Abstract: No Abstract available
Abstract: Understanding the influence of ethnicity on drug exposure is key to patient safety and could minimize repetitive clinical studies. This analysis aimed to evaluate the ability of physiologically-based pharmacokinetic modelling to predict exposure of CYP2C19 substrates (lansoprazole, (es)citalopram, voriconazole) across Caucasian and East Asian populations. CYP2C19 abundance levels in Japanese and Chinese populations have been re-assessed based on clinical evidence. Model performance in each population was evaluated by predicted-over-observed AUC ratios and comparison of observed data with simulated plasma concentration profiles. Exposures in 84.4% (76 out of 90) of the clinical studies were predicted within 1.5-fold of observed values. The reported concentration-time profiles were well-captured within the 90% prediction intervals. With specified CYP2C19 phenotype, PBPK modelling is capable to predict systemic exposure of drugs largely metabolized by CYP2C19 in different ethnic populations. This study demonstrated PBPK modelling can be applied to assess genotype-dependent exposure difference across ethnicities.