QT time prolongation
Adverse drug events
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Explanations of the substances for patients
We have no additional warnings for the combination of abarelix and famotidine. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We do not expect any change in exposure for abarelix, when combined with famotidine (100%). We do not expect any change in exposure for famotidine, when combined with abarelix (100%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
The bioavailability of abarelix is unknown. The terminal half-life [ t12 ] is rather long at 316.8 hours and constant plasma levels [ Css ] are only reached after more than 1267.2 hours. The protein binding [ Pb ] is 97.5% strong. The metabolism via cytochromes is currently still being worked on.
Famotidine has a mean oral bioavailability [ F ] of 43%, which is why the maximum plasma levels [Cmax] tend to change with an interaction. The terminal half-life [ t12 ] is rather short at 3 hours and constant plasma levels [ Css ] are reached quickly. The protein binding [ Pb ] is very weak at 17.5%. About 27.5% of an administered dose is excreted unchanged via the kidneys and this proportion is seldom changed by interactions. The metabolism does not take place via the common cytochromes and the active transport takes place in particular via PGP.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor famotidine increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, abarelix does not increase anticholinergic activity. The anticholinergic effect of famotidine is not relevant.
QT time prolongation
Rating: In combination, abarelix and famotidine can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||fam|
|Stevens johnson syndrome||0.0 %||n.a.||0.0|
|Toxic epidermal necrolysis||0.0 %||n.a.||0.0|
|Allergic skin reactions like pruritus and rash||0.0 %||n.a.||0.1|
|Anaphylactic reaction||0.0 %||n.a.||0.0|
Interstitial pneumonia: famotidine
Based on your answers and scientific information, we assess the individual risk of undesirable side effects. These recommendations are intended to advise professionals and are not a substitute for consultation with a doctor. In the restricted test version (alpha), the risk of all substances has not yet been conclusively assessed.
Abstract: AIMS: To investigate spontaneous reports of TdP present in the public version of the FDA Adverse Event Reporting System (AERS) in the light of what is already known on their TdP-liability. METHODS: Reports of TdP from January 2004 through December 2007 were retrieved from the public version of the AERS database. All reports were selected from REACTION files and the relevant suspected and/or interacting drugs were identified from DRUG files. Qualitative analysis was performed by the case/non-case method. Cases were represented by TdP reports, whereas non-cases were all reports of adverse drug reactions other than TdP. Quantitative analysis was assessed by calculating the crude and adjusted reporting odds ratio (ROR), as a measure of disproportionality, with the 95% confidence interval. RESULTS: Reports of TdP were 1665 over a 4-year period, involving 376 active substances. Thirty-five drugs with at least 10 reports were identified: amiodarone and methadone were associated with the highest number of cases (113 and 83 respectively) and most of the other reports were ascribable to antibacterials, antidepressants and antipsychotics; remarkable differences in number of cases and ROR were present among agents within each therapeutic class. A disproportionate reporting was also observed for other compounds such as donepezil, famotidine and mitoxantrone. CONCLUSIONS: Large spontaneous reporting databases represent an important source for signal detection of rare adverse drug reactions (ADR), such as TdP. The number of reports associated to donepezil, famotidine and mitoxantrone could be considered unexpected on the basis of current evidence and needs further investigations on their true TdP-liability.
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: Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers.