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 moxifloxacin and abarelix. 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 moxifloxacin, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with moxifloxacin (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.
Moxifloxacin has a high oral bioavailability [ F ] of 86%, which is why the maximum plasma level [Cmax] tends to change little during an interaction. The terminal half-life [ t12 ] is 12.1 hours and constant plasma levels [ Css ] are reached after approximately 48.4 hours. The protein binding [ Pb ] is rather weak at 47%. The metabolism does not take place via the common cytochromes and the active transport takes place in particular via PGP.
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.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither moxifloxacin nor abarelix increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither moxifloxacin nor abarelix increase anticholinergic activity.
QT time prolongation
Rating: In combination, moxifloxacin and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||mox||aba|
|Abdominal pain||2.0 %||2.0||n.a.|
|Pain in eye||1.0 %||+||n.a.|
Feeling nervous: moxifloxacin
Renal failure: moxifloxacin
Stevens johnson syndrome: moxifloxacin
Toxic epidermal necrolysis: moxifloxacin
Clostridium difficile diarrhea: moxifloxacin
Aplastic anemia: moxifloxacin
Hemolytic anemia: moxifloxacin
Liver failure: moxifloxacin
Hypersensitivity reaction: moxifloxacin
Myasthenia gravis: moxifloxacin
Rupture of tendon: moxifloxacin
Disturbance of attention: moxifloxacin
Memory impairment: moxifloxacin
Peripheral neuropathy: moxifloxacin
Pseudotumor cerebri: moxifloxacin
Raised intracranial pressure: moxifloxacin
Aortic aneurysm: moxifloxacin
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: STUDY OBJECTIVE: To compare the rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin administration. DESIGN: Retrospective database analysis. INTERVENTION: Evaluation of reported rates of torsades de pointes in patients who received these quinolones between January 1, 1996, and May 2, 2001. MEASUREMENTS AND MAIN RESULTS: In the United States, 25 cases of torsades de pointes associated with these quinolones (ciprofloxacin 2, ofloxacin 2, levofloxacin 13, gatifloxacin 8, moxifloxacin 0) were identified. Ciprofloxacin was associated with a significantly lower rate of torsades de pointes (0.3 cases/10 million prescriptions, 95% confidence interval [CI] 0.0-1.1) than levofloxacin (5.4/10 million, 95% CI 2.9-9.3, p<0.001) or gatifloxacin (27/10 million, 95% CI 12-53, p<0.001 for comparison with ciprofloxacin or levofloxacin). When the analysis was limited to the first 16 months after initial U.S. approval of the agent, the rates for levofloxacin (16/10 million) and gatifloxacin (27/10 million) were similar (p>0.5). CONCLUSION: Levofloxacin should be administered with caution in patients with risk factors for QT prolongation. Gatifloxacin should be avoided in the same patient population, and the recommended dosage of 400 mg/day should not be exceeded.
Abstract: Recent attention has been called to the interpretation of studies of antiinfective agents demonstrating effects on the QTc interval. It seems that the effects of many of these agents on the QTc interval are small, but in some patient populations, these drugs may cause morbidity and mortality related to TdP. It would be beneficial to researchers and clinicians alike for the FDA to standardize the types of studies designed to assess the QTc interval prolongation potential of a drug, methodologies, and interpretation criteria. To this end, it would increase the efficiency of the drug-approval process, give regulatory agencies and clinicians guidance, and increase patient safety. In summary we congratulate Dr. Frothingham for attempting to address the challenging issue of postmarketing safety surveillance. A critical review of his analysis of fluoroquinolone-associated TdP as well as other data on this potentially life-threatening adverse event support the following conclusions: Information from spontaneous reports is generally useful as an early warning system for excess adverse events, but reporting rates are not synonymous with incidence rates. The deficiencies of Dr. Frothingham's analysis lead to serious questions regarding the validity of both the numerators and denominators used in the incidence calculations (e.g., exclusion of European results, use ot extrapolated outpatient prescriptions, failure to account for inpatient versus outpatient utilization, failure to apply the appropriate statistical test to a rarely occurring, adverse event) and call into question conclusions about the relative risk of TdP with different fluoroquinolones. The association between which of the fluoroquinolones was administered to high-risk patients, which is important in the multiple-hit hypothesis, remains nebulous (e.g., failure to separate cases by route of drug administration and failure to identify which fluoroquinolones were given to patients with electrolyte abnormalities, concurrent QT interval-prolonging drugs, comorbid disease states). Preclinical and clinical trial data, as well as data from phase IV studies, indicate that levofloxacin, moxifloxacin, and gatifloxacin prolong the QTc interval, and the potential for TdP to develop as a result is rare and is influenced by many independent variables (e.g., concurrent drug administration of class Ia and III antiarrhythmic agents). These results should make clear that assessment of the cardiotoxicity of any new drug must take into account information (and its limitations) from several sources: preclinical studies that test effects on mechanisms underlying potential toxic reactions, controlled toxicodynamic studies in human volunteers safety results from controlled clinical trials, findings from phase IV studies, and postmarketing surveillance that includes spontaneously reported adverse events. One message that must not be lost in this discussion over the use of this reporting system to calculate incidences to incriminate certain agents is its overall importance, over time, in assisting governing bodies and clinicians alike in identifying compounds that may place certain patient populations at risk. It is imperative that clinicians not only submit adverse event reports to the FDA, but provide complete and accurate information. For moxifloxacin, levofloxacin, and gatifloxacin, the point must be clear that these agents should not be used in patients with risk factors predisposing them to TdP.
Abstract: The new respiratory fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and on the horizon, garenoxacin) offer many improved qualities over older agents such as ciprofloxacin. These include retaining excellent activity against Gram-negative bacilli, with improved Gram-positive activity (including Streptococcus pneumoniae and Staphylococcus aureus). In addition, gatifloxacin, moxifloxacin and garenoxacin all demonstrate increased anaerobic activity (including activity against Bacteroides fragilis). The new fluoroquinolones possess greater bioavailability and longer serum half-lives compared with ciprofloxacin. The new fluoroquinolones allow for once-daily administration, which may improve patient adherence. The high bioavailability allows for rapid step down from intravenous administration to oral therapy, minimizing unnecessary hospitalization, which may decrease costs and improve quality of life of patients. Clinical trials involving the treatment of community-acquired respiratory infections (acute exacerbations of chronic bronchitis, acute sinusitis, and community-acquired pneumonia) demonstrate high bacterial eradication rates and clinical cure rates. In the treatment of community-acquired respiratory tract infections, the various new fluoroquinolones appear to be comparable to each other, but may be more effective than macrolide or cephalosporin-based regimens. However, additional data are required before it can be emphatically stated that the new fluoroquinolones as a class are responsible for better outcomes than comparators in community-acquired respiratory infections. Gemifloxacin (except for higher rates of hypersensitivity), levofloxacin, and moxifloxacin have relatively mild adverse effects that are more or less comparable to ciprofloxacin. In our opinion, gatifloxacin should not be used, due to glucose alterations which may be serious. Although all new fluoroquinolones react with metal ion-containing drugs (antacids), other drug interactions are relatively mild compared with ciprofloxacin. The new fluoroquinolones gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin have much to offer in terms of bacterial eradication, including activity against resistant respiratory pathogens such as penicillin-resistant, macrolide-resistant, and multidrug-resistant S. pneumoniae. However, ciprofloxacin-resistant organisms, including ciprofloxacin-resistant S. pneumoniae, are becoming more prevalent, thus prudent use must be exercised when prescribing these valuable agents.
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.