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 lopinavir and trifluoperazine. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We did not detect any change in exposure to lopinavir. We currently cannot estimate the influence of trifluoperazine. We do not expect any change in exposure for trifluoperazine, when combined with lopinavir (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 lopinavir is unknown. Protein binding [ Pb ] is not known. The metabolism mainly takes place via CYP3A4 and the active transport takes place in particular via PGP.
The bioavailability of trifluoperazine is unknown. The terminal half-life [ t12 ] is 15 hours and constant plasma levels [ Css ] are reached after approximately 60 hours. Protein binding [ Pb ] is not known. The metabolism via cytochromes is currently still being worked on.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither lopinavir nor trifluoperazine increase serotonergic activity.
|Kiesel & Durán b||1||Ø||+|
Recommendation: As a precaution, attention should be paid to anticholinergic symptoms, especially after increasing the dose and at doses in the upper therapeutic range.
Rating: Trifluoperazine only has a mild effect on the anticholinergic system. The risk of anticholinergic syndrome with this medication is rather low if the dosage is in the usual range. According to our knowledge, lopinavir does not increase anticholinergic activity.
QT time prolongation
Rating: In combination, lopinavir and trifluoperazine can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||lop||tri|
|Orthostatic hypotension||1.0 %||n.a.||+|
Blurred vision: trifluoperazine
Ineffective thermoregulation: trifluoperazine
Neuroleptic malignant syndrome: trifluoperazine
Tardive dyskinesia: trifluoperazine
Urinary retention: trifluoperazine
Thromboembolic disorder: trifluoperazine
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: On the basis of a single clinical trial in first-line treatment, the atazanavir and ritonavir combination appears to be no more effective than the fixed-dose combination of lopinavir and ritonavir. The adverse effect profiles were slightly different, but atazanavir carries a troubling risk of torsades de pointes.
Abstract: BACKGROUND: Drug-induced torsades de pointes (TdP) is a complex regulatory and clinical problem due to the rarity of this sometimes fatal adverse event. In this context, the US FDA Adverse Event Reporting System (AERS) is an important source of information, which can be applied to the analysis of TdP liability of marketed drugs. OBJECTIVE: To critically evaluate the risk of antimicrobial-induced TdP by detecting alert signals in the AERS, on the basis of both quantitative and qualitative analyses. METHODS: Reports of TdP from January 2004 through December 2008 were retrieved from the public version of the AERS. The absolute number of cases and reporting odds ratio as a measure of disproportionality were evaluated for each antimicrobial drug (quantitative approach). A list of drugs with suspected TdP liability (provided by the Arizona Centre of Education and Research on Therapeutics [CERT]) was used as a reference to define signals. In a further analysis, to refine signal detection, we identified TdP cases without co-medications listed by Arizona CERT (qualitative approach). RESULTS: Over the 5-year period, 374 reports of TdP were retrieved: 28 antibacterials, 8 antifungals, 1 antileprosy and 26 antivirals were involved. Antimicrobials more frequently reported were levofloxacin (55) and moxifloxacin (37) among the antibacterials, fluconazole (47) and voriconazole (17) among the antifungals, and lamivudine (8) and nelfinavir (6) among the antivirals. A significant disproportionality was observed for 17 compounds, including several macrolides, fluoroquinolones, linezolid, triazole antifungals, caspofungin, indinavir and nelfinavir. With the qualitative approach, we identified the following additional drugs or fixed dose combinations, characterized by at least two TdP cases without co-medications listed by Arizona CERT: ceftriaxone, piperacillin/tazobactam, cotrimoxazole, metronidazole, ribavirin, lamivudine and lopinavir/ritonavir. DISCUSSION: Disproportionality for macrolides, fluoroquinolones and most of the azole antifungals should be viewed as 'expected' according to Arizona CERT list. By contrast, signals were generated by linezolid, caspofungin, posaconazole, indinavir and nelfinavir. Drugs detected only by the qualitative approach should be further investigated by increasing the sensitivity of the method, e.g. by searching also for the TdP surrogate marker, prolongation of the QT interval. CONCLUSIONS: The freely available version of the FDA AERS database represents an important source to detect signals of TdP. In particular, our analysis generated five signals among antimicrobials for which further investigations and active surveillance are warranted. These signals should be considered in evaluating the benefit-risk profile of these drugs.