rcanidipine, lidocaine, methadone, rifabutin, tamoxifen, terfenadine, vincristine, zolpidem, nevirapine, carvedilol, codeine, flecainide, mexiletine, oxycodone, risperidone, thioridazine, diphenhydramine 55 DDI pairs COX-2 review identified from all three sources (FDA, Stockley’s and Flockhart) Buspirone, tacrolimus, alfentanil, alprazolam, aprepitant, atorvastatin, eplerenone, felodipine, indinavir, lovastatin, midazolam, pimozide, quetiapine, saquinavir, sildenafil, simvastatin, sirolimus, erythromycin, itraconazole, cimetidine, clarithromycin, cyclosporine, diltiazem, imatinib, ketoconazole, nefazodone, nelfinavir, ritonavir, verapamil, voriconazole, carbamazepine, efavirenz, phenobarbital, phenytoin, rifampin, pioglitazone, HIV drug repaglinide, gemfibrozil, trimethoprim, desipramine, dextromethorphan, imipramine, metoprolol, nortriptyline, propafenone, propranolol, venlafaxine, bupropion, fluoxetine, paroxetine, quinidine, terbinafine, duloxetine, amiodarone, sertralineTA B L E two List of 29 potential clinically substantial severe DDI pairs of HCQ as identified in the FDA and Flockhart CYP clinical tables of robust inhibitors involving CYP3A4/5, CYP2C8 and CYP2D6 enzymesCYP enzyme CYP3A4/Severe DDI pairs HCQ+Clarithromycin; HCQ+Telithromycin; HCQ+Troleandomycin; HCQ+Itraconazole; HCQ+Ketoconazole; HCQ+Posaconazole; HCQ+Nefazodone; HCQ+Idelalisib; HCQ+Boceprevir; HCQ+Cobicistat; HCQ+Ribociclib; HCQ+Voriconazole; HCQ+Nelfinavir; HCQ+Ritonavir; HCQ+Indinavir; HCQ+Saquinavir; HCQ+Danoprevir; HCQ+Elvitegravir; HCQ+Lopinavir; HCQ+Paritaprevir; HCQ+Telaprevir; HCQ+Tipranavir HCQ+Gemfibrozil HCQ+Bupropion; HCQ+Fluoxetine; HCQ+Paroxetine; HCQ+Quinidine; HCQ+Terbinafine; HCQ+CinacalcetCYP2C8 CYP2DAbbreviations: CYP, cytochrome P450; DDI, drug-drug interaction; FDA, Meals and Drug Administration; HCQ, hydroxychloroquine.have been not taken seriously for clinical manifestations. By way of example, it was discovered probably the most serious DDIs of HCQ with azithromycin in patients with COVID-19 in which these drug pairs escalating the risk of life-threatening Q and T wave (QT) prolongation. This in turn results in cardiac arrhythmias and sudden cardiac deaths of quite a few COVID-19 sufferers as evidenced in current two studies.19,20 Altogether, 185 interacting drugs had been identified from the Liverpool COVID-19 interaction resource predicted to bring about clinically important DDIs with HCQ. Soon after combining this Liverpool COVID-19 interacting drugs of HCQ together with the FDA, Stockley’s and Flockhart lists of interacting drugs and removing duplicates, it was located that inside a total of 423 DDI pairs of HCQ have been identified in this evaluation predicted to lead to clinically considerable DDIs. Of these, 238 (56.three ) and 94 (22.2 ) special (devoid of becoming duplicated with two/ three-way mixture) DDI pairs had been identified from all 3 resources (FDA, Stockley’s and Flockhart lists) and Liverpool DDIlists, respectively. Of interest, only 3 (0.7 ) DDI pairs have been recognised by each the 3 international sources and Liverpool DDI lists of HCQ. Given that chloroquine (CQ) has comparable PK properties with HCQ and can also be metabolised by CYP2C8, CYP3A4/5 and CYP2D6 enzymes,6 as a result the potential clinically substantial DDIs identified for HCQ may possibly also frequently be applicable to CQ. In summary, a minimum of 29 DDI pairs ought to be taken into clinical considerations to optimise safety of HCQ considering that these drugs had been predicted to cause clinically substantial extreme DDIs.4|D I S CU S S I O NAs HCQ is employing in several countries for comb
