Terfenadine SSRIs

SSRIs TERFENADINE Possibility oft plasma concentrations of these drugs and potential risk of dangerous arrhythmias These drugs are metabolized mainly by CYP3A4. Fluvoxamine and fluoxetine are inhibitors of CYP3A4 but are relatively weak compared with ketoconazole, which is possibly 100 times more potent as an inhibitor The interaction is unlikely to be of clinical significance but need to be aware... 

Clinically important, potentially hazardous interactions with amiodarone, azithromycin, bepredil, bosentan, bretylium, cisapride, clarithromycin, disopyramide, erythromycin, erythromycin fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, miconazole, nefazodone, nilotinib, paroxetine, pimozide, probucol, procainamide, quinidine, quinine, ritonavir, saquinavir, sertraline, sotalol, SSRIs, terfenadine, troleandomycin, voriconazole, zileuton, ziprasidone... 

All SSRIs (e.g., Feonard et ah, 1997) and in particular fluoxetine, Fluvosamine and paroxetine are metabolized by hepatic cytochrome P450 enzymes. Therefore, it is important to be aware of the possibility that the therapeutic or toxic effects of other medications metabolized by the cytochrome P450 isoenzyme system can be increased. Substantial inhibition of these isoenzymes converts a normal metabolizer into a slow metabolizer with regard to this specific pathway. Inhibition of the hepatic oxidative isoenzymes has been associated with a reduction, to a varying extent, in the clearance of many therapeutic agents, including the TCAs, several neuroleptics, antiarrhythmics, theophy-lene, terfenadine, benzodiazepines, carbamazepine, and warfarin (for a complete list, see Nemeroff et ak, 1996). 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

P450 enzyme inhibition by SSRIs may also augment effects of alcohol, tramadol, methadone, terfenadine (danger of cardiac arrhythmia), -caine anaesthetics and theophylline. 

Two isolated reports describe cardiotoxicity, which was attributed to the concurrent use of terfenadine and fluoxetine, although other evidence su ests that an interaction is unlikely. Terfenadine does not appear to interact with paroxetine or sertraline. Nonetheless, the manufacturers of both astemizole and terfenadine contraindicate the concurrent use of SSRIs. There does not... 

The interaction between the SSRIs and terfenadine is not adequately established, and there is little evidence regarding interactions between the SSRIs and astemizole, although it is possible that the contraindication with astemizole has contributed to minimal usage of the combination and therefore a lack of reported interactions. In addition to fluoxetine and paroxetine, the manufacturers of terfenadine list fluvoxamine and citalo-pram as drugs that are expected to increase terfenadine serum levels, but direct evidence of this seems to be lacking. Nonetheless, the manufacturer contraindicates the use of all these SSRIs with terfenadine. Due to the severity of the potential interaction, it would appear prudent to use caution if terfenadine is used with any SSRI (excepting perhaps sertraline), and consider an alternative antihistamine without cardiac effects (see Table 15.2 , (p.583)), wherever possible. Desloratadine appears to be a non-interacting alternative. 

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