Terfenadine Atorvastatin

Atorvastatin, although a substrate for CYP3A4, does not affect blood terfenadine concentrations to a clinically significant extent (34). 

Stern RH, Smithers JA, Olson SC. Atorvastatin does not produce a clinically significant effect on the pharmacokinetics of terfenadine. J Clin Pharmacol 1998 38(8) 753-7. 

These two prehepatic systems have been shown to contribute to the limited oral bioavailability of many lipophilic drugs including cyclosporine [8], terfenadine [9], saquinavir [10], midazolam [11], tacrolimus [12], atorvastatin [13], and others. 

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

Terfenadine is normally metabolized by CYP3A4 to fexofenadine, which has negligible cardiac effects. Atorvastatin is also a CYP3A4 substrate, and its effects on the pharmacokinetics of terfenadine have been studied in healthy volunteers who took atorvastatin 80 mg/day from 7 days before to 2 days after terfenadine 120 mg (8). Concentrations of terfenadine and fexofenadine were measured for 72 hours. There were no alterations in the pharmacokinetics of the parent compound or of its metabolite and there were no alterations in QTc intervals after terfenadine alone or with atorvastatin. 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

Atorvastatin does not appear to alter the pharmacokinetics of terfenadine. 

A group of healthy subjects were given a single 120-mg dose of terfenadine on day 8 of a 10-day course of atorvastatin 80 mg daily. It was found that the atorvastatin caused some small to moderate changes in the pharmacokinetics of the terfenadine and its metabolite fexofenadine (AUC increased by 35% and decreased by 2% respectively, maximum serum levels decreased by 8% and decreased by 16% respectively), none of which reached statistical significance. More importantly there were no changes in the QTc interval, which indicates that atorvastatin does not increase the cardiotoxicity of the terfenadine. There would therefore appear to be no reason for avoiding concurrent use. 

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