Erythromycin Atorvastatin

When erythromycin was co-administered with atorvastatin, the mean Cmax and AUC of atorvastatin increased by more than 30% (29,30). 

In 12 healthy volunteers, erythromycin increased both the maximal plasma concentration and AUC of co-administered atorvastatin (31). 

Siedlik PH, Olson SC, Yang BB, Stern RH. Erythromycin coadministration increases plasma atorvastatin concentrations. J Clin Pharmacol 1999 39(5) 501 l. 

CYP3A4 Inhibition Amiodarone, clarithromycin, erythromycin, cimetidine, cyclosporine, fluoxetine fluvoxamine, itraconazole, ketoconazole, nefazodone, verapamil, diltiazem HIV antivirals delaviridine, indanavire, nelfmavire, ritonavire, sequinavire Atorvastatin Lovastatin Simvastatin ... 

ATORVASTATIN, SIMVASTATIN MACROLIDES Macrolides may t levels of atorvastatin and simvastatin the risk of myopathy t over 10-fold when eiythromycin is co-administered with a statin Macrolides inhibit CYP3A4-mediated metabolism of atorvastatin and simvastatin. Also, erythromycin and clarithromycin inhibit intestinal P-gp, which may t the bioavailability of statins Avoid co-administration of macrolides with atorvastatin or simvastatin (temporarily stop the statin if the patient needs macrolide therapy). Manufacturers also recommend that patients be warned to look for the early signs of rhabdomyolysis when other statins are co-ingested with macrolides... 

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,... 

Abacavir Adinazolam 5-Aminosalicylic acid Atorvastatin Avitriptan Bromazepam Bumetanide Celecoxib CGP 43371 Clodronate Cyclosporin Danazol Didanosine Erythromycin Fexofenadine Furosemide Ganciclovir Halofantrine Inidnavir Itraconazole Levofloxacin Methotrexate Nifedipine Pravastatin Rifabutin Stavudine Tacrine... 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

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... 

Clinically important, potentially hazardous interactions with acebutolol, amiodarone, aspirin, atenolol, atorvastatin, betaxolol, carbamazepine, carteolol, celiprolol, donidine, dabigatran, dantrolene, digoxin, dofetilide, epirubicin, eplerenone, erythromycin, esmolol, eucalyptus, everolimus, lovastatin, metoprolol, mistletoe, nadolol, oxprenolol, penbutolol, pindolol, propranolol, quinidine, ranolazine, sibutramine, simvastatin, timolol, trabectedin... 

Siedlik, P.H., Olson, S.C.. Yang. B.B.. and Stern, R.H. (1999) Erythromycin coadministration increases plasma atorvastatin concentrations. Journal of Clinical Pharmacology, 39, 501-504. 

Transporter efflux transporter effects predominant Examples Amiodarone Atorvastatin Azithromycin Carbamazepine Carvediioi Chlorpromazine Ciprofloxacin Cisapride Cyciosporine Danazoi Dapsone Diclofenac Diflunisal Digoxin Erythromycin Flurbiprofen Glipizide Glyburide Griseofulvin Ibuprofen Indinavir Indomethacin Itraconazole Ketoconazole Lansoprazole Lovastatin Mebendazole Naproxen Nelfinavir Ofloxacin Oxaprozin Phenazopyridine Phenytoin Piroxicam Raloxifene Ritonavir Saquinavir Saquinavir Sirolimus Sirolimus Spironolactone Spironolactone Tacrolimus Tacrolimus ... 

It seems probable that clarithromycin, erythromycin and troleandomycin, and to a lesser extent some of the other macrolides, slow the rate of metabolism of the carbamazepine by the cytochrome P450 isoenzyme CYP3A4 so that the anticonvulsant accumulates within the body." " Telithromycin is predicted to interact similarly." It was suggested that the carbamazepine toxicity seen with roxithromycin may have been mediated by P-glycoprotein inhibition, which occurred as a result of an interaction between roxithromycin and atorvastatin. 

Yang B-B, Siedlik PH, Smilhers JA, Sedman AJ, Stem RH. Atorvastatin pharmacokinetic interactions with other CYP3A4 substrates erythromycin and ethinyl estradiol. Pharm Res ( 996) 13 (9 Suppl), S-437. 

Cases of acnte rhabdomyolysis have been reported between lovas-tatin and azithromycin, clarithromycin, or erythromycin and between simvastatin and clarithromycin or roxithromycin. Macrolide antibacterials have also been potentially implicated in cases of rhabdomyolysis with atorvastatin and pravastatin. Pharmacokinetic stndies sn est that the macrolides increase the levels of the statins metabolised by CYP3A4 (namely atorvastatin, Iovastatin and simvastatin). 

Twelve healthy subjects were given a single 10-mg dose of atorvastatin on day 7 of an 11-day course of erythromycin 500 mg four times daily. The maximum serum atorvastatin levels were raised by 38% and the AUC was raised by 33% by the erythromycin. Either Iovastatin or pravastatin 40 mg daily was given to 12 healthy subjects for 14 days, with erythromycin 500 mg three times daily for the last 7 days. The erythromycin caused the maximum serum levels and AUC of Iovastatin to rise more than fivefold. The pharmacokinetics of the pravastatin remained unchanged. Similarly, fiuvastatin levels are not significantly altered by erythromycin. ... 

Especially the inhibition or induction of cytochrome P450 subtype 3A4 (CYP 3A4) is clinically relevant, because a variety of active substances and food substances (e.g. grapefruit juice) are able to affect this enzyme. Substances inhibiting CYP 3A4 include ciclosporin, dihydropyridines, verapamil, midazolam, paclitaxel, simvastatin, lovastatin, atorvastatin, cimetidine, erythromycin, troleandomycin, ketoconazole (and other azoles). Substances inducing CYP 3A4 include steroids, rifampicin, phenobarbital and St John s wort. 

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