Simvastatin Erythromycin

Simvastatin Erythromycin Increase in AUC (6.2-fold) and Cmax (3.4-fold)... 

Lovastatin, simvastatin Ketoconazole, erythromycin, etc. CYP3A4 Rhabdomyolysis... 

Drugs that may affect repaglinide include CYP 450 inhibitors (eg, clarithromycin, erythromycin, ketoconazole, miconazole), CYP 450 inducers (eg, barbiturates, carbamazepine, rifampin), beta blockers, calcium channel blockers, chloramphenicol, corticosteroids, coumarins, estrogens, gemfibrozil, isoniazid, itraconazole, levonorgestrel and ethinyl estradiol, MAOIs, nicotinic acid, NSAIDs, oral contraceptives, phenothiazines, phenytoin, probenecid, salicylates, simvastatin, sulfonamides, sympathomimetics, thiazides and other diuretics, and thyroid products. 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

Erythromycin interacts with simvastatin, probably by inhibiting its metabolism by CYP3A4. In a randomized, double-blind crossover study in 12 healthy volunteers, erythromycin significantly increased mean peak serum concentration and AUC for both unchanged simvastatin and its active metabolite simvastatin acid. However, there was extensive interindividual variability in the extent of this interaction (50). 

A case-control analysis of 7405 cases and 28 327 controls suggested that concomitant use of simvastatin and erythromycin is associated with an increased risk of cataract (53). Studies in dogs have shown that some statins are associated with cataract when given in excessive doses (54). 

Kantola T, Kivisto KT, Neuvonen PJ. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 1998 64(2) 177-82. 

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

A4 Midazolam, Testosterone (strongly recommended to use at least two structurally unrelated substrates) Nifedipine, Felodipine, Cyclosporine, Terfenadine, Erythromycin, Simvastatin Ketoconazole (recent evidence that it is also a potent inhibitor of 2C8), Troleandomycin Cyclosporine... 

Erythromycin may cause increases in the semm levels of simvastatin. The CSM has advised that this should not be co-prescribed with simvastatin. In the first instance the pharmacist should check local policies for management of hospital acquired chest infections/pneumonia to ascertain first and second line choices. If erythromycin or any macrolide cannot be avoided then a practical way forward may be to avoid taking any dose of simvastatin for the duration of the course of macrolide. In addition a recent Dmg Safety Update from the Medicines and Healthcare Products Regulatory Agency (MHRA, 2008) on statins has highlighted statin dmg interactions and the appropriate actions to take. 

Erythromycin should be administered slowly and at an appropriate dilution to avoid thrombophlebitis and a risk of prolonged QT interval. Erythromycin is an inhibitor of cytochrome P450 enzymes and concomitant administration with simvastatin is not recommended. Simvastatin treatment may be suspended or azithromycin substituted for erythromycin. 

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... 

The most serious adverse effect of simvastatin is myopathy, which rarely may progress to rhabdomyolysis. Abnormalities of liver function may also occur. These effects are dose-dependent, and a number of drugs and foods may inhibit the metabolism of simvastatin, thereby increasing its toxicity. Examples of these are grapefruit juice and erythromycin, both of which should be avoided in patients taking simvastatin. 

It has been proposed that the risk of myotoxicity increases when statins are prescribed concurrently with erythromycin (83). There are no data for any pharmacokinetic interaction with fluvastatin or pravastatin, but as in the case of simvastatin the major route of metabolism of these drugs is by CYP3A4 and there is potential for an adverse interaction. 

Mibefradil inhibits CYP3A4 (2). Other drugs that are metabolized by this pathway accumulate as a result. Drugs that were commonly affected included amiodarone, astemizole, ciclosporin, cisapride, erythromycin, imi-pramine, lovastatin, propafenone, quinidine, simvastatin (9), tacrohmus (10), tamoxifen, terfenadine, thioridazine, and drugs that impair sinoatrial node function (for example beta-blockers) (6). 

The effects of a combination of erythromycin and verapamil on the pharmacokinetics of a single dose of simvastatin have been studied in a randomized, double-blind, cross-over study in 12 healthy volunteers simultaneously taking the three drugs. Both erythromycin and verapamil interacted with simvastatin, producing significant increases in the serum concentrations of simvastatin and its active metabolite simvastatin acid. The mean C ax of active simvastatin acid was increased about five-fold and the AUCo 24 four-fold by erythromycin verapamil increased the C ax of simvastatin acid 3.4-fold and the AUCo 24 2.8-fold. There was a substantial interindividual variation in the extent of these interactions. Concomitant use of erythromycin, verapamil, and simvastatin should be avoided (35). 

E Itraconazole. Imatinib is primarily metabolized by the CYP3A4 hepatic enzyme system. Drugs that may inhibit this enzyme (such as ketoconazole, itraconazole, erythromycin, clarithromycin, etc.) may impair clearance of imatinib and result in increased toxicity. Imatinib itself is also a fairly potent inhibitor of the CYP3A4 enzyme and may result in toxicity due to other drugs that are substrates for this enzyme (such as simvastatin, warfarin, benzodiazepines, etc.). The other medications iisted are uniikeiy to affect the function of 0 P3A4 or interact adversely with imatinib. 

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 alfuzosin, amiodarone, aprepitant, carbamazepine, celiprolol, corticosteroids, cyclosporine, epirubicin, erythromycin, mistletoe, moricizine, oxprenolol, ranolazine, simvastatin, sulpiride... 

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 cyclosporine, diltiazem, dofetilide, erythromycin, grapefruit, ketoconazole, quinidine, ritonavir, simvastatin, sotalol, thioridazine, verapamil, ziprasidone... 

Clinically important, potentially hazardous interactions with amiodarone, beta-blockers, caspofungin, cyclosporine, dairy products, danazol, erythromycin, etoricoxib, grapefruit juice, hemophilus B vaccine, HMG-CoA reductase inhibitors, ibuprofen, immunosuppressants, ketoconazole, lopinavir, lovastatin, mycophenolate, peanuts, potassium, potassium-sparing diuretics, rifabutin, rifampin, rifapentine, simvastatin, St John s wort, telithromycin, vaccines... 

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... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

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