Vytorin drug interactions

No clinically significant pharmacokinetic interaction was seen when ezetimibe was coadministered with simvastatin. Specific pharmacokinetic drug interaction studies with Ezetimibe/Simvastatin (Vytorin) have not been performed.

List of drug interactions
Cytochrome P450 Antacids Cholestyramine Cyclosporine Fenofibrate Gemfibrozil Grapefruit Juice Drug Interactions with Simvastatin Drug Interactions with Ezetimibe

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Cytochrome P450
Ezetimibe had no significant effect on a series of probe drugs (caffeine, dextromethorphan, tolbutamide, and IV midazolam) known to be metabolized by cytochrome P450 (1A2, 2D6, 2C8/9 and 3A4) in a “cocktail” study of twelve healthy adult males. This indicates that ezetimibe is neither an inhibitor nor an inducer of these cytochrome P450 isozymes, and it is unlikely that ezetimibe will affect the metabolism of drugs that are metabolized by these enzymes.

In a study of 12 healthy volunteers, simvastatin at the 80-mg dose had no effect on the metabolism of the probe cytochrome P450 isoform 3A4 (CYP3A4) substrates midazolam and erythromycin. This indicates that simvastatin is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4.

Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of HMG-CoA reductase inhibitors. The increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4.

Simvastatin is a substrate for CYP3A4. Potent inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy.

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Antacids
In a study of twelve healthy adults, a single dose of antacid (SupraloxTM 20 mL) administration had no significant effect on the oral bioavailability of total ezetimibe, ezetimibe-glucuronide, or ezetimibe based on AUC values. The Cmax value of total ezetimibe was decreased by 30%.

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Cholestyramine
In a study of forty healthy hypercholesterolemic (LDL-C ≥130 mg/dL) adult subjects, concomitant cholestyramine (4 g twice daily) administration decreased the mean AUC of total ezetimibe and ezetimibe approximately 55% and 80%, respectively.

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Cyclosporine
In a study of eight post-renal transplant patients with mildly impaired or normal renal function (creatinine clearance of >50 mL/min), stable doses of cyclosporine (75 to 150 mg twice daily) increased the mean AUC and Cmax values of total ezetimibe 3.4-fold (range 2.3- to 7.9-fold) and 3.9-fold (range 3.0- to 4.4-fold), respectively, compared to a historical healthy control population (n=17). In a different study, a renal transplant patient with severe renal insufficiency (creatinine clearance of 13.2 mL/min/1.73 m2) who was receiving multiple medications, including cyclosporine, demonstrated a 12-fold greater exposure to total ezetimibe compared to healthy subjects. In a two-period crossover study in twelve healthy subjects, daily administration of 20 mg ezetimibe for 8 days with a single 100-mg dose of cyclosporine on Day 7 resulted in a mean 15% increase in cyclosporine AUC (range 10% decrease to 51% increase) compared to a single 100-mg dose of cyclosporine alone.

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Fenofibrate
In a study of thirty-two healthy hypercholesterolemic (LDL-C ≥130 mg/dL) adult subjects, concomitant fenofibrate (200 mg once daily) administration increased the mean Cmax and AUC values of total ezetimibe approximately 64% and 48%, respectively. Pharmacokinetics of fenofibrate were not significantly affected by ezetimibe (10 mg once daily).

Coadministration of fenofibrate (160 mg daily) with simvastatin (80 mg daily) for 7 days had no effect on plasma AUC (and Cmax) of either total HMG-CoA reductase inhibitory activity or fenofibric acid; there was a modest reduction (approximately 35%) of simvastatin acid which was not considered clinically significant.

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Gemfibrozil
In a study of twelve healthy adult males, concomitant administration of gemfibrozil (600 mg twice daily) significantly increased the oral bioavailability of total ezetimibe by a factor of 1.7. Ezetimibe (10 mg once daily) did not significantly affect the bioavailability of gemfibrozil.

Coadministration of gemfibrozil (600 mg twice daily for 3 days) with simvastatin (40 mg daily) resulted in clinically significant increases in simvastatin acid AUC (185%) and Cmax (112%), possibly due to inhibition of simvastatin acid glucuronidation by gemfibrozil.

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Grapefruit Juice
Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4. In one study1, 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with, and 30 and 90 minutes following, a single dose of 60 mg simvastatin on the third day. This regimen of grapefruit juice resulted in mean increases in the concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity [measured using a radioenzyme inhibition assay both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 2.4-fold and 3.6-fold, respectively, and of simvastatin and its β-hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/tandem mass spectrometry] of 16-fold and 7-fold, respectively. In a second study, 16 subjects consumed one 8 oz glass of single-strength grapefruit juice (one can of frozen concentrate diluted with 3 cans of water) with breakfast for 3 consecutive days and a single dose of 20 mg simvastatin in the evening of the third day. This regimen of grapefruit juice resulted in a mean increase in the plasma concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity [using a validated enzyme inhibition assay different from that used in the first1 study, both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 1.13-fold and 1.18-fold, respectively, and of simvastatin and its β-hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/tandem mass spectrometry] of 1.88-fold and 1.31-fold, respectively. The effect of amounts of grapefruit juice between those used in these two studies on simvastatin pharmacokinetics has not been studied.

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Major Interactions

 * Agenerase
 * amiodarone
 * amprenavir
 * Antara
 * Aptivus
 * atazanavir
 * Atromid-S
 * B-3-50
 * B3-500-Gr
 * Biaxin
 * Biaxin XL
 * Biaxin XL-Pak
 * Calan
 * Calan SR
 * clarithromycin
 * clarithromycin extended release
 * clofibrate
 * clotrimazole
 * conivaptan
 * Cordarone
 * Cordarone I.V.
 * Covera-HS
 * Crixivan
 * cycloSPORINE
 * danazol
 * Danocrine
 * darunavir
 * delavirdine
 * Diflucan
 * Dom-Fenofibrate
 * E-Mycin
 * E.E.S. Granules
 * E.E.S.-200
 * E.E.S.-400
 * E.E.S.-400 Filmtab
 * Ery-Tab
 * Eryc
 * EryPed
 * EryPed 200
 * EryPed 400
 * Erythrocin Lactobionate
 * Erythrocin Stearate Filmtab
 * Erythrocot
 * erythromycin
 * erythromycin base
 * erythromycin estolate
 * erythromycin ethylsuccinate
 * erythromycin lactobionate
 * erythromycin stearate
 * fenofibrate
 * Fenoglide
 * fluconazole
 * Fortovase
 * fosamprenavir
 * gemfibrozil
 * Gengraf
 * Ilosone
 * Ilotycin Gluceptate
 * indinavir
 * Invirase
 * Isoptin
 * Isoptin I.V.
 * Isoptin SR
 * itraconazole
 * Ketek
 * Ketek Pak
 * ketoconazole
 * Lexiva
 * Lipidil EZ
 * Lipidil Micro
 * Lipidil Supra
 * Lipofen
 * Lofibra
 * Lopid
 * mibefradil
 * miconazole
 * Monistat I.V.
 * MY-E
 * Mycelex Troche
 * nefazodone
 * nelfinavir
 * Neoral
 * niacin
 * niacin extended release
 * Niacin SR
 * Niacor
 * Niacor B3
 * Niaspan ER
 * Niaspan ER Starter Pack
 * Nico-400
 * Nicobid Tempules
 * Nicolar
 * Nicotinex
 * Nicotinic Acid
 * Nizoral
 * Norvir
 * Norvir Soft Gelatin
 * Noxafil
 * Pacerone
 * PCE Dispertab
 * posaconazole
 * Posicor
 * Prezista
 * Rescriptor
 * Reyataz
 * ritonavir
 * Robimycin
 * Sandimmune
 * saquinavir
 * saquinavir mesylate
 * Serzone
 * Slo-Niacin
 * Sporanox
 * Tao
 * telithromycin
 * Telzir
 * tipranavir
 * TriCor
 * Triglide
 * troleandomycin
 * Vaprisol
 * verapamil
 * verapamil 24 hour extended release
 * verapamil extended release
 * Verelan
 * Verelan PM
 * Viracept
 * vitamin B3

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Moderate Interactions

 * 8-Mop
 * Abraxane
 * Accolate
 * Adalat
 * Adalat CC
 * Afeditab CR
 * aminolevulinic acid topical
 * Antabuse
 * aprepitant
 * Arava
 * armodafinil
 * Arranon
 * Avonex
 * Avonex Prefilled Syringe
 * azithromycin
 * Azithromycin 3 Day Dose Pack
 * Azithromycin 5 Day Dose Pack
 * azithromycin extended release
 * AZT
 * Betaseron
 * bortezomib
 * bosentan
 * bromocriptine
 * carbamazepine
 * carbamazepine extended release
 * Carbatrol
 * carboplatin
 * Carboplatin Novaplus
 * Cardizem
 * Cardizem CD
 * Cardizem LA
 * Cardizem Monovial
 * Cardizem SR
 * Cartia XT
 * Chloracol
 * chloramphenicol
 * Chloromycetin
 * Chloromycetin Sodium Succinate
 * cholestyramine
 * Cholestyramine Light
 * cisapride
 * cisplatin
 * clofarabine
 * Clolar
 * Colestid
 * Colestid Flavored
 * colestipol
 * Cubicin
 * D.H.E. 45
 * d4T
 * dalfopristin
 * daptomycin
 * dasatinib
 * ddC
 * ddI
 * didanosine
 * didanosine delayed release capsule
 * dihydroergotamine
 * dihydroergotamine nasal
 * Dilacor XR
 * Diltia XT
 * diltiazem
 * diltiazem 24 hour extended release
 * diltiazem extended release
 * Diltiazem Hydrochloride CD
 * Diltiazem Hydrochloride SR
 * Diltiazem Hydrochloride XR
 * Diltiazem Hydrochloride XT
 * Diquinol
 * disulfiram
 * docetaxel
 * echinacea
 * efavirenz
 * Eloxatin
 * Emend
 * Emend 3-Day
 * Emend for Injection
 * Epitol
 * Equetro
 * Ergomar
 * ergotamine
 * esomeprazole
 * etravirine
 * ezetimibe
 * Fasigyn
 * FK506
 * Flagyl
 * Flagyl 375
 * Flagyl ER
 * Flagyl I.V.
 * Flagyl I.V. RTU
 * fluvoxamine
 * fluvoxamine extended release
 * Folex PFS
 * fosaprepitant
 * Furadantin
 * Gleevec
 * goldenseal
 * grepafloxacin
 * Hivid
 * hypericum perforatum
 * imatinib
 * INH
 * Intelence
 * interferon beta-1a
 * interferon beta-1b
 * iodoquinol
 * isoniazid
 * ixabepilone
 * Ixempra
 * lanreotide
 * lansoprazole
 * lapatinib
 * leflunomide
 * Levulan Kerastick
 * Luvox
 * Luvox CR
 * Macrobid
 * Macrodantin
 * methotrexate
 * Methotrexate Sodium
 * Preservative Free
 * methoxsalen
 * Metro I.V.
 * metronidazole
 * metronidazole extended release
 * Metryl
 * Mifeprex
 * mifepristone
 * Migranal
 * modafinil
 * naltrexone
 * Navelbine
 * nelarabine
 * nevirapine
 * Nexium
 * Nexium I.V.
 * Nifediac CC
 * Nifedical XL
 * Nifedipine
 * Nifedipine extended release
 * nilotinib
 * Nitro Macro
 * nitrofurantoin
 * nitrofurantoin dual release
 * nitrofurantoin macrocrystals
 * nitrofurantoin regular release
 * Nuvigil
 * Nydrazid
 * octreotide
 * omeprazole
 * Oncovin
 * Onxol
 * oxaliplatin
 * oxcarbazepine
 * Oxsoralen-Ultra
 * paclitaxel
 * paclitaxel protein-bound
 * pantoprazole
 * Paraplatin
 * Parlodel
 * pectin
 * Platinol-AQ
 * Prevacid
 * Prevacid I.V.
 * Prevacid SoluTab
 * Prevalite
 * Priftin
 * Prilosec
 * Prilosec OTC
 * Procardia
 * Procardia XL
 * Prograf
 * Propulsid
 * Protonix
 * Protonix IV
 * Protostat
 * Provigil
 * Questran
 * Questran Light
 * Ranexa
 * ranolazine
 * Rapamune
 * Raxar
 * Rebif
 * Retrovir
 * ReVia
 * Rezulin
 * Rheumatrex Dose Pack
 * Rifadin
 * Rifadin IV
 * rifampin
 * rifapentine
 * Rimactane
 * RU-486
 * Sandostatin
 * Sandostatin LAR Depot
 * sirolimus
 * Somatuline Depot
 * Sprycel
 * St. John's wort
 * stavudine
 * stavudine extended release
 * Sustiva
 * tacrolimus
 * Tasigna
 * Taxol
 * Taxotere
 * Taztia XT
 * Tegretol
 * Tegretol XR
 * telbivudine
 * temsirolimus
 * thalidomide
 * Thalomid
 * thioguanine
 * Tiazac
 * Tindamax
 * tinidazole
 * Torisel
 * Tracleer
 * Trexall
 * Trileptal
 * troglitazone
 * Tykerb
 * Tyzeka
 * Uvadex
 * Velban
 * Velcade
 * verteporfin
 * VFEND
 * Videx
 * Videx EC
 * vinblastine
 * Vincasar PFS
 * vincristine
 * vinorelbine
 * Viramune
 * Visudyne
 * Vivitrol
 * voriconazole
 * Yodoxin
 * Z-Pak
 * zafirlukast
 * zalcitabine
 * Zegerid (Original Formulation)
 * Zerit
 * Zerit XR
 * Zetia
 * zidovudine
 * Zithromax
 * Zithromax IV
 * Zithromax TRI-PAK
 * Zithromax Z-Pak
 * Zmax

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Minor Interactions

 * Anisindione
 * Armour Thyroid
 * bexarotene
 * Coumadin
 * Cytomel
 * Dicumarol
 * Dynacirc
 * Dynacirc CR
 * Eltroxin
 * Euthyrox
 * Eutroxsig
 * Evotrox
 * Isradipine
 * Isradipine extended release
 * Jantoven
 * L Thyroxine Roche
 * L-thyroxine
 * Levo-T
 * Levotabs
 * Levotec
 * Levothroid
 * Levothyrox
 * Levothyroxine
 * Levoxyl
 * liothyronine
 * liotrix
 * Miradon
 * Nature-Throid
 * Oroxine
 * Synthroid
 * Targretin
 * thyroid desiccated
 * Thyrolar-1
 * Thyrolar-1/2
 * Thyrolar-1/4
 * Thyrolar-2
 * Thyrolar-3
 * Tirosint
 * Triostat
 * Unithroid
 * warfarin
 * Westhroid

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Moderate Interactions

 * Altocor
 * Altoprev
 * Antara
 * atorvastatin
 * Atromid-S
 * Baycol
 * cerivastatin
 * Cholestin (obsolete)
 * cholestyramine
 * Cholestyramine Light
 * clofibrate
 * colesevelam
 * Colestid
 * Colestid Flavored
 * colestipol
 * Crestor
 * cycloSPORINE
 * Dom-Fenofibrate
 * fenofibrate
 * Fenoglide
 * fluvastatin
 * fluvastatin extended release
 * gemfibrozil
 * Gengraf
 * Lescol
 * Lescol XL
 * Lipidil EZ
 * Lipidil Micro
 * Lipidil Supra
 * Lipitor
 * Lipofen
 * Lofibra
 * Lopid
 * lovastatin
 * lovastatin extended release
 * Mevacor
 * monascus
 * Neoral
 * Pravachol
 * pravastatin
 * Prevalite
 * Questran
 * Questran Light
 * Rapamune
 * red yeast rice
 * rosuvastatin
 * Sandimmune
 * simvastatin
 * sirolimus
 * temsirolimus
 * Torisel
 * TriCor
 * Triglide
 * Welchol
 * Zocor

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Minor Interactions

 * anisindione
 * Coumadin
 * dicumarol
 * Jantoven
 * Miradon
 * warfarin

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