Panents W1th severe hypercholesterolemra LDL-C reductron was srmrlar (-53%) when UPITOR 40 mg and colestipol 20 g were coadministered when compared to that wrth LIPITOR 80 mg alone Plasma concentration of atQMistatin was lower (appro~mately 26%) when UPITOR 40 mg plus colestrpol 20 g were coadmrmstered compared W1th UPITOR 40 mg alone However. the combmanon drug therapy was less effective rn lowenng the tng~ndes than UPITOR monotherapy in both types of hYPercholesterolemiC patients (see PHARMACOLOGY, Clincal Studres). When UPITOR is used concurrently W1th colesbpol or any other resrn, an rnteMI of at least tv.o hours should be marntarned between the tv.o drugs, srnce the absorpbOn of LIPITOR may be impared by the resin. Fibric Acid Derivatives (Gemfibrozil, Fenofibrate, Bezafibrate) and Niacin (Nicotinic Acid): Although there rs no experience W1th the use of UPITOR grven concurrently Wlth fibnc acrd denvaoves and macrn. the benefits and nsks of such combrned therapy should be carefully consrdered The nsk of myopathy during treaonent Wlth other drugs in thrs class rs rncreased wrth concurrent admrmstration (see WARNINGS, Muscle Effects) Coumarin Anticoagulants: UPITOR had no cllnrcally srgnrfrcant effect on prothrombrn nme when admrmstered to patients receivmg chrome wartann therapy (see SELECTED BIBLIOGRAPHY rn product monograph) Digoxin: In healthy subjects, digoxrn pharmaco~neocs at steady-state were not srgnificantly altered by coadmrnistration of drgoxrn 0 25 mg and UPITOR 10 mg darly However, drgoxrn steady-state coocentranons rncreased approxrmately 20% fjtochrome P-450-mediated Interactions: Atorvastaon rs metabolized by the cytochrome P-450 rsoenzyme, GYP 3A4 Erythrornyon, a GYP 3A4 rnhibltor, rncreased atorvastann plasma levels by 40% Coadmrnrstrabon of GYP 3A4 rnhrbitors, such as grapefruit JUCe, some macrolide antibiotics Qe erythromycn, danthromycin), Immunosuppressants (cyclosporrne). azole anotungal agents e rtraconazole, ketoconazole). protease rnhrbitors. or the antrdepressant, nefazodone. may have the potential to rncrease plasma concentranons of HMG-CoA reductase rnhrbrtors. includrng LIPITOR (see SELECTED BIBUOGRAPHY rn product monograph) Cauoon should thus be exerciSed W1th ooncomrtant use of these agents (see WARNINGS, Pharma~nellc lnteracbQns. Muscle Effects; PRECAUTIONS, Renal lnsufficrency and Endocnne Function. DOSAGE AND AOMINISTRATlON, SELECTED BIBLIOGRAPHY rn product monograph) In healthy subjects. coadmrnistraoon of maxrmum doses of both atorvastann (80 mg) and tertenad1ne (120 mg), a CYP 3A4 substrate, was shoW1n to produce a modest increase in tertenadme AUG. The Ol e rnteMI remarned unchanged However, srnce an rnteraction between these tv.o drugs cannot be excluded in patients w1th predrspos1ng factors for arrhythmia, (e.g preexrsong prolonged OT 1nterval, severe coronary anery d~ . hypokalemra). caunon should be exercised when these agents are coadm1mstered (see WARNINGS, Pharmacokmenc lnteracMns; DOSAGE AND ADMINISTRATlON) Antipyrine: Anopynne was used as a non-specific model for drugs metaboliZed by the microsomal hepatic enzyme system (cytochrome P-450 system). UPITOR had no effect on the pharmaco~nencs of antipyrine. thus 1nteractrons with other drugs metabolized v1a the same cytochrome rsozymes are not expected Macrolide Antibiotics (azithromycin, cfarithromycin, erythromycin): In healthy adults, coadm1nistratron of UPITOR (10 mg 00) and azrthrornycn (500 mg 00) d1d not ~gnrticantly al1er the plasma concentranons of atOMistann However. coadmrmstraoon of atorvastaon (1 0 mg 00) W1th erythromycrn (500 mg 010) or clarithromycin (500 mg BID), which are both GYP 3A4 1nh1bltors, Increased plasma concentrations of atorvastatin approxrmate~ 40% and 80%, respectively (see WARNINGS, Muscle Effects. Human Pharrna~neocs) Protease Inhibitors (nelfinavir mesylate): In healthy adults, coadm1mstration of nelfinavir mesylate (1250 mg BID), a known GYP 3A4 1nh1brtor, and atorvastatin (1 0 mg 00) resulted rn 1ncreased plasma concentratrons of atorvastaon AUG and C...... of atorvastatin were mcreased by 74% and 122% respectvely Patients wi!!J Severe HyPercholesterolemia· H1gher drug dosages (80 mg/day) required for some patients wr1h severe hYPfrcholester 'J work 101001 Plizer Canada Inc. Kukland, Quebec H9J 1M5 • TM Pfizer Ireland Pharmaceuticals pfizer Canada Inc., licensee 75291