Drug Class Overview1 -5 Drug Dose range Pharmacokinetics Drug

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Drug Class Overview1 -5 Drug Dose range Pharmacokinetics Drug Powered By Docstoc
					                                                                                            1-5
                                                                Drug Class Overview
            Drug            Dose range                               Pharmacokinetics                                         Drug - Drug Interactions
 Statins (HMG Co-A reductase inhibitors): Inhibit cholesterol biosynthesis in the liver
 Atorvastatin          10-80 mg/day                Extensive CYP450 3A4 metabolism to active                         CYP 3A4 inhibitors (amiodarone,
 (Lipitor®)                                        metabolites                                                       erythromycin, clarithromycin, ketoconazole,
                                                                                                                     verapamil, nefazodone, fluvoxamine,
                                                        May be administered at any time of day.                      cyclosporine, grapefruit juice) can ↑ levels
                                                                                                                     but less effect than with lovastatin &
                                                                                                                     simvastatin
 Fluvastatin                 20-80 mg/day               CYP450 2C9 (75%), 2C8 (5%), 3A4 (20%)                        Fluvastatin can ↑ phenytoin, diclofenac, and
 (Lescol®)                                              metabolism, no active metabolite                             glyburide levels
                                                                                                                     Rifampin can ↓ fluvastatin levels
                                                        Administer in evening for better LDL lowering due            Warfarin: can cause increased INR due to
                                                        to short t½.                                                 inhibition of warfarin metabolism
 Lovastatin                  10-80 mg/day               95% protein bound                                            CYP 3A4 inhibitors (amiodarone,
 (Mevacor®, Altoprev®)                                                                                               erythromycin, clarithromycin, ketoconazole,
                                                        Administration before evening meal is preferred to           verapamil, diltiazem, nefazodone,
                                                        increase extent of absorption and due to short t½.           fluvoxamine, cyclosporine, grapefruit juice)
                                                                                                                     can significantly ↑ levels of lovastatin
 Pravastatin                 40-80 mg/day               Extensive metabolism to inactive metabolites by p-           Less likely than other statins due to lack of
 (Pravachol®)                                           glycoprotein                                                 CYP450 metabolism.
                                                        May be administered at any time of day.                      Cyclosporine can ↑ levels.
 Rosuvastatin                5-40 mg/day                Minimal CYP450 3A4 metabolism to active metabolite           Less likely than other statins due to minimal
 (Crestor®)                  **40 mg only if failed                                                                  CYP 3A4 metabolism.
                             20 mg trial                Better LDL lowering with evening administration.             Use lower doses of rosuvastatin with
                                                                                                                     cyclosporine or gemfibrozil.
 Simvastatin                 5-80 mg/day                95% protein bound                                            CYP 3A4 inhibitors (amiodarone,
 (Zocor®)                                               Extensive CYP450 3A4 metabolism to active                    erythromycin, clarithromycin, ketoconazole,
                                                        metabolite                                                   verapamil, diltiazem, nefazodone,
                                                                                                                     fluvoxamine, cyclosporine, grapefruit juice)
                                                     Better LDL lowering with evening administration.                can significantly ↑ levels of simvastatin.
 Bile Acid Sequestrants (BAS): Bind bile salts in intestines, interrupt enterohepatic recycling of bile salts
 Cholestyramine           4-24 grams/day             Separate administration with other medications. Give       BAS can bind to and ↓ absorption of many
 (Questran®)                                         other med 1 hour before or 4 hours after BAS.              concurrent drugs, especially warfarin,
 Colesevelam              3-7 tabs/day               May interfere with absorption of fat soluble vitamins (A, levothyroxine, digoxin, thiazide diuretics
 (Welchol®)               (625 mg/tab)               D, E, K)                                                   ↑ risk of cholelithiasis when combined with
 Colestipol               Powder: 5-30 g/day,                                                                   ezetimibe
 (Colestid®)              Tablets: 2-16 g/day
 Cholesterol Absorption Inhibitor: Inhibits biliary and dietary cholesterol absorption at the brush border of small intestine
 Ezetimibe                10 mg/day                  >90% protein bound, t ½ = 19-30 hrs                        ↑ risk of cholelithiasis with fibrates, BAS
 (Zetia™)                                            Glucuronidation in liver and intestinal wall to active     Decreased levels with concurrent BAS
                                                     metabolite                                                 Cyclosporine: ↑ both drug levels
                                                                                                                Risk of ↑ INR with warfarin
 Fibric Acid Derivatives: Decreases plasma triglyceride levels via various mechanisms
 Fenofibrate                 48-150 mg/day              99% protein bound                                            ↑ risk of myopathy with statins
 (Tricor®, Triglide™,                                   60-90% renally excreted, 5-25% fecal                         Caution ↑ INR with warfarin
 Lipofen™)                                              Adjust dose in renal failure                                 ↑ risk of nephrotoxicity with cyclosporine
                                                                                                                     ↓ absorption with BAS
 Fenofibrate,                43-130 mg/day              99% protein bound                                            ↑ risk of myopathy with statins
 micronized (Antara™,        (Antara®)                  60% renal excretion, 25% fecal                               Caution ↑ INR with warfarin
 Lofibra™)                   67-200 mg/day              Adjust dose in renal failure                                 ↑ risk of nephrotoxicity with cyclosporine
                             (Lofibra®)                                                                              ↓ absorption with BAS
 Gemfibrozil (Lopid®)        600 mg BID              99% protein bound                                               ↑ risk of myopathy with statins
                                                     70% renal excretion, 6% fecal                                   ↑ risk of cholelithiasis with ezetimibe
                                                     Renal dose adjustment = GFR 10-50 ml/min: give 50%              ↑ bleeding risk with warfarin
                                                     of dose. GFR<10 ml/min: give 25% of dose
 Nicotinic Acid: B-complex vitamin with anti-hyperlipidemic effects of unknown mechanism
 Niacin                      IR: 1000-3000 mg/day Extensive hepatic conjugation to active metabolite         ↑ risk of myopathy with statins
 (Niaspan®, Slo-             ER: 1000-2000 mg/day 60-76% renally excreted, 12% unchanged                     ↓ niacin absorption with BAS
 Niacin®)                                         Renal dose adjustment = GFR 10-50 ml/min: give 50%
                                                  of dose. GFR<10 ml/min: give 25% of dose
 Omega-3 fatty acids: Reduces hepatic synthesis of triglycerides is possible mechanism; not completely defined.
 Omega-3-fatty acid          4 capsules/day                                                                          ↑ bleeding risk with warfarin
 (Omacor®)

 Combination                            Available Doses (mg)                                                                Other Drug Classes Represented
 antihyperlipidemics
 Ezetimibe / Simvastatin                10/10, 10/20, 10/40, 10/80
 (Vytorin®)
 Amlodipine / Atorvastatin              2.5/10, 2.5/20, 2.5/40, 5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, 10/80          Calcium Channel Blocker
 (Caduet®)
 Aspirin / Pravastatin                  81/20, 81/40, 81/80, 325/20, 325/40, 325/80                                         Anti-platelet agent
 (Pravigard Pac™)
 Lovastatin / Niacin                    20/500, 20/750, 20/1000, 40/1000
 (Advicor®)
Prepared by: Kim Scott Kell, PharmD candidate 2007 and Elizabeth Beuter, PharmD candidate 2007.                                          February 22, 2007
                                                                                                                                                     6 - 16
                                        Effects of Lipid-Lowering Drugs on Lipid Levels (% Change from Baseline)
                                  Drug Class                            LDL                     HDL                                                               TG
                  Statins                                           ↓ 18 – 55%               ↑ 5 – 15%                                                        ↓ 7 – 30%
                     Atorvastatin 20 mg                                ↓ 43%                   ↑ 9%                                                             ↓ 26%
                     Fluvastatin 20 mg                                 ↓ 22%                   ↑ 3%                                                             ↓ 12%
                     Lovastatin 40 mg                                  ↓ 30%                   ↓ 26%                                                            ↓ 14%
                     Pravastatin 20 mg                                 ↓ 32%                   ↑ 2%                                                             ↓ 11%
                     Rosuvastatin 20 mg                                ↓ 55%                   ↑ 8%                                                             ↓ 23%
                     Simvastatin 20 mg                                 ↓ 38%                   ↑ 8%                                                             ↓ 19%
                  Bile Acid Sequestrants                            ↓ 15 – 30%               ↑ 3 – 5%                                                           ↔ or ↑
                  Nicotinic Acid                                     ↓ 5 – 25%              ↑ 15 – 35%                                                        ↓ 20 – 50%
                      Niaspan® 1500 mg                                 ↓ 20%                   ↑ 20%                                                            ↓ 13%
                                                                    ↓ 5 – 20%∗              ↑ 10 – 35%                                                        ↓ 20 – 50%
                                                                                                       #
                  Fibric Acid Derivatives
                                         ®
                      Fenofibrate (Tricor )                            ↓ 21%                   ↑ 11%                                                            ↓ 29%
                      Gemfibrozil                                     ↓0-10%                  ↑6-11%                                                           ↓31-35%
                  Ezetimibe 10 mg                                      ↓ 18%                   ↑ 1%                                                              ↓ 8%
                  Ezetimibe 10 mg + Statin                             ↓ 25%                   ↑ 3%                                                             ↓ 14%
                          ®
                  Omacor 4g                                            ↑ 45%                  ↑ 9.1%                                                            ↓ 52%
                                                          ∗In nonhypertriglyeridemic persons; may be increased in hypertriglyeridemic persons.
                                                                                  # More in severe hypertriglyeridemia.

                                                                                                                                 17,18
                                                                 Effects of Statin Dosage on LDL (% decrease)
  Dose (mg/day)                    Fluvastatin                  Pravastatin          Lovastatin        Simvastatin                                   Atorvastatin                Rosuvastatin
         10                                                        19%                                    28%                                           38%                         46%
         20                            17%                         24%                 29%                35%                                           46%                         52%
         40                            23%                         34%                 31%                41%                                           51%                         55%
         80                                                                            48%                                                              54%


                                                                                                                                   6,19
                                                                 Monitoring Parameters and Follow-up Schedule
    Drug Class                        Monitoring                                                                              Follow-up
                       Muscle soreness, tenderness or pain                           Evaluate muscle soreness & CK initially & at follow-up. Obtain a CK when persons
                                                                                     have muscle soreness, tenderness, or pain.
                       ALT, AST                                                      Atorvastatin: Baseline, 12 weeks, 12 weeks after dose elevation, every 6 months
                                                                                     thereafter
                                                                                     Fluvastatin: Baseline, 12 weeks, 12 weeks after dose elevation
  Statins                                                                            Lovastatin: Baseline, prior to doses > 40 mg/day, when clinically indicated
                                                                                     Pravastatin: Baseline, prior to dose elevation, when clinically indicated
                                                                                     Rosuvastatin: Baseline, 12 weeks, 12 weeks after dose elevation, every 6 months
                                                                                     thereafter
                                                                                     Simvastatin: Baseline, when clinically indicated. With 80 mg dose: at 3, 6, 12 months
                                                                                     after titration
  Bile Acid            Indigestion, bloating, constipation,                          Evaluate symptoms initially & at follow-up visits. Check time of administration with
  Sequestrants         abdominal pain, flatulence, and nausea                        other drugs.
                       Flushing, itching, tingling, HA, nausea, gas,                 Evaluate initially & at each follow-up visit.
                       heartburn, fatigue, and rash
                       Peptic ulcer                                                  Evaluate initially & as needed.
  Nicotinic Acid       Fasting blood sugar                                           Obtain FBS & uric acid initially, 6 – 8 weeks after starting therapy, then annually or
                       Uric acid                                                     more frequently if indicated to monitor for hyperglycemia or hyperuricemia.
                       ALT, AST                                                      Obtain initially, 6 – 8 weeks after reaching a daily dose of 1500 mg, 6 – 8 weeks after
                                                                                     reaching a max daily dose, & then annually or more frequently if indicated.
                       Abdominal pain, dyspepsia, HA, drowsiness                     Evaluate initially & at each follow-up visit.
  Fibrates             Cholelithiasis                                                Evaluate history & symptoms initially & then as needed.
                       ALT, AST                                                      When used in with fenofibrate, monitor LFTs & signs and symptoms of cholelithiasis.
                       Cholelithiasis
  Ezetimibe            Headache*, diarrhea, arthralgia, abdominal                    Evaluate initially & at each follow-up visit.
                       pain, chest pain, dizziness, and fatigue
*Most frequent adverse reaction reported (8%).
     1.     Micromedex® Healthcare Series. www.thomsonhc.com. Accessed via VCU Libraries Website: 01/2007.
     2.     Bays HE. Clinical Overview of Omacor: A concentrated Formulation of Omega-3 Polyunsaturated Fatty Acids. Am J Cardiol; 2006;98[suppl]:71i-76i
     3.     Cholesterol-lowering agents. Pharmacist’s Letter/Prescriber’s Letter. 2006; 22(8): 220802.
     4.     Andersson TB, Bredberg E, Ericsson H, Sjoberg H. An Evaluation of the In-vitro Metabolism Data for Predicting the Clearance and Drug-Drug Interaction Potential of CYP 2C9 Substrates. Drug
            Metabolism and Disposition, 2004;32:715.
     5.     Plakogiannis R, Cohen H. Optimal Low-Density Lipoprotein Cholesterol Lowering – Morning Versus Evening Statin Administration. Ann Pharmacother 2007;41:106.
     6.     Third Report of the NCEP on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002 Dec 17;106(25):3143.
     7.     Product information. Lipitor, Pfizer, New York NY, December 2006.
     8.     Product information. Lescol, Novartis Pharmaceuticals Corporation, East Hanover NJ, April 2006.
     9.     Product information. lovastatin, Andrx Pharmaceuticals, Inc., Fort Lauderdale FL, February 2006.
     10.    Product information. Pravachol, Bristol-Myers Squibb Co., Princeton NJ, August 2005.
     11.    Product information. Crestor, AstraZeneca Pharmaceuticals, Wilmington DE, December 2005.
     12.    Product information. Zocor, Merck & Co., Inc., Whitehouse Station NJ, August 2005.
     13.    Product information. Niaspan, Kos Pharmaceuticals, Inc., Cranbury NJ, 2005.
     14.    Product information. Tricor, Abbott Laboratories, North Chicago IL, November 2004.
     15.    Product information. Zetia, Merck/Schering-Plough Pharmaceuticals, North Wales PA, November 2006.
     16.    Product information. Omacor, Reliant Pharmaceuticals, Inc., Durham NC, 2005.
     17.    Hilleman DE, Heineman SM, Foral PA. Pharmacoeconomic Assessment of HMG-CoA reductase Inhibitor Therapy: An Analysis Based on the CURVES Study. Pharmacotherapy, 2000;20:819.
     18.    Jones PH, Davidson MH, Stein EA, et al. Comparison of the Efficacy and Safety of Rosuvastatin Versus Atorvastatin, Simvastatin, and Pravastatin Across Doses (STELLAR Trial). Am J Cardiol,
            2003;92:152.
     19.    Ezetimibe. Lexi-Comp Online. www.lexi.com. Accessed on 01/29/07.

Prepared by: Kim Scott Kell, PharmD candidate 2007 and Elizabeth Beuter, PharmD candidate 2007.                                                                          February 22, 2007

				
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