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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
