| Agent |
Mechanism
of Action |
Dosage |
Benefits |
Side
Effects |
Notes |
| Colestipol
(Colestid®) |
Interrupts
bile-acid reabsorption requiring bile acid synthesis from cholesterol. |
2
scoops bid or tid (use bulk form). Begin with 1 scoop in the morning. 30
minutes before meal, increase to bid, then to 2 scoops
bid. |
Nonabsorbed
with long-term safety established. LDL-C lowering 10%–15%
(LRC-CPPT1). |
Taste/texture,
bloating, heartburn, constipation, drug interaction (avoidable by administration
of drugs 1 hour before or 4 hours after) and TG increase. |
Drug
of choice for LDL-C lowering in children and in women with childbearing
potential. Often used as second-line drug with statins because it acts
synergistically to induce LDL receptors. Do not use in patients with TG
>300 or in those with GI motility disorders. |
| Colesevelam
hydrochloride (WelChol®) |
Interrupts
bile-acid reabsorption requiring bile
acid synthesis from cholesterol. |
Three
625-mg tablets bid (3.8 g total). 3 tablets with breakfast and 3 tablets
with dinner. |
Nonabsorbed
with long-term safety established. LDL-C lowering
10%–15%.1 |
Taste/texture,
bloating, heartburn, constipation, drug interaction (avoidable by administration
of drugs 1 hour before or 4 hours after) and TG increase. |
Drug
of choice for LDL-C lowering in children and in women with childbearing
potential. Often used as second line drug with statins because it acts
synergistically to induce LDL receptors. Do not use in patients with TG
>300 or those with GI motility disorders. |
| Ezetimibe
(Zetia®) |
Selectively
inhibits the intestinal absorption of cholesterol and related
phytosterols. |
10
mg qd. |
Decreases
the delivery of intestinal cholesterol to the liver, thereby reducing hepatic
cholesterol stores and increases the clearance of cholesterol from the blood
rather than inhibiting cholesterol synthesis. Reduces LDL-C by 18%, TG by
8%, and apolipoprotein B by 16%(EASE2). |
Well
tolerated with few adverse reactions similar to placebo. |
Can
use in combination with statins; however, contraindicated in patients with
active liver disease or elevated LFTs. When used in combination with statins,
yields an additional LDL-C reduction of 12%, an increase in HDL-C of 3%,
and a TG reduction of 8%. Statin plus ezetimibe yield a total LDL-C reduction
of 25.8%2. Do not use in combination with resins, fibrates, or
cyclosporine. May take at the same time as statin. |
| Ezetimibe
and simvastatin (Vytorin®) |
Combination
of intestinal absorption blocker and statin. Both selectively inhibit the
intestinal absorption of cholesterol and partially inhibit HMG-CoA
reductase. |
Ezetimibe:
10 mg Simvastatin: 10, 20, 40, or 80 mg
qhs. |
Combination
therapy fosters patient adherence with dosing. Synergistic benefits of both
inhibition of intestinal cholesterol absorption by 54% and statin LDL-C lowering
of 45%–60% depending on dose3. |
Abnormal
LFTs, myositis/myalgias. |
Contraindicated
in patients with active liver disease or elevated LFTs, pregnant patients,
and nursing mothers. Do not use in combination with gemfibrozil, other fibrates,
>1 g niacin amiodarone, or verapamil due to an increased risk of
myopathy. |
| Gemfibrozil
(Lopid®) |
Reduces
VLDL-C synthesis and induces lipoprotein lipase. |
600
mg bid. |
Best
TG-reducing drugs, lowering 50% or more in many patients. Raises HDL-C 15%.
Reduces CHD events by 24% in patients with low HDL-C, high TGs
(Helsinki4, VA-HIT5). |
Nausea
and skin rash. |
Does
not lower LDL-C reliably or LDL-C may increase in one third of patients.
Used in combination therapy with statins for combined hyperlipidemia; however
use should be cautious, due to increased myositis/myalgias. Alters statin
metabolism and causes an increase in statin plasma concentration. Use with
caution in patients with renal insufficiency and gallbladder disease. |
| Fenofibrate
(Tricor®, Antara™,
Lofibra™) |
Reduces
VLDL-C synthesis and induces lipoprotein lipase. |
Tricor:
48, 145 mg/d Antara: 43, 87, 130 mg/d Lofibra: 54, 67, 134, 160, 200
mg/d. |
Best
TG-reducing drugs, lowering TG 50% or more in many patients. Raises HDL-C
15%. Reduces CHD in patients with low HDL-C, high
TG.4-5 |
Nausea
and skin rash. |
Does
not lower LDL-C reliably or LDL-C may increase in one third of patients.
Used in combination therapy with statins for combined hyperlipidemia; however
use should be cautious, due to increased myositis/myalgias. Use with caution
in patients with renal insufficiency and gallbladder disease. Use with
repaglinide (Prandin®) may cause prolonged severe
hypoglycemia. |
| Atorvastatin
(Lipitor®) |
Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol synthesis.
This induces LDL receptor formation and removal of LDL-C from blood. |
10–80
mg qd. |
Well-studied
for safety and efficacy in many trials. Lowers LDL-C 39%–60% depending
on dose and drugs. Raises HDL-C 5%–9%; however, at higher doses
(>40 mg), can lower HDL-C. Lowers TG
19%–37%.6 |
Abnormal
LFTs, myositis/myalgias. |
Drug
of choice for elevated LDL-C based on safety and efficacy. Intensive lipid
lowering with 80 mg of atorvastatin in patients with CHD provides significant
benefit (percent reduction in CHD events) compared with 10 mg.6
Liver function abnormalities less common than previously thought. The 6 statins
have different metabolism allowing substitution if side effects occur. Used
in combination with bile-acid binding resins to synergistically lower
LDL-C. Used in combination with niacin and fibrates in patients with combined
hyperlipidemia. Use cautiously in patients on fibrates due to increased risk
of myalgia/myositis. |
| Amlodipine
and atorvastatin (Caduet®) |
|
Amlodipine:
10, 20, 40, or 80 mg Atorvastatin: 5 or 10 mg qd. |
Combination
therapy fosters patient adherence with dosing. Treats both lipid disorder
and hypertension concomitantly using a statin and calcium channel
blocker. |
Edema,
dizziness, headache, flushing, and palpitations. |
Do
not use in patients with congestive heart failure or severe aortic
stenosis. |
| Fluvastatin
(Lescol®, Lescol® XL) |
Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol synthesis.
This induces LDL receptor formation and removal of LDL-C from blood. |
Lescol:
20–40 mg qhs
Lescol XL: 80 mg qhs |
Well-studied
for safety and efficacy in many trials. Lowers LDL-C 22%–36% depending
on dose and drugs. Raises HDL-C 3%–11%. Lowers TG
12%–25%.7 |
Abnormal
LFTs, myositis/myalgias. |
Drug
of choice for elevated LDL-C based on safety and efficacy. Liver function
abnormalities less common than previously thought. The 6 statins have different
metabolism allowing substitution if side effects occur. Used in combination
with bile-acid binding resins to synergistically lower
LDL-C. Used in combination with niacin and fibrates in patients with combined
hyperlipidemia. Use cautiously in patients on fibrates due to increased risk
of myalgia/myositis. |
| Niacin
and lovastatin |
Combination
product of both extended-release niacin (niaspan) and statin
(lovastatin). |
Niacin:
500 mg Lovastatin: 20 mg Niacin: 2000 mg lovastatin: 40 mg
qhs. |
Combination
therapy fosters patient adherence with dosing. Lowers LDL-C 30%–42%.
Raises HDL-C 20%–30%. Reduces TG 32%–44%.8 |
Flushing,
nausea, glucose intolerance, gout, LFT abnormalities, and elevated uric acid
levels. Myositis/myalgias. |
Drug
of choice for combined hyperlipidemia and for patients who require simplified
dosing. May use a nonenteric coated aspirin taken 1 hour before evening dose
along with a light snack to minimize flushing. Do not take with hot
beverage. |
| Lovastatin
(Mevacor®, Altoprev™) |
Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol synthesis.
This induces LDL receptor formation and removal of LDL-C from blood. |
20–80
mg qhs. |
Well-studied
for safety and efficacy in many trials. Lowers LDL-C 20%–60% depending
on dose and drugs. Raises HDL-C 10%. Lowers TG 15%–25%. (4S9,
WOSCOPS10, CARE11) |
Abnormal
LFTs myositis/myalgias. |
Drug
of choice for elevated LDL-C based on safety and efficacy. Liver function
abnormalities less common than previously thought. The 6 statins have different
metabolism allowing substitution if side effects occur. Used in combination
with bile-acid binding resins to synergistically lower
LDL-C. Used in combination with niacin and fibrates in patients with combined
hyperlipidemia. Use cautiously in patients on fibrates, due to increased
risk of myalgia/myositis. |
| Pravastatin
(Pravachol®) |
Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol synthesis.
This induces LDL receptor formation and removal of LDL-C from blood. |
10–40
mg qhs. |
Well-studied
for safety and efficacy in many trials. Lowers LDL-C 20%–40% depending
on dose and drugs (28% decrease in LDL-C in the ALLHAT-LLT12 trial).
Raised HDL-C 10%. Lowers TG 15%–25%.10-11 (WOSCOPS, CARE).
Reduces the risk of major CHD events by 19%–24%.13 |
Abnormal
LFTs, myositis/myalgias. |
Drug
of choice for elevated LDL-C based on safety and efficacy. Liver function
abnormalities less common than previously thought. The 6 statins have different
metabolism allowing substitution if side effects occur. Used in combination
with bile-acid binding resins to synergistically lower
LDL-C. Used in combination with niacin and fibrates in patients with combined
hyperlipidemia. Use cautiously in patients on fibrates, due to increased
risk of myalgia/myositis. |
| Aspirin
and pravastatin (Pravigard™ PAC) |
|
Aspirin:
81 or 325 mg
Pravastatin: 20, 40, or 80 mg qhs. |
|
|
|
| Rosuvastatin
(Crestor®) |
Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol synthesis.
This induces LDL receptor formation and removal of LDL-C from blood. |
5–40
mg qhs. |
Effective
in lowering LDL-C 45%–63% depending on dose and drugs. Raises HDL-C
8%–14%. Lowers TG 10%–35% (STELLAR trial14). |
Abnormal
LFTs, myositis/myalgias. |
Newest
of the 6 statins and therefore not as heavily studied in clinical trials
to date; however, numerous industry trials having been conducted. Do not
coadminister with warfarin or gemfibrozil. May be coadministered with fenofibrate
and bile acid-binding resins to synergistically lower
LDL-C. |
| Simvastatin
(Zocor®) |
Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol synthesis.
This induces LDL receptor formation and removal of LDL-C from blood. |
5–80
mg qhs. |
Well-studied
for safety and efficacy in many trials. Lowers LDL-C 20%–60% depending
on dose and drugs. Raises HDL-C 10%. Lowers TG 15%–25% (4S). |
Abnormal
LFTs, myositis/myalgias. |
Drug
of choice for elevated LDL-C based on safety and efficacy. Liver function
abnormalities less common than previously thought. The 6 statins have different
metabolism allowing substitution if side effects occur. Used in combination
with bile acid binding resins to synergistically lower
LDL-C. Used in combination with niacin and fibrates in patients with combined
hyperlipidemia. Use cautiously in patients on fibrates, due to increased
risk of myalgia/myositis. |
| Niacin |
Largely
unknown. Reduces hepatic production of B-containing lipoproteins, increases
HDL-C production. |
500
mg to 1 g tid. |
Lowers
LDL-C and TG 10%–30%. Most effective drug at raising HDL-C (25%–35%).
Long-term efficacy studies (CDP15). |
Flushing,
nausea, glucose intolerance, gout, LFT abnormalities, and elevated uric acid
levels. May potentially increase homocysteine levels. |
Drug
of choice for combined hyperlipidemia and in patients with low HDL-C.
Extended-release preparations limit flushing and LFT abnormalities. OTC
long-acting niacin preparations are not recommended as they increase the
incidence of hepatotoxicity. Also lowers lipoprotein (a). Used in combination
with statins or bile-acid binding resins in combined hyperlipidemia. To minimize
flushing, nonenteric coated aspirin can be taken 1 hour before evening dose
along with a light snack. Do not take with hot beverages such as tea or
coffee. |
| Niacin
(Niaspan extended release®) |
Largely
unknown. Reduces hepatic production of B-containing lipoproteins, increases
HDL-C production. |
500
mg to 2 g qhs. |
Lowers
LDL-C and TG 10%–30%. Most effective drug at raising HDL-C (25%–35%).
Long term efficacy studies.15 |
Flushing,
nausea, glucose intolerance, gout, LFT abnormalities, and elevated uric acid
levels. May potentially increase homocysteine levels. |
Drug
of choice for combined hyperlipidemia and in patients with low HDL-C.
Extended-release preparations limit flushing and LFT abnormalities. Also
lowers lipoprotein (a). Used in combination with statins or bile-acid binding
resins in combined hyperlipidemia. To minimize flushing, nonenteric coated
aspirin can be taken 1 hour before evening dose along with a light snack.
Do not take with hot beverages such as tea or coffee. |
| Omega-3
polyunsaturated fatty acids (Lovaza™) |
Inhibits
hepatic TG synthesis and augments chylomicron TG clearance secondary to increased
activity of lipoprotein lipase. |
4
g/d (4 tablets). |
Effective
in controlling TG levels up to 45%. Raises HDL-C 9%.16 |
Dyspepsia,
nausea. |
Can
increase LDL-C in some patients with hypertriglyceridemia. May increase bleeding
time; therefore, use with caution in patients receiving anticoagulant
therapy. |
Q-Notes
for Adult Medicine 
