"Feb. 28, 2012 -- Memory loss, confusion, high blood sugar, and type 2 diabetes are possible side effects of the popular cholesterol-lowering drugs known as statins, the FDA warns.
Brand name and generic versions of statin drugs must c"...
Therapy with lipid-altering agents should be only one component of multiple risk-factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate (see also 8 and the NCEP treatment guidelines1).
ADVICOR (niacin extended-release and lovastatin) is indicated for use when treatment with both NIASPAN and lovastatin is appropriate. As described in the labeling for Niaspan and lovastatin below, the components of ADVICOR are both indicated for the treatment of hypercholesterolemia. Patients receiving treatment with ADVICOR should be on a standard cholesterol-lowering diet and should continue on this diet during treatment.
NIASPAN (niacin extended-release)
NIASPAN is indicated as an adjunct to diet for reduction of elevated TC, LDL-C, Apo B and TG levels, and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Table 7), when the response to an appropriate diet has been inadequate.
Secondary Prevention of Cardiovascular Events
Niacin is also indicated as adjunctive therapy for treatment of adult patients with very high serum triglyceride levels (Table 7) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them. Such patients typically have serum TG levels over 2000 mg/dL and have elevations of VLDL-C as well as fasting chylomicrons ( Table 7). Patients who consistently have total serum or plasma TG below 1000 mg/dL are unlikely to develop pancreatitis. Therapy with niacin may be considered for those patients with TG elevations between 1000 and 2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. Some patients with TG under 1000 mg/dL may, through dietary or alcohol indiscretion, convert to a pattern with massive TG elevations accompanying fasting chylomicronemia, but the influence of niacin therapy on risk of pancreatitis in such situations has not been adequately studied. Drug therapy is not indicated for patients with hyperlipoproteinemia, who have elevations of chylomicrons and plasma TG, but who have normal levels of VLDL-C.
Lovastatin is indicated as an adjunct to diet for the reduction of elevated TC and LDL-C levels in patients with primary hypercholesterolemia ( Table 7), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate.
Primary Prevention of Cardiovascular Events
In individuals without symptomatic cardiovascular disease, average to moderately elevated TC and LDL-C, and below average HDL-C, lovastatin is indicated to reduce the risk of:
- Myocardial infarction
- Unstable angina
- Coronary revascularization procedures
Secondary Prevention of Cardiovascular Events
The National Cholesterol Education Program (NCEP) Treatment Guidelines are summarized below:
Table 7 : Classification of Hyperlipoproteinemias
|Type||Lipoproteins Elevated||Lipid Elevations|
|V (rare)||Chylomicrons, VLDL||TG||↑→TC|
|TC = total cholesterol; TG = triglycerides; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein; IDL = intermediate-density lipoprotein ↑→ = increased or no change|
Prior to initiating therapy with a lipid-lowering agent, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure TC, HDL-C, and TG. For patients with TG < 400 mg/dL, LDL-C can be estimated using the following equation:
LDL-C = TC – [(0.20 x TG) + HDL-C]
For TG levels > 400 mg/dL, this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. Lipid determinations should be performed at intervals of no less than 4 weeks and dosage adjusted according to the patient's response to therapy. The NCEP Treatment Guidelines are summarized in Table 8.
Table 8: NCEP Treatment
Guidelines: LDL-C Goals and Cutpoints for Therapeutic Lifestyle Changes and
Drug Therapy in Different Risk Categories
|Risk Category||LDL Goal (mg/dL)||LDL Level at Which to Initiate Therapeutic Lifestyle Changes (mg/dL)||LDL Level at Which to Consider Drug Therapy (mg/dL)|
|CHD† or CHD risk equivalents (10-year risk >20%)||<100||≥ 100||≥ 130 (100-129:drug optional) ††|
|2+ Risk factors (10-year risk ≤ 20%)||<130||≥ 130||10-year risk 10%-20%: ≥ 130 10-year risk <10%: ≥ 160|
|0-1 Risk factor †††||<160||≥ 160||≥ 190 (160-189:LDL-lowering drug optional)|
|† CHD, coronary heart disease
†† Some authorities recommend use of LDL-lowering drugs in this category if an LDL-C level of <100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL-C, e.g., nicotinic acid or fibrate. Clinical judgement also may call for deferring drug therapy in this subcategory.
††† Almost all people with 0-1 risk factor have 10-year risk <10%; thus, 10-year risk assessment in people with 0-1 risk factor is not necessary.
After the LDL-C goal has been achieved, if the TG is still ≥200 mg/dL, non-HDL-C (TC minus HDL-C) becomes a secondary target of therapy. Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category.
DOSAGE AND ADMINISTRATION
The patient should be placed on a standard cholesterol-lowering diet before receiving ADVICOR or its individual active components and should continue on this diet during treatment with lipid-altering therapy (see NCEP Treatment Guidelines for details on dietary therapy).
ADVICOR should be taken at bedtime, with a low-fat snack. ADVICOR tablets should be taken whole and should not be broken, crushed, or chewed before swallowing. Patients not currently on NIASPAN must start ADVICOR at the lowest initial ADVICOR dose, a single 500 mg/20 mg tablet once daily at bedtime. The dose of ADVICOR should not be increased by more than 500 mg daily (based on the NIASPAN component) every 4 weeks. The dose of ADVICOR should be individualized based on targeted goals for cholesterol and triglycerides, and on patient response. Doses of ADVICOR greater than 2000 mg/40 mg daily are not recommended. If ADVICOR therapy is discontinued for an extended period ( >7 days), reinstitution of therapy should begin with the lowest dose of ADVICOR.
Flushing of the skin (see ADVERSE REACTIONS) may be reduced in frequency or severity by pretreatment with aspirin up to the recommended dose of 325 mg (taken up to approximately 30 minutes prior to ADVICOR dose). Flushing, pruritus, and gastrointestinal distress are also greatly reduced by slowly increasing the dose of niacin and avoiding administration on an empty stomach.
Equivalent doses of ADVICOR may be substituted for equivalent doses of NIASPAN but should not be substituted for other modified-release (sustained-release or time-release) niacin preparations or immediate-release (crystalline) niacin preparations (see WARNINGS). Patients previously receiving niacin products other than NIASPAN should be started on NIASPAN with the recommended NIASPAN titration schedule, and the dose should subsequently be individualized based on patient response. A relative bioavailability study results indicated that ADVICOR tablet strengths (i.e. two tablets of 500 mg/20 mg and one tablet of 1000 mg/40 mg) are not interchangeable.
NIASPAN should be taken at bedtime, after a low-fat snack, and doses should be individualized according to patient response. Therapy with NIASPAN must be initiated at 500mg at bedtime in order to reduce the incidence and severity of side effects which may occur during early therapy. NIASPAN must be titrated and the dose should not be increased by more than 500 mg every 4 weeks up to a maximum dose of 2000 mg a day. The recommended dose escalation is shown in Table 11 below. Patients already receiving a stable dose of NIASPAN may be switched directly to a niacin-equivalent dose of ADVICOR.
Table 11: Recommended Dosing
|Week(s)||Daily dose||NIASPAN Dosage|
|INITIAL TITRATION SCHEDULE||1 to 4||500 mg||1 NIASPAN 500 mg tablet at bedtime|
|5 to 8||1000mg||2 NIASPAN 500 mg tablet at bedtime|
|*||1500 mg||2 NIASPAN 750 mg tablet or 3 NIASPAN 500 mg tablet at bedtime|
|*||2000 mg||2 NIASPAN 1000 mg tablet or 4 NIASPAN 500 mg tablet at bedtime|
The daily dosage of NIASPAN should not be increased by more than 500 mg in any 4-week period. The recommended maintenance dose is 1000 mg (two 500 mg tablets) to 2000 mg (two 1000 mg tablets or four 500 mg tablets) once daily at bedtime. Doses greater than 2000 mg daily are not recommended. Women may respond at lower NIASPAN doses than men.
Flushing of the skin (see ADVERSE REACTIONS) may be reduced in frequency or severity by pretreatment with aspirin up to the recommended dose of 325 mg (taken 30 minutes prior to NIASPAN dose). Tolerance to this flushing develops rapidly over the course of several weeks. Flushing, pruritus, and gastrointestinal distress are also greatly reduced by slowly increasing the dose of niacin and avoiding administration on an empty stomach. Concomitant alcoholic, hot drinks or spicy foods may increase the side effects of flushing and pruritus and should be avoided around the time of ADVICOR ingestion.
Equivalent doses of NIASPAN should not be substituted for sustained-release (modified-release, timed-release) niacin preparations or immediate-release (crystalline) niacin (see WARNINGS). Patients previously receiving other niacin products should be started with the recommended NIASPAN titration schedule (see Table 11), and the dose should subsequently be individualized based on patient response. Single-dose bioavailability studies have demonstrated that NIASPAN tablet strengths are not interchangeable.
If NIASPAN therapy is discontinued for an extended period, reinstitution of therapy should include a titration phase (see Table 11).
NIASPAN tablets should be taken whole and should not be broken, crushed or chewed before swallowing.
Concomitant Therapy with Lovastatin
Patients already receiving a stable dose of lovastatin who require further TG-lowering or HDL-raising (e.g., to achieve NCEP non-HDL-C goals), may receive concomitant dosage titration with NIASPAN per NIASPAN recommended initial titration schedule (see Table 10, DOSAGE AND ADMINISTRATION section). For patients already receiving a stable dose of NIASPAN who require further LDL-lowering (e.g., to achieve NCEP LDL-C goals; Table 8), the usual recommended starting dose of lovastatin is 20 mg once a day. Dose adjustments should be made at intervals of 4 weeks or more. Combination therapy with NIASPAN and lovastatin should not exceed doses of 2000 mg and 40 mg daily, respectively.
Dosage in Patients with Renal or Hepatic Insufficiency
Use of NIASPAN in patients with renal or hepatic insufficiency has not been studied. NIASPAN is contraindicated in patients with significant or unexplained hepatic dysfunction (see WARNINGS, PRECAUTIONS). NIASPAN should be used with caution in patients with renal insufficiency (see CLINICAL PHARMACOLOGY).
The usual recommended starting dose is 20 mg once a day given with the evening meal. The recommended dosing range is 10-80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day. Doses should be individualized according to the recommended goal of therapy (see NCEP Guidelines and CLINICAL PHARMACOLOGY). Patients requiring reductions in LDL cholesterol of 20% or more to achieve their goal (see INDICATIONS AND USAGE) should be started on 20 mg/day of lovastatin. A starting dose of 10 mg may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more.
Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of lovastatin if cholesterol levels fall significantly below the targeted range.
Dosage in Patients taking Danazol, Diltiazem or Verapamil
In patients taking danazol, diltiazem, or verapamil concomitantly with lovastatin (see WARNINGS, Myopathy/Rhabdomyolysis), therapy should begin with 10 mg of lovastatin and should not exceed 20 mg/day.
Dosage in Patients taking Amiodarone
Concomitant Lipid-Lowering Therapy
Use of lovastatin with gemfibrozil should be avoided.
Caution should be used when prescribing other fibrates with lovastatin, as fibrates can cause myopathy when given alone.
Dosage in Patients with Renal Insufficiency
In patients with severe renal insufficiency (creatinine clearance <30 mL/min), dosage increases above 20 mg/day should be carefully considered and, if deemed necessary, implemented cautiously (see CLINICAL PHARMACOLOGY and WARNINGS, Myopathy/Rhabdomyolysis).
ADVICOR is an unscored capsule-shaped tablet containing either 500, 750, or 1000 mg of extended-release niacin, and 20 mg of immediate-release lovastatin (ADVICOR 500 mg/20 mg, 750 mg/20 mg, 1000 mg/20 mg), or 1000 mg of extended-release niacin and 40 mg of immediate-release lovastatin (ADVICOR 1000 mg/40 mg). Tablets are color-coated and printed with the Abbott 'A' logo and a code number specific to the tablet strength on the same side. ADVICOR 500 mg/20 mg tablets are light yellow, code “502”. ADVICOR 750 mg/20 mg tablets are light orange, code “752”. ADVICOR 1000 mg/20 mg tablets are dark pink/light purple, code “1002”. ADVICOR 1000 mg/40 mg tablets are reddish brown, code “1004.” Tablets are supplied in bottles of 90 tablets as shown below.
500 mg/20 mg tablets: bottles of 90 - NDC# 0074-3005-90
750 mg/20 mg tablets: bottles of 90 - NDC# 0074-3072-90
1000 mg/20 mg tablets: bottles of 90 - NDC# 0074-3007-90
1000 mg/40 mg tablets: bottles of 90 - NDC# 0074-3010-90
Store at room temperature (20° to 25°C or 68° to 77°F).
1. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285:2486-2497.
Manufactured by Abbott Pharmaceuticals PR Ltd., Barceloneta, PR 00617 for Abbott Laboratories, North Chicago, IL 60064, U.S.A. Revised: 04/2012
Last reviewed on RxList: 4/26/2012
This monograph has been modified to include the generic and brand name in many instances.
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