Advicor

Name: Advicor

Advicor Precautions

Serious side effects have been reported with Advicor including the following:

  • Liver Dysfunction. Cases of severe hepatic toxicity, including fulminant hepatic necrosis, have occurred in patients who have substituted sustained-release niacin products for immediate-release niacin at equivalent doses. Advicor should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.  Active liver disease or unexplained transaminase elevations are contraindications to the use of Advicor. Niacin preparations and lovastatin have been associated with abnormal liver tests. It is recommended that liver enzyme tests be obtained prior to initiating therapy with Advicor and repeated as clinically indicated.
  • Myopathy/Rhabdomyolysis. Lovastatin occasionally cause myopathy, which is manifested as muscle pain or weakness associated with grossly elevated creatine kinase. Rhabdomyolysis, with or without acute renal failure secondary to myogobinuria, has been reported rarely and can occur at any time. The risk of rhabdomyolysis is increased by concomitant use of lovastatin with the following:
    • strong inhibitors of CYP3A4: itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, boceprevir, telaprevir, nefazodone, large quantities of grapefruit juice (>1 quart daily).  
    • gemfibrozil: The combined use of lovastatin with gemfibrozil should be avoided.
    • other fibrates: The benefit of further alterations in lipid levels by the combined use of lovastatin with other fibrates should be carefully weighed against the potential risks of this combination.
    • cyclosporine: The combined use of lovastatin and cyclosporine should be avoided
    • danazol, diltiazem, or verapamil with higher doses of lovastatin:  The dose of lovastatin should not exceed 20mg as the risk of myopathy increases at higher doses
    • amiodarone: The dose of lovastatin should not exceed 40mg.
    • colchicine: Use caution
    • Ranolazine: Dose adjustment of lovastatin may be considered.

Do not take Advicor if you:

  • are allergic to niacin, lovastatin, or any component of this medication
  • have active liver disease or unexplained elevations in serum transaminases
  • have active peptic ulcer disease
  • have arterial bleeding
  • are pregnant or breastfeeding

Advicor Dosage

Take this medication exactly as prescribed by your doctor.  Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your height
  • your weight
  • your age
  • your gender

Patients not currently on Niaspan must start Advicor at the lowest initial dose, a single 500mg/20mg tablet once daily at bedtime. The dose of Advicor should not be increased by more than 500mg 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 greater than 2000mg/40mg daily are not recommended. If Advicor therapy is discontinued for an extended period greater than 7 days, reinitiation of therapy should begin with the lowest dose.

Uses For Advicor

Niacin and lovastatin combination is used together with a proper diet to help lower cholesterol and triglyceride (fat) levels in the blood. This medicine may help prevent medical problems (eg, heart attacks, stroke) that are caused by fat clogging the blood vessels.

Niacin and lovastatin combination medicine is a combination of two drugs that work together to lower cholesterol and lipid (fat) disorders. Niacin is vitamin B3, which reduces the amount of cholesterol in the blood. Lovastatin belongs to the group of medicines called HMG-CoA reductase inhibitors, or statins. It works to reduce the amount of cholesterol in the blood by blocking an enzyme that is needed to make cholesterol.

This medicine was available only with your doctor's prescription. The Advicor(R) product will no longer be marketed in the United States as of April 18, 2016.

What are some things I need to know or do while I take Advicor?

  • Tell all of your health care providers that you take Advicor. This includes your doctors, nurses, pharmacists, and dentists.
  • If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
  • Have your blood work checked. Talk with your doctor.
  • This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
  • Follow the diet and workout plan that your doctor told you about.
  • Do not take colesevelam, colestipol, or cholestyramine within 4 hours of Advicor.
  • Avoid grapefruit and grapefruit juice.
  • Avoid or limit drinking alcohol to less than 3 drinks a day. Drinking too much alcohol may raise your chance of liver disease. Alcohol may cause more flushing.
  • If you are 65 or older, use this medicine with care. You could have more side effects.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking Advicor, call your doctor right away.
  • Use birth control that you can trust to prevent pregnancy while taking this medicine.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Advicor?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Indications and Usage for Advicor

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 Table 8 and the NCEP treatment guidelines1).

Advicor

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)

Hypercholesterolemia

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

In patients with a history of myocardial infarction and hypercholesterolemia, niacin is indicated to reduce the risk of recurrent nonfatal myocardial infarction.

Hypertriglyceridemia

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

Hypercholesterolemia

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

Lovastatin is also indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower TC and LDL-C to target levels.

The National Cholesterol Education Program (NCEP) Treatment Guidelines are summarized below:

TC = total cholesterol; TG = triglycerides; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein; IDL = intermediate-density lipoprotein ↑→ = increased or no change
Table 7. Classification of Hyperlipoproteinemias
Type Lipoproteins Elevated Lipid Elevations
I (rare) Chylomicrons Major Minor
IIa LDL TG ↑→TC
IIb LDL,VLDL TC     -
III (rare) IDL TC      TG
IV VLDL TC/TG   -
V (rare) Chylomicrons, VLDL TG ↑→TC

General Recommendations

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.

Overdosage

Information on acute overdose with Advicor in humans is limited. Until further experience is obtained, no specific treatment of overdose with Advicor can be recommended. The patient should be carefully observed and given supportive treatment.

Niacin

The s.c. LD50 of niacin is 5 g/kg in rats.

The signs and symptoms of an acute overdose of niacin can be anticipated to be those of excessive pharmacologic effect: severe flushing, nausea/vomiting, diarrhea, dyspepsia, dizziness, syncope, hypotension, possibly cardiac arrhythmias and clinical laboratory abnormalities. Insufficient information is available on the potential for the dialyzability of niacin.

Lovastatin

After oral administration of lovastatin to mice the median lethal dose observed was >15 g/m2.

Five healthy human volunteers have received up to 200 mg of lovastatin as a single dose without clinically significant adverse experiences. A few cases of accidental overdose have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 5 to 6 g. The dialyzability of lovastatin and its metabolites in man is not known at present.

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