Advicor Information
Advicor (Niacin) Description
Advicor (Niacin) (niacin extended-release and lovastatin) is intended to facilitate the daily administration of its individual components, Niaspan and lovastatin, when used together for the intended patient population (see and ).
Advicor (Niacin) contains niacin extended-release and lovastatin in combination. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and niacin are both lipid-altering agents.
Niacin is nicotinic acid, or 3-pyridinecarboxylic acid. Niacin is a white, nonhygroscopic crystalline powder that is very soluble in water, boiling ethanol and propylene glycol. It is insoluble in ethyl ether. The empirical formula of niacin is CHNO and its molecular weight is 123.11. Niacin has the following structural formula:
Lovastatin is [1S -[1(alpha)(R *), 3(alpha), 7(beta), 8(beta)(2S *, 4S *), 8a(beta)]]-1,2,3, 7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl) ethyl]-1-naphthalenyl 2-methylbutanoate. Lovastatin is a white, nonhygroscopic crystalline powder that is insoluble in water and sparingly soluble in ethanol, methanol, and acetonitrile. The empirical formula of lovastatin is CHO and its molecular weight is 404.55. Lovastatin has the following structural formula:
Advicor (Niacin) tablets contain the labeled amount of niacin and lovastatin and have the following inactive ingredients: hypromellose, povidone, stearic acid, polyethylene glycol, titanium dioxide, polysorbate 80.
The individual tablet strengths (expressed in terms of mg niacin/mg lovastatin) contain the following coloring agents:
Advicor (Niacin) 500 mg/20 mg - Iron Oxide Yellow, Iron Oxide Red.Advicor (Niacin) 750 mg/20 mg – FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake.Advicor (Niacin) 1000 mg/20 mg - Iron Oxide Red, Iron Oxide Yellow, Iron Oxide Black.Advicor (Niacin) 1000 mg/40 mg – Iron Oxide Red.
Advicor (Niacin) Clinical Pharmacology
A variety of clinical studies have demonstrated that elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B-100 (Apo B) promote human atherosclerosis. Similarly, decreased levels of high-density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis. Epidemiological investigations have established that cardiovascular morbidity and mortality vary directly with the level of TC and LDL-C, and inversely with the level of HDL-C.
Cholesterol-enriched triglyceride-rich lipoproteins, including very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and their remnants, can also promote atherosclerosis. Elevated plasma triglycerides (TG) are frequently found in a triad with low HDL-C levels and small LDL particles, as well as in association with non-lipid metabolic risk factors for coronary heart disease (CHD). As such, total plasma TG have not consistently been shown to be an independent risk factor for CHD.
As an adjunct to diet, the efficacy of niacin and lovastatin in improving lipid profiles (either individually, or in combination with each other, or niacin in combination with other statins) for the treatment of dyslipidemia has been well documented. The effect of combined therapy with niacin and lovastatin on cardiovascular morbidity and mortality has not been determined.
Advicor (Niacin) Indications And Usage
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 and the NCEP treatment guidelines).
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
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 .
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.
Advicor (Niacin) Contraindications
Advicor (Niacin) is contraindicated in patients with a known hypersensitivity to niacin, lovastatin or any component of this medication, active liver disease or unexplained persistent elevations in serum transaminases (see ), active peptic ulcer disease, or arterial bleeding.
Advicor (Niacin) Warnings
Advicor (Niacin) should not be substituted for equivalent doses of immediate-release (crystalline) niacin. For patients switching from immediate-release niacin to NIASPAN, therapy with NIASPAN should be initiated with low doses (i.e., 500 mg once daily at bedtime) and the NIASPAN dose should then be titrated to the desired therapeutic response (see ).
Advicor (Niacin) Precautions
Before instituting therapy with a lipid-altering medication, an attempt should be made to control dyslipidemia with appropriate diet, exercise, and weight reduction in obese patients, and to treat other underlying medical problems (see ).
Patients with a past history of jaundice, hepatobiliary disease, or peptic ulcer should be observed closely during Advicor (Niacin) therapy. Frequent monitoring of liver function tests and blood glucose should be performed to ascertain that the drug is producing no adverse effects on these organ systems.
Diabetic patients may experience a dose-related rise in fasting blood sugar (FBS). In three clinical studies, which included 1028 patients exposed to Advicor (Niacin) (6 to 22% of whom had diabetes type II at baseline), increases in FBS above normal occurred in 46 to 65% of patients at any time during study treatment with Advicor (Niacin) . Fourteen patients (1.4%) were discontinued from study treatment: 3 patients for worsening diabetes, 10 patients for hyperglycemia and 1 patient for a new diagnosis of diabetes. In the studies in which lovastatin and NIASPAN were used as active controls, 24 to 41% of patients receiving lovastatin and 43 to 58% of patients receiving NIASPAN also had increases in FBS above normal. One patient (1.1%) receiving lovastatin was discontinued for hyperglycemia. Diabetic or potentially diabetic patients should be observed closely during treatment with Advicor (Niacin) , and adjustment of diet and/or hypoglycemic therapy may be necessary.
In one long-term study of 106 patients treated with Advicor (Niacin) , elevations in prothrombin time (PT) >3 times ULN occurred in 2 patients (2%) during study drug treatment. In a long-term study of 814 patients treated with Advicor (Niacin) , 7 patients were noted to have platelet counts
Caution should also be used when Advicor (Niacin) is used in patients with unstable angina or in the acute phase of MI, particularly when such patients are also receiving vasoactive drugs such as nitrates, calcium channel blockers, or adrenergic blocking agents.
Elevated uric acid levels have occurred with niacin therapy; therefore, in patients predisposed to gout, niacin therapy should be used with caution. Niacin is rapidly metabolized by the liver, and excreted through the kidneys. Advicor (Niacin) is contraindicated in patients with significant or unexplained hepatic dysfunction (see and ) and should be used with caution in patients with renal dysfunction.
No studies have been conducted with Advicor (Niacin) in nursing mothers.
Because of the potential for serious adverse reactions in nursing infants from lipid-altering doses of niacin and lovastatin (see ), Advicor (Niacin) should not be taken while a woman is breastfeeding.
Niacin has been reported to be excreted in human milk. It is not known whether lovastatin is excreted in human milk. A small amount of another drug in this class is excreted in human breast milk.
Advicor (Niacin) Adverse Reactions
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. The adverse reaction information from clinical studies does, however provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
The data described in this section reflect the exposure to Advicor (Niacin) in two double-blind, controlled clinical studies of 400 patients. The population was 28 to 86 years-of-age, 54% male, 85% Caucasian, 9% Black, and 7% Other, and had mixed dyslipidemia.
In addition to flushing, other adverse events occurring in 5% or greater of patients treated with Advicor (Niacin) are shown in below.
See also the full prescribing information for niacin extended release (Niaspan) and lovastatin products.
The following adverse events have also been reported with niacin, lovastatin, and/or other HMG-CoA reductase inhibitors, but not necessarily with Advicor (Niacin) , either during clinical studies or in routine patient management.
Advicor (Niacin) Drug Abuse And Dependence
Neither niacin nor lovastatin is a narcotic drug. Advicor (Niacin) has no known addiction potential in humans.
Advicor (Niacin) Overdosage
Information on acute overdose with Advicor (Niacin) in humans is limited. Until further experience is obtained, no specific treatment of overdose with Advicor (Niacin) can be recommended. The patient should be carefully observed and given supportive treatment.
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.
After oral administration of lovastatin to mice the median lethal dose observed was >15 g/m.
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.
Advicor (Niacin) Dosage And Administration
The patient should be placed on a standard cholesterol-lowering diet before receiving Advicor (Niacin) or its individual active components and should continue on this diet during treatment with lipid-altering therapy (see ).
Advicor (Niacin) should be taken at bedtime, with a low-fat snack. Advicor (Niacin) tablets should be taken whole and should not be broken, crushed, or chewed before swallowing. Patients not currently on NIASPAN must start Advicor (Niacin) at the lowest initial Advicor (Niacin) dose, a single 500 mg/20 mg tablet once daily at bedtime. The dose of Advicor (Niacin) should not be increased by more than 500 mg daily (based on the NIASPAN component) every 4 weeks. The dose of Advicor (Niacin) should be individualized based on targeted goals for cholesterol and triglycerides, and on patient response. Doses of Advicor (Niacin) greater than 2000 mg/40 mg daily are not recommended.
Flushing of the skin (see ) 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 (Niacin) 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 (Niacin) 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 ). 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 (Niacin) 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 below. Patients already receiving a stable dose of NIASPAN may be switched directly to a niacin-equivalent dose of Advicor (Niacin) .
Table 9. Recommended Dosing
Advicor (Niacin) How Supplied
Advicor (Niacin) 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 (Niacin) 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 (Niacin) 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 (Niacin) 500 mg/20 mg tablets are light yellow, code “502”. Advicor (Niacin) 750 mg/20 mg tablets are light orange, code “752”. Advicor (Niacin) 1000 mg/20 mg tablets are dark pink/light purple, code “1002”. Advicor (Niacin) 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).
NIASPAN is a registered trademark of Abbott Laboratories, and Mevacor is a registered trademark of Merck & Co., Inc.
Advicor (Niacin) References
Manufactured by Abbott Pharmaceuticals PR Ltd., Barceloneta, PR 00617for Abbott Laboratories, North Chicago, IL 60064, U.S.A.
© 2010 Abbott Laboratories
Advicor (Niacin)
