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{{DrugProjectFormSinglePage
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|authorTag={{KS}}
|authorTag={{KS}}
|aOrAn=a
|genericName=niacin
|aOrAn=an
|drugClass=antihyperlipedemic agent
|indicationType=treatment
|indicationType=treatment
|adverseReactions=<!--Black Box Warning-->
|indication=[[hypertriglyceredemia]], [[hypercholesterolemia|primary hypercholesterolemia]], [[hyperlipidemia]]
|adverseReactions=[[dyspepsia]], [[vomiting]], [[diarrhea]], [[jaundice]], [[pruritus]], [[hyperpigmentation]], [[acanthosis nigricans]], [[dry skin]] and [[headache]]
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
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|fdaLIADAdult===Indications==
|fdaLIADAdult===Indications==


* 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 hyperlipidemia. Niacin 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.
* Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to [[hypercholesterolemia]]. Nicotinic acid, alone or in combination with a bile-acid binding resin, is indicated as an adjunct to diet for the reduction of elevated total and LDL cholesterol levels in patients with [[hypercholesterolemia|primary hypercholesterolemia]] (Types IIa and IIb)†, when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate (see also the NCEP treatment guidelines6). Prior to initiating therapy with nicotinic acid, 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 total [[cholesterol]], [[HDL]] [[cholesterol]], and [[triglycerides]].


* NIASPAN is indicated to reduce elevated [[TC]], [[LDL-C]], [[Apo B]] and [[TG]] levels, and to increase HDL-C in patients with primary [[hyperlipidemia]] and mixed [[dyslipidemia]].
* Nicotinic acid is also indicated as adjunctive therapy for the treatment of adult patients with very high serum [[triglyceride]] levels (Types IV and V [[hyperlipidemia]])† 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 triglyceride levels over 2000 mg/dL and have elevations of VLDL cholesterol as well as fasting chylomicrons (Type V hyperlipidemia)†. Subjects who consistently have total serum or plasma [[triglycerides]] below 1000 mg/dL are unlikely to develop [[pancreatitis]]. Therapy with nicotinic acid may be considered for those subjects with triglyceride elevations between 1000 and 2000 mg/dL who have a history of [[pancreatitis]] or of recurrent [[abdominal pain]] typical of [[pancreatitis]]. Some Type IV patients with triglycerides under 1000 mg/dL may, through dietary or alcoholic indiscretion, convert to a Type V pattern with massive [[triglyceride]] elevations accompanying fasting chylomicronemia, but the influence of nicotinic acid therapy on the risk of [[pancreatitis]] in such situations has not been adequately studied. Drug therapy is not indicated for patients with Type I [[hyperlipoproteinemia]], who have elevations of chylomicrons and plasma [[triglycerides]], but who have normal levels of VLDL. Inspection of plasma refrigerated for 14 hours is helpful in distinguishing Types I, IV, and V hyperlipoproteinemia7.


* NIASPAN in combination with simvastatin or lovastatin is indicated for the treatment of primary [[hyperlipidemia]] and mixed [[dyslipidemia]] when treatment with NIASPAN, simvastatin, or lovastatin monotherapy is considered inadequate.
[[File:Niacor classification.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
* In patients with a history of [[myocardial infarction]] and [[hyperlipidemia]], niacin is indicated to reduce the risk of recurrent nonfatal [[myocardial infarction]].
 
* In patients with a history of [[coronary artery disease]] ([[CAD]]) and [[hyperlipidemia]], niacin, in combination with a bile acid binding resin, is indicated to slow progression or promote regression of [[atherosclerotic disease]].
 
* NIASPAN in combination with a bile acid binding resin is indicated to reduce elevated [[TC]] and LDL-C levels in adult patients with primary [[hyperlipidemia]].
 
* Niacin is also indicated as adjunctive therapy for treatment of adult patients with severe [[hypertriglyceridemia]] who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them.
 
==Limitations of Use==
 
* No incremental benefit of NIASPAN coadministered with simvastatin or lovastatin on cardiovascular morbidity and mortality over and above that demonstrated for niacin, simvastatin, or lovastatin monotherapy has been established.
 
* NIASPAN, at doses of 1,500-2,000 mg/day, in combination with simvastatin, did not reduce the incidence of cardiovascular events more than simvastatin in a randomized controlled trial of patients with cardiovascular disease and mean baseline LDL-C levels of 74 mg per deciliter


==Dosage==
==Dosage==


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 500 mg at bedtime in order to reduce the incidence and severity of side effects which may occur during early therapy. The recommended dose escalation is shown in table 1 below.
* The usual adult dosage of nicotinic acid is 1 to 2 grams two or three times a day. Doses should be individualized according to the patient's response. Start with one-half tablet (250 mg) as a single daily dose following the evening meal. The frequency of dosing and total daily dose can be increased every four to seven days until the desired LDL cholesterol and/or triglyceride level is achieved or the first-level therapeutic dose of 1.5 to 2 grams/day is reached. If the patient's hyperlipidemia is not adequately controlled after 2 months at this level, the dosage can then be increased at two to four week intervals to 3 grams/day (1 gram three times per day). In patients with marked lipid abnormalities, a higher dose is occasionally required, but generally should not exceed 6 grams/day.


[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
* [[Flushing]] of the skin appears frequently and can be minimized by pretreatment with aspirin or non-steroidal anti-inflammatory drugs. 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 nicotinic acid and avoiding administration on an empty stomach.


'''Maintenance Dose'''
* Sustained-release (modified-release, timed-release) nicotinic acid preparations should not be substituted for equivalent doses of immediate-release (crystalline) nicotinic acid.
 
* 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 or one 1000 mg tablet) 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.
 
* Single-dose bioavailability studies have demonstrated that two of the 500 mg and one of the 1000 mg tablet strengths are interchangeable but three of the 500 mg and two of the 750 mg tablet strengths are not interchangeable.
 
* If lipid response to NIASPAN alone is insufficient or if higher doses of NIASPAN are not well tolerated, some patients may benefit from combination therapy with a bile acid binding resin or statin, Concomitant Therapy below and Clinical Studies.
 
* [[Flushing]] of the skin 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 NIASPAN ingestion.
 
* Equivalent doses of NIASPAN should not be substituted for sustained-release (modified-release, timed-release) niacin preparations or immediate-release (crystalline) niacin. Patients previously receiving other niacin products should be started with the recommended NIASPAN titration schedule (see table 1), and the dose should subsequently be individualized based on patient response.
 
* If NIASPAN therapy is discontinued for an extended period, reinstitution of therapy should include a titration phase (see table 1).
 
* NIASPAN tablets should be taken whole and should not be broken, crushed or chewed before swallowing.
 
'''Concomitant Therapy'''
 
''Concomitant Therapy with Lovastatin or Simvastatin''
 
* Patients already receiving a stable dose of lovastatin or simvastatin 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. For patients already receiving a stable dose of NIASPAN who require further LDL-lowering (e.g., to achieve NCEP LDL-C goals), the usual recommended starting dose of lovastatin and simvastatin is 20 mg once a day. Dose adjustments should be made at intervals of 4 weeks or more. Combination therapy with NIASPAN and lovastatin or NIASPAN and simvastatin should not exceed doses of 2000 mg NIASPAN and 40 mg lovastatin or simvastatin daily.
 
''Dosage in Patients with Renal or Hepatic Impairment''
 
* Use of NIASPAN in patients with renal or hepatic impairment has not been studied. NIASPAN is contraindicated in patients with significant or unexplained [[hepatic dysfunction]]. NIASPAN should be used with caution in patients with [[renal impairment]].
 
==DOSAGE FORMS AND STRENGTHS==
 
* 500 mg unscored, medium-orange, film-coated, capsule-shaped tablets
* 750 mg unscored, medium-orange, film-coated, capsule-shaped tablets
* 1000 mg unscored, medium-orange, film-coated, capsule-shaped tablets
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|fdaLIADPed=There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.






<!--Guideline-Supported Use (Pediatric)-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|contraindications=* NIASPAN is contraindicated in the following conditions:
|contraindications=* Nicotinic acid is contraindicated in patients with a known [[hypersensitivity]] to any component of this medication; significant or unexplained [[hepatic dysfunction]]; active [[peptic ulcer]] disease; or arterial bleeding.
 
|warnings='''Liver Dysfunction'''
:*Active liver disease or unexplained persistent elevations in hepatic transaminases
 
:*Patients with active [[peptic ulcer]] disease


:*Patients with arterial bleeding
* Cases of severe hepatic toxicity, including [[fulminant hepatic necrosis]] have occurred in patients who have substituted sustained-release (modified-release, timed-release) nicotinic acid products for immediate-release (crystalline) nicotinic acid at equivalent doses.


:*[[Hypersensitivity]] to niacin or any component of this medication
* Liver function tests should be performed on all patients during therapy with nicotinic acid. Serum transaminase levels, including ALT (SGPT), should be monitored before treatment begins, every six weeks to twelve weeks for the first year, and periodically thereafter (e.g., at approximately 6 month intervals). Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently. If the transaminase levels show evidence of progression, particularly if they rise to three times the upper limit of normal and are persistent, the drug should be discontinued. Liver biopsy should be considered if elevations persist beyond discontinuation of the drug.
|warnings=* NIASPAN preparations 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 at bedtime) and the NIASPAN dose should then be titrated to the desired therapeutic response .


* Caution should also be used when NIASPAN is used in patients with [[unstable angina]] or in the acute phase of an [[MI]], particularly when such patients are also receiving vasoactive drugs such as [[nitrates]], [[calcium channel blockers]], or [[adrenergic blocking agents]].
* Nicotinic acid should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of nicotinic acid.
 
* Niacin is rapidly metabolized by the liver, and excreted through the kidneys. NIASPAN is contraindicated in patients with significant or unexplained [[hepatic impairment]] and should be used with caution in patients with [[renal impairment]]. Patients with a past history of [[jaundice]], [[hepatobiliary disease]], or [[peptic ulcer]] should be observed closely during NIASPAN therapy.
 
'''Mortality and Coronary Heart Disease Morbidity'''
 
* The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial was a randomized placebo-controlled trial of 3414 patients with stable, previously diagnosed cardiovascular disease. Mean baseline lipid levels were LDL-C 74 mg/dL, HDL-C 35 mg/dL, non-HDL-C 111 mg/dL and median triglyceride level of 163-177 mg/dL. Ninety-four percent of patients were on background statin therapy prior to entering the trial. All participants received simvastatin, 40 to 80 mg per day, plus ezetimibe 10 mg per day if needed, to maintain an LDL-C level of 40-80 mg/dL, and were randomized to receive NIASPAN 1500-2000 mg/day (n=1718) or matching placebo (IR Niacin, 100-150 mg, n=1696). On-treatment lipid changes at two years for LDL-C were -12.0% for the simvastatin plus NIASPAN group and -5.5% for the simvastatin plus placebo group. HDL-C increased by 25.0% to 42 mg/dL in the simvastatin plus NIASPAN group and by 9.8% to 38 mg/dL in the simvastatin plus placebo group (P<0.001). Triglyceride levels decreased by 28.6% in the simvastatin plus NIASPAN group and by 8.1% in the simvastatin plus placebo group. The primary outcome was an ITT composite of the first study occurrence of [[coronary heart disease]] death, nonfatal [[myocardial infarction]], [[ischemic stroke]], hospitalization for [[acute coronary syndrome]] or symptom-driven coronary or cerebral revascularization procedures. The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. The primary outcome occurred in 282 patients in the simvastatin plus NIASPAN group (16.4%) and in 274 patients in the simvastatin plus placebo group (16.2%) (HR 1.02 [95% CI, 0.87-1.21], P=0.79. In an ITT analysis, there were 42 cases of first occurrence of [[ischemic stroke]] reported, 27 (1.6%) in the simvastatin plus NIASPAN group and 15 (0.9%) in the simvastatin plus placebo group, a non-statistically significant result (HR 1.79, [95%CI = 0.95-3.36], p=0.071).  The on-treatment [[ischemic stroke]] events were 19 for the simvastatin plus NIASPAN group and 15 for the simvastatin plus placebo group.


'''Skeletal Muscle'''
'''Skeletal Muscle'''


* Cases of [[rhabdomyolysis]] have been associated with concomitant administration of lipid-altering doses (≥1 g/day) of niacin and statins. Physicians contemplating combined therapy with statins and NIASPAN should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of [[muscle pain]], [[tenderness]], or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Periodic serum creatine phosphokinase (CPK) and potassium determinations should be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy.
* Rare cases of [[rhabdomyolysis]] have been associated with concomitant administration of lipid-altering doses (≥1 g/day) of nicotinic acid and [[HMG-CoA reductase inhibitors]]. Physicians contemplating combined therapy with [[HMG-CoA reductase inhibitors]] and nicotinic acid should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Periodic serum creatine phosphokinase (CPK) and potassium determinations should be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe [[myopathy]].
 
|clinicalTrials=* '''Cardiovascular''' : [[Atrial fibrillation]] and other [[cardiac arrhythmias]], [[orthostasis]], [[hypotension]].
* The risk for [[myopathy]] and [[rhabdomyolysis]] are increased when lovastatin or simvastatin are coadministered with NIASPAN, particularly in elderly patients and patients with [[diabetes]], [[renal failure]], or uncontrolled [[hypothyroidism]].
 
'''Liver Dysfunction'''
 
* Cases of severe [[hepatic toxicity]], including [[fulminant hepatic necrosis]], have occurred in patients who have substituted sustained-release (modified-release, timed-release) niacin products for immediate-release (crystalline) niacin at equivalent doses.
 
* NIASPAN should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of NIASPAN.
 
* Niacin preparations have been associated with abnormal liver tests. In three placebo-controlled clinical trials involving titration to final daily NIASPAN doses ranging from 500 to 3000 mg, 245 patients received NIASPAN for a mean duration of 17 weeks. No patient with normal serum transaminase levels (AST, ALT) at baseline experienced elevations to more than 3 times the upper limit of normal (ULN) during treatment with NIASPAN. In these studies, fewer than 1% (2/245) of NIASPAN patients discontinued due to transaminase elevations greater than 2 times the ULN.
 
* In three safety and efficacy studies with a combination tablet of NIASPAN and lovastatin involving titration to final daily doses (expressed as mg of niacin/ mg of lovastatin) 500 mg/10 mg to 2500 mg/40 mg, ten of 1028 patients (1.0%) experienced reversible elevations in AST/ALT to more than 3 times the ULN. Three of ten elevations occurred at doses outside the recommended dosing limit of 2000 mg/40 mg; no patient receiving 1000 mg/20 mg had 3-fold elevations in AST/ALT.
 
* Niacin extended-release and simvastatin can cause abnormal liver tests. In a simvastatin-controlled, 24 week study with a fixed dose combination of NIASPAN and simvastatin in 641 patients, there were no persistent increases (more than 3x the ULN) in serum transaminases. In three placebo-controlled clinical studies of extended-release niacin there were no patients with normal serum transaminase levels at baseline who experienced elevations to more than 3x the ULN. Persistent increases (more than 3x the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminases levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. There was no evidence of [[hypersensitivity]].
 
* In the placebo-controlled clinical trials and the long-term extension study, elevations in transaminases did not appear to be related to treatment duration; elevations in [[AST]] levels did appear to be dose related. Transaminase elevations were reversible upon discontinuation of NIASPAN.
 
* [[Liver function tests]] should be performed on all patients during therapy with NIASPAN. Serum transaminase levels, including AST and ALT (SGOT and SGPT), should be monitored before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (e.g., at approximately 6-month intervals). Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently. If the transaminase levels show evidence of progression, particularly if they rise to 3 times ULN and are persistent, or if they are associated with symptoms of [[nausea]], [[fever]], and/or [[malaise]], the drug should be discontinued.
 
'''Laboratory Abnormalities'''
 
* Increase in Blood Glucose: Niacin treatment can increase fasting blood glucose. Frequent monitoring of blood glucose should be performed to ascertain that the drug is producing no adverse effects. Diabetic patients may experience a dose-related increase in glucose intolerance. Diabetic or potentially diabetic patients should be observed closely during treatment with NIASPAN, particularly during the first few months of use or dose adjustment; adjustment of diet and/or [[hypoglycemic]] therapy may be necessary.
 
* Reduction in platelet count: NIASPAN has been associated with small but statistically significant dose-related reductions in platelet count (mean of -11% with 2000 mg). Caution should be observed when NIASPAN is administered concomitantly with anticoagulants; platelet counts should be monitored closely in such patients.
 
* Increase in Prothrombin Time (PT): NIASPAN has been associated with small but statistically significant increases in prothrombin time (mean of approximately +4%); accordingly, patients undergoing surgery should be carefully evaluated. Caution should be observed when NIASPAN is administered concomitantly with anticoagulants; prothrombin time should be monitored closely in such patients.
 
* Increase in Uric Acid: Elevated uric acid levels have occurred with niacin therapy, therefore use with caution in patients predisposed to [[gout]].
 
* Decrease in Phosphorus: In placebo-controlled trials, NIASPAN has been associated with small but statistically significant, dose-related reductions in phosphorus levels (mean of -13% with 2000 mg). Although these reductions were transient, phosphorus levels should be monitored periodically in patients at risk for hypophosphatemia.
|clinicalTrials=* Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the 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 practice.
 
'''Clinical Studies Experience'''
 
* In the placebo-controlled clinical trials database of 402 patients (age range 21-75 years, 33% women, 89% Caucasians, 7% Blacks, 3% Hispanics, 1% Asians) with a median treatment duration of 16 weeks, 16% of patients on NIASPAN and 4% of patients on placebo discontinued due to adverse reactions. The most common adverse reactions in the group of patients treated with NIASPAN that led to treatment discontinuation and occurred at a rate greater than placebo were flushing (6% vs. 0%), rash (2% vs. 0%), diarrhea (2% vs. 0%), nausea (1% vs. 0%), and vomiting (1% vs. 0%). The most commonly reported adverse reactions (incidence >5% and greater than placebo) in the NIASPAN controlled clinical trial database of 402 patients were [[flushing]], [[diarrhea]], [[nausea]], [[vomiting]], increased [[cough]] and [[pruritus]].
 
* In the placebo-controlled clinical trials, [[flushing]] episodes (i.e., warmth, [[redness]], [[itching]] and/or [[tingling]]) were the most common treatment-emergent adverse reactions (reported by as many as 88% of patients) for NIASPAN. Spontaneous reports suggest that flushing may also be accompanied by symptoms of [[dizziness]], [[tachycardia]], [[palpitations]], [[shortness of breath]], [[sweating]], [[burning]] sensation/skin burning sensation, [[chills]], and/or [[edema]], which in rare cases may lead to [[syncope]]. In pivotal studies, 6% (14/245) of NIASPAN patients discontinued due to flushing. In comparisons of immediate-release (IR) niacin and NIASPAN, although the proportion of patients who [[flushed]] was similar, fewer flushing episodes were reported by patients who received NIASPAN. Following 4 weeks of maintenance therapy at daily doses of 1500 mg, the incidence of flushing over the 4-week period averaged 8.6 events per patient for IR niacin versus 1.9 following NIASPAN.
 
* Other adverse reactions occurring in ≥5% of patients treated with NIASPAN and at an incidence greater than placebo are shown in TABLE 2 below.
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
* In general, the incidence of adverse events was higher in women compared to men.
 
'''Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH)'''
 
* In AIM-HIGH involving 3414 patients (mean age of 64 years, 15% women, 92% Caucasians, 34% with [[diabetes mellitus]]) with stable, previously diagnosed cardiovascular disease, all patients received simvastatin, 40 to 80 mg per day, plus ezetimibe 10 mg per day if needed, to maintain an LDL-C level of 40-80 mg/dL, and were randomized to receive NIASPAN 1500-2000 mg/day (n=1718) or matching placebo (IR Niacin, 100-150 mg, n=1696).  The incidence of the adverse reactions of “blood glucose increased” (6.4% vs. 4.5%) and “[[diabetes mellitus]]” (3.6% vs. 2.2%) was significantly higher in the simvastatin plus NIASPAN group as compared to the simvastatin plus placebo group.  There were 5 cases of rhabdomyolysis reported, 4 (0.2%) in the simvastatin plus NIASPAN group and one (<0.1%) in the simvastatin plus placebo group.
|postmarketing=* Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
 
* The following additional adverse reactions have been identified during post-approval use of NIASPAN:
 
:*[[Hypersensitivity reactions]], including [[anaphylaxis]], [[angioedema]], [[urticaria]], [[flushing]], [[dyspnea]], tongue [[edema]], larynx [[edema]], face [[edema]], [[peripheral edema]], laryngismus, and vesiculobullous [[rash]]; maculopapular rash; dry skin; tachycardia; palpitations; atrial fibrillation; other [[cardiac arrhythmias]]; [[syncope]]; [[hypotension]]; postural [[hypotension]]; [[blurred vision]]; [[macular edema]]; [[peptic ulcer]]s; eructation; [[flatulence]]; [[hepatitis]]; [[jaundice]]; decreased glucose tolerance; [[gout]]; [[myalgia]]; myopathy; dizziness; [[insomnia]]; [[asthenia]]; [[nervousness]]; [[paresthesia]]; [[dyspnea]]; [[sweating]]; burning sensation/skin burning sensation; skin discoloration, and [[migraine]].
 
'''Clinical Laboratory Abnormalities'''
 
* ''Chemistry'': Elevations in serum transaminases, LDH, fasting glucose, uric acid, total bilirubin, amylase and creatine kinase, and reduction in phosphorus.
 
* ''Hematology'': Slight reductions in platelet counts and prolongation in prothrombin time
|drugInteractions='''Statins'''
 
* Caution should be used when prescribing niacin (≥1 gm/day) with statins as these drugs can increase risk of myopathy/rhabdomyolysis. Combination therapy with NIASPAN and lovastatin or NIASPAN and simvastatin should not exceed doses of 2000 mg NIASPAN and 40 mg lovastatin or simvastatin daily.
 
'''Bile Acid Sequestrants'''
 
* An in vitro study results suggest that the bile acid-binding resins have high niacin binding capacity. Therefore, 4 to 6 hours, or as great an interval as possible, should elapse between the ingestion of bile acid-binding resins and the administration of NIASPAN.


'''Aspirin'''
* '''Gastrointestinal''' : [[Dyspepsia]], [[vomiting]], [[diarrhea]], [[peptic ulceration]], [[jaundice]], [[abnormal liver function tests]].


* Concomitant aspirin may decrease the metabolic clearance of nicotinic acid. The clinical relevance of this finding is unclear.
* '''Skin''' : Mild to severe cutaneous [[flushing]], [[pruritus]], [[hyperpigmentation]], [[acanthosis nigricans]], [[dry skin]].


'''Antihypertensive Therapy'''
* '''Metabolic''' : Decreased glucose tolerance, [[hyperuricemia]], [[gout]].


* Niacin may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural [[hypotension]].
* '''Eye''' : Toxic [[amblyopia]], cystoid macular [[edema]].


'''Other'''
* '''Nervous System''' / '''Psychiatric''' : [[Headache]].
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
|drugInteractions='''HMG-CoA Reductase Inhibitors''':


* Vitamins or other nutritional supplements containing large doses of niacin or related compounds such as nicotinamide may potentiate the adverse effects of NIASPAN.
'''Antihypertensive Therapy''' : Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural [[hypotension]].


'''Laboratory Test Interactions'''
'''Aspirin''' : Concomitant aspirin may decrease the metabolic clearance of nicotinic acid. The clinical relevance of this finding is unclear.


* Niacin may produce false elevations in some fluorometric determinations of plasma or urinary [[catecholamines]]. Niacin may also give false-positive reactions with cupric sulfate solution (Benedict’s reagent) in urine glucose tests.
'''Other''': Concomitant alcohol or hot drinks may increase the side effects of [[flushing]] and [[pruritus]] and should be avoided at the time of drug ingestion.
|useInPregnancyFDA='''Pregnancy Category C'''.
|useInPregnancyFDA='''Pregnancy Category C'''.


* Animal reproduction studies have not been conducted with niacin or with NIASPAN. It is also not known whether niacin at doses typically used for lipid disorders can cause fetal harm when administered to pregnant women or whether it can affect reproductive capacity. If a woman receiving niacin for primary [[hyperlipidemia]] becomes pregnant, the drug should be discontinued. If a woman being treated with niacin for [[hypertriglyceridemia]] conceives, the benefits and risks of continued therapy should be assessed on an individual basis.
* Animal reproduction studies have not been conducted with nicotinic acid. It is also not known whether nicotinic acid at doses typically used for lipid disorders can cause fetal harm when administered to pregnant women or whether it can affect reproductive capacity. If a woman receiving nicotinic acid for primary hypercholesterolemia (Types IIa or IIb) becomes pregnant, the drug should be discontinued. If a woman being treated with nicotinic acid for [[hypertriglyceridemia]] (Types IV or V) conceives, the benefits and risks of continued drug therapy should be assessed on an individual basis.
 
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
* All statins are contraindicated in pregnant and nursing women. When NIASPAN is administered with a statin in a woman of childbearing potential, refer to the pregnancy category and product labeling for the statin.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=* Niacin is excreted into human milk but the actual infant dose or infant dose as a percent of the maternal dose is not known. Because of the potential for serious adverse reactions in nursing infants from lipid-altering doses of nicotinic acid, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. No studies have been conducted with NIASPAN in nursing mothers.
|useInNursing=* It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from lipid-altering doses of nicotinic acid, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
|useInPed=* Safety and effectiveness of niacin therapy in pediatric patients (≤16 years) have not been established
|useInPed=* Safety and effectiveness in children and adolescents have not been established.
|useInGeri=* Of 979 patients in clinical studies of NIASPAN, 21% of the patients were age 65 and over. No overall differences in safety and effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=* Data from the clinical trials suggest that women have a greater hypolipidemic response than men at equivalent doses of NIASPAN.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=* No studies have been performed in this population. NIASPAN should be used with caution in patients with renal impairment.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=* No studies have been performed in this population. NIASPAN should be used with caution in patients with a past history of liver disease and/or who consume substantial quantities of alcohol. Active liver disease, unexplained transaminase elevations and significant or unexplained [[hepatic dysfunction]] are contraindications to the use of NIASPAN
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=* Oral
|administration=* Oral
* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose=* Supportive measures should be undertaken in the event of an overdose.
|overdose=* Supportive measures should be undertaken in the event of an overdose.
|drugBox=<!--Mechanism of Action-->
|drugBox=[[File:Niacin wikipedia.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|mechAction=*  
|mechAction=There is limited information regarding <i>Mechanism of action</i> of {{PAGENAME}} in the drug label.
|structure=* Niacin or nicotinic acid, a water-soluble B-complex vitamin and antihyperlipidemic agent, is 3-pyridinecarboxylic acid. It is a white, crystalline powder, sparingly soluble in water. It has the following structural formula:


<!--Structure-->
[[File:Niacor structure.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|structure=*


: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
* Each NIACOR® Tablet, for oral administration, contains 500 mg of nicotinic acid. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, hydrogenated vegetable oil, magnesium stearate and microcrystalline cellulose.
 
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
|PK=* Following an oral dose, the pharmacokinetic profile of nicotinic acid is characterized by rapid absorption from the gastrointestinal tract and a short plasma elimination half-life. At a 1 gram dose, peak plasma concentrations of 15 to 30 μg/mL are reached within 30 to 60 minutes. Approximately 88% of an oral pharmacologic dose is eliminated by the kidneys as unchanged drug and nicotinuric acid, its primary metabolite. The plasma elimination half-life of nicotinic acid ranges from 20 to 45 minutes.
|nonClinToxic='''Carcinogenesis, Mutagenesis, Impairment of Fertility'''


<!--Pharmacokinetics-->
* Nicotinic acid administered to mice for a lifetime as a 1% solution in drinking water was not carcinogenic. The mice in this study received approximately 6-8 times a human dose of 3000 milligrams/day as determined on a milligram/square meter basis. Nicotinic acid was negative for mutagenicity in the Ames test. No studies on impairment of fertility have been performed.
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
 
|howSupplied='''NIACOR®(Niacin Tablets, USP) 500 mg'''.
<!--Nonclinical Toxicology-->
|nonClinToxic='''Carcinogenesis and Mutagenesis and Impairment of Fertility'''
 
* Niacin administered to mice for a lifetime as a 1% solution in drinking water was not carcinogenic. The mice in this study received approximately 6 to 8 times a human dose of 3000 mg/day as determined on a mg/m2 basis. Niacin was negative for mutagenicity in the Ames test. No studies on impairment of fertility have been performed. No studies have been conducted with NIASPAN regarding carcinogenesis, mutagenesis, or impairment of fertility.
|clinicalStudies='''Niacin Clinical Studies'''
 
* The role of LDL-C in [[atherogenesis]] is supported by pathological observations, clinical studies, and many animal experiments. Observational epidemiological studies have clearly established that high TC or LDL-C and low HDL-C are risk factors for CHD. Additionally, elevated levels of Lp(a) have been shown to be independently associated with CHD risk.
 
* Niacin’s ability to reduce mortality and the risk of definite, nonfatal [[myocardial infarction]] ([[MI]]) has been assessed in long-term studies. The Coronary Drug Project, completed in 1975, was designed to assess the safety and efficacy of niacin and other lipid-altering drugs in men 30 to 64 years old with a history of MI. Over an observation period of 5 years, niacin treatment was associated with a statistically significant reduction in nonfatal, recurrent MI. The incidence of definite, nonfatal [[MI]] was 8.9% for the 1,119 patients randomized to nicotinic acid versus 12.2% for the 2,789 patients who received placebo (p<0.004). Total mortality was similar in the two groups at 5 years (24.4% with nicotinic acid versus 25.4% with placebo; p=N.S.). At the time of a 15-year follow-up, there were 11% (69) fewer deaths in the niacin group compared to the placebo cohort (52.0% versus 58.2%; p=0.0004). However, mortality at 15 years was not an original endpoint of the Coronary Drug Project. In addition, patients had not received niacin for approximately 9 years, and confounding variables such as concomitant medication use and medical or surgical treatments were not controlled.
 
* The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol and niacin therapy in 162 non-smoking males with previous coronary bypass surgery. The primary, per-subject cardiac endpoint was global coronary artery change score. After 2 years, 61% of patients in the placebo cohort showed disease progression by global change score (n=82), compared with only 38.8% of drug-treated subjects (n=80), when both native arteries and grafts were considered (p<0.005); disease regression also occurred more frequently in the drug-treated group (16.2% versus 2.4%; p=0.002). In a follow-up to this trial in a subgroup of 103 patients treated for 4 years, again, significantly fewer patients in the drug-treated group demonstrated progression than in the placebo cohort (48% versus 85%, respectively; p<0.0001).
 
* The Familial Atherosclerosis Treatment Study (FATS) in 146 men ages 62 and younger with Apo B levels ≥125 mg/dL, established [[coronary artery disease]], and family histories of vascular disease, assessed change in severity of disease in the proximal coronary arteries by quantitative arteriography. Patients were given dietary counseling and randomized to treatment with either conventional therapy with double placebo (or placebo plus colestipol if the LDL-C was elevated); lovastatin plus colestipol; or niacin plus colestipol. In the conventional therapy group, 46% of patients had disease progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11%. In contrast, progression (as the only change) was seen in only 25% in the niacin plus colestipol group, while regression was observed in 39%. Though not an original endpoint of the trial, clinical events (death, MI, or revascularization for worsening angina) occurred in 10 of 52 patients who received conventional therapy, compared with 2 of 48 who received niacin plus colestipol.
 
* The Harvard Atherosclerosis Reversibility Project (HARP) was a randomized placebo-controlled, 2.5-year study of the effect of a stepped-care antihyperlipidemic drug regimen on 91 patients (80 men and 11 women) with CHD and average baseline TC levels less than 250 mg/dL and ratios of TC to HDL-C greater than 4.0. Drug treatment consisted of an HMG-CoA reductase inhibitor administered alone as initial therapy followed by addition of varying dosages of either a slow-release nicotinic acid, cholestyramine, or gemfibrozil. Addition of nicotinic acid to the HMG-CoA reductase inhibitor resulted in further statistically significant mean reductions in TC, LDL-C, and TG, as well as a further increase in HDL-C in a majority of patients (40 of 44 patients). The ratios of TC to HDL-C and LDL-C to HDL-C were also significantly reduced by this combination drug regimen.
 
'''NIASPAN Clinical Studies'''
 
* Placebo-Controlled Clinical Studies in Patients with Primary Hyperlipidemia and Mixed Dyslipidemia: In two randomized, double-blind, parallel, multi-center, placebo-controlled trials, NIASPAN dosed at 1000, 1500 or 2000 mg daily at bedtime with a low-fat snack for 16 weeks (including 4 weeks of dose escalation) favorably altered lipid profiles compared to placebo (table 3). Women appeared to have a greater response than men at each NIASPAN dose level (see Gender Effect, below).
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
In a double-blind, multi-center, forced dose-escalation study, monthly 500 mg increases in NIASPAN dose resulted in incremental reductions of approximately 5% in LDL-C and Apo B levels in the daily dose range of 500 mg through 2000 mg (TABLE 4). Women again tended to have a greater response to NIASPAN than men (see Gender Effect, below).
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
''Gender Effect'': Combined data from the three placebo-controlled NIASPAN studies in patients with primary hyperlipidemia and mixed dyslipidemia suggest that, at each NIASPAN dose level studied, changes in lipid concentrations are greater for women than for men (TABLE 6).
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
''Other Patient Populations'': In a double-blind, multi-center, 19-week study the lipid-altering effects of NIASPAN (forced titration to 2000 mg at bedtime) were compared to baseline in patients whose primary lipid abnormality was a low level of HDL-C (HDL-C ≤40 mg/dL, TG ≤400 mg/dL, and LDL-C ≤160, or <130 mg/dL in the presence of CHD). Results are shown below (TABLE 7).
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
* At NIASPAN 2000 mg/day, median changes from baseline (25th, 75th percentiles) for LDL-C, HDL-C, and TG were -3% (-14, +12%), +27% (+13, +38%), and -33% (-50, -19%), respectively.
 
'''NIASPAN and Lovastatin Clinical Studies'''
 
* Combination NIASPAN and Lovastatin Study: In a multi-center, randomized, double-blind, parallel, 28-week study, a combination tablet of NIASPAN and lovastatin was compared to each individual component in patients with Type IIa and IIb [[hyperlipidemia]]. Using a forced dose-escalation study design, patients received each dose for at least 4 weeks. Patients randomized to treatment with the combination tablet of NIASPAN and lovastatin initially received 500 mg/20 mg (expressed as mg of niacin/mg of lovastatin) once daily before bedtime. The dose was increased by 500 mg at 4-week intervals (based on the NIASPAN component) to a maximum dose of 1000 mg/20 mg in one-half of the patients and 2000 mg/40 mg in the other half. The NIASPAN monotherapy group underwent a similar titration from 500 mg to 2000 mg. The patients randomized to lovastatin monotherapy received 20 mg for 12 weeks titrated to 40 mg for up to 16 weeks. Up to a third of the patients randomized to the combination tablet of NIASPAN and lovastatin or NIASPAN monotherapy discontinued prior to Week 28. Results from this study showed that combination therapy decreased LDL-C, TG and Lp(a), and increased HDL-C in a dose-dependent fashion (Tables 8, 9, 10, and 11). Results from this study for LDL-C mean percent change from baseline (the primary efficacy variable) showed that:
 
:*LDL-lowering with the combination tablet of NIASPAN and lovastatin was significantly greater than that achieved with lovastatin 40 mg only after 28 weeks of titration to a dose of 2000 mg/40 mg (p<0.0001)
 
:*The combination tablet of NIASPAN and lovastatin at doses of 1000 mg/20 mg or higher achieved greater LDL-lowering than NIASPAN (p<0.0001)
 
* The LDL-C results are summarized in TABLE 8.
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
* Combination therapy achieved significantly greater HDL-raising compared to lovastatin and NIASPAN monotherapy at all doses (TABLE 9).
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
In addition, combination therapy achieved significantly greater TG lowering at doses of 1000 mg/20mg or greater compared to lovastatin and NIASPAN monotherapy (TABLE 10).


[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
* Each tablet is a white, capsule-shaped, scored, uncoated tablet, debossed “US” to the left and “67” to the right of the score, with “500” strength on the unscored side.


The Lp(a)-lowering effects of combination therapy and NIASPAN monotherapy were similar, and both were superior to lovastatin (TABLE 11). The independent effect of lowering Lp(a) with NIASPAN or combination therapy on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
* NIACOR® is available in bottles of 100 tablets (NDC 0245-0067-11).


[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
* Dispense in a tight container as defined in the USP, with a child-resistant closure.
|storage=* Store at controlled room temperature, 15-30°C (59-86°F).
|packLabel=[[File:Niacor image.jpg|thumb|none|600px|This image is provided by the National Library of Medicine.]]


'''NIASPAN and Simvastatin Clinical Studies'''
[[File:Niacor ingredients and appearance.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
* In a double-blind, randomized, multicenter, multi-national, active-controlled, 24-week study, the lipid effects of a combination tablet of NIASPAN and simvastatin were compared to simvastatin 20 mg and 80 mg in 641 patients with type II hyperlipidemia or mixed dyslipidemia. Following a lipid qualification phase, patients were eligible to enter one of two treatment groups. In Group A, patients on simvastatin 20 mg monotherapy, with elevated non-HDL levels and LDL-C levels at goal per the NCEP guidelines, were randomized to one of three treatment arms: combination tablet of NIASPAN and simvastatin 1000/20 mg, combination tablet of NIASPAN and simvastatin 2000/20 mg, or simvastatin 20 mg. In Group B, patients on simvastatin 40 mg monotherapy, with elevated non-HDL levels per the NCEP guidelines regardless of attainment of LDL-C goals, were randomized to one of three treatment arms: combination tablet of NIASPAN and simvastatin 1000/40 mg, combination tablet of NIASPAN and simvastatin 2000/40 mg, or simvastatin 80 mg. Therapy was initiated at the 500 mg dose of combination tablet of NIASPAN and simvastatin and increased by 500 mg every four weeks. Thus patients were titrated to the 1000 mg dose of combination tablet of NIASPAN and simvastatin after four weeks and to the 2000 mg dose of combination tablet of NIASPAN and simvastatin after 12 weeks. All patients randomized to simvastatin monotherapy received 50 mg immediate-release niacin daily in an attempt to keep the study from becoming unblinded due to flushing in the combination tablet of NIASPAN and simvastatin groups. Patients were instructed to take one 325 mg aspirin or 200 mg ibuprofen 30 minutes prior to taking the double-blind medication to help minimize flushing effects.
 
* In Group A, the primary efficacy analysis was a comparison of the mean percent change in non-HDL levels between the combination tablet of NIASPAN and simvastatin 2000/20 mg and simvastatin 20 mg groups, and if statistically significant, then a comparison was conducted between the combination tablet of NIASPAN and simvastatin 1000/20 mg and simvastatin 20 mg groups. In Group B, the primary efficacy analysis was a determination of whether the mean percent change in non-HDL in the combination tablet of NIASPAN and simvastatin 2000/40 mg group was non-inferior to the mean percent change in the simvastatin 80 mg group, and if so, whether the mean percent change in non-HDL in the combination tablet of NIASPAN and simvastatin 1000/40 mg group was non-inferior to the mean percent change in the simvastatin 80 mg group.
 
* In Group A, the non-HDL-C lowering with combination tablet of NIASPAN and simvastatin 2000/20 and combination tablet of NIASPAN and simvastatin 1000/20 was statistically significantly greater than that achieved with simvastatin 20 mg after 24 weeks (p<0.05; TABLE 12). The completion rate after 24 weeks was 72% for the combination tablet of NIASPAN and simvastatin arms and 88% for the simvastatin 20 mg arm. In Group B, the non-HDL-C lowering with combination tablet of NIASPAN and simvastatin 2000/40 and combination tablet of NIASPAN and simvastatin 1000/40 was non-inferior to that achieved with simvastatin 80 mg after 24 weeks (TABLE 13). The completion rate after 24 weeks was 78% for the combination tablet of NIASPAN and simvastatin arms and 80% for the simvastatin 80 mg arm.
 
* The combination tablet of NIASPAN and simvastatin was not superior to simvastatin in lowering LDL-C in either Group A or Group B. However, the combination tablet of NIASPAN and simvastatin was superior to simvastatin in both groups in lowering TG and raising HDL (Tables 14 and 15).
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
 
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
 
|howSupplied=* NIASPAN tablets are supplied as unscored, medium-orange, film-coated, capsule-shaped (containing 500 or 750 mg of niacin) or oval shaped (containing 1000 mg of niacin) tablets, in an extended-release formulation. Tablets are printed with the “a” logo and the tablet strength (500, 750 or 1000). Tablets are supplied in bottles of 30 and 90 as shown below.
 
:*500 mg tablets: bottles of 30 - NDC# 0074–3074–30
 
:*500 mg tablets: bottles of 90 - NDC# 0074–3074–90
 
:*750 mg tablets: bottles of 30 - NDC# 0074–3079–30
 
:*750 mg tablets: bottles of 90 - NDC# 0074–3079–90
 
:*1000 mg tablets: bottles of 30 - NDC# 0074–3080–30
 
1000 mg tablets: bottles of 90 - NDC# 0074–3080–90
|storage=* Storage: Store at room temperature 20° to 25°C (68° to 77°F).
|packLabel=<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
<!--Precautions with Alcohol-->
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
 
|brandNames=* NIACOR ®<ref>{{Cite web | title =niacin tablet| url =http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ce739d68-d89c-437c-90fb-3c0c45140f22 }}</ref>
<!--Brand Names-->
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
 
<!--Look-Alike Drug Names-->
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>
<!--Drug Shortage Status-->
|drugShortage=
|drugShortage=
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}}

Latest revision as of 16:47, 20 August 2015

Niacin (tablet)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Disclaimer

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Overview

Niacin (tablet) is an antihyperlipedemic agent that is FDA approved for the treatment of hypertriglyceredemia, primary hypercholesterolemia, hyperlipidemia. Common adverse reactions include dyspepsia, vomiting, diarrhea, jaundice, pruritus, hyperpigmentation, acanthosis nigricans, dry skin and headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

  • Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Nicotinic acid, alone or in combination with a bile-acid binding resin, is indicated as an adjunct to diet for the reduction of elevated total and LDL cholesterol levels in patients with primary hypercholesterolemia (Types IIa and IIb)†, when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate (see also the NCEP treatment guidelines6). Prior to initiating therapy with nicotinic acid, 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 total cholesterol, HDL cholesterol, and triglycerides.
  • Nicotinic acid is also indicated as adjunctive therapy for the treatment of adult patients with very high serum triglyceride levels (Types IV and V hyperlipidemia)† 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 triglyceride levels over 2000 mg/dL and have elevations of VLDL cholesterol as well as fasting chylomicrons (Type V hyperlipidemia)†. Subjects who consistently have total serum or plasma triglycerides below 1000 mg/dL are unlikely to develop pancreatitis. Therapy with nicotinic acid may be considered for those subjects with triglyceride elevations between 1000 and 2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. Some Type IV patients with triglycerides under 1000 mg/dL may, through dietary or alcoholic indiscretion, convert to a Type V pattern with massive triglyceride elevations accompanying fasting chylomicronemia, but the influence of nicotinic acid therapy on the risk of pancreatitis in such situations has not been adequately studied. Drug therapy is not indicated for patients with Type I hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of VLDL. Inspection of plasma refrigerated for 14 hours is helpful in distinguishing Types I, IV, and V hyperlipoproteinemia7.
This image is provided by the National Library of Medicine.

Dosage

  • The usual adult dosage of nicotinic acid is 1 to 2 grams two or three times a day. Doses should be individualized according to the patient's response. Start with one-half tablet (250 mg) as a single daily dose following the evening meal. The frequency of dosing and total daily dose can be increased every four to seven days until the desired LDL cholesterol and/or triglyceride level is achieved or the first-level therapeutic dose of 1.5 to 2 grams/day is reached. If the patient's hyperlipidemia is not adequately controlled after 2 months at this level, the dosage can then be increased at two to four week intervals to 3 grams/day (1 gram three times per day). In patients with marked lipid abnormalities, a higher dose is occasionally required, but generally should not exceed 6 grams/day.
  • Flushing of the skin appears frequently and can be minimized by pretreatment with aspirin or non-steroidal anti-inflammatory drugs. 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 nicotinic acid and avoiding administration on an empty stomach.
  • Sustained-release (modified-release, timed-release) nicotinic acid preparations should not be substituted for equivalent doses of immediate-release (crystalline) nicotinic acid.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Niacin (tablet) in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Niacin (tablet) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Niacin (tablet) in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Niacin (tablet) in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Niacin (tablet) in pediatric patients.

Contraindications

Warnings

Liver Dysfunction

  • Cases of severe hepatic toxicity, including fulminant hepatic necrosis have occurred in patients who have substituted sustained-release (modified-release, timed-release) nicotinic acid products for immediate-release (crystalline) nicotinic acid at equivalent doses.
  • Liver function tests should be performed on all patients during therapy with nicotinic acid. Serum transaminase levels, including ALT (SGPT), should be monitored before treatment begins, every six weeks to twelve weeks for the first year, and periodically thereafter (e.g., at approximately 6 month intervals). Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently. If the transaminase levels show evidence of progression, particularly if they rise to three times the upper limit of normal and are persistent, the drug should be discontinued. Liver biopsy should be considered if elevations persist beyond discontinuation of the drug.
  • Nicotinic acid should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of nicotinic acid.

Skeletal Muscle

  • Rare cases of rhabdomyolysis have been associated with concomitant administration of lipid-altering doses (≥1 g/day) of nicotinic acid and HMG-CoA reductase inhibitors. Physicians contemplating combined therapy with HMG-CoA reductase inhibitors and nicotinic acid should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Periodic serum creatine phosphokinase (CPK) and potassium determinations should be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy.

Adverse Reactions

Clinical Trials Experience

  • Nervous System / Psychiatric : Headache.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Niacin (tablet) in the drug label.

Drug Interactions

HMG-CoA Reductase Inhibitors:

Antihypertensive Therapy : Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension.

Aspirin : Concomitant aspirin may decrease the metabolic clearance of nicotinic acid. The clinical relevance of this finding is unclear.

Other: Concomitant alcohol or hot drinks may increase the side effects of flushing and pruritus and should be avoided at the time of drug ingestion.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Pregnancy Category C.

  • Animal reproduction studies have not been conducted with nicotinic acid. It is also not known whether nicotinic acid at doses typically used for lipid disorders can cause fetal harm when administered to pregnant women or whether it can affect reproductive capacity. If a woman receiving nicotinic acid for primary hypercholesterolemia (Types IIa or IIb) becomes pregnant, the drug should be discontinued. If a woman being treated with nicotinic acid for hypertriglyceridemia (Types IV or V) conceives, the benefits and risks of continued drug therapy should be assessed on an individual basis.


Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Niacin (tablet) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Niacin (tablet) during labor and delivery.

Nursing Mothers

  • It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from lipid-altering doses of nicotinic acid, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

  • Safety and effectiveness in children and adolescents have not been established.

Geriatic Use

There is no FDA guidance on the use of Niacin (tablet) with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Niacin (tablet) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Niacin (tablet) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Niacin (tablet) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Niacin (tablet) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Niacin (tablet) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Niacin (tablet) in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

There is limited information regarding Monitoring of Niacin (tablet) in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Niacin (tablet) in the drug label.

Overdosage

  • Supportive measures should be undertaken in the event of an overdose.

Pharmacology

This image is provided by the National Library of Medicine.

Mechanism of Action

There is limited information regarding Mechanism of action of Niacin (tablet) in the drug label.

Structure

  • Niacin or nicotinic acid, a water-soluble B-complex vitamin and antihyperlipidemic agent, is 3-pyridinecarboxylic acid. It is a white, crystalline powder, sparingly soluble in water. It has the following structural formula:
This image is provided by the National Library of Medicine.
  • Each NIACOR® Tablet, for oral administration, contains 500 mg of nicotinic acid. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, hydrogenated vegetable oil, magnesium stearate and microcrystalline cellulose.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Niacin (tablet) in the drug label.

Pharmacokinetics

  • Following an oral dose, the pharmacokinetic profile of nicotinic acid is characterized by rapid absorption from the gastrointestinal tract and a short plasma elimination half-life. At a 1 gram dose, peak plasma concentrations of 15 to 30 μg/mL are reached within 30 to 60 minutes. Approximately 88% of an oral pharmacologic dose is eliminated by the kidneys as unchanged drug and nicotinuric acid, its primary metabolite. The plasma elimination half-life of nicotinic acid ranges from 20 to 45 minutes.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

  • Nicotinic acid administered to mice for a lifetime as a 1% solution in drinking water was not carcinogenic. The mice in this study received approximately 6-8 times a human dose of 3000 milligrams/day as determined on a milligram/square meter basis. Nicotinic acid was negative for mutagenicity in the Ames test. No studies on impairment of fertility have been performed.

Clinical Studies

There is limited information regarding Clinical Studies of Niacin (tablet) in the drug label.

How Supplied

NIACOR®(Niacin Tablets, USP) 500 mg.

  • Each tablet is a white, capsule-shaped, scored, uncoated tablet, debossed “US” to the left and “67” to the right of the score, with “500” strength on the unscored side.
  • NIACOR® is available in bottles of 100 tablets (NDC 0245-0067-11).
  • Dispense in a tight container as defined in the USP, with a child-resistant closure.

Storage

  • Store at controlled room temperature, 15-30°C (59-86°F).

Images

Drug Images

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Package and Label Display Panel

This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Niacin (tablet) in the drug label.

Precautions with Alcohol

  • Alcohol-Niacin (tablet) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ "niacin tablet".
  2. ↑ "http://www.ismp.org". External link in |title= (help)

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