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Should liver enzymes be checked in a patient taking niacin?
No randomized trials directly address the question of frequency of liver enzyme monitoring with niacin use. Niacin use is associated with early and late hepatotoxicity (strength of recommendation [SOR]: B, based on incidence data from randomized controlled trials and systematic reviews of cohort studies). Long-acting forms of niacin (Slo-Niacin) are more frequently associated with hepatotoxicity than the immediate-release (Niacor, Nicolar) or extended-release (Niaspan) forms (SOR: B, based on 1 randomized controlled trial and systematic reviews of cohort studies).
The combination of statins and niacin at usual doses does not increase the risk of hepatotoxicity (SOR: A, based on randomized controlled trials). Screening has been recommended at baseline, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually (SOR: C, based on expert opinion).
Evidence summary
Three forms of niacin exist: immediate-release (IR), sustained-release/long-acting (SR/LA), and extended-release (ER), which is currently available only as Niaspan.1 Published incidence of niacin-induced hepatotoxicity varies according to the definition of hepatotoxicity, with a 0% to 46% rate of elevated hepatic enzymes. Hepatotoxicity includes mild liver enzyme elevations, steatosis, hepatitis, abnormal liver biopsies, or fulminant hepatic failure.2,3 Between 1982 and 1992, 11 case reports have linked IR nicotinic acid to a wide range of hepatotoxicities. For patients taking LA/SR niacin doses ≥3 g/d or switching from the IR to the LA product, 21 case reports have linked LA/SR niacin with adverse outcomes.3,4 In several of the LA/SR cases, patients were rechal-lenged with IR formulations with no recurrent hepatocellular damage.3,4 In these case reports, onset of hepatotoxicity ranged from 2 days to 18 months. In a retrospective cohort of 969 veterans taking LA/SR niacin, those who developed hepatotoxicity had onset between 1 and 28 months of initiating treatment.2 Studies evaluating the risk of hepatotoxicity with niacin alone and in combination with statins are summarized in the Table .
Because LA/SR niacin has an active metabolite (nicotinamide), hepatotoxicity is more likely to occur with the LA/SR formulation than with IR niacin.3 In a small prospective comparative study of IR and LA/SR niacin (n=46), 0/23 patients taking IR niacin exhibited hepatic toxicity, compared with 12/23 (52%) of patients taking the LA/SR formulation.5 In this study, patients receiving 1 g/d of LA/SR niacin had increases in transaminases similar to those of patients on 3 g/d of IR niacin. It is therefore recommended that if a patient cannot tolerate IR niacin and is switched to the LA/SR form, the dosage be reduced by 50% to 70%.5 At doses >2 g/d of LA/SR niacin, mean transaminases approached 3 times the upper limit of normal (ULN), supporting recommendations not to exceed this dose for LA/SR niacin.5
Several LA/SR products exist, and their differing pharmacologic and clinical properties necessitate monitoring as though starting anew when changing from one LA/SR formulation to another.1 Because of the unfavorable risk-benefit ratio of LA/SR formulations compared with other niacin formulations, production and marketing of many LA/SR niacin brands has ceased. The ER formulation (Niaspan), only available by prescription, has a balanced metabolism resulting in less hepatotoxicity (<1%).1,6 Expert opinion mandates continued annual monitoring of liver function tests (LFT) for all patients, including those on a stable ER niacin dose, no new risk factors for hepatotoxicity, and a series of normal LFTs.7
TABLE
Studies of niacin toxicity
| Author, evidence | Pts/duration of Rx | Lipid therapy | Hepatotoxicity |
|---|---|---|---|
| Gray,2 retrospective cohort | 896 pts/1–3 mos | LA/SR (Slo-Niacin) avg 1500 mg/d | 2.2% probable, 4.7% possible or probable |
| Capuzzi,6 open-label, prospective | 517 pts/≤96 wks | ER (Niaspan) 1000–3000 mg/d | <1% w/transaminases >3 times ULN |
| McKenney,5 randomized, double-blind, placebo-controlled | 46 pts/30 wks | LA/SR niacin or IR niacin: titrated from 500 mg/d to 3000 mg/d | 52% SR pts with transaminases (78% SR pts withdrew); 0% IR pts with transaminases |
| Grundy,9 randomized, double-blind, placebo-controlled | 97 pts/16 wks | ER (Niaspan) 1000–1500 mg/d | 0% with transaminases >3 times ULN |
| Zhao,10 randomized, double-blind, placebo-controlled | 80 pts/38 mos | LA/SR niacin (Slo-Niacin) 250 mg twice daily titrated to 1000 mg twice daily or switched to IR (Niacor) titrated to 3000–4000 mg/d + simvastatin 10 mg/d titrated to maintain LDL-C | 3% w/transaminases >3 times ULN (transient— resolved with temporary halt or decrease in med) |
| Parra,3 randomized, double-blind | 74 pts/9 wks | IR niacin titrated to max of 3000 mg/d + fluvastatin 20 mg/d | 0% with transaminases >3 times ULN |
| Davignon,11 randomized, placebo-controlled | 168 pts/96 wks | LA/SR niacin (Nicobid) 1000 mg twice daily vs Nicobid 1000 mg twice daily + pravastatin 40 mg nightly | 3% > 3 times baseline transaminases (Nicobid alone) vs 1.2% >3 times baseline transaminases (Nicobid + pravastatin) |
| LA/SR, long-acting/sustained release; IR, immediate release; ER, extended release; ULN, upper limit of normal; LDL-C; low-density lipoprotein cholesterol. | |||
Recommendations from others
Elevated hepatic enzymes <3 times the ULN may occur but usually resolve with continued therapy or reduced doses. Enzymes >3 times the ULN require discontinuation of therapy.8 The American Society of Health-System Pharmacists (ASHP) recommends screening at baseline, every 2 to 3 months for the first year and every 6 to 12 months there-after.8 The ASHP also recommends that patients be started on IR niacin products, with consideration of ER products only when IR products are not tolerated or alternative products are ineffective. ASHP makes no mention of LA/SR products in their recommendations.8 They recommend more frequent monitoring for high-risk patients—risks include doses >2 g/d for LA/SR and >3 g/d for IR; LA/SR formulations; switching between formulations; taking concomitant drugs that interact (ie, sulfonylureas); excessive alcohol use (undefined); and preexisting liver disease (based on a bivariate analysis of factors associated with increased risk of hepatic toxicity from a single retrospective cohort study)5 — and for patients who demonstrate signs/symptoms of toxicity (nausea, vomiting, malaise, loss of appetite, right upper quadrant pain, jaundice, and dark urine).8 The National Cholesterol Education Program Expert Panel update in 2004 recommended obtaining ALT/AST initially, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually or more frequently if indicated.7
Risk of toxicity with long-acting niacin is significant enough to avoid use
Louis Sanner, MD
University of Wisconsin Medical School, Madison Family Practice Residency
Our clinical experience is that once our patients are on stable doses of most medicines and have had a series of normal lab tests, we are unlikely to find toxicities from continued routine testing. That appears to be the case with niacin and liver toxicity, but long-term data are lacking for asymptomatic late reactions to usual niacin doses. The risk of toxicity with “long-acting” forms of niacin is significant enough that I see no reason to use them at all. If one wants to save money, use IR niacin. If cost is not an issue or regular niacin is not tolerated, I use the ER Niaspan. Both of these forms have very low rates of liver toxicity.
1. McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.
2. Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-258.
3. Parra JL, Reddy KR. Hepatotoxicity of hypolipidemic drugs. Clin Liver Dis 2003;7:415-433.
4. Ferenchick G, Rovner D. Hepatitis and hematemesis complicating nicotinic acid use. Am J Med Sci 1989;298:191-193.
5. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs. immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-700.
6. Capuzzi DM, Guyton JR, Morgan JM, et al. Efficacy and safety of an extended-release niacin (Niaspan): A long-term study. Am J Cardiol 1998;82:74U-86U.
7. Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
8. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. American Society of Health System Pharmacists. Am J Health-Syst Pharm 1997;54:2815-2819.
9. Grundy SM, Vega GL, McGovern ME, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of Niaspan trial. Arch Intern Med 2002;162:1568-1576.
10. Zhao XQ, Morse JS, Dowdy AA, et al. Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study). Am J Cardiol 2004;93:307-312.
11. Davignon J, Roederer G, Montigny M, et al. Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994;73:339-345.
No randomized trials directly address the question of frequency of liver enzyme monitoring with niacin use. Niacin use is associated with early and late hepatotoxicity (strength of recommendation [SOR]: B, based on incidence data from randomized controlled trials and systematic reviews of cohort studies). Long-acting forms of niacin (Slo-Niacin) are more frequently associated with hepatotoxicity than the immediate-release (Niacor, Nicolar) or extended-release (Niaspan) forms (SOR: B, based on 1 randomized controlled trial and systematic reviews of cohort studies).
The combination of statins and niacin at usual doses does not increase the risk of hepatotoxicity (SOR: A, based on randomized controlled trials). Screening has been recommended at baseline, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually (SOR: C, based on expert opinion).
Evidence summary
Three forms of niacin exist: immediate-release (IR), sustained-release/long-acting (SR/LA), and extended-release (ER), which is currently available only as Niaspan.1 Published incidence of niacin-induced hepatotoxicity varies according to the definition of hepatotoxicity, with a 0% to 46% rate of elevated hepatic enzymes. Hepatotoxicity includes mild liver enzyme elevations, steatosis, hepatitis, abnormal liver biopsies, or fulminant hepatic failure.2,3 Between 1982 and 1992, 11 case reports have linked IR nicotinic acid to a wide range of hepatotoxicities. For patients taking LA/SR niacin doses ≥3 g/d or switching from the IR to the LA product, 21 case reports have linked LA/SR niacin with adverse outcomes.3,4 In several of the LA/SR cases, patients were rechal-lenged with IR formulations with no recurrent hepatocellular damage.3,4 In these case reports, onset of hepatotoxicity ranged from 2 days to 18 months. In a retrospective cohort of 969 veterans taking LA/SR niacin, those who developed hepatotoxicity had onset between 1 and 28 months of initiating treatment.2 Studies evaluating the risk of hepatotoxicity with niacin alone and in combination with statins are summarized in the Table .
Because LA/SR niacin has an active metabolite (nicotinamide), hepatotoxicity is more likely to occur with the LA/SR formulation than with IR niacin.3 In a small prospective comparative study of IR and LA/SR niacin (n=46), 0/23 patients taking IR niacin exhibited hepatic toxicity, compared with 12/23 (52%) of patients taking the LA/SR formulation.5 In this study, patients receiving 1 g/d of LA/SR niacin had increases in transaminases similar to those of patients on 3 g/d of IR niacin. It is therefore recommended that if a patient cannot tolerate IR niacin and is switched to the LA/SR form, the dosage be reduced by 50% to 70%.5 At doses >2 g/d of LA/SR niacin, mean transaminases approached 3 times the upper limit of normal (ULN), supporting recommendations not to exceed this dose for LA/SR niacin.5
Several LA/SR products exist, and their differing pharmacologic and clinical properties necessitate monitoring as though starting anew when changing from one LA/SR formulation to another.1 Because of the unfavorable risk-benefit ratio of LA/SR formulations compared with other niacin formulations, production and marketing of many LA/SR niacin brands has ceased. The ER formulation (Niaspan), only available by prescription, has a balanced metabolism resulting in less hepatotoxicity (<1%).1,6 Expert opinion mandates continued annual monitoring of liver function tests (LFT) for all patients, including those on a stable ER niacin dose, no new risk factors for hepatotoxicity, and a series of normal LFTs.7
TABLE
Studies of niacin toxicity
| Author, evidence | Pts/duration of Rx | Lipid therapy | Hepatotoxicity |
|---|---|---|---|
| Gray,2 retrospective cohort | 896 pts/1–3 mos | LA/SR (Slo-Niacin) avg 1500 mg/d | 2.2% probable, 4.7% possible or probable |
| Capuzzi,6 open-label, prospective | 517 pts/≤96 wks | ER (Niaspan) 1000–3000 mg/d | <1% w/transaminases >3 times ULN |
| McKenney,5 randomized, double-blind, placebo-controlled | 46 pts/30 wks | LA/SR niacin or IR niacin: titrated from 500 mg/d to 3000 mg/d | 52% SR pts with transaminases (78% SR pts withdrew); 0% IR pts with transaminases |
| Grundy,9 randomized, double-blind, placebo-controlled | 97 pts/16 wks | ER (Niaspan) 1000–1500 mg/d | 0% with transaminases >3 times ULN |
| Zhao,10 randomized, double-blind, placebo-controlled | 80 pts/38 mos | LA/SR niacin (Slo-Niacin) 250 mg twice daily titrated to 1000 mg twice daily or switched to IR (Niacor) titrated to 3000–4000 mg/d + simvastatin 10 mg/d titrated to maintain LDL-C | 3% w/transaminases >3 times ULN (transient— resolved with temporary halt or decrease in med) |
| Parra,3 randomized, double-blind | 74 pts/9 wks | IR niacin titrated to max of 3000 mg/d + fluvastatin 20 mg/d | 0% with transaminases >3 times ULN |
| Davignon,11 randomized, placebo-controlled | 168 pts/96 wks | LA/SR niacin (Nicobid) 1000 mg twice daily vs Nicobid 1000 mg twice daily + pravastatin 40 mg nightly | 3% > 3 times baseline transaminases (Nicobid alone) vs 1.2% >3 times baseline transaminases (Nicobid + pravastatin) |
| LA/SR, long-acting/sustained release; IR, immediate release; ER, extended release; ULN, upper limit of normal; LDL-C; low-density lipoprotein cholesterol. | |||
Recommendations from others
Elevated hepatic enzymes <3 times the ULN may occur but usually resolve with continued therapy or reduced doses. Enzymes >3 times the ULN require discontinuation of therapy.8 The American Society of Health-System Pharmacists (ASHP) recommends screening at baseline, every 2 to 3 months for the first year and every 6 to 12 months there-after.8 The ASHP also recommends that patients be started on IR niacin products, with consideration of ER products only when IR products are not tolerated or alternative products are ineffective. ASHP makes no mention of LA/SR products in their recommendations.8 They recommend more frequent monitoring for high-risk patients—risks include doses >2 g/d for LA/SR and >3 g/d for IR; LA/SR formulations; switching between formulations; taking concomitant drugs that interact (ie, sulfonylureas); excessive alcohol use (undefined); and preexisting liver disease (based on a bivariate analysis of factors associated with increased risk of hepatic toxicity from a single retrospective cohort study)5 — and for patients who demonstrate signs/symptoms of toxicity (nausea, vomiting, malaise, loss of appetite, right upper quadrant pain, jaundice, and dark urine).8 The National Cholesterol Education Program Expert Panel update in 2004 recommended obtaining ALT/AST initially, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually or more frequently if indicated.7
Risk of toxicity with long-acting niacin is significant enough to avoid use
Louis Sanner, MD
University of Wisconsin Medical School, Madison Family Practice Residency
Our clinical experience is that once our patients are on stable doses of most medicines and have had a series of normal lab tests, we are unlikely to find toxicities from continued routine testing. That appears to be the case with niacin and liver toxicity, but long-term data are lacking for asymptomatic late reactions to usual niacin doses. The risk of toxicity with “long-acting” forms of niacin is significant enough that I see no reason to use them at all. If one wants to save money, use IR niacin. If cost is not an issue or regular niacin is not tolerated, I use the ER Niaspan. Both of these forms have very low rates of liver toxicity.
No randomized trials directly address the question of frequency of liver enzyme monitoring with niacin use. Niacin use is associated with early and late hepatotoxicity (strength of recommendation [SOR]: B, based on incidence data from randomized controlled trials and systematic reviews of cohort studies). Long-acting forms of niacin (Slo-Niacin) are more frequently associated with hepatotoxicity than the immediate-release (Niacor, Nicolar) or extended-release (Niaspan) forms (SOR: B, based on 1 randomized controlled trial and systematic reviews of cohort studies).
The combination of statins and niacin at usual doses does not increase the risk of hepatotoxicity (SOR: A, based on randomized controlled trials). Screening has been recommended at baseline, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually (SOR: C, based on expert opinion).
Evidence summary
Three forms of niacin exist: immediate-release (IR), sustained-release/long-acting (SR/LA), and extended-release (ER), which is currently available only as Niaspan.1 Published incidence of niacin-induced hepatotoxicity varies according to the definition of hepatotoxicity, with a 0% to 46% rate of elevated hepatic enzymes. Hepatotoxicity includes mild liver enzyme elevations, steatosis, hepatitis, abnormal liver biopsies, or fulminant hepatic failure.2,3 Between 1982 and 1992, 11 case reports have linked IR nicotinic acid to a wide range of hepatotoxicities. For patients taking LA/SR niacin doses ≥3 g/d or switching from the IR to the LA product, 21 case reports have linked LA/SR niacin with adverse outcomes.3,4 In several of the LA/SR cases, patients were rechal-lenged with IR formulations with no recurrent hepatocellular damage.3,4 In these case reports, onset of hepatotoxicity ranged from 2 days to 18 months. In a retrospective cohort of 969 veterans taking LA/SR niacin, those who developed hepatotoxicity had onset between 1 and 28 months of initiating treatment.2 Studies evaluating the risk of hepatotoxicity with niacin alone and in combination with statins are summarized in the Table .
Because LA/SR niacin has an active metabolite (nicotinamide), hepatotoxicity is more likely to occur with the LA/SR formulation than with IR niacin.3 In a small prospective comparative study of IR and LA/SR niacin (n=46), 0/23 patients taking IR niacin exhibited hepatic toxicity, compared with 12/23 (52%) of patients taking the LA/SR formulation.5 In this study, patients receiving 1 g/d of LA/SR niacin had increases in transaminases similar to those of patients on 3 g/d of IR niacin. It is therefore recommended that if a patient cannot tolerate IR niacin and is switched to the LA/SR form, the dosage be reduced by 50% to 70%.5 At doses >2 g/d of LA/SR niacin, mean transaminases approached 3 times the upper limit of normal (ULN), supporting recommendations not to exceed this dose for LA/SR niacin.5
Several LA/SR products exist, and their differing pharmacologic and clinical properties necessitate monitoring as though starting anew when changing from one LA/SR formulation to another.1 Because of the unfavorable risk-benefit ratio of LA/SR formulations compared with other niacin formulations, production and marketing of many LA/SR niacin brands has ceased. The ER formulation (Niaspan), only available by prescription, has a balanced metabolism resulting in less hepatotoxicity (<1%).1,6 Expert opinion mandates continued annual monitoring of liver function tests (LFT) for all patients, including those on a stable ER niacin dose, no new risk factors for hepatotoxicity, and a series of normal LFTs.7
TABLE
Studies of niacin toxicity
| Author, evidence | Pts/duration of Rx | Lipid therapy | Hepatotoxicity |
|---|---|---|---|
| Gray,2 retrospective cohort | 896 pts/1–3 mos | LA/SR (Slo-Niacin) avg 1500 mg/d | 2.2% probable, 4.7% possible or probable |
| Capuzzi,6 open-label, prospective | 517 pts/≤96 wks | ER (Niaspan) 1000–3000 mg/d | <1% w/transaminases >3 times ULN |
| McKenney,5 randomized, double-blind, placebo-controlled | 46 pts/30 wks | LA/SR niacin or IR niacin: titrated from 500 mg/d to 3000 mg/d | 52% SR pts with transaminases (78% SR pts withdrew); 0% IR pts with transaminases |
| Grundy,9 randomized, double-blind, placebo-controlled | 97 pts/16 wks | ER (Niaspan) 1000–1500 mg/d | 0% with transaminases >3 times ULN |
| Zhao,10 randomized, double-blind, placebo-controlled | 80 pts/38 mos | LA/SR niacin (Slo-Niacin) 250 mg twice daily titrated to 1000 mg twice daily or switched to IR (Niacor) titrated to 3000–4000 mg/d + simvastatin 10 mg/d titrated to maintain LDL-C | 3% w/transaminases >3 times ULN (transient— resolved with temporary halt or decrease in med) |
| Parra,3 randomized, double-blind | 74 pts/9 wks | IR niacin titrated to max of 3000 mg/d + fluvastatin 20 mg/d | 0% with transaminases >3 times ULN |
| Davignon,11 randomized, placebo-controlled | 168 pts/96 wks | LA/SR niacin (Nicobid) 1000 mg twice daily vs Nicobid 1000 mg twice daily + pravastatin 40 mg nightly | 3% > 3 times baseline transaminases (Nicobid alone) vs 1.2% >3 times baseline transaminases (Nicobid + pravastatin) |
| LA/SR, long-acting/sustained release; IR, immediate release; ER, extended release; ULN, upper limit of normal; LDL-C; low-density lipoprotein cholesterol. | |||
Recommendations from others
Elevated hepatic enzymes <3 times the ULN may occur but usually resolve with continued therapy or reduced doses. Enzymes >3 times the ULN require discontinuation of therapy.8 The American Society of Health-System Pharmacists (ASHP) recommends screening at baseline, every 2 to 3 months for the first year and every 6 to 12 months there-after.8 The ASHP also recommends that patients be started on IR niacin products, with consideration of ER products only when IR products are not tolerated or alternative products are ineffective. ASHP makes no mention of LA/SR products in their recommendations.8 They recommend more frequent monitoring for high-risk patients—risks include doses >2 g/d for LA/SR and >3 g/d for IR; LA/SR formulations; switching between formulations; taking concomitant drugs that interact (ie, sulfonylureas); excessive alcohol use (undefined); and preexisting liver disease (based on a bivariate analysis of factors associated with increased risk of hepatic toxicity from a single retrospective cohort study)5 — and for patients who demonstrate signs/symptoms of toxicity (nausea, vomiting, malaise, loss of appetite, right upper quadrant pain, jaundice, and dark urine).8 The National Cholesterol Education Program Expert Panel update in 2004 recommended obtaining ALT/AST initially, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually or more frequently if indicated.7
Risk of toxicity with long-acting niacin is significant enough to avoid use
Louis Sanner, MD
University of Wisconsin Medical School, Madison Family Practice Residency
Our clinical experience is that once our patients are on stable doses of most medicines and have had a series of normal lab tests, we are unlikely to find toxicities from continued routine testing. That appears to be the case with niacin and liver toxicity, but long-term data are lacking for asymptomatic late reactions to usual niacin doses. The risk of toxicity with “long-acting” forms of niacin is significant enough that I see no reason to use them at all. If one wants to save money, use IR niacin. If cost is not an issue or regular niacin is not tolerated, I use the ER Niaspan. Both of these forms have very low rates of liver toxicity.
1. McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.
2. Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-258.
3. Parra JL, Reddy KR. Hepatotoxicity of hypolipidemic drugs. Clin Liver Dis 2003;7:415-433.
4. Ferenchick G, Rovner D. Hepatitis and hematemesis complicating nicotinic acid use. Am J Med Sci 1989;298:191-193.
5. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs. immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-700.
6. Capuzzi DM, Guyton JR, Morgan JM, et al. Efficacy and safety of an extended-release niacin (Niaspan): A long-term study. Am J Cardiol 1998;82:74U-86U.
7. Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
8. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. American Society of Health System Pharmacists. Am J Health-Syst Pharm 1997;54:2815-2819.
9. Grundy SM, Vega GL, McGovern ME, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of Niaspan trial. Arch Intern Med 2002;162:1568-1576.
10. Zhao XQ, Morse JS, Dowdy AA, et al. Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study). Am J Cardiol 2004;93:307-312.
11. Davignon J, Roederer G, Montigny M, et al. Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994;73:339-345.
1. McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.
2. Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-258.
3. Parra JL, Reddy KR. Hepatotoxicity of hypolipidemic drugs. Clin Liver Dis 2003;7:415-433.
4. Ferenchick G, Rovner D. Hepatitis and hematemesis complicating nicotinic acid use. Am J Med Sci 1989;298:191-193.
5. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs. immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-700.
6. Capuzzi DM, Guyton JR, Morgan JM, et al. Efficacy and safety of an extended-release niacin (Niaspan): A long-term study. Am J Cardiol 1998;82:74U-86U.
7. Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
8. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. American Society of Health System Pharmacists. Am J Health-Syst Pharm 1997;54:2815-2819.
9. Grundy SM, Vega GL, McGovern ME, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of Niaspan trial. Arch Intern Med 2002;162:1568-1576.
10. Zhao XQ, Morse JS, Dowdy AA, et al. Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study). Am J Cardiol 2004;93:307-312.
11. Davignon J, Roederer G, Montigny M, et al. Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994;73:339-345.
Evidence-based answers from the Family Physicians Inquiries Network