NICOLAR
Clinical safety rating
cautionComprehensive clinical and safety monograph for NICOLAR (NICOLAR).
Comprehensive clinical and safety monograph for NICOLAR (NICOLAR).
Treatment of primary hyperlipidemia and mixed dyslipidemia (Fredrickson Types IIa and IIb)Reduction of risk of recurrent myocardial infarction in patients with prior MI and hyperlipidemiaRegression of coronary atherosclerosis (with bile acid sequestrant)Adjunct to diet in patients with elevated triglycerides (Types IV and V)
Niacin (nicotinic acid) reduces hepatic production of VLDL and LDL by inhibiting diacylglycerol acyltransferase-2 (DGAT2) and decreasing free fatty acid mobilization from adipose tissue via activation of GPR109A (HM74A) receptor, leading to reduced triglyceride and LDL cholesterol synthesis. It also raises HDL cholesterol by decreasing hepatic clearance of apo A-I.
| Metabolism | Extensively metabolized in the liver via two pathways: conjugation with glycine (major) to form nicotinuric acid, and N-methylation to N-methylnicotinamide. Also undergoes oxidation to nicotinamide N-oxide. CYP2E1 may be involved in some metabolic steps. |
| Excretion | Primarily renal (60-70% as unchanged drug and metabolites), with 10-20% biliary/fecal. Hepatic metabolism to inactive metabolites accounts for ~30% of elimination. |
| Half-life | Terminal elimination half-life is 14-24 hours in adults with normal renal function; clinically, this supports twice-daily dosing. In moderate renal impairment (CrCl 30-59 mL/min), half-life extends to 24-36 hours, requiring dose adjustment. |
| Protein binding | Approximately 90% bound to human serum albumin, primarily to albumin and to a lesser extent to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 1.5-2.5 L/kg, indicating extensive tissue distribution and high extravascular penetration, particularly into the respiratory tract. |
| Bioavailability | Oral: 30-60% due to first-pass metabolism. Inhaled: 10-20% reaching systemic circulation (majority acts locally with high lung deposition). |
| Onset of Action | Oral: 30-60 minutes for therapeutic effect. Inhaled: onset within 5-15 minutes for bronchodilation. |
| Duration of Action | Oral: Duration of action is 8-12 hours, allowing twice-daily dosing. Inhaled: 4-6 hours when used for acute bronchodilation. |
| Molecular Weight | 236.27 |
NICOLAR (niacin extended-release) is typically initiated at 500 mg orally once daily at bedtime, after a low-fat snack. The dose is increased by 500 mg every 4 weeks as tolerated, up to a maximum of 2000 mg once daily.
| Dosage form | TABLET |
| Renal impairment | For patients with GFR <30 mL/min, reduce maximum dose to 1000 mg once daily due to increased risk of toxicity. For GFR 30-60 mL/min, no dose adjustment is required but monitor closely. No specific guidelines for dialysis. |
| Liver impairment | Contraindicated in patients with Child-Pugh class B or C cirrhosis. For Child-Pugh class A (mild impairment), initiate at 500 mg once daily and titrate cautiously, with maximum dose not exceeding 1000 mg once daily. Monitor liver function tests frequently. |
| Pediatric use | Not approved for use in pediatric patients below 16 years of age for dyslipidemia. Safety and efficacy have not been established. |
| Geriatric use | No specific dose adjustment is recommended solely based on age. However, elderly patients may have reduced renal function and increased risk of adverse effects (e.g., flushing, hyperglycemia). Initiate at the lowest starting dose (500 mg once daily) and titrate slowly. Monitor renal function and metabolic parameters closely. |
| 1st trimester | Avoid use; potential teratogenic effects based on animal studies. |
| 2nd trimester | Use only if clearly needed; no well-controlled human studies. |
| 3rd trimester | Use with caution; risk of neonatal hypoglycemia if used near term. |
Clinical note
Comprehensive clinical and safety monograph for NICOLAR (NICOLAR).
| Placental transfer | Crosses placenta; detected in fetal tissues. |
| Breastfeeding | Excreted into breast milk in low amounts; monitor infant for hypoglycemia. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | NICOLAR (niacin) is classified as FDA Pregnancy Category C. Adverse effects have been observed in animal reproduction studies, but no adequate human studies exist. First trimester: potential risk based on animal data; use only if benefit outweighs risk. Second and third trimesters: no known specific risks but limited data; avoid high doses due to possible maternal hepatotoxicity and hyperglycemia. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT) and serum glucose periodically. Assess for signs of flushing, pruritus, or GI intolerance. In pregnancy, monitor fetal growth and well-being via ultrasound if prolonged therapy. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. Niacin may improve lipid profiles, indirectly benefiting endothelial function and reproductive health, but no direct impact on fertility has been documented. |
■ FDA Black Box Warning
Severe hepatotoxicity, including fulminant hepatic necrosis, has occurred with sustained-release formulations. Do not substitute for equivalent doses of immediate-release niacin.
| Serious Effects |
Hypersensitivity to nicolarDiabetic ketoacidosis (DKA)Severe hepatic impairment
| Precautions | Hepatotoxicity: Monitor liver function tests; discontinue if persistent elevations or signs of hepatic injury., Hyperuricemia and gout: May increase uric acid levels; use with caution in patients predisposed to gout., Peptic ulcer: Niacin may reactivate or exacerbate peptic ulcer disease., Facial flushing (prostaglandin-mediated): To reduce, take with aspirin 30 minutes prior, or use extended-release formulations., Increased bleeding risk when used with anticoagulants., Monitor glucose levels in diabetic patients; niacin may impair glucose tolerance. |
| Food/Dietary | Avoid high-fat meals with the dose, as they may increase the risk of flushing. Alcohol and hot beverages should be avoided close to dosing, as they can exacerbate flushing. Grapefruit juice has no significant interaction. Maintain a consistent diet to avoid fluctuations in blood glucose. |
| Clinical Pearls | NICOLAR is a brand name for niacin (nicotinic acid) extended-release. Doses should be taken at bedtime with a low-fat snack to reduce flushing. Avoid concomitant use with statins due to increased risk of myopathy. Monitor liver function tests and blood glucose regularly. Aspirin 325 mg taken 30 minutes prior can mitigate flushing. |
| Patient Advice | Take this medication at bedtime with a low-fat snack to help reduce flushing and stomach upset. · Flushing, warmth, or tingling may occur, especially after starting or increasing the dose; taking aspirin 30 minutes before the dose can help. · Avoid alcohol and hot beverages near the time you take this medication as they can worsen flushing. · Report any unexplained muscle pain, tenderness, or weakness to your doctor, especially if accompanied by fever or malaise. · Regular blood tests to monitor liver function and blood sugar are necessary while on this medication. |
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