Acipimox

Acipimox is a lipid regulating drug, belongs to nicotinic acid group. It reduces blood lipid level by inhibiting the release of fatty acids from fat tissues. Acipimox is used for the treatment of hyperlipidemias of type IIa, IIb and IV in patients not responded adequately to diet and other appropriate measures.

Acipimox is primarily indicated in conditions like Hypertriglyceridemia.

Acipimox is contraindicated in conditions like Peptic ulcer, Hypersensitivity.

Acipimox produces potentially life-threatening effects which include Bronchospasm, Anaphylactic reactions, Angioedema. which are responsible for the discontinuation of Acipimox therapy. The symptomatic adverse reactions produced by Acipimox are more or less tolerable and if they become severe, they can be treated symptomatically, these include Headache, Nausea, Diarrhea, Rashes, Urticaria, Itching, Malaise, Flushing, Heart burn, Epigastric pain, Dry eye.

Concerns related to adverse effects: • Cholelithiasis: May cause cholelithiasis; discontinue if gallstones are found upon gallbladder studies. • HDL cholesterol: A paradoxical, severe, and reversible decrease in HDL-C (as low as 2 mg/dL) with a simultaneous decrease in apolipoprotein A1 has been reported within 2 weeks to years after initiation of fibrate therapy; clinical significance unknown. Monitor HDL-C within a few months of initiation of therapy and discontinue if HDL-C becomes severely depressed; do not restart therapy. • Hematologic effects: May cause mild-to-moderate decreases in hemoglobin, hematocrit and WBC upon initiation of therapy which usually stabilizes with long-term therapy. Agranulocytosis and thrombocytopenia have been reported. Periodic monitoring of blood counts is recommended during the first year of therapy. • Hepatic effects: Hepatic transaminases can become significantly elevated (dose-related); hepatocellular, chronic active, and cholestatic hepatitis have been reported after weeks to several years of therapy. Baseline and regular monitoring of liver function tests is required; discontinue therapy in patients whose enzyme levels persist above 3 times the upper limit of normal. • Hypersensitivity reactions: Acute hypersensitivity reactions, including anaphylaxis and angioedema, have been reported. Additionally, delayed hypersensitivity reactions, including severe cutaneous adverse reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported, occurring days to weeks following fenofibrate initiation. Discontinue immediately for severe acute or delayed hypersensitivity reactions. • Myopathy/Rhabdomyolysis: Has been associated with rare myositis, myopathy, or rhabdomyolysis; monitor patients closely. Risk increased in the elderly, those receiving concomitant HMG-CoA reductase inhibitors or colchicine, and patients with diabetes mellitus, renal insufficiency, or hypothyroidism. Instruct patients to report unexplained muscle pain, tenderness, weakness, especially if accompanied with malaise or fever; or brown urine. Discontinue therapy in patients who develop markedly elevated CPK concentrations or if myopathy/myositis is suspected or diagnosed. • Pancreatitis: Pancreatitis has been reported with fenofibrate use; may be secondary to a failure of efficacy in patients with severe hypertriglyceridemia, medication side effect, or due to biliary tract stone or sludge formation from bile duct obstruction. • Photosensitivity: Photosensitivity reactions have been reported, sometimes days to months after therapy was initiated; some patients reported previous photosensitivity to ketoprofen. • Renal effects: Increases in serum creatinine (>2 mg/dL) have been observed with use; clinical significance unknown. These elevations tend to return to baseline following discontinuation of fenofibrate. Fenofibrate has been shown to increase creatinine production (unknown mechanism) resulting in an equal increase of creatinuria thereby demonstrating that the increase does not reflect a reduction in creatinine clearance (Hottelart 2002). Monitor renal function in patients with renal impairment; consider monitoring renal function in patients with increased risk for developing renal impairment (eg, elderly and patients with diabetes). • Venous thromboembolism: Use has been associated with PE and DVT. Use with caution in patients with risk factors for VTE. Disease-related concerns: • Cardiovascular disease: Fibric acid derivatives have not demonstrated significant efficacy in altering cardiovascular disease mortality in major clinical studies. In two large randomized controlled clinical trials, neither fenofibrate monotherapy (Keech 2005) nor the addition of fenofibrate to simvastatin (ACCORD Study Group 2010) compared to placebo were shown to reduce cardiovascular disease morbidity and mortality in patients with type 2 diabetes. • Hepatic impairment: Contraindicated in patients with active liver disease, including primary biliary cirrhosis and unexplained persistent liver function abnormalities. • Renal impairment: Use with caution in patients with mild to moderate renal impairment; dosage adjustment required. Contraindicated in patients with severe renal impairment including those receiving dialysis. Concurrent drug therapy issues: • HMG-CoA reductase inhibitors: Use caution with HMG-CoA reductase inhibitors; may lead to myopathy, rhabdomyolysis. No incremental benefit of combination therapy on cardiovascular morbidity and mortality over statin monotherapy has been established. In combination with HMG-CoA reductase inhibitors, fenofibrate is generally regarded as safer than gemfibrozil due to limited pharmacokinetic interaction with statins. Fenofibrate may be considered in patients on low- or moderate-intensity statin therapy (ie, statin therapy intended to lower LDL-C by <30% or ~30% to 50%, respectively) only if the benefits from atherosclerotic cardiovascular disease (ASCVD) risk reduction or triglyceride lowering when triglycerides are >500 mg/dL, outweigh the potential risk for adverse effects (ACC/AHA [Stone 2013]). Special populations: • Elderly: Use with caution in the elderly; dosage adjustment may be required. Dosage form specific issues: • Peanut or arachis oil: Some products may contain peanut or arachis oil; use is contraindicated in patients with a peanut or arachis allergy for applicable formulations. • Soya lecithin: Some products may contain soya lecithin; use is contraindicated in patients with a soya lecithin allergy for applicable formulations. Other warnings/precautions: • Appropriate use: Fenofibrate is not a first- or second-line choice in patients with hypercholesterolemia; other agents may be more suitable (ACC/AHA [Stone 2013]). Secondary causes of hyperlipidemia should be ruled out prior to therapy. • Optimal response: Therapy should be withdrawn if an adequate response is not obtained after 2 to 3 months of therapy at the maximal daily dose. In patients with severe hypertriglyceridemia, the occurrence of pancreatitis may represent a failure of efficacy, a direct effect of the drug, or obstruction of the common bile duct due to biliary tract stone or sludge formation.

Concerns related to adverse effects: • Cholelithiasis: May cause cholelithiasis; discontinue if gallstones are found upon gallbladder studies. • HDL cholesterol: A paradoxical, severe, and reversible decrease in HDL-C (as low as 2 mg/dL) with a simultaneous decrease in apolipoprotein A1 has been reported within 2 weeks to years after initiation of fibrate therapy; clinical significance unknown. Monitor HDL-C within a few months of initiation of therapy and discontinue if HDL-C becomes severely depressed; do not restart therapy. • Hematologic effects: May cause mild-to-moderate decreases in hemoglobin, hematocrit and WBC upon initiation of therapy which usually stabilizes with long-term therapy. Agranulocytosis and thrombocytopenia have been reported. Periodic monitoring of blood counts is recommended during the first year of therapy. • Hepatic effects: Hepatic transaminases can become significantly elevated (dose-related); hepatocellular, chronic active, and cholestatic hepatitis have been reported after weeks to several years of therapy. Baseline and regular monitoring of liver function tests is required; discontinue therapy in patients whose enzyme levels persist above 3 times the upper limit of normal. • Hypersensitivity reactions: Acute hypersensitivity reactions, including anaphylaxis and angioedema, have been reported. Additionally, delayed hypersensitivity reactions, including severe cutaneous adverse reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported, occurring days to weeks following fenofibrate initiation. Discontinue immediately for severe acute or delayed hypersensitivity reactions. • Myopathy/Rhabdomyolysis: Has been associated with rare myositis, myopathy, or rhabdomyolysis; monitor patients closely. Risk increased in the elderly, those receiving concomitant HMG-CoA reductase inhibitors or colchicine, and patients with diabetes mellitus, renal insufficiency, or hypothyroidism. Instruct patients to report unexplained muscle pain, tenderness, weakness, especially if accompanied with malaise or fever; or brown urine. Discontinue therapy in patients who develop markedly elevated CPK concentrations or if myopathy/myositis is suspected or diagnosed. • Pancreatitis: Pancreatitis has been reported with fenofibrate use; may be secondary to a failure of efficacy in patients with severe hypertriglyceridemia, medication side effect, or due to biliary tract stone or sludge formation from bile duct obstruction. • Photosensitivity: Photosensitivity reactions have been reported, sometimes days to months after therapy was initiated; some patients reported previous photosensitivity to ketoprofen. • Renal effects: Increases in serum creatinine (>2 mg/dL) have been observed with use; clinical significance unknown. These elevations tend to return to baseline following discontinuation of fenofibrate. Fenofibrate has been shown to increase creatinine production (unknown mechanism) resulting in an equal increase of creatinuria thereby demonstrating that the increase does not reflect a reduction in creatinine clearance (Hottelart 2002). Monitor renal function in patients with renal impairment; consider monitoring renal function in patients with increased risk for developing renal impairment (eg, elderly and patients with diabetes). • Venous thromboembolism: Use has been associated with PE and DVT. Use with caution in patients with risk factors for VTE. Disease-related concerns: • Cardiovascular disease: Fibric acid derivatives have not demonstrated significant efficacy in altering cardiovascular disease mortality in major clinical studies. In two large randomized controlled clinical trials, neither fenofibrate monotherapy (Keech 2005) nor the addition of fenofibrate to simvastatin (ACCORD Study Group 2010) compared to placebo were shown to reduce cardiovascular disease morbidity and mortality in patients with type 2 diabetes. • Hepatic impairment: Contraindicated in patients with active liver disease, including primary biliary cirrhosis and unexplained persistent liver function abnormalities. • Renal impairment: Use with caution in patients with mild to moderate renal impairment; dosage adjustment required. Contraindicated in patients with severe renal impairment including those receiving dialysis. Concurrent drug therapy issues: • HMG-CoA reductase inhibitors: Use caution with HMG-CoA reductase inhibitors; may lead to myopathy, rhabdomyolysis. No incremental benefit of combination therapy on cardiovascular morbidity and mortality over statin monotherapy has been established. In combination with HMG-CoA reductase inhibitors, fenofibrate is generally regarded as safer than gemfibrozil due to limited pharmacokinetic interaction with statins. Fenofibrate may be considered in patients on low- or moderate-intensity statin therapy (ie, statin therapy intended to lower LDL-C by <30% or ~30% to 50%, respectively) only if the benefits from atherosclerotic cardiovascular disease (ASCVD) risk reduction or triglyceride lowering when triglycerides are >500 mg/dL, outweigh the potential risk for adverse effects (ACC/AHA [Stone 2013]). Special populations: • Elderly: Use with caution in the elderly; dosage adjustment may be required. Dosage form specific issues: • Peanut or arachis oil: Some products may contain peanut or arachis oil; use is contraindicated in patients with a peanut or arachis allergy for applicable formulations. • Soya lecithin: Some products may contain soya lecithin; use is contraindicated in patients with a soya lecithin allergy for applicable formulations. Other warnings/precautions: • Appropriate use: Fenofibrate is not a first- or second-line choice in patients with hypercholesterolemia; other agents may be more suitable (ACC/AHA [Stone 2013]). Secondary causes of hyperlipidemia should be ruled out prior to therapy. • Optimal response: Therapy should be withdrawn if an adequate response is not obtained after 2 to 3 months of therapy at the maximal daily dose. In patients with severe hypertriglyceridemia, the occurrence of pancreatitis may represent a failure of efficacy, a direct effect of the drug, or obstruction of the common bile duct due to biliary tract stone or sludge formation.

500 to 750 mg/day (620 (625)) As recommended. PO — In particular the lower dose is advised in type IV and the higher dose in types IIa and IIb hyperlipoproteinaemias. Daily dose should be divided and taken with main meals. Scraped Dose — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product Capsule, Oral, as fenofibrate: Antara: 30 mg [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)] Antara: 90 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)] Lipofen: 50 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #10 (quinoline yellow)] Lipofen: 150 mg Lofibra: 67 mg [DSC], 134 mg [DSC], 200 mg [DSC] Generic: 43 mg, 50 mg, 67 mg, 130 mg, 134 mg, 150 mg, 200 mg Capsule Delayed Release, Oral, as choline fenofibrate: Trilipix: 45 mg Trilipix: 135 mg [contains fd&c blue #2 (indigotine)] Generic: 45 mg, 135 mg Tablet, Oral, as fenofibrate: Fenoglide: 40 mg, 120 mg Lofibra: 54 mg [DSC] [contains fd&c yellow #10 aluminum lake] Lofibra: 160 mg [DSC] Tricor: 48 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin] Tricor: 145 mg [contains soybean lecithin] Triglide: 160 mg [DSC] Triglide: 160 mg [DSC] [contains egg phospholipids (egg lecithin)] Generic: 40 mg, 48 mg, 54 mg, 120 mg, 145 mg, 160 mg Tablet, Oral, as fenofibric acid: Fibricor: 35 mg, 105 mg Generic: 35 mg, 105 mg

No child dosage information is recorded for this medicine yet.

No neonatal dosage information is recorded for this medicine yet.

Acipimox: May enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. Monitor therapy Bile Acid Sequestrants: May decrease the absorption of Fibric Acid Derivatives. Management: Separate doses by at least 2 hours to minimize this interaction; fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant. Consider therapy modification Chenodiol: Fibric Acid Derivatives may diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any fibric acid derivative. Monitor therapy Ciprofibrate: May enhance the adverse/toxic effect of Fibric Acid Derivatives. Avoid combination Colchicine: Fibric Acid Derivatives may enhance the myopathic (rhabdomyolysis) effect of Colchicine. Monitor therapy CycloSPORINE (Systemic): May enhance the nephrotoxic effect of Fibric Acid Derivatives. Fibric Acid Derivatives may decrease the serum concentration of CycloSPORINE (Systemic). Management: Careful consideration of the risks and benefits should be undertaken prior to use of this combination; extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary. Consider therapy modification Ezetimibe: Fenofibrate and Derivatives may enhance the adverse/toxic effect of Ezetimibe. Specifically, the risk of myopathy and cholelithiasis may be increased. Fenofibrate and Derivatives may increase the serum concentration of Ezetimibe. Monitor therapy Fosphenytoin-Phenytoin: CYP2C9 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Monitor therapy HMG-CoA Reductase Inhibitors (Statins): Fenofibrate and Derivatives may enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Monitor therapy Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. Monitor therapy Sulfonylureas: Fibric Acid Derivatives may enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy Tacrolimus (Systemic): May enhance the nephrotoxic effect of Fenofibrate and Derivatives. Monitor therapy Ursodiol: Fibric Acid Derivatives may diminish the therapeutic effect of Ursodiol. Monitor therapy Vitamin K Antagonists (eg, warfarin): Fibric Acid Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider reducing the oral anticoagulant dose by 25% to 33% when initiating a fibric acid derivative. Monitor for toxic or reduced anticoagulant effects if a fibric acid derivative is initiated/dose increased, or discontinued/dose decreased, respectively. Consider therapy modification Warfarin: Fenofibrate and Derivatives may enhance the anticoagulant effect of Warfarin. Fenofibrate and Derivatives may increase the serum concentration of Warfarin. Management: Monitor for signs and symptoms of bleeding, and increase INR monitoring in patients taking warfarin who are initiated on fenofibrate derivatives. Warfarin dose reductions will likely be required. Consider therapy modification

Caps Store at room temperature, Below 30°C. Protect from Moisture.