"The U.S. Food and Drug Administration today approved Kynamro (mipomersen sodium) injection as an addition to lipid-lowering medications and diet to treat patients with a rare type of high cholesterol called homozygous familial hypercholesterolemi"...
In controlled clinical studies, 40/214 (19%) of patients randomized to ADVICOR discontinued therapy prior to study completion. Of the 214 patients enrolled 18 (8%) discontinued due to flushing. In the same controlled studies, 9/94 (10%) of patients randomized to lovastatin and 19/92 (21%) of patients randomized to NIASPAN also discontinued treatment prior to study completion secondary to adverse events. Flushing episodes (i.e., warmth, redness, itching and/or tingling) were the most common treatment-emergent adverse events, and occurred in 53% to 83% of patients treated with ADVICOR. Spontaneous reports with NIASPAN and clinical studies with ADVICOR suggest that flushing may also be accompanied by symptoms of dizziness or syncope, tachycardia, palpitations, shortness of breath, sweating, burning sensation/skin burning sensation, chills, and/or edema.
Adverse Reactions Information
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. The adverse reaction information from clinical studies does, however provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
The data described in this section reflect the exposure to ADVICOR in two double-blind, controlled clinical studies of 400 patients. The population was 28 to 86 years-of-age, 54% male, 85% Caucasian, 9% Black, and 7% Other, and had mixed dyslipidemia.
In addition to flushing, other adverse events occurring in 5% or greater of patients treated with ADVICOR are shown in Table 10 below.
Table 10: Treatment-Emergent
Adverse Events in ≥ 5% of Patients (Events Irrespective of Causality;
Data from Controlled, Double-Blind Studies)
|Total Number of Patients||214||92||94|
|Cardiovascular||163 (76%)||66 (72%)||24 (26%)|
|Flushing||152 (71%)||60 (65%)||17 (18%)|
|Body as a Whole||104 (49%)||50 (54%)||42 (45%)|
|Asthenia||10 ( 5%)||6 ( 7%)||5 ( 5%)|
|Flu Syndrome||12 ( 6%)||7 ( 8%)||4 ( 4%)|
|Headache||20 ( 9%)||12 (13%)||5 ( 5%)|
|Infection||43 (20%)||14 (15%)||19 (20%)|
|Pain||18 ( 8%)||3 ( 3%)||9 (10%)|
|Pain, Abdominal||9 ( 4%)||1 ( 1%)||6 ( 6%)|
|Pain, Back||10 ( 5%)||5 ( 5%)||5 ( 5%)|
|Digestive System||51 (24%)||26 (28%)||16 (17%)|
|Diarrhea||13 ( 6%)||8 ( 9%)||2 ( 2%)|
|Dyspepsia||6 ( 3%)||5 ( 5%)||4 ( 4%)|
|Nausea||14 ( 7%)||11 (12%)||2 ( 2%)|
|Vomiting||7 ( 3%)||5 ( 5%)||0|
|Metabolic and Nutrit. System||37 (17%)||18 (20%)||13 (14%)|
|Hyperglycemia||8 ( 4%)||6 ( 7%)||6 ( 6%)|
|Musculoskeletal System||19 ( 9%)||9 (10%)||17 (18%)|
|Myalgia||6 ( 3%)||5 ( 5%)||8 ( 9%)|
|Skin and Appendages||38 (18%)||19 (21%)||11 (12%)|
|Pruritus||14 ( 7%)||7 ( 8%)||3 ( 3%)|
|Rash||11 ( 5%)||11 (12%)||3 ( 3%)|
Note: Percentages are calculated from the total number of patients in each column.
See also the full prescribing information for niacin extended release (Niaspan) and lovastatin products.
The following adverse events have also been reported with niacin, lovastatin, and/or other HMG-CoA reductase inhibitors, but not necessarily with ADVICOR, either during clinical studies or in routine patient management.
|Body as a Whole:||chest pain; abdominal pain; edema; chills; malaise|
|Cardiovascular:||atrial fibrillation; tachycardia; palpitations, and other cardiac arrhythmias; postural hypotension, orthostasis; hypotension; syncope|
|Eye:||toxic amblyopia; cystoid macular edema; ophthalmoplegia; eye irritation, blurred vision, progression of cataracts|
|Gastrointestinal:||activation of peptic ulcers and peptic ulceration; dyspepsia; vomiting; anorexia; constipation; flatulence, pancreatitis; hepatitis; fatty change in liver; jaundice; and rarely, cirrhosis, fulminant hepatic necrosis, and hepatoma, eructation, fatal and non-fatal hepatic failure|
|Metabolic:||gout, decreased glucose tolerance|
|Musculoskeletal:||muscle cramps; myopathy; rhabdomyolysis; arthralgia, myalgia|
|Nervous:||dizziness; insomnia; dry mouth; paresthesia; anxiety; tremor; vertigo; peripheral neuropathy; psychic disturbances; dysfunction of certain cranial nerves, nervousness, burning sensation/skin burning sensation, peripheral nerve palsy|
|Skin:||hyper-pigmentation; acanthosis nigricans; urticaria; alopecia; dry|
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Clinical Laboratory Abnormalities
Elevations in serum transaminases (see WARNINGS - Liver Dysfunction), CPK and fasting glucose, and reductions in phosphorus. Niacin extended-release tablets have been associated with slight elevations in LDH, uric acid, total bilirubin, amylase and creatine kinase. Lovastatin and/or HMG-CoA reductase inhibitors have been associated with elevations in alkaline phosphatase, γ-glutamyl transpeptidase and bilirubin, and thyroid function abnormalities.
Niacin extended-release tablets have been associated with slight reductions in platelet counts and prolongation in PT (see WARNINGS).
Drug Abuse And Dependence
Neither niacin nor lovastatin is a narcotic drug. ADVICOR has no known addiction potential in humans.
Read the Advicor (niacin xr and lovastatin) Side Effects Center for a complete guide to possible side effects
Antihypertensive Therapy – Niacin may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension.
Aspirin: Concomitant aspirin may decrease the metabolic clearance of niacin. The clinical relevance of this finding is unclear.
Bile Acid Sequestrants – An in vitro study was carried out investigating the niacin-binding capacity of colestipol and cholestyramine. About 98% of available niacin was bound to colestipol, with 10 to 30% binding to cholestyramine. These results suggest that 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 ADVICOR.
Other – Concomitant alcohol or hot drinks may increase the side effects of flushing and pruritus and should be avoided around the time of ADVICOR ingestion. Vitamins or other nutritional supplements containing large doses of niacin or related compounds such as nicotinamide may potentiate the adverse effects of ADVICOR.
Lovastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, and erythromycin), and large quantities of grapefruit juice ( >1 quart daily) increase the risk of myopathy by reducing the elimination of lovastatin (See WARNINGS, Myopathy/Rhabdomyolysis).
In vitro studies have demonstrated that voriconazole inhibits the metabolism of lovastatin. Adjustment of the lovastatin dose may be needed to reduce the risk of myopathy, including rhabdomyolysis, if voriconazole must be used concomitantly with lovastatin.
Interactions With Lipid-Lowering Drugs That Can Cause Myopathy When Given Alone
The risk of myopathy is also increased by the following lipid-lowering drugs that are not strong CYP3A4 inhibitors, but which can cause myopathy when given alone. See WARNINGS, Myopathy/Rhabdomyolysis.
Other Drug Interactions
Cyclosporine: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of cyclosporine (see WARNINGS, Myopathy/Rhabdomyolysis).
Danazol, Diltiazem, or Verapamil: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of danazol, diltiazem, or verapamil particularly with higher doses of lovastatin (see WARNINGS, Myopathy/Rhabdomyolysis and CLINICAL PHARMACOLOGY, Pharmacokinetics).
Amiodarone: The risk of myopathy/rhabdomyolysis is increased when amiodarone is used concomitantly with a closely related member of the HMG-CoA reductase inhibitor class (see WARNINGS, Myopathy/Rhabdomyolysis)
Coumarin Anticoagulants – In a small clinical study in which lovastatin was administered to warfarin-treated patients, no effect on PT was detected. However, another HMG-CoA reductase inhibitor has been found to produce a less than two seconds increase in PT in healthy volunteers receiving low doses of warfarin. Also, bleeding and/or increased PT have been reported in a few patients taking coumarin anticoagulants concomitantly with lovastatin. It is recommended that in patients taking anticoagulants, PT be determined before starting ADVICOR and frequently enough during early therapy to insure that no significant alteration of PT occurs. Once a stable PT has been documented, PT can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of ADVICOR is changed, the same procedure should be repeated.
Colchicine – Cases of myopathy, including rhabdomyolysis, have been reported with lovastatin coadministered with colchicine.
Ranolazine – The risk of myopathy, including rhabdomyolysis, may be increased by concomitant administration of ranolazine.
Propranolol – In normal volunteers, there was no clinically significant pharmacokinetic or pharmacodynamic interaction with concomitant administration of single doses of lovastatin and propranolol.
Digoxin – In patients with hypercholesterolemia, concomitant administration of lovastatin and digoxin resulted in no effect on digoxin plasma concentrations.
Oral Hypoglycemic Agents – In pharmacokinetic studies of lovastatin in hypercholesterolemic, non-insulin dependent diabetic patients, there was no drug interaction with glipizide or with chlorpropamide.
Drug/Laboratory Test Interactions
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.
Read the Advicor Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 4/26/2012
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