SIMCOR® (niacin extended-release/simvastatin tablets)
Flushing
Flushing Data
Tips to Help Manage Flushing
Heart Alliance Patient Support Program

Flushing

Flushing Data

Flushing decreased as treatment continued

Flushing (warmth, redness, itching and/or tingling of the skin) is the most common side effect associated with SIMCOR. Flushing most often occurs on the skin of the face, neck, chest and back. It is caused by vasodilation.

Flushing was transient in the OCEANS Study


Percent of Patients Experiencing at Least 1 Flushing Episode in the OCEANS study1-3,a

Flushing in Simcor treatment case study

aDue to protocol amendment required by the FDA, study duration was changed from 52 weeks to 24 weeks during the course of study. The mean time patients were on study medication was 31.6 weeks.

CL indicates the number of patients who completed flushing logs. For weeks 25–32, 26% (CL=283) of patients flushed. For weeks 33–40, 33% (CL=213) of patients flushed.

In the OCEANS study (N=509), at least 1 episode of flushing occurred in 71% of patients. In patients taking up to a maximum dose of SIMCOR (2000/40 mg), 7% of patients discontinued due to flushing. 92% of flushing episodes were mild or moderate in intensity. a,4

Adverse events (≥3%) in addition to flushing: In the OCEANS study, SIMCOR (n=509) up to 1 year: pruritus 5.1%, nausea 4.1%, HbA1c increased 4.1%, serum CPK increased 3.3%, blood glucose increased by 3.1%.a,3

Flushing in the SEACOAST Clinical Trial

The percentage of SIMCOR-treated patients experiencing at least 1 flushing event (warmth, redness, itching, and/or tingling of the skin) was 59% in the SEACOAST study (n=403)1,*
85.5% of flushing episodes were mild to moderate1,†
6% of patients discontinued in the SEACOAST study due to flushing4

SEACOAST high-dose flushing data:

Of all SEACOAST II study completers in the 1000/40-mg dose group who flushed at least once during the first 12 weeks and remained in the study for the full 24 weeks, 46% did not flush during the second 12 weeks.2 Of those in the 2000/40-mg dose group who flushed at least once during the first 12 weeks and remained in the study for the full 24 weeks, 52% did not flush during the second 12 weeks.

Patients were permitted to take 325 mg of aspirin 30 minutes prior to study drug to help manage flushing.4

* In the SEACOAST study, the incidence of flushing (percentage of patients reporting at least 1 flushing event) and flushing intensity (mild, moderate, severe) were measured by flushing logs.1 In the OCEANS study, the incidence of flushing (percentage of patients) and the median flushing intensity were measured by flushing logs. Flushing intensity was categorized as mild (patients aware of event, easily tolerated it, did not limit usual activities), moderate (event caused some limitation to usual activities), or severe (patients unable to carry out usual activities due to event).

For SEACOAST and OCEANS full study designs, click here to expand. To hide study design details, please click here.

SEACOAST study design4,2,5
A double-blind, randomized, multicenter, active-controlled, 24-week study compared the efficacy and safety of SIMCOR with low-dose and high-dose simvastatin in adult patients (N=641) with Type II hyperlipidemia or mixed dyslipidemia.

Low-dose
Depending on their baseline lipid levels, patients (n=319) were either treatment naïve or received simvastatin 20-mg/day run-in for ≥2 weeks. Patients were then randomized to receive simvastatin 20 mg, SIMCOR 1000/20 mg, SIMCOR 2000/20 mg daily. All randomized patients had elevated non–HDL-C levels and LDL-C levels that were at goal. The primary efficacy endpoint was percentage change from baseline to Week 24 in non–HDL-C. Secondary efficacy endpoints were percentage change from baseline to Week 24 in other lipids, including LDL-C and HDL-C. SIMCOR is not supplied in a 2000/20-mg tablet.

High-dose
Patients (n=343) received simvastatin 40 mg/day run-in for ≥2 weeks and then were randomized to receive SIMCOR 1000/40 mg, SIMCOR 2000/40 mg, or simvastatin 80 mg daily. All randomized patients had elevated non–HDL-C levels and LDL-C levels that were either elevated or at goal. The primary efficacy endpoint was percentage change from baseline to Week 24 in non–HDL-C. Secondary efficacy endpoints were percentage change from baseline to Week 24 in other lipids, including LDL-C, HDL-C, and TG.

OCEANS study design1,3
An open-label, randomized, multicenter study evaluated the safety and efficacy of SIMCOR in adult patients (N=520) with primary Type II hyperlipidemia or mixed dyslipidemia. Patients who continued to have elevated non–HDL-C after receiving simvastatin 40 mg/day run-in for ≥4 weeks were randomized to receive 1 of 2 SIMCOR titration regimens for up to 52 weeks. Doses were titrated over an 8- or 12-week period to a maximum dose of SIMCOR 2000/40 mg/day. The primary objective was to evaluate the long-term safety of SIMCOR 2000/40 mg. The secondary objective was to determine percent change from baseline to Week 24 in non-HDL-C and other lipid parameters, including LDL-C, HDL-C, and TG. Efficacy analyses were performed on (1) a modified intention-to-treat (mITT) patient population consisting of all patients contributing efficacy data at baseline and at least one post-baseline visit and (2) an on-treatment population consisting of all patients in pooled titration groups contributing efficacy data at baseline and at least one post-baseline visit beyond Week 24.

† 55.6% of flushing episodes were mild and 29.9% were moderate.1

Indications and Important Safety Information4

INDICATIONS FOR SIMCOR® (niacin extended-release/simvastatin)

Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and other nonpharmacological measures alone has been inadequate.
SIMCOR is indicated as an adjunct to diet to reduce total-C, LDL-C, Apo B, non–HDL-C, or TG, or to increase HDL-C in patients with primary hypercholesterolemia and mixed dyslipidemia when treatment with simvastatin monotherapy or niacin extended-release monotherapy is considered inadequate.
SIMCOR is indicated to reduce TG in patients with hypertriglyceridemia when treatment with simvastatin monotherapy or niacin extended-release monotherapy is considered inadequate.
Limitations of Use: No incremental benefit of SIMCOR on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin monotherapy and niacin monotherapy has been established.
The AIM-HIGH study (terminated due to futility) showed no cardiovascular outcome benefit in patients with well-controlled LDL-C (40-80 mg/dL) using niacin extended-release/simvastatin vs. simvastatin.6

IMPORTANT SAFETY INFORMATION FOR SIMCOR

SIMCOR is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases, active peptic ulcer disease, or arterial bleeding; in women who are pregnant or may become pregnant; in nursing mothers; in patients with hypersensitivity to any product ingredient; and with concomitant administration of strong CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, and nefazodone), gemfibrozil, cyclosporine, danazol, verapamil, or diltiazem.
SIMCOR contains simvastatin, which occasionally causes myopathy manifested as muscle pain, tenderness, or weakness with CK levels above 10X ULN. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Risks of myopathy increase with higher doses, concomitant use of certain medicines (e.g. amiodarone, amlodipine, ranolazine, and colchicine), and consuming large quantities of grapefruit juice (>1 quart daily). Predisposing factors include advanced age (≥65), female gender, uncontrolled hypothyroidism, renal impairment, and Chinese ethnicity.
Myopathy and/or rhabdomyolysis have been reported when simvastatin is used in combination with lipid-altering doses (≥1 g/day) of niacin. All patients starting therapy with SIMCOR, or whose dose of SIMCOR is being increased, should be advised of the risk of myopathy, including rhabdomyolysis, and told to report symptoms promptly. SIMCOR therapy should be discontinued if markedly elevated creatine phosphokinase (CPK) levels occur or myopathy is diagnosed or suspected. Periodic serum creatine kinase (CK) tests should be considered in this situation.
SIMCOR should not be substituted for equivalent doses of immediate-release niacin. Severe hepatic toxicity has occurred in patients substituting sustained-release niacin for immediate-release niacin at equivalent doses. If switching from niacin preparations other than niacin extended-release, initiate with the lowest SIMCOR dose. The efficacy and safety of doses of SIMCOR >2000/40 mg daily have not been studied and are therefore not recommended.
SIMCOR can increase serum transaminases. Check liver enzymes before initiating treatment and as clinically indicated thereafter. If serious liver injury with clinical symptoms occurs during treatment with SIMCOR, promptly interrupt therapy.
SIMCOR should be used with caution in patients with renal disease, a past history of liver disease, and/or who consume substantial quantities of alcohol.
SIMCOR can increase serum glucose levels. Glucose levels should be monitored in diabetic or potentially diabetic patients, particularly during the first few months of use.
SIMCOR can reduce platelet count and phosphorus levels, and increase uric acid levels and prothrombin time (PT). In patients taking coumarin anticoagulants, monitor PT and INR before and during treatment.
Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors,including simvastatin
The most common adverse event with SIMCOR is flushing (warmth, redness, itching, and/or tingling of the skin). Flushing may vary in severity and is more likely to occur with initiation of therapy or during dose increases. Advise patients of the symptoms of flushing and how they differ from the symptoms of an MI.
Other common adverse events reported by ≥3% of patients receiving SIMCOR were headache, pruritus, nausea, back pain, and diarrhea.

Please see full Prescribing Information.

References

  1. Data on file, Abbott Laboratories.
  2. Ballantyne CM, Davidson MH, McKenny JM, et al. Comparison of the efficacy and safety of a combination tablet of niacin extended-release and simvastatin with simvastatin 80 mg monotherapy: the SEACOAST II (high-dose) study. J Clin Lipid. 2008;2:79-90.
  3. Karas RH, Kashyap ML, Knopp RH, et al. Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS Study. Am J Cardiovasc Drugs. 2008;8:69-81.
  4. SIMCOR [package insert]. North Chicago, IL: Abbott Laboratories.
  5. Ballantyne CM, Davidson MH, McKenney J, et al. Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non–HDL cholesterol: from the SEACOAST I study. Am J Cardiol. 2008;101:1428–1436.
  6. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Eng J Med. 2011;365:2255-2267.
Important Safety Information| Prescribing Information| Home| Terms of Use| Privacy Policy| Site Map| Contact Us
Copyright © 2012 Abbott Laboratories. Abbott Park, Illinois, U.S.A.

306-777613