Included as part of the PRECAUTIONS section.
NIASPAN preparations should
not be substituted for equivalent doses of immediate-release (crystalline)
niacin. For patients switching from immediate-release niacin to NIASPAN, therapy
with NIASPAN should be initiated with low doses (i.e., 500 mg at bedtime) and
the NIASPAN dose should then be titrated to the desired therapeutic response [see
DOSAGE AND ADMINISTRATION].
Caution should also be used
when NIASPAN is used in patients with unstable angina or in the acute phase of
an MI, particularly when such patients are also receiving vasoactive drugs such
as nitrates, calcium channel blockers, or adrenergic blocking agents.
Niacin is rapidly metabolized
by the liver, and excreted through the kidneys. NIASPAN is contraindicated in
patients with significant or unexplained hepatic impairment [see CONTRAINDICATIONS
and Liver Dysfunction below] and should be used with caution in patients
with renal impairment. Patients with a past history of jaundice, hepatobiliary
disease, or peptic ulcer should be observed closely during NIASPAN therapy.
Mortality And Coronary Heart
NIASPAN has not been shown to
reduce cardiovascular morbidity or mortality among patients already treated
with a statin.
Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on
Global Health Outcomes (AIM-HIGH) trial was a randomized placebo-controlled
trial of 3414 patients with stable, previously diagnosed cardiovascular
disease. Mean baseline lipid levels were LDL-C 74 mg/dL, HDL-C 35 mg/dL,
non-HDL-C 111 mg/dL and median triglyceride level of 163-177 mg/dL. Ninety-four
percent of patients were on background statin therapy prior to entering the
trial. All participants received simvastatin, 40 to 80 mg per day, plus ezetimibe
10 mg per day if needed, to maintain an LDL-C level of 40-80 mg/dL, and were randomized
to receive NIASPAN 1500-2000 mg/day (n=1718) or matching placebo (IR Niacin, 100-150
mg, n=1696). On-treatment lipid changes at two years for LDL-C were -12.0% for
the simvastatin plus NIASPAN group and -5.5% for the simvastatin plus placebo
group. HDL-C increased by 25.0% to 42 mg/dL in the simvastatin plus NIASPAN
group and by 9.8% to 38 mg/dL in the simvastatin plus placebo group
(P < 0.001). Triglyceride levels decreased by 28.6% in the simvastatin plus
NIASPAN group and by 8.1% in the simvastatin plus placebo group. The primary
outcome was an ITT composite of the first study occurrence of coronary heart
disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization
for acute coronary syndrome or symptom-driven coronary or cerebral
revascularization procedures. The trial was stopped after a mean follow-up
period of 3 years owing to a lack of efficacy. The primary outcome occurred in
282 patients in the simvastatin plus NIASPAN group (16.4%) and in 274 patients
in the simvastatin plus placebo group (16.2%) (HR 1.02 [95% CI, 0.87-1.21],
P=0.79. In an ITT analysis, there were 42 cases of first occurrence of ischemic
stroke reported, 27 (1.6%) in the simvastatin plus NIASPAN group and 15 (0.9%)
in the simvastatin plus placebo group, a non-statistically significant result
(HR 1.79, [95%CI = 0.95-3.36], p=0.071). The on-treatment ischemic stroke
events were 19 for the simvastatin plus NIASPAN group and 15 for the simvastatin
plus placebo group [see ADVERSE REACTIONS].
Cases of rhabdomyolysis have
been associated with concomitant administration of lipid-altering doses ( ≥ 1 g/day) of niacin and statins. Elderly patients and patients with diabetes,
renal failure, or uncontrolled hypothyroidism are particularly at risk. Monitor
patients for any signs and symptoms of muscle pain, tenderness, or weakness,
particularly during the initial months of therapy and during any periods of
upward dosage titration. Periodic serum creatine phosphokinase (CPK) and
potassium determinations should be considered in such situations, but there is
no assurance that such monitoring will prevent the occurrence of severe
Cases of severe hepatic
toxicity, including fulminant hepatic necrosis, have occurred in patients who
have substituted sustained-release (modified-release, timed-release) niacin products
for immediate-release (crystalline) niacin at equivalent doses.
NIASPAN should be used with
caution in patients who consume substantial quantities of alcohol and/or have a
past history of liver disease. Active liver diseases or unexplained transaminase
elevations are contraindications to the use of NIASPAN.
Niacin preparations have been
associated with abnormal liver tests. In three placebo-controlled clinical
trials involving titration to final daily NIASPAN doses ranging from 500 to
3000 mg, 245 patients received NIASPAN for a mean duration of 17 weeks. No
patient with normal serum transaminase levels (AST, ALT) at baseline
experienced elevations to more than 3 times the upper limit of normal (ULN)
during treatment with NIASPAN. In these studies, fewer than 1% (2/245) of
NIASPAN patients discontinued due to transaminase elevations greater than 2
times the ULN.
Liver-related tests should be
performed on all patients during therapy with NIASPAN. Serum transaminase
levels, including AST and ALT (SGOT and SGPT), should be monitored before treatment
begins, every 6 to 12 weeks for the first year, and periodically thereafter
(e.g., at approximately 6-month intervals). Special attention should be paid to
patients who develop elevated serum transaminase levels, and in these patients,
measurements should be repeated promptly and then performed more frequently. If
the transaminase levels show evidence of progression, particularly if they rise
to 3 times ULN and are persistent, or if they are associated with symptoms of
nausea, fever, and/or malaise, the drug should be discontinued.
Increase in Blood Glucose
Niacin treatment can increase
fasting blood glucose. Frequent monitoring of blood glucose should be performed
to ascertain that the drug is producing no adverse effects. Diabetic patients
may experience a dose-related increase in glucose intolerance. Diabetic or
potentially diabetic patients should be observed closely during treatment with NIASPAN,
particularly during the first few months of use or dose adjustment; adjustment
of diet and/or hypoglycemic therapy may be necessary.
Reduction in Platelet Count
NIASPAN has been associated
with small but statistically significant dose-related reductions in platelet
count (mean of -11% with 2000 mg). Caution should be observed when NIASPAN is
administered concomitantly with anticoagulants; platelet counts should be
monitored closely in such patients.
Increase in Prothrombin Time
NIASPAN has been associated
with small but statistically significant increases in prothrombin time (mean of
approximately +4%); accordingly, patients undergoing surgery should be
carefully evaluated. Caution should be observed when NIASPAN is administered
concomitantly with anticoagulants; prothrombin time should be monitored closely
in such patients.
Increase in Uric Acid
Elevated uric acid levels have
occurred with niacin therapy, therefore use with caution in patients
predisposed to gout.
Decrease in Phosphorus
In placebo-controlled trials,
NIASPAN has been associated with small but statistically significant,
dose-related reductions in phosphorus levels (mean of -13% with 2000 mg).
Although these reductions were transient, phosphorus levels should be monitored
periodically in patients at risk for hypophosphatemia.
Patient Counseling Information
Patients should be advised to
adhere to their National Cholesterol Education Program (NCEP) recommended diet,
a regular exercise program, and periodic testing of a fasting lipid panel.
Patients should be advised to
inform other healthcare professionals prescribing a new medication that they
are taking NIASPAN.
The patient should be informed
of the following:
NIASPAN tablets should be taken
at bedtime, after a low-fat snack. Administration on an empty stomach is not
NIASPAN tablets should not be
broken, crushed or chewed, but should be swallowed whole.
If dosing is interrupted for
any length of time, their physician should be contacted prior to restarting
therapy; re-titration is recommended.
Notify their physician of any
unexplained muscle pain, tenderness, or weakness promptly. They should discuss
all medication, both prescription and over the counter, with their physician.
Flushing (warmth, redness,
itching and/or tingling of the skin) is a common side effect of niacin therapy
that may subside after several weeks of consistent NIASPAN use. Flushing may
vary in severity and is more likely to occur with initiation of therapy, or
during dose increases. By dosing at bedtime, flushing will most likely occur
during sleep. However, if awakened by flushing at night, the patient should get
up slowly, especially if feeling dizzy, feeling faint, or taking blood pressure
medications. Advise patients of the symptoms of flushing and how they differ
from the symptoms of a myocardial infarction.
Use of Aspirin Medication
Taking aspirin (up to the
recommended dose of 325 mg) approximately 30 minutes before dosing can minimize
Avoid ingestion of alcohol, hot
beverages and spicy foods around the time of taking NIASPAN to minimize
Notify their physician if they
are taking vitamins or other nutritional supplements containing niacin or
Notify their physician if
symptoms of dizziness occur.
If diabetic, to notify their
physician of changes in blood glucose.
Discuss future pregnancy plans
with your patients, and discuss when to stop NIASPAN if they are trying to
conceive. Patients should be advised that if they become pregnant, they should
stop taking NIASPAN and call their healthcare professional.
Women who are breastfeeding
should be advised to not use NIASPAN. Patients, who have a lipid disorder and
are breastfeeding, should be advised to discuss the options with their healthcare
Carcinogenesis And Mutagenesis
and Impairment Of Fertility
Niacin administered to mice for
a lifetime as a 1% solution in drinking water was not carcinogenic. The mice in
this study received approximately 6 to 8 times a human dose of 3000 mg/day as
determined on a mg/m² basis. Niacin was negative for mutagenicity in the Ames
test. No studies on impairment of fertility have been performed. No studies
have been conducted with NIASPAN regarding carcinogenesis, mutagenesis, or
impairment of fertility.
Use In Specific Populations
Pregnancy Category C.
Animal reproduction studies
have not been conducted with niacin or with NIASPAN. It is also not known
whether niacin at doses typically used for lipid disorders can cause fetal harm
when administered to pregnant women or whether it can affect reproductive capacity.
If a woman receiving niacin for primary hyperlipidemia becomes pregnant, the
drug should be discontinued. If a woman being treated with niacin for
hypertriglyceridemia conceives, the benefits and risks of continued therapy
should be assessed on an individual basis.
Niacin is excreted into human
milk but the actual infant dose or infant dose as a percent of the maternal
dose is not known. Because of the potential for serious adverse reactions in
nursing infants from lipid-altering doses of nicotinic acid, a decision should
be made whether to discontinue nursing or to discontinue the drug, taking into
account the importance of the drug to the mother. No studies have been
conducted with NIASPAN in nursing mothers.
Safety and effectiveness of
niacin therapy in pediatric patients ( ≤ 16 years) have not been established.
Of 979 patients in clinical
studies of NIASPAN, 21% of the patients were age 65 and over. No overall
differences in safety and effectiveness were observed between these patients
and younger patients, and other reported clinical experience has not identified
differences in responses between the elderly and younger patients, but greater
sensitivity of some older individuals cannot be ruled out.
No studies have been performed
in this population. NIASPAN should be used with caution in patients with renal
impairment [see WARNINGS AND PRECAUTIONS].
No studies have been performed
in this population. NIASPAN should be used with caution in patients with a past
history of liver disease and/or who consume substantial quantities of alcohol. Active
liver disease, unexplained transaminase elevations and significant or
unexplained hepatic dysfunction are contraindications to the use of NIASPAN [see
CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].
Data from the clinical trials
suggest that women have a greater hypolipidemic response than men at equivalent
doses of NIASPAN.